Mastering Advanced

Surface Ablation Techniques

 Mastering Advanced
Surface Ablation Techniques
Editors
Ashok Garg MS, PhD, FIAO (Bel), FRSM, ADM, FAIMS, FICA Jorge L Alio MD, PhD
International and National Gold Medalist Chairman and Professor of OphthalmologyInstituto
Chairman and Medical Director Oftalmologico De Alicante
Garg Eye Institute and Research Centre Avda. Denia 111, 03015
235-Model Town, Dabra Chowk, Hisar-125005 (India) Alicante
JT Lin PhD Spain
Technical Director, New Visionul Inc. Frank Jozef Goes FD
Room 826, No. 144, Section 3 Medical Director
Min-Chuan East Road Taipei, Taiwan 105 Goes Eye Centre, W Klooslaan 6 B2050
Christopher J Rapuano MD Antwerp
Co-Director, Cornea Service and Refractive Belgium
Surgery Deptt., Wills Eye Institute Jerome Jean Bovet MD
Prof Jefferson Medical College Consultant Ophthalmic Surgeon FMH
Of Thomas Jefferson University Clinique de L’oeil, 15
Philadelphia, PA 19170 Avenyue Du Bois-de-law Chapelle
A John Kanellopoulos MD CH-1213, Onex
Director, Laservision gr. Institute Switzerland
Mesogeion 2 Str Roberto Pinelli MD
Athens Tower Building B
Director, Istituto Laser Microchirurgia
11527–Athens, Greece
Oculare Crystal Palace, Via Cefalonia
Frederic Hehn MD 70, 25124, Brescia
Chief and Medical Director Italy
Centre de La Vision, Nations-Vision
Bojan Pajic MD
23, Boulevard de l’europe
Chief of the Cornea and Refractive
54500, Vandoeuvre, France
Surgery Department
Cyres K Mehta MS, FSVH, FAGE Klinik Pallas
Director and Consultant Louis Giroud-Str. 20
Mehta International Eye Institute 147, Colaba Road
Seaside, 147, Colaba Road, Seaside 4600 Olten
147, Colaba Road, Mumbai–400005, India Switzerland

Foreword
Emanuel Rosen
®

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Mastering Advanced Surface Ablation Techniques

© 2008, Jaypee Brothers Medical Publishers
All rights reserved. No part of this publication and DVD-ROM should be reproduced, stored in a retrieval system, or transmitted
in any form or by any means: electronic, mechanical, photocopying, recording, or otherwise, without the prior written permission
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This book has been published in good faith that the materials provided by contributors is original. Every effort is made to
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First Edition: 2008

ISBN 978-81-8448-218-8
Typeset at JPBMP typesetting unit
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 Dedicated to
My Respected Param Pujya Guru Sant Gurmeet Ram Rahim Singh Ji for his blessings and motivation.
My respected parents, teachers, my wife Aruna Garg, son Abhishek and daughter Anshul for their constant
support and patience during all these days of hard work.
My dear friend Amar Agarwal, a renowned International Ophthalmologist for
his constant support, guidance and expertise.
— Ashok Garg

To Mayca, Jorge, Fernando and Maria Lucia and most especially to my beloved wife Maria, for the hours
that were taken from our family life to make this book possible.
— Jorge L Alio

My wife, Jeanette and my sons Alex and Tao, who have been giving me constant support and love.
— JT Lin

My wife, Rita, for the support in my Professional Career and to my four grandchildren—Stephanie,
William, Louise and Vincent – with the hope that at least one of them will become an ophthalmologist—
as their father and
their Daddy did.
— Frank Jozef Goes

My wounderful wife, Sara, a terrific partner at home and at work and to my children, Michael, Patrick,
Daniel and Megan, who never stop reminding me what is important in life.
— Christopher J Rapuano

Yveric, Luc and Fanny Laur.

Silvio Korol, who was not only a teacher but also an intellectual guide and a friend.
— Jerome Bovet

My parents, the endless and willing teachers and my family: my wonderful wife Nathalie, and our
children: Alexander, Angelina and Konstantine.
— A John Kanellopoulos

I dedicate this book to India’s Talented ophthalmologists, in the fervent hope that they may become
increasingly devoted to refractive surgery.
— Roberto Pinelli

My wife, Marie Laurence and my children Thibaut, David, Carole and Lola.
— Frederic Hehn

To my son Valentin Aleksandar.

— Bojan Pajic

My parents for everything.

To Vini my Best friend.
— Cyres K Mehta
 CONTRIBUTORS

A John Kanellopoulos MD Ashok Garg MS, PhD, FRSM,

Director, Laser Vision Gr. Institute Chairman and Medical Director,
Athens, Greece. Garg Eye Institute and Research Centre,
235-Model Town, Dabra Chowk,
Ahmad Salamat Rad MD
Hisar–125005, India.
CustomVis Ground Floor, 110 Erindale Road,
Balcatta - Western Australia-6021 Auguste Chiou MD
Australia. Consultant Ophthalmic Surgeon, FMH
Clinique de I’oeil, 15, Avenue du Bois-de-la-
Annick Ludwig PhD
Chapelle, CH-1213 Onex, Switzerland.
Laboratory of Pharmaceutical
Technology and Biopharmacy, Bahri Aydin
University of Antwerp, Fath University,
Antwerp, Belgium. Opthalmology Department,
Aplarslan Turkep Cad. No.57,
Antonio Calossi MD
06510 Emek, ANKARA
Via 2 Giugno 52, 50053, Certaldo (FI),
Italy. Belquiz A Nassaralla MD, PhD
Goiania Eye Institute,
António Marinho MD, PhD
Department of Cornea and Refractive
Professor of Ophthalmology
Surgery, Goiania, GO,
University of Porto, R Crasto 708,
Brazil.
4150-243, Porto, Portugal.
Bojan Pajic MD
Arthur Cheng MD
Chief of the Cornea and Refractive
Department of Ophthalmology and Visual
Surgery Department,
Sciences,
Klinik Pallas, Louis Giroud-Str. 20
The Chinese University of Hongkong
4600 Olten, Switzerland.
C/o Prince of Wales Hospital,
7B, Staff Quarters, Shatin, NT, Hong Kong SAR, C Banu Cosar MD
PRC, China. Associate Professor of Ophthalmology
Sinpas Aqua City 1. Etap
Arturo Pérez-Artega MD
H Block D:13A. Dudullu 80260
Medical Director,
Istanbul, Turkey.
Centro Oftalmologico Tlalnepantla,
Dr Perez-Arteaga Vallarta no. 42, Caitriona Kirwan MD
Tlalnepantla, Centro, Estado de Mexico Department of Refractive Surgery
54000, Mexico. Mater Private Hospital,
Eccles St, Dublin 7, Ireland.
Arun C Gulani MD
Director Gulani Vision Institute, Carlo Francesco Lovisolo MD
8075 Gate Parkway (W), Medical Director, QuattroElle Eye Center,
Suite 102 and 103, Jacksonville, via Cusani, 7-9, 20121, Milano,
Florida—32216, USA. Italy.
VIII Mastering Advanced Surface Ablation Techniques
Charles WM Stewart MD Danny Mathysen MSc
QuattroElle Eye Center, Department of Ophthalmology,
via Cusani, 7-9, 20121, Milano, Italy. University Hospital of Antwerp,
Antwerp, Belgium.
Chitra Ramamurthy MD
The Eye Foundation, 582-A, DB Road, David Donate PhD
RS Puram, Coimbatore–641002 Laboratorie Biotechnologie et Oeil
Tamil Nadu, India. Universite Paris V, 1, Place du Parvis Notre-Dame
75181 Paris cedex 4, France.
Chris P Lohmann MD, PhD
Universitats-Augenklinik David PS O’Brart MD, FRCS, FRCOphth
Franz-Josef-Strau B-Allee Department of Ophthalmology,
D-93042, Regensburg, Germany St. Thomas’ Hospital, London,
UK.
Christopher J Rapuano MD
Co-Director, Cornea Service, Wills Eye Institute Dennis SC Lam MD, FRCO
Co-Director, Refractive Surgery Department, Wills Professor of Ophthalmology
Eye Institute, Professor of Ophthalmology Dept. of Ophthalmology and Visual Sciences,
Jefferson Medical College, Thomas Jefferson The Chinese University of Hong Kong
University, Philadelphia, Pennsylvania 3/F, Hong Kong Eye Hospital, 147K Argyle Street,
Cornea Service, Wills Eye Institute Kowloon, HKSAR PRC, China.
840 Walnut Street, Suite 920, Philadelphia, PA 19107
Dimitrii Dementiev MD
USA
Chief and Medical Director,
Chu Renyuan MD Blue Eye Centro di, Michro Chirurgia Oculare Eye
Eye and ENT Hospital Clinic, Arese 20020 (MI), Via Campo
Fudan University, allo 21/10, Italy.
Shanghai, China.
Doga A MD
Claes Feinbaum MD S. Fyodorov Eye Microsurgery
Professor Emeritus Optometry, Complex State Institution,
OkoMedica, Warsaw, Poland 127486 Moscow, Beskudnikovsky blvd 59A
Russia.
D Ramamurthy MD
Medical Director, The Eye Foundation E Milani MD
582-A, DB Road, RS Puram, QuattroElle Eye Center, via Cusani, 7-9, 20121
Coimbatore–641002 Milano, Italy.
Tamil Nadu, India. Edward E Manche MD
Dai Jinhui MD Director of Cornea and Refractive
Eye and ENT Hospital Surgery, Associate Professor
Fudan University, Shanghai, Stanford University School of
China. Medicine, 900 Blake Wilbur Drive,
W 3002, Stanford, CA 94304,
Daniel S Durrie MD USA.
Medical Director
Durrie Vision, 5520 College Boulevard Emanuel Rosen MD
Overland Park, Kansas 66211 Rosen Eye Associates, Harbour City,
USA. Salford Quays, M50 3 BH, UK
 Contributors IX
FJ Zhang MD Jean-Marc Legeais MD PhD
Department of Ophthalmology, Hopital HOTEL DIEU, Service d’Ophthalmologie
The First Affiliated Hospital, 1, Place du Parvis Notre Dame
Dalian Medical University, 75181, Paris Cedex 04, France.
Dalian, China–116011.
Jenna M Burka
Frank Goes MD 3000 Washington Blvd,
Director, Goes Eye Centre, #526, Arlington,
W Klooslaan 6 B2050, Antwerp, Belgium. VA. 22201,
Frederic Hehn MD USA
Centre de La Vision, Nations - Vision, Jeroen JG Beerthuizen MD FEBOphth.
23, Boulevard de l’europe 54500, Vandoeuvre, Department of Ophthalmology,
France.
VU University Medical Center,
George A Kounis BSc, PhD De Boelelaan 1117, 1081 HV, Amsterdam,
Department of Ophthalmology, Institute of Vision Netherland.
and Optics, University of Crete, Greece.
Jerome Bovet MD
George D Kymionis MD, PhD Consultant Ophthalmic Surgeon, FMH
Department of Ophthalmology, Clinique de I’oeil,
Institute of Vision and Optics, 15, Avenue du Bois-de-la-Chapelle,
University of Crete, Greece. CH-1213 Onex, Switzerland.
Grace Lie MD Jes Mortensen MD
Department of Ophthalmology, The Eye Department, Orebro University Hospital
University Hospital Antwerp, Wilrijkstraat 10,
SE-70185 Orebro, Sweden.
B-2650, Edegem (Antwerp) Belgium.
Jichang He PhD
Hermann Anhalm PhD
Tianjin Medical University,
Senior Optometrist, Deptt. of Ophthalmology,
Tianjin Eye Hospial and Eye Institute
Klinik Pallas, Louis Giroud-Str. 20
No.4, Gansu Rd, Tianjin 20020, China
4600 Olten, Switzerland.
João J Nassaralla Jr MD PhD
I-Jong Wang MD PhD
Faculty of Health Sciences
Department of Ophthalmology
University of Brasilia, DF
National Taiwan University Hospital, Goiania Eye Institute,
Taipei, Taiwan. Department of Retina and Vitreosu
Ioannis G Pallikaris MD PhD Goiania, GO, Brazil.
Director, Department of Ophthalmology, Jörg Müller MS
Institute of Vision and Optics, Department of Ophthalmology, Klinik Pallas,
University of Crete, Greece. Louis Giroud-Str. 20 4600 Olten
Iwona Liberek MD PhD Switzerland.
Head of the Ophthalmology Clinic Jorge L Alió MD, PhD
Post Graduate Centre of Medical Professor and Chairman,
Education, SPSK im. Prof. W. Or3owswkiego Instituto Oftalmologico De Alicante,
00-416, Warszawa, tul. Czerniakowska 231 Avda. Denia 111, 03016, Edificio Vissum, Alicante,
Poland. Spain.
X Mastering Advanced Surface Ablation Techniques
JT Lin PhD Maria I Kalyvianaki MD
Technical Director, New Vision, Inc. Department of Ophthalmology,
Room # 826, Section 3, No. 144, University of Crete, Heraklion, Crete, Greece.
Min-Chuan East Road, Taipei, Taiwan 105.
Marie-José Tassignon MD PhD
Juha M Holopainen MD Department of Ophthalmology,
Department of Ophthalmology, University Hospital Antwerp,
University of Helsinki, Finland. Wilrijkstraat 10, B-2650,
Edegem (Antwerp) Belgium.
Justyna Izdebska MD PhD
Department of Ophthalmology, Massimo Camellin MD
Warsaw Medical University, Consultant Ophthalmologist
Warsaw, Poland. Rovigo, Italy.

Kachalina G MD Maychuk N MD
Department of Ophthalmology S Fyodorov Eye Microsurgery
S Fyodorov Eye Microsurgery Complex State Institution, 127486 Moscow,
Complex State Institution, Beskudnikovsky blvd 59A,
127486 Moscow, Beskudnikovsky blvd 59A Russia.
Russia.
Michael O’ Keefe FRCS
Kanxing Zhao MD PhD Professor, Department of Refractive Surgery
Tianjin Medical University, Mater Private Hospital,
Tianjin Eye Hospital and Eye Institute Eccles St, Dublin 7, Ireland.
No.4, Gansu Rd, Tianjin 20020
Miguel A Teus MD
China.
Consultant Ophthalmologist,
Laura de Benito-Llopis MD Universidad de Alcla Madrid, Spain.
Consultant Ophthalmologist,
Mikhail Pojaritsky MD
Vissum Madrid, Spain. Blue Eye Centro di,
Lee T Nordan MD Michro Chirurgia Oculare Eye Clinic,
Gulani Vision Institute, 8075 Gate Parkway (W), Arese 20020 (MI) Via Campo Gallo 21/10, Italy.
Suite 102 and 103, Jacksonville, Florida-32216,
Mohamed H Shabayek MD
USA.
Instituto Oftalmologico De Alicante,
Lu Yang MD Avda. Denia 111, 03016, Edificio Vissum, Alicante,
Department of Ophthalmology, Spain.
The First Affiliated Hospital,
Dalian Medical University, Neil Vice MD
Dalian, China–116011. CustomVis Ground Floor, 110 Erindale Road,
Balcatta-Western Australia–6021,
Lung-Kun Yeh MD Australia.
Department of Ophthalmology
Chang-Gung Memorial Hospital Nikolaos S Tsiklis MD
(Linko), Chang-Gung University, Department of Ophthalmology,
College of Medicine, Taipei, Institute of Vision and Optics,
Taiwan. University of Crete, Greece.
 Contributors XI
Nurullah Cagil Stephen D McLeod MD
Ataturk Research and Training Hospital Department of Ophthalmology
Ophthalmology Department University of California,
06800 Bilkent, San Francisco, CA, USA
ANKARA
Takhchidi K MD
Okihiro Nishi MD Director General, S Fyodorov Eye Microsurgery
Higashinari-Ku, Nakamichi 4-14-26, Complex State Institution, 127486 Moscow,
537-0025, Osaka, Beskudnikovsky blvd 59A, Russia.
Japan.
Tarak Pujara MS
Patrick Schraepen MD CustomVis Ground Floor, 110 Erindale Road,
Department of Ophthalmology, Balcatta - Western Australia–6021
University Hospital Antwerp, Australia.
Wilrijkstraat 10, B-2650, Edegem (Antwerp)
Belgium. Timo MT Tervo MD
Department of Ophthalmology
Ramiro Salgado MD
University of Helsinki,
University of Porto, R Crasto 708
PO Box 220, 00029 HUS, Finland.
4150-243, Porto, Portugal.
Vikentia J Katsanevaki MD
René Trau MD Department of Ophthalmology
Department of Ophthalmology, University of Crete, Heraklion Crete
University Hospital Antwerp, Greece.
Wilrijkstraat 10, B-2650,
Edegem (Antwerp), Belgium. Waldir Neira Zalentein MD
Department of Ophthalmology
Roberto Pinelli MD University of Helsinki,
Director, Istituto Laser Microchirurgia Oculare PO Box 220, 00029 HUS,
Crystal Palace, Via Cefalonia, 70 Finland.
25124 Brescia, Italy.
Wei Wang MD
Ronald Singal MD Tianjin Medical University,
Blue Eye Centro di, Tianjin Eye Hospital and Eye Institute
Michro Chirurgia Oculare Eye Clinic, No. 4, Gansu Rd, Tianjin 20020
Arese 20020 (MI), Via Campo Gallo 21/10, China.
Italy.
Weldon W Haw MD
Sanjay Chaudhary MS Associate Clinical Professor
Chaudhary Eye Centre and Laser Vision, Corneal, Cataract and Refractive Surgery
4802, Bharat Ram Road, UCSD School of Medicine
Ansari Road, 24, Darya Ganj, 9415 Campus Point Drive
New Delhi–110002. La Jollam, CA 92093-0946, USA.
Srinivas K Rao MD Wim Weyenberg PhD
Director, Darshan Eye Clinic, Laboratory of Pharmaceutical,
T 80, Fifth Main Road, Technology and Biopharmacy,
Anna Nagar, Chennai–600017. University of Antwerp, Wilrijkstraat 10, B-2650,
India. Edegem (Antwerp), Belgium.
XII Mastering Advanced Surface Ablation Techniques
Wu Ying MD Yongji Liu PhD
Eye and ENT Hospital Tianjin Medical University,
Fudan University, Tianjin Eye Hospital and Eye Institute
Shanghai, China. No. 4, Gansu Rd,
Tianjin 20020, China.
Yan Wang MD
Professor, Tianjin Medical University, Yutaro Nishi MD
Director, Refractive Surgery Center Higashinari-Ku,
Tianjin Eye Hospital and Eye Institute Nakamichi 4-14-26,
No. 4, Gansu Rd, 537-0025, Osaka, Japan.
Tianjin 20020, China
Zhou Xingtao MD
Yao Peijun MD Eye and ENT Hospital
Eye and ENT Hospital, Fudan University, Fudan University
Shanghai, China. Shanghai, China
 FOREWORD

As our knowledge advances in the sphere of corneal biomechanics, surface

ablation for laser vision correction once again increases its appeal. A resurgence
of photorefractive keratectomy, whatever other name may be applied to the
technique, limits the structural alteration of the cornea. Topography guided
ablation for irregular corneal surfaces or wavefront guided ablation for correction
of eye aberrations are indicators of the increasing sophistication of the ablative
process.
The text is supported by DVD video ROM with reviews of the basic science
of corneal ablations including biophysics of thermal as well as non-thermal
techniques. Experienced surgeons share their pearls which is an invaluable guide
for surgeons to avoid pitfalls during their learning curve. Adjunctive methods
include reviews of the role of mitomycin C, anti-inflammatory and antibiotic medications to prevent adverse
events after treatment. Corneal laser vision correction in common with so many aspects of modern medicine
in general and ophthalmology in particular, is a rapidly developing subject and this volume provides immediate
insights into the current status of surface corneal ablations.
Surface and near surface ablative techniques form the subject matter of this volume variously characterized
as PRK, Epi-LASIK, LASEK and SBK. The collective experience of the world’s leading laser vision correction
surgeons, have been drawn together by that master of the genre of clinical ophthalmic textbooks
Dr Ashok Garg. He always provides up to the minute information for the enlightenment of his readers for
he recognized the rapid evolution of knowledge and the need to bring it to notice as soon as possible. Once
again he is to be congratulated on another masterly volume which will contribute greatly to the welfare of
countless patients who undergo treatment for low and moderate myopia, astigmatism and low hyperopia
by the various techniques described herein. Dr Garg’s productivity is a modern marvel that deserves all our
congratulations and support.

Professor Dr Emanuel Rosen

BSc, MD, FRCSEd, FRCOphth, FRPS
10 St John Street Manchester M3 4DY UK
Tel 44 161 832 8778, Fax 44 161 832 1486
Email contact; [email protected]
 PREFACE

Since the inception of PRK as Refractive Surgery procedure 20 years back the Laser Refractive Surgery has
gone full circle. For the last a few years LASIK has been the attractive and popular refractive procedure
worldwide. Recently due to LASIK postoperative long- and short-term severe complications there is renewed
interest in Laser Surface Ablation procedure among Refractive Surgeons. Indeed there is resurgence of
Advanced Surface Ablation procedures with a bang. Laser vision correction without preparation of a LASIK
flap include LASEK, Epi-LASIK, Surface LASIK and SBK which are known as Advanced Surface Ablation
Techniques (ASA). As an appeal derives from two unique factors (a) For an equivalent correction (b). It
leaves a structurally stronger cornea than LASIK thus lower incidence of corneal ectasia. Advanced Surface
Ablation is certainly a better procedure than LASIK for High Myopia, atypical corneal topography, inferior
steepning, steep central cornea and high oblique astigmatism. The ASA offers a more conservative option
than LASIK.
64 chapters in this International Book practically covers all techniques of Advanced Surface Ablation in
comprehensive manner. Leading International Refractive Surgeons have shared their experiences in these
chapters and are of opinion that ASA is more safe and stable than that of First Generation Surface Ablation
performed with excimer laser. Video DVD ROM is also provided with the book showing ASA surgical
techniques step-by-step by International Experts for the benefit of viewers.
Hats off to our publisher Sh Jitendar P Vij (CEO), M/s Jaypee Brothers Medical Publishers Pvt Ltd
(India), Mr Tarun Duneja (General Manager – Publishing) and all staff members who took keen interest and
done hard work in timely preparation of this ASA book first of its kind in the world. With renewed interest
in Advanced Laser Surface Ablation procedure worldwide, we are hopeful this unique book shall provide
complete information on ASA techniques to every Refractive Surgeon. Next decade certainly belongs to
Resurgent Advanced Surface Ablations.

Editors
 CONTENTS

SECTION 1: EVOLUTION AND RESURGENCE OF SURFACE ABLATIONS

1. The Excimer Laser as a New Surface Approach .......................................................................................... 3

Arturo Pérez-Arteaga (Mexico)
2. Biophysics for Thermal and Non-Thermal Laser Processes ..................................................................... 8
JT Lin (Taiwan)
3. Regenerative Aspects of Excimer Laser Ablation .................................................................................... .16
K Takhchidi, A Doga, G Kachalina, N Maychuk (Russia)
4. Different Techniques to Change the Corneal Surface ............................................................................ 35
Jes Mortensen (Sweden)
5. Resurgences of Surface Ablations ............................................................................................................... 43
D Ramamurthy (India)
6. Pearls of Surface Ablation: When and How ? .......................................................................................... 46
Ramiro Salgado, António Marinho (Portugal)
7. Advances of Solid-State Ophthalmic Laser Technologies .................................................................... 53
JT Lin (Taiwan)
8. New Techniques for Improving Laser Ablation Efficiency and Accuracy ......................................... 63
JT Lin (Taiwan)
9. The Genetic Effect on Anterior Corneal Aberration ............................................................................... 73
Lung-Kun Yeh, I-Jong Wang (Taiwan)
10. Comparative Profile of Methods for IOL Power Calculation after Incisional and
Photoablative Refractive Surgery ................................................................................................................ 78
Antonio Calossi, Massimo Camellin (Italy)
11. Update on IOL Power Calculations after Corneal Refractive Surgery .............................................. 102
Srinivas K Rao (India), Arthur Cheng, Dennis SC Lam (China)
12. Advanced Surface Ablation Techniques: Current Scenario ................................................................ 111
Ashok Garg (India)
13. My Journey with Surface Ablation ........................................................................................................... 114
Christopher J Rapuano (USA)
14. Advances in Refractive Surgery: Surface Ablation ............................................................................... 118
Ronald Singal (USA), Mikhail Pojaritsky, Dimitrii Dementiev (Italy)
XVIII Mastering Advanced Surface Ablation Techniques
SECTION 2: ADVANCED SURFACE ABLATION TECHNIQUE I : PRK

15. PRK Patient Evaluation ............................................................................................................................... 127

Christopher J Rapuano (USA)
16. PRK for Low to Moderate Myopia ............................................................................................................ 132
Michael O’Keefe, Caitriona Kirwan (Ireland)
17. The History of PRK and the Position of PRK in Refractive Surgery Today ................................... 137
Jes Mortensen (Sweden)
18. The Excimer Laser as Instrument in Phototherapeutic Laser Treatment ........................................... 153
Jes Mortensen (Sweden)
19. Myopic Photorefractive Keratectomy using Solid State Laser ............................................................ 172
Nikolas S Tsiklis, George D Kymionis, George A Kounis, Ioannis G Pallikaris, Ioannis G Pallikaris (Greece)
20. Wavefront Guided Photorefractive Keratectomy—Today and the Future ....................................... 182
Weldon W Haw, Edward E Manche (USA)
21. Mitomycin C in Surface Ablation: Benefits and Practical Use ........................................................... 187
Laura De Benito–Llopis, Miguel A Teus, Jorge L Alió (Spain)
22. Cross-Linking Plus Topography-Guided PRK for Post-LASIK Ectasia Management ................. 204
A John Kanellopoulos (Greece)
23. Wavefront Optimization and Astigmatism Correction with the Allegretto® Excimer Laser ........ 215
Jerome Bovet, Auguste Chiou (Switzerland)
24. Optical Quality Analysis after Surface Excimer Laser Ablation ........................................................ 223
Yan Wang, Wei Wang, Jichang He, Kanxing Zhao, Yongji Liu (China)
25. Treatment of Epithelial Irregular Astigmatism ...................................................................................... 240
Waldir Neira Zalentein, Juha M Holopainen, Timo MT Tervo (Finland)
26. Excimer Laser PRK and Corneal Scars : Refractive Surgery to the Rescue ....................................... 246
Arun C Gulani (USA)
27. Corneal Wound Healing after Excimer Laser Ablation ........................................................................ 249
Jes Mortensen (Sweden)
28. The Effect of Moxifloxacin and Gatifloxacin on Short-term and Long-term Outcomes
following PRK ............................................................................................................................................... 254
Jenna M Burka (USA)
29. Prophylactic Mitomycin C to Inhibit Haze Formation after Photorefractive Keratectomy
for Residual Myopia following Radial Keratotomy ............................................................................. 257
Belquiz A Nassaralla, Stephen D McLeod, João J Nassaralla Jr (Brazil)
30. Recent Advances in Photorefractive Keratectomy ................................................................................. 263
C Banu Cosar (Turkey)
31. Clinical Comparisons Regarding Surface Ablation between H EYE TECH B and L and
MEL 80 Zeiss Excimer Laser ........................................................................................................................ 271
Bojan Pajic, Herman Anhalm, Jörg Müller (Switzerland)
 Contents XIX
32. PRK—Past, Present and Future .................................................................................................................. 278
Srinivas K Rao (India), Dennis SC Lam (China)

SECTION 3: ADVANCED SURFACE ABLATION TECHNIQUE II: EPI-LASIK

33. Epi-LASIK Personal Experience with the Amadeus II ......................................................................... 289

Frank Goes (Belgium)
34. Presby-Epi-LASIK in Pseudophakic Eyes with the Wavelight Allegretto ..................................... 312
Frederic Hehn (France)
35. Advances in Epi-LASIK: Surface Ablation Procedure ......................................................................... 322
Vikentia J Katsanevaki, Maria I Kalyvianaki, Ioannis G Pallikaris (Greece)
36. Angle Kappa Management ......................................................................................................................... 327
Frederic Hehn (France)
37. Pain Reduction after Epi-LASIK ............................................................................................................... 334
Yutaro Nishi, Okihiro Nishi (Japan)
38. Painless Epi-LASIK. ..................................................................................................................................... 337
Chu Renyuan, Zhou Xingtao, Wu Ying (China)
39. Epi-LASIK with Mitomycin C ................................................................................................................... 341
D Ramamurthy, Chitra Ramamurthy (India)

SECTION 4: ADVANCED SURFACE ABLATION TECHNIQUE III : LASEK

40. Advances in Excimer Laser Subepithelial Ablation (ELSA) or LASEK ........................................... 349
Chris P Lohmann (Germany)
41. Pearls and Pitfalls of LASEK ...................................................................................................................... 354
Sanjay Chaudhary (India)
42. LASEK Procedure with the Use of Mitomycin C .................................................................................. 358
Iwona Liberek, Justyna Izdebska (Poland)
43. Corneal Permeability after LASEK Measured with Fluorophotometry ........................................... 364
Marie-José Tassignon, Wim Weyenberg, Patrick Schraepen, Grace Lie, Annick Ludwig, Danny Mathysen,
René Trau (Belgium)
44. Laser Epithelial Keratomileusis (LASEK) for the Correction of Hyperopia ................................... 371
David PS O’Brart (UK)
45. The Disruption and Healing of Corneal Nerve Fibers after
Laser Subepithelial Keratomileusis .......................................................................................................... 381
Chu Renyuan, Zhou Xingtao, Wu Ying (China)
46. Update on LASEK ......................................................................................................................................... 388
Chu Renyuan, Zhou Xingtao, Wu Ying, Dai Jinhui, Yao Peijun (China)
47. Management of Corneal Haze after LASEK with Mitomycin C ........................................................ 391
Sanjay Chaudhary (India)
XX Mastering Advanced Surface Ablation Techniques
48. Advanced Surface Ablations ...................................................................................................................... 393
Claes Feinbaum (Poland)
49. Pitfalls in Advanced Surface Ablations. ................................................................................................. 406
Claes Feinbaum (Poland)

SECTION 5: INNOVATIONS IN SURFACE ABLATION TECHNIQUES

50. Sub-Bowman’s Keratomileusis: Combining the Best of PRK and LASIK

for Optimal Outcomes .................................................................................................................................. 421
Daniel S Durrie (USA)
51. Advances in Epi-LASIK and LASEK ....................................................................................................... 436
Bojan Pajic (Switzerland)
52. One-shot Epithelium-Rhexis: Personal Technique............................................................................... 444
Roberto Pinelli (Italy)
53. Transepithelial Cross-linking for the Treatment of Keratoconus ...................................................... 449
Roberto Pinelli, E Milani (Italy)
54. cTENTM — Custom Transepithelial ‘‘No-touch, One-step, All-laser’’ Refractive and
Therapeutic Ablations with the IVISTM Suite ........................................................................................ 453
Carlo F Lovisolo, Charles WM Stewart (Italy)
55. Ocular Pharmacokinetics in Advanced Surface Ablations .................................................................. 469
Ashok Garg (India)
56. Theoretical Aspects of Customized Surface Ablation........................................................................... 475
JT Lin (Taiwan)
57. Clinical Aspects of High-order Aberration after Myopia LASIK ...................................................... 485
JT Lin (Taiwan), FJ Zhang, Lu Yang (China)
58. Solid State Lasers for Advanced Surface Ablation ............................................................................... 490
Emanuel Rosen (UK), Tarak Pujara (Australia)
59. Advances in Femtosecond Laser ................................................................................................................ 501
David Donate, Olivier Albert, Jean Marc Legeais (France)
60. Advanced Surface Ablation (ASA) ........................................................................................................... 509
Ahmad Salamat Rad, Neil Vice, Tarak Pujara (Australia)
61. Advances in CorneoplastiqueTM : Art of Laser Vision Surgery ........................................................... 531
Arun C Gulani, Lee T Nordan (USA)
62. Corneal Biomechanical Properties ............................................................................................................. 538
Jorge L Alió, Mohamed H Shabayek (Spain)
63. Surface Ablation after Laser in situ Keratomileusis; Retreatment on the Flap ............................... 541
Jeroen JG Beerthuizen (Netherland)
64. Surface Retreatments for Residual Myopic Refractive Errors after LASIK ....................................... 544
Bahri Ayodin, Norullah Cagil (Turkey)

Index .................................................................................................................................................................. 547

Section
1

Evolution and
Resurgence of
Surface Ablations
 CHAPTER

1 The Excimer Laser as a New

Surface Approach

Arturo Pérez-Arteaga (Mexico)

INITIAL SURFACE APPROACH the cornea and the stability of the refractive results;
it became more predictable, easier and safer to
The main circumstance that lead the excimer laser to perform refractive corneal surgery than other
go inside the refractive surgery field was the fact modalities of corneal refractive surgery used before.
that more than burning or cutting the material, the But also during the first years we started to fight
excimer laser adds enough energy to disrupt the with some new troubles with this technique like pain
molecular bonds of the surface tissue, which and delayed visual recovery because the epithelial
effectively disintegrates into the air in a tightly management; also the phantom of haze appeared. We
controlled manner through ablation rather than started to notice that it was not a free-complications
burning. Thus excimer lasers have the useful property procedure; our first way of thinking that it will be a
that they can remove exceptionally fine layers of technology able to correct “every possible refractive
surface material with almost no heating or change to error” without complications, started to change.
the remainder of the material which is left intact. At the end of this step we learned from the early
Because of these physic properties and thanks to days of PRK:
people like Rangaswamy Srinivasan, the excimer laser - The management of epithelium in different ways.
went inside the refractive corneal surgery field and - The need to control the postoperative pain
it has been accepted worldwide. Nevertheless the - The need to avoid very deep ablations; at this
ophthalmic surgeons must never forget that we are time to avoid haze, and not as a biomechanical
disintegrating live corneal tissue each time we are concept
performing an excimer laser procedure. - The need to have large follow-up of our patients.
Photorefractive keratectomy, it means the surface With success but also with complications we
approach, was the door of entrance of excimer laser learned that the corneal surface had limitations and
in the refractive arena. Methods for epithelium that this “reshaping of the future” was not as magical
removal were then described in order to lead the as we thought.
excimer laser be in complete touch with the sub- Then LASIK came from Dr Pallikaris to the excimer
epithelial tissue. laser refractive surgery theatre. It was the technique
We started to notice the benefits of excimer laser that dominated refractive surgery for many years.
surgery like predictable ablations, the easy way to The ophthalmic community started noticed that the
perform this surgery, the well controlled reshape of flap-retaled complications were the most powerful
4 Mastering Advanced Surface Ablation Techniques
complications of LASIK. Finally the long term described the use of LASIK years before, recently he
complications started to occur, like the corneal ectasia described a microkeratome able to perform an
or iatrogenic queratoconus. The LASIK experienced epithelial flap and so avoid the use of alcohol to do
important reconsiderations worldwide. The inclusion the detachment and of course avoid the cut of the
criteria for stromal ablation decreased and so a new corneal stroma. Because the epithelial cells were not
born of the surface ablative procedures came to the injured with any chemical agent, he proposed that
light. the epithelial flap was alive and so the replacement
of it over the cornea can assure an easy attach. The
ADVANCED SURFACE ABLATIONS main advantage of the epi-LASIK was to make an
easy transition ageing to the surface of the cornea,
The history of humanity teach us that we learn much
avoid the use of alcohol (that is also aggressive with
more from our own mistakes rather than our success.
the corneal stroma, and not only for the epithelium)
Recently at the American Academy Meeting 2006 in
and to produce a very smooth sub-epithelial surface
Las Vegas, Nevada, Marguerite B. McDonald, who
to apply the ablation. But finally we saw that what
pioneered PRK 20 years ago, outlined the reasons
really kills the epithelial cells is the detachment it
why she has recently returned to corneal surface
self and not only the alcohol, so recently the
ablation in a presentation titled “Why I hung up my
discussion about replace or not to replace the
microkeratome”. In this point of the history of
epithelial flap emerged. Some surgeons are currently
refractive surgery, more and more surgeons
replacing the epithelial flap in favor to obtain less
worldwide are changing ageing their practice style
postoperative symptoms, even they are observing at
to the surface ablations under the premise: if you do
the end, the death of this first epithelial layer and a
not have a flap, you can not have flap complications.
Another important tool for this race back to the second one (new) emerge; by the other hand some
surface are the advantages of the flying spot pattern other surgeons prefer to cut the flap at the end of the
of laser ablation that decreased the problems procedure permitting a re-epithelization process and
experienced with surface ablation in the early days. controlling the postoperative symptoms with
The first attempt to go back to the surface was medication and bandage contact lens.
from Massimo Camellin in Italy. He developed the After all this discussion the idea to detach the
LASEK technique; he described the use of alcohol epithelium with some mechanical method (non
for the epithelial detachment to obtain a complete chemical) that lead the same result of desepithelization
epithelial flap which is replaced ageing over the without the risk and expenses of the use of a epithelial
cornea after the ablation. The idea of decrease the microkeratome is now in the air.
problems of the early days of PRK like delayed visual Anyhow you are able to perform surface ablation,
recovery, pain and haze with the fact of replace the be sure to do it with a mechanical method instead a
epithelium was very attractive. Unfortunately, if well chemical one. With the new era of the surface ablation
some controlled studies demonstrated that the pain (Avanced Surface Ablation) many problems that were
was less with LASEK in comparison to PRK, the main presented before like, corneal haze, pain and delayed
problem was the death of the epithelial cells; so at visual recovery have been reduced. The surface
the end we had to wait until the formation of a new ablation permits to work in thinner corneas rather
epithelial layer under the dead one in the outer than LASIK. In terms of efficacy the results of
surface. At this point the studies demonstrated that customized ablation treatments are also better with
the death of the epithelium was because the use of surface ablations that with LASIK.
alcohol. Recently, the idea that a Sub-Bowman’s
Then came ageing to the refractive field Prof Keratomileusis (SBK) will become the next trend in
Palikaris from Grece with the epi-LASIK. Even he laser refractive surgery, combining advantages of
 The Excimer Laser as a New Surface Approach 5
both PRK and LASIK, merged. Eyes treated with the for many surgeons worldwide, still LASIK is the first
SBK procedure, showed decreased postoperative dry way to approach to the excimer laser surgery.
eye, lower reported corneal sensitivity, similar
amounts of higher-order aberrations and a higher Methods for Epithelial Removal
rate of overall patient satisfaction, according to First of all, the surgeon must dominate one or some
investigators. Are we now moving beyond PRK and of the methods for epithelial removal. Currently there
LASIK? Maybe this procedure will be the future. are different methods:
Still at this time visual recovery is slower with l. Amoils Brush
surface ablations in comparison to LASIK but the 2. Mechanical Scrape
good communication with the patients is mandatory. 3. Trans-epithelial scrape-limited diameter
We have to speak a long time with our patients 4. Dilute alcohol
regarding the long term benefits with the fact of 5. Proparacaine
taking care of the corneal biomechanics avoiding “to 6. Balances saline solutions (BSS)
cut” the cornea. We must let them know by the other 7. Epi-LASIK
hand about the symptoms that they are going to Some method offers advantages over others, but
experience during the first days and how to manage finally we think that the surgeon must do the one
them; tell them that this is a worth attitude, because that he is accustomed to use and manage, since the
at the end we will have a long term healthy cornea. preparation in the preoperative period until the
We must speak also about the depth of ablation complete postoperative time.
according to their own pachimetry; they must know
since the preoperative period how much corneal tissue PEARLS FOR THE CARE IN SURFACE ABLATION
will be ablate; they have to know that the success is PATIENTS
not only a refractive result, it is also to obtain a
The issues that the surgeon must take in count during
planned ablation and a planned postoperative
the performance of surface ablation are:
topography map.
1. Pain control. For the pain prevention the surgeon
has as part of the treatment some important
Indications for Surface Ablations medications.
a. Use of non-steroidal anti-inflammatory drugs
There has been a change in indications for surface
(e.g. Acular, Voltaren ...).
ablations with the new approach from recent years.
b. Oral steroids and analgesics.
The Advanced Surface Ablation (ASA) has
c. Cox II inhibitors (e.g. Celebrex ...).
incorporated new techniques, new methods for
d. Contact lens preferences.
epithelial removal, new pre and postoperative care e. Comfort drops (diluted tetracaine).
all of them in order to obtain best predictable results, f. Narcotic-like medications in some particular
less symptoms for the patient and less postoperative patients.
complications. 2. Speed of epithelial healing. The surgeon must take
With this new approach we can currently be sure in count that each patient has a different speed of
that all patients eligible for excimer laser surgery are epithelial healing. The patient must know this fact
suitable to be operated with some surface approach since the preoperative period and the surgeon
technique. Maybe we are now at one particular step must take care of it during the first days of
of excimer laser surgery where the choose of the postoperative period.
technique, between surface and stromal ablations, 3. Haze prevention. Maybe haze is the worst
depended just upon the surgeon preferences. complication of surface ablation and maybe the
Nevertheless still controversy is going on because main reason why intrastromal approach has not
of the possible side effects of surface ablation and end. Some methods to prevent haze formation are:
6 Mastering Advanced Surface Ablation Techniques
a. The choice of preserve or remove flap, in 6. Mithomicin use. If the surgeon finally decides the
particular in epi-LASIK where the epithelial cells use of MMC, so much attention must be placed in
has not suffered the aggression of alcohol. order to achieve the exact concentration and the
b. Pre and postop vitamin C; it is well known the exact exposure time. Severe damage can be caused
benefit effect of vitamic C over the corneal to the tissues if MMC is not used properly.
epithelium healing. 7. PRK vs LASEK vs epi-LASIK. The decisión
c. Ice cold BSS. Used by some surgeons to decrease between the surface techniques should be
inflammatory process and so the possibility of troublesome. There are factors influencing this
haze formation. decision like surgical skills, time of follow up and
d. Topical steroids. It is well known that the benefit economics between others. Anyhow we must
effect of topical steroids in the reduction of haze. maintain in our minds, like in other kind of
For many surgeons the therapy must be surgeries, that the best technique for the patient
followed for several weeks in order to decrease is the better the surgeon can dominate.
the inflammatory response. 8. Haze treatment. Because haze is an important
e. Mitomicin C (MMC). There is still controversy complication of surface ablations, the surgeon must
regarding the use of this medication. Many
prepare not only to take the measures in order to
surgeons are using MMC but some others
avoid it, like was purposed before; the surgeon
believe that if there is a respect for the depth of
also must know and manage the treatment
ablation and the postoperative medication, there
strategies. If well the rule is that the possibility to
is no need for the use of MMC.
produce haze is in direct proportion to the depth
f. Oral steroids. The value of oral steroids maybe
of ablation, sometimes it has been seen in low
much more in the decrease of postoperative
symptoms. profundity ablations.
g. Choice of best contact lens. The must amount of
water in the contact lens, more oxygenation to CONCLUSION
the cornea and so more rapid epithelial healing.
ASA appears to have more safety and stability that
4. Topical steroids side effects. If we are talking about
the first generation of surface ablations performed
the possibility of the long term use of topical
with excimer laser. New surgical techniques, new
steroids, we must concern about the side effects of
generations of machines, improvements in
this medication. Some physicians like to use drops
preparation and postoperative care, as well as new
of antiglaucoma medication to avoid increase in
the intraocular pressure but also as a help in faster medications introduced for the attention of the
visual recovery because of its pupilary effects, like patients, are achieving tools to increase the success.
brimonidine. Some others do not use medication if As was shown by Richard J. Duffey, who
there is not an increase in the intraocular pressure. presented the results of the 2006 survey of trends in
Anyhow the postoperative visits must be refractive surgery during 2007 ASCRS meeting, there
frequented to be in care of this situation. is an increase in surface ablation techniques; he
5. Enhancement time. There is always a controversy showed that during 2006, 10% of respondents ASCRS
regarding the exact time to perform an members indicated that they did not perform
enhancement. Sometimes the patient with wavefront-guided ablations, in comparison to 26%
undercorrection pushes too much to the surgeon of respondents to the 2005 survey, where was
because the impaired vision, but the surgeon must indicated that they did not perform wavefront-
keep the mind cool and speak with the patient a guided ablations. In addition, LASEK/epi-LASIK saw
lot, about the need to wait enough time to have a a dramatic increase in volume, with about 207,000
stable refraction and so improve, in case of an procedures performed in 2006 compared with about
enhancement, the final visual result. 33,000 procedures in 2005.
 The Excimer Laser as a New Surface Approach 7
Maybe the 3 most important reasons that are 11. Femtosecond laser versus mechanical keratome flaps in
wavefront-guided laser in situ keratomileusis: Prospec-
leading the way to this change in excimer laser
tive contralateral eye study. Durrie DS, Kezirian GM. Jour-
practice style are: nal of Cataract and Refractive Surgery 2005;31,(1): 120-6.
1. Improvement in care of the patients who undergo 12. Flap thickness accuracy: Comparison of 6 microkeratome
through surface ablations. models. Solomon KD, Donnenfeld E, Sandoval HP, Al
Sarraf O, Kasper TJ, Holzer MP, Slate EH, Vroman DT,
2. The increase in wavefront guided ablations, with Group FTS. Journal of Cataract and Refractive Surgery
better results in surface rather than stromal 2004;30,(5):964-77.
surgery 13. LASEK results. Feit R, Taneri S, Azar DT, Chen Chen C,
Ang RT: Ophthalmology Clinics 2003;16,(1):127-35.
3. The flap-related complications of LASIK. 14. Lindstrom RL. The surgical correction of astigmatism: a
clinician’s perspective. Refract Corneal Surg 1990;6(6):
BIBLIOGRAPHY 441-54[Medline].
15. Mack RJS. Iatrogenic keratectasia. J Cataract Refract Surg
1. Analysis of the efficacy, predictability, and safety of 2001;27:4-6[letter]
LASEK for myopia and myopic astigmatism using the 16. Nordan LT. Quantifiable astigmatism correction: con-
Technolas 217 excimer laser. Partal AE, Rojas MC, cepts and suggestions, 1986. J Cataract Refract Surg
Manche EE. Journal of Cataract and Refractive Surgery 1986;12(5): 507-18[Medline].
2004;30,(10):2138-44. 17. Price FW, Grene RB, Marks RG, Gonzales JS. Astigma-
2. ASCRS members adopting latest refractive advances, tism reduction clinical trial: a multicenter prospective
survey finds Ocular Surgery News US Edition 2007. evaluation of the predictability of arcuate keratotomy.
3. Barraquer JI. Queratomileusis y Queratofaquia. Bogota, Evaluation of surgical nomogram predictability. ARC-T
Colombia, Instituto Barraquer de America 1980;340–42, Study Group. Arch Ophthalmol 1995;113(3):277-
82[Medline].
405–06.
18. Ruiz LA, Rowsey JJ. In situ keratomileusis. ARVO ab-
4. Buzard K, Haight D, Troutman R. Ruiz procedure for
stract 55. Invest Ophthalmol Vis Sci 1988;29(suppl):392.
postkeratoplasty astigmatism. J Refractive Surgery 1987;
19. Safety, efficacy, and stability indices of LASEK correc-
3: 40-5.
tion in moderate myopia and astigmatism. Taneri S,
5. Clinical results, safety led surgeon to “hang up her
Feit R, Azar DT. Journal of Cataract and Refractive Sur-
microkeratome” OSN SuperSite Top Story 11/11/2006.
gery 2004; 30,(10):2130-37.
6. Comparison of postoperative pain in patients following
20. Seiler T. Iatrogenic keratectasia: academic anxiety or se-
photorefractive keratectomy versus advanced surface
rious risk? J Cataract Refract Surg 1999;25:1307-08.
ablation. Blake CR, Cervantes-Castañeda RA, Macias-
21. Sub-Bowman’s will be next trend in laser refractive sur-
Rodríguez Y, Anzoulatous G, Anderson R, Chayet AS. gery, surgeon predicts Ocular Surgery News US Edition
Journal of Cataract and Refractive Surgery. 2006.
7. Ectasia after laser in situ keratomileusis. Binder. PS. Jour- 22. Thornton SP, Sanders DR. Graded nonintersecting trans-
nal of Cataract and Refractive Surgery 2003; 29, (12): verse incisions for correction of idiopathic astigmatism.
2419-29. J Cataract Refract Surg 1987;13(1):27-31[Medline].
8. Electron microscopy of the epithelial flap created by etha- 23. Troutman RC, Swinger C. Relaxing incision for control
nol treatment in the rabbit corneal epithelium Serrano D, of postoperative astigmatism following keratoplasty.
Hibino S, Nishida K, Maeda N, Tano Y. Journal of Cata- Ophthalmic Surg 1980;11(2):117-20[Medline].
ract and Refractive Surgery 2003;29, (7):1389-96. 24. Vitality of epithelial cells after alcohol exposure during
9. Epi-LASIK: Preliminary clinical results of an alternative laser-assisted subepithelial keratectomy flap prepara-
surface ablation procedure Pallikaris IG, Kalyvianaki MI, tion Gabler B, Winkler von Mohrenfels C, Dreiss AK,
Katsanevaki VJ, Ginis HS. Journal of Cataract and Re- Marshall J, Lohmann CP. Journal of Cataract and Re-
fractive Surgery 2005;31 (5):879-85. fractive Surgery 2002;28, (10):1841-46.
10. Evolution, techniques, clinical outcomes, and pathophysi- 25. Wang Z, Chen J, Yang B. Posterior corneal surface topo-
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2004;49(6):576-602. ogy 1999;106:406-9.
8 Mastering Advanced Surface Ablation Techniques

CHAPTER

2 Biophysics for Thermal and

Non-Thermal Laser Processes

JT Lin (Taiwan)

INTRODUCTION and biological aspects of a medical system as shown

in Table 2.1 and the basic mechanisms to be addressed
LASER stands for “Light Amplification by Stimulated
later.
Emission of Radiation”, first predicted theoretically
in 1916 by Albert Einstein, the well-known A and B Table 2.1: Biophysical and biophotonic aspects of medical systems
coefficients. The first solid-state Ruby laser (at 694 nm) Photonics Biomedical
from ruby crystal was built by TH Maiman; the first • Laser sources Tissue engineering (welding, regeneration)
gas laser at 633 nm and 1150 nm from helium-neon • Nonlinear optics Photodynamic therapy (PDT)
was developed by Javan and associates in the 1960’s. • Optical process Drug delivery
• Imaging/Sensor Photochemistry
In the past 4 decades, lasers have been widespread • Optical diagnosis Physiological response
used in many areas including industrial, medical and
military. One of the most important medical laser a. Absorption (or transmittance) and scattering of
applications is an ophthalmic refractive surgery the tissues: water, blood cell, melanin pigment or
procedure called LASIK (an improved procedure protein
after PRK) which affects the vision of millions of b. Laser wavelength: defining a hot (thermal) or cold
people worldwide each year. Lasers at visible and (non-thermal) laser or having a combined effect
infrared spectra have also been used for other eye in a particular target subject.
disorders such as cataracts, glaucoma and age-related c. Laser power (intensity), fluence and spot size at a
given energy per pulse.
macular degeneration (AMD). In this Chapter, I will
d. Laser pulse width: CW, free running, Q-switch
present the biophysics aspects, the principles of laser-
or mode-locked;
tissue interaction in general, and their ophthalmic
e. Penetration depth: Defined by the laser
applications. Another aspect dealing with photo-
wavelength and absorption/scattering coefficients
dynamic therapy (PDT) will be presented at a
of the tissue.
separate Chapter of Lin in this book.
f. Energy delivery means: including optical fiber,
THE KEY ISSUES focusing lens, scanning mirror and articulated arm.
g. Bio-sensors, bio-imaging and other diagnosis
Lasers for medical applications are governed by the devices.
following key issues which define the physical, optical h. Photosensitizers for light-based therapy.
 Biophysics for Thermal and Non-Thermal Laser Processes 9
LASER PRINCIPLES example, a laser weapon will require features (c), (d)
and (e); and a medical laser would require a selective
A laser system consists of the elements of (Svelto,
spectrum or feature (a) for best tissue absorption or
1995) (: (1) laser medium (gas, liquid or crystal), (2)
ablation, and feature (e) for small spot microsurgeries.
power supply for pumping high voltage, (3) resonator
(or cavity) with a pair of reflecting optics. It may LASER PARAMETERS
further include a Q-switch device in order to produce
a short pulse output, which otherwise will be It is important to know the definition and laser
operated at so called “free running” mode with a parameters which have been commonly used. These
pulse width about few hundreds of microseconds definitions are critical in understanding system design
governed by the lifetime of the upper-level (E2) or a and specifications to be discussed later. In general, a
CW (continuous wave) output. The Q-switch devices pulsed laser has high peak-power and small energy
have two major types: the EO-switch using electro- per pulse; whereas a CW laser (or high repetition
optical materials such as lithium niobate to produce rate kHz laser) has lower peak-power, but high
nanosecond pulsed output, whereas the AO-switch average-power. The commonly used units are mJ (or J)
using acoustic-optics to produce a longer pulse for a pulsed laser and mW (or W) for a CW laser. For
(microseconds) but much higher repetition rate of example, a laser with a pulse energy (E) of 10 mJ at a
kHz to MHz. The output of the Q-switch laser may pulse width (T) of 10 ns will have an intensity (I) of
be further “mode locked” to produce ultra-short I = E/T = 1.0 MW, which increases to 100 MW, when
pulse in the picosecond and femtosecond. the laser width is shorter at 10 picosecond and having
In addition to the conventional flash-lamp pump, a smaller energy of 1.0 mJ. In a femtosecond laser
optical-pump using a laser to pump another laser (used in photodisruption of lens) typically has a laser
medium has been well developed. For examples: energy only micro joule which gives an intensity of
diode laser (at 810 nm) pumped Nd:YAG and cooper 20 MW for a pulse width of 500 femtosecond.
laser (at 580 nm) pumped dye lasers. “Injecting However, the tightly focused spot size about few
seeded” laser amplify was also developed for microns would result in an intensity density as high
improved quality. For a laser to function, Einstein as few thousand MW per cm square, or in the GW
proposed two conditions: (1) there is a process range. Short pulse lasers from femtosecond to
stimulated emission that leads to light amplification, nanosecond have been used for cataract and laser
and (2) achievement of population inversion of atoms phaco. Figure 2.1 for a list of various CW and pulsed
in energy levels. Therefore, the output power of the laser from UV to IR spectra.
coherent light (LASER) is proportional to the pumping
power for a given laser cavity design. LIGHT-MATTER INTERACTION
Laser light has the following characteristics which Photo-biology and bio-photonics (Prasad, 2003) are
make it unique comparing to a regular incoherent new fields dealing with the interaction of light
light: (coherent and non-coherent) with matter ranging in
a. highly monochromatic, or narrow band (or line size scale from about 100 nm (cells) to macro-objects
width), only few nm, (living organisms). These interactions, in general,
b. highly coherent (temporarily and spatially), should include physical, chemical, thermal, mechanical
c. highly directional (with small angular beam and their combined effects. Light-matter interaction
spread), may be categorized as two major types based on the
d. high intensity, and nature of the interactions:
e. high focusability. a. Molecular-level: Producing absorption,
These characteristics make a laser different from spontaneous and stimulated emission and Raman
an incoherent light in many of its applications. For scattering.
10 Mastering Advanced Surface Ablation Techniques
and d=(2 – 6) mm for near IR laser (at about 1.0 micron),
where it also shows that focused beam can increase
the penetration depth of the non-focused beam.

Figure 2.2: Penetration depth of UV and IR lasers (non-focused)

For laser-matter in the molecular-level or the light-

induced photochemistry involves: (i) photoaddition,
and (ii) photo-oxidation. The light-activated process
called photodynamic therapy (PDT) using photo-
sensitizers will be discussed in another chapter by
Lin in this book. This Chapter will emphasize on the
Figure 2.1: Laser spectra (from UV to IR) light-tissue interaction and their ophthalmic
applications.
b. Bulk-level: Producing absorption, refraction,
LASER-TISSUE INTERACTION
reflection and scattering.
Furthermore, light scattering in bulk-level (such Laser-induced processes in tissues include:
as tissues) may be categorized by: (i) elastic
(Rayleigh, Mie), and (ii) inelastic (Brillouin, Raman) Radioactive type (or tissue auto fluorescence)
in which the scattered photons have different These light-induced processes are in the cellular level such
frequencies (or wavelengths) than the incident light. as fluorophors from selected proteins and DNA or RNA
Light absorption and scattering create a loss of constituents (A, C, T, G). Process (a) involves with PDT
intensity (or energy) when it propagates through a will be presented in another Chapter by Lin in this book.
tissue. The intensity attenuation in a tissue may be
described by the Beer-Lambert’s law, for the given Non-radioactive types (Table 2.2)
absorption (A) and scattering (A’) coefficients,
Thermal (coagulation, evaporation, carbonation,
I(z) = (Io)exp[–(A+A’)z], (1.a)
melting); photochemical (single and multi-photon
for a un-focused beam, or a revised Lin’s law (Lin,
absorption); photo-ablation (direct cellular bond
2006)
breading); photo-disruption (shock wave mechanical
I’(z) = BI(z), (1.b)
force); plasma-induced (assisted) ablation (due to
for a focused beam, where B is an enhanced
dielectric breakdown).
penetration factor defined by the square of the surface
and focal point beam spot size. Table 2.2: Laser-tissue interaction mechanisms for ophthalmic uses

Figure 2.2 shows the typical penetration depth d Mechanism Applications

(defined by when Io reduces to 1/e) are (in mm): 1. Thermal Coagulation, glaucoma, LTK, DTK
2. Photo-ablation PRK, LASIK, LASEK, LASA (LPT)
d=(0.05 – 0.2) for CO2-laser, Er:YAG and UV laser; 3. Photo-disruption Posterior capsulotomy, laser phaco
d=(0.4 – 0.6) for Ho:AG; d=(0.5 – 2.0) for argon laser; 4. Photo-dynamic Therapy (PDT), AMD, CNN
 Biophysics for Thermal and Non-Thermal Laser Processes 11
Further discussion of above process (b) and their
applications are shown as follows.

COLD vs. HOT LASERS

The nature of laser tissue interaction is categorized

as a “cold” (non-thermal) or “hot” (thermal) laser by
its peak power level and pulse width, in addition to
its wavelength. The definition of thermal or non-
thermal may be quantified by the “size” of the
thermal damage zone.
“Cold” lasers include:
– ultra-short pulsed laser at IR or green for photo-
decomposition or plasma-assisted ablation,
having peak power in the Giga-Watt; Figure 2.3: Absorption in tissues melanin and hemoglobin (Hb)
– nanosecond lasers with Mega-Watt peak power
(or intensity) used for ablation, excitation and
evaporation, such as UV solid state laser at 213
to 266 nm, excimer laser at 193 to 308 nm.
– tightly focused laser beam with high peak power
density (or irradiance).
“Hot” lasers include:
– long pulsed (millisecond); or
– CW laser with peak power in the range of few
Watts to few hundred Watts and used for
heating, coagulation and welding.
It should be noted that the ultra-short
(femtosecond to picosecond) laser will perform
ablation via plasma or shockwave assisted process
and almost independent to its wavelength, even it
may be highly transparent to the targeted tissue. On
the other hand, for a laser with extremely high
absorption coefficient (A) such as Er:YAG, A is about Figure 2.4: Schematic diagram of water absorption spectrum showing
three major absorption peaks at 1.45, 1.92 and 2.94 microns
150 to 250 cm-1, an ablative-type process is expected
(with partial thermal effects involved) even the laser
is operated at long pulse free running mode, about thermal keratoplasty (LTK) for wrinkle removal and
500 microseconds (or 0.5 ms) in pulse width. the treatment of acne, because of its lower absorption
Figure 2.3 shows the absorption of melanin and in tissues.
hemoglobin. Furthermore, a cold (or partially cold) laser may
Figure 2.4 shows the water absorption peaks at perform as a hot laser when it is operated at a large
1.45, 1.92 and 2.94 microns. The 2.94 IR laser has been spot (or low intensity). For example, an Er:YAG or
commercialized for invasive resurface and was CO2 laser may be used for cutting/evaporation with
proposed for laser phaco; whereas the 1.45 laser has a focused small spot (or high intensity), whereas for
been used for non-invasive vision correction by coagulation with a large spot (or low intensity).
12 Mastering Advanced Surface Ablation Techniques
SELECTIVE INTERACTION frequency converter (Figures 2.5 and 2.6) which
includes the use of nonlinear crystals such as CDA,
In many of the medical applications, ‘selective’ KDP, KTP, BBO, LBO, KNbO3, for harmonic
treatment is required, where the laser energy is generation (or frequency-mixing), optical parametric
selectively absorbed by the target area/tissue without oscillation (OPO), or the use of methane for Raman-
causing too much damage of the surrounding areas. shift in a Stimulated Raman Scattering (SRS) process.
Various dyes have been used as photosensitizers These three major frequency conversion methods are
for the treated tissue to selectively absorb the laser detailed as follows.
(photon) energy matching the dye’s absorption. For
example, indocyanin green (ICG) and verteporfin are Harmonic Generation (Figure 2.7)
used to absorb a laser at about 689 and 805 nm in a
For given laser frequencies of V1 and V2, or
procedure called PDT (photodynamic therapy) for
wavelength of W1 and W2, one may perform the
the treatment of CNV in age related macular
following mixing process governed by the
degeneration (AMD). In addition, a procedure called
conservation of photon energy (Ej) defined by
SLT (selective laser trabeculoplasty) was used to treat
Ej = hVj = hC/Wj, where C is the speed of light.
open-angle glaucoma and ocular hypertension using
E1 + E2 = E3, (2.a)
argon laser at 488/514 nm or more recently by a
hV1 + hV2 = hV3, (2.b)
pulsed green laser, 5 ns at 532 nm from a double-
1/W1 + 1/W2 = 1/W3 (2.c)
YAG. Greater detail of PDT will be presented in a
For example, an Nd:YAG laser with a fundamental
separate Chapter.
IR wavelength W1 = 1064 nm can be frequency
Another means of selective interaction is to use a
doubled via so called second harmonic generation
focused laser beam having its focal point at the selected
(SHG) to green W3 = 532 nm using Eq. (2.2) 1/1064 +
target area to generate a higher intensity (or fluence) at
1/1064 = 1/532, those two photons at 1064 nm is
the focused spot and protect the surrounding area where
combined to produce one photon at 532 nm which
the laser beam is expanded with low intensity. For
has twice of the energy due to the shorter
example, an Nd:YAG laser is focused to a spot about 50
wavelength. By mixing the IR and the green 1/1064
micron to rupture the unwanted opacified membranes
+ 1/532 = 1/355, one obtains the UV laser at 355 nm
in a procedure called posterior capsulotomy to treat
via a third harmonic generation (THG).
secondary cataracts. The YAG laser may be further
Similarly, one may further obtain the fourth
focused to few microns spot for a plasma-mediated
harmonic generation (4HG) at 266 nm by doubling
photodisruption of lens nuclei, where the laser power
the green 1/532 + 1/532 = 1/266. Furthermore, one
density could reach GW per cm square. Greater details
may mix the green (532) and UV (355), 1/532 + 1/355
of laser phaco will be shown later.
= 1/213 or IR and 4HG, 1/1064 + 1/266 = 1/213 to
To summarize, the nature (either ablative or
obtain the fifth harmonic (5HG) at 213 nm. See Figure
thermal) of laser-tissue interaction is determined by
2.7 to 9 for a diagram of multiple color laser
the combined factors of laser energy, pulse width,
generation.
spot size, intensity (or fluence), wavelength and the
The solid-state UV laser at 266 and 213 nm via
associated absorption coefficients.
4HG and 5HG of Nd:YAG was first proposed by J.
FREQUENCY CONVERSION (LIN, 1989) T. Lin (US Patent, 5,144,630, 1992) for medical use in
corneal reshaping which was normally conducted by
Medical applications of lasers have been significantly ArF excimer laser involving toxic gas.
broadened by the development of frequency The SHG at green (532 nm) has been used for
conversion devices which expand the existing laser retinal treatment and cosmetic uses. The 4HG or 5HG
spectra covering deep UV (0.2 um) to mid-IR (3.2 um). UV laser (212 to 266 nm) can be used also for
Laser spectrum (or color) can be changed by a microsurgeries and lithography which requires a short
 Biophysics for Thermal and Non-Thermal Laser Processes 13
wavelength for fine resolution. Short wavelength
excimer lasers at (150 to 193 nm) were proposed for
nanometer devices. The deep UV source (shorter than
200 nm), in principle, may be generated via the
frequency conversion technologies which however,
requires a highly transparent deep UV crystals better
than BBO or LBO. Tunable deep UV lasers (0.2 to 0.4
um) generated from a Ti:sapphire laser was also first
Figure 2.5: Harmonic Nd:YAG laser using nonlinear crystals (from
Lin, US Pat. 5,144,630,1996) proposed by Lin et al. (US Patent, 1997).
For stable efficiency, a heat controlled (at about
35 degree C) crystal housing is normally used in high-
power lasers. The typical conversion efficiency is
about 40 to 60% in SHG and THG and an overall
efficiency of 10 to 15% in 4HG, 5 to 8% in 5HG,
assuming the fundamental is a single mode (good
quality).
The frequency conversion efficiency in nonlinear
crystals is determined by the nonlinear coefficiency
(NLC) and the available phase matching angle. KTP
crystal with very high NLC has been the most
popular crystal for SHG, particularly in diode-
Figure 2.6: Tunable laser source by OPO and IR-laser from SRS
pumped lasers. BBO and LBO are used in high power
lasers due to their high damage threshold.
Greater details may be found in a review paper
by Lin (Laser Focus, 1985) and the SPIE proceedings:
Growth and application of laser crystals and
nonlinear crystal (Ed. by Lin, 1989).

Raman Shift (SRS)

Another example is the Raman shift of Nd:YAG laser
in a methane (CH4) Raman cell which generates a so
called “eye safe” laser at 1.54 micron from the
fundamental at 1.064 micron. This eye-safe laser has
been used as a ‘range-finder” for military applications
which require a “friendly” laser for training.

OPO
OPO is a “reverse” process of harmonic generation,
and “down converts” the fundamental frequency to
a longer wavelength and similar to the Stokes
generated from SRS. Both OPO and SRS have been
used to generate tunable mid-IR lasers at 1.0 to 3.5
microns for medical and industrial uses. Greater
Figure 2.7: Energy level description of linear (1-photon) and
details may be found in the SPIE proceeding of Lin
nonlinear (multiphoton) processes (1989).
14 Mastering Advanced Surface Ablation Techniques
NONLINEAR PROCESSES (BOYD, 1992) FDA approved, other than the conventional Nd:YAG
laser for posterior capsulotomy. Furthermore, some
Laser-matter interaction may be under: (i) linear
remaining technical and clinical issues still remain and
response such as laser-induced thermal process in
limit the use of IR lasers for lens nuclei disruption.
tissues, or (ii) non-linear response including 2-photon,
Nd:YAG laser with nanosecond pulse duration was
3-photon processes occurring in high intensity lasers
first proposed for phaco procedure which, however,
to be detailed as follows.
was abandoned due to its inefficiency and safety
Laser-matter interaction may be described, in
issues comparing to the conventional ultrasound
general, by a Hamiltonian function (Lin, 1981)
phaco (USP). Dr. Agarwal proposed the use of
H = U · E, (3)
combining USP and Ho:YAG laser for faster
where U is the laser-induced dipole moment of
procedure, particularly for soft cataracts. The use of
the medium under the electric field of the laser (E).
IR laser has been recently shifted to new application
By expanding U into high-order terms (nonlinear
for presbyopia treatment by photophaco “modulation”
response).
of the crystalline lens to be discussed as follows.
U = Uo + aE + bE·E + cE·E·E, (4)
Table 2.3: Summary of ophthalmic lasers
one obtains the interacting Hamiltonian function
becomes Laser (wavelength, pulse width) Applications

H = UoE + aE2 + bE3 + cE4, (5) 1. Excimer ArF (193 nm, 5-20 ns) PRK, LASIK, LASEK
2. Excimer XeCl (308 nm, 200 ns) Glaucoma
which indicates that the linear and nonlinear 3. Argon ion (488/514 nm, cw) Coagulation, glaucoma
processes are proportional to the first and high-order 4. HeCd (695 nm, cw) Glaucoma, coagulation
5. Diode laser (810 nm, cw) TTT (thermal for CNV or
of the laser electric field (E). The first term leads to AMD)
absorption or elastic scattering where the laser (1.4 to 2.1 micron, cw) DTK (hyperopia)
frequency remains. The high-order terms leads to 6. Nd:YAG (1064 nm, pulsed) Posterior capsulotomy,
phaco
non-linear responses which change the frequency of 7. Green Nd:YAG (532 nm, 3-10 ns) PDT (for CNV or AMD)
the initial laser. The bulk polarization (P) is 8. UV:YAG (213-266 nm, 3-20 ns) LASIK, LASA (presbyopia,
glaucoma)
proportional to the induced dipole moment (U) and 9. Ho:YAG (2.1 micron, 200 us) LTK (hyperopia)
defines the nonlinear processes. The second harmonic 10. Er:YAG and YSGG LASA (presbyopia),
generation (SHG) is governed by the second term of (2.8-2.94 micron, 200 us) phacoemulsification,
blepharoplasty
Eq. (5), whereas OPO, SRS and third harmonic 11. CO2 (10.6 micron, ultra-pulsed) Blepharoplasty
generation (THG) is governed by the third-term. 12. Ultrashort laser Photodisruption, cataract
(1064, 532, 780 nm, f.s. to n.s.)
The energy level description of the linear and
nonlinear processes is shown in Figure 2.7 which may
be compared to Figure 2.5 and 2.6. Greater details Table 2.4: Laser candidates for laser phaco or
photodisruption of ocular lens
may be found in the SPIE proceeding of Lin (1989).
Laser type Wavelength (pulse width) Energy/pulse
LASER PHACOEMULSIFICATION Nd:YAG 1064 nm (n.s. and p.s.) (1.0 – 20) mJ
Nd:YLF 1053 nm (n.s., p.s. and f.s.) (0.05 – 20) mJ
Table 2.3 shows a variety of ophthalmic lasers and Ti:sapphire 780 nm (p.s. and f.s.) (0.01 – 0.1) mJ
Ho:YAG 2100 nm (μs) (10 – 20) mJ
Table 2.4 shows lasers for phaco including Nd, Ho
Er:YAG 2940 nm (μs) (10 – 20) mJ
and Er:dopped YAG laser with long and short pulse
duration have been proposed as alternatives for the Presbyopia resulting from age may be treated by
conventional ultrasound phaco. The possible restoring or improving the accommodation via
advantages of laser phaco, or laser disruption of lens several means: the scleral expansion band (SEB)
nuclei include: less invasive, more efficient and might method by Schachar, the ciliary scleratomy by
be used for both soft and hard cataracts. However, Fukusaku and the laser scleral ablation by Lin (2005).
as of today, none of the laser methods have been Alternatively, accommodation may be improved by
 Biophysics for Thermal and Non-Thermal Laser Processes 15
direct modification of the modulus (or elasticity) of selective tissue (matter) interaction by a focused beam
the aging lenses, or reduction of the lens volume at a specific spectrum for strong absorption
proposed by Krueger. Thermal shrinkage of the lens (interaction).
by lasers was also proposed by O’Donnell (US Patent)
to reshape the lens surface for refractive power CONCLUSION AND NEW DIRECTIONS
change.
The bi-physical and bi-photonic aspects of light-
One of the critical issues in laser photodisruption
matter interactions provide us the fundamentals of
(LPD) of lens nuclei for the increase of accommodation
medical uses. These interactions include thermal and
is how to modify the lens without forming a cataract.
non-thermal in response to “hot” and “cold” lasers,
The early work of LPD was conducted with rabbit
respectively. Furthermore, light-(or laser) induced
eye experiment and showed that the postoperative
processes also include linear (absorption, scattering
lenticular opacity with a laser of nanosecond duration
auto-fluorescence) and nonlinear (multiphoton
was absent when a shorter picoseconds laser was
excitations). The frequency conversion devices further
used. Experimental increase of accommodation in
broaden the medical uses of the existing lasers by
animal lens was also conducted by using a
expanded spectra from deep UV (for tissue ablation)
femtosecond Nd:YAG laser of Ti:sapphire laser (at
to IR (for tissue coagulation and thermal therapy).
780 nm wavelength) showing no cataract formation
New medical uses of lasers and other incoherent
after 3 months. The concept of modulating the elastic
lights (such as lamp light, LED) depend on the in-
properties of the crystalline lenses by a low energy
depth understanding of the biophysical, biochemical
short pulse laser may be an alternative for the long-
and biological aspects of light-tissue (or light-cell)
pulse Er:YAG laser modification of the scleral tissue
interactions, in addition to the development of new
for the treatment of presbyopia. Scleral tissue
light sources and new photosensitizers (for PDT) to
elasticity may be also modified by a UV laser ablation
be presented in a separate Chapter of this book.
as proposed by Lin (2005). In comparison, scleral
Medical lasers have also been widely used in other
ablation method (using IR or UV laser) has the
areas of dermatology and cosmetology (Lin, 2006).
advantages over femtosecond laser method being low
system cost and non-invasive to the lens. It, however, BIBLIOGRAPHY
is more invasive to the eye involving scleral ablation. 1. Boyd, RW. (1992) Nonlinear Optics, Academic Press, NY.
Laser phaco may be an alternative for conventional Lin, JT. George T. (1981) Quantum dynamical model of
ultrasound phaco under certain cataract conditions. laser/surface-induced predissociation. Surface Science
(1981);108;340-356.
However, deeper understanding of the biophysical
2. Lin, JT. Ed. Growth and applications of laser host and
aspect of the laser-lens interaction and the system nonlinear crystals. SPIE Proc. 1989;1104.
design aspect are required, in addition to longer term 3. Lin, JT. Scanning laser technology for refractive surgery.
clinical studies. The new application for presbyopia In: Garg A, (Ed) Mastering the techniques of corneal
refractive surgery. New Delhi: Jaypee Brothers 2005;
using the short-pulse IR lasers to modify the elasticity 20-36.
of the lens showed certain initial safety progress. 4. Lin, JT. Recent progress of medical lasers for
However, the efficacy remains unknown. Combining ophthalmology, dermatology and cosmetology. Scientific
Research Monthly. 2006: (in press).
ultrasound and laser device may be explored for 5. Prasad, P. Introduction to biophotonics. John Wiley &
potential new applications or for clinical advantages. Sons, Inc. NJ. 2003.
Laser phaco represents one of the examples of 6. Svelto O. Principles of lasers. Plenum Press, NY 1995.
16 Mastering Advanced Surface Ablation Techniques

CHAPTER

3 Regenerative Aspects of
Excimer Laser Ablation

Takhchidi K, Doga A, Kachalina G, Maychuk N (Russia)

INTRODUCTION – Edema and non-infectious inflammation of corneal

flap;
Refraction abnormalities prevail in the world profile – Non-specific diffuse intralamellar keratitis;
of ophthalmic diseases and require timely correction, – Early subepithelial fibroplasias – haze;
including surgery.6 Recently, both ophthalmologists – Certain forms of secondary syndrome of dry eye;
and patients show increasing interest to different – Allergic keratoconjunctivitis;
keratorefractive interventions.12,17,51 However, some – Retardation of re-epithelialization of the zone of
authors suppose it should be taken into account that surgery;
in patients with ametropia, routine methods, i.e. – Hyperplasic processes (for example, epithelial
spectacle and contact lenses, can provide high hyperplasia) and some other.38,45
functional results.19 It means that surgery is aimed at Epidemiological data about KRO complications
cosmetic effect. And only in astigmatism, vary within wide range because of, in particular,
keratorefractive operations (KRO) are considered to different approaches to interpretation of the term
be pathogenetically substantiated. Thus, ”complication”. Routine criterion for development of
requirements to results of the correction should be KRO complication implies deterioration of corrected
rather high.10,11,46,57 visual acuity as compared to preoperative values.
Despite high level of modern KRO, adequate Thus, published data on postoperative complications
equipment and minimal possible trauma, any do not exceed several percents.2,23,32
operation causes complex of biochemical, Lately, more rigid criteria have been formulated
immunological, and morpho-functional alterations in for the term: “KRO complication” means any
eye tissues, that can provoke in certain conditions aberration in the normal course of surgery or
development of postoperative complications.7,11,20 postoperative period, which requires additional
In all cases, compensatory mechanisms start manipulations or drug therapy even without
directed towards restoration of homeostasis but in deterioration of final result of the surgery.3,29,41
some cases they appear to be insufficient13,37,61. According to this approach, the rate of
In this case, postoperative complications of KRO complications is rather higher:
caused by failure of regenerative process develop 1. The rate of subepithelial fibroplasias (haze) one
such as the following: month after PRK achieves 60% (in patients with
– Neurotrophic epitheliopathy; high degree of ametropia). Under the influence
 Regenerative Aspects of Excimer Laser Ablation 17
of intense drug therapy (corticosteroids, enzyme eye and the organism, on the whole.5,27 This prolongs
therapy (Lidaza), and application of anti- significantly the period of visual and social rehabilitation
proliferative agents such as mytomycin) and as a of patients, deteriorates life quality of patients of active
result of spontaneous regression, rate of residual working people, and prolongs sick-list time.42
fibroplasias one year after PRK does not exceed It was noted that these KRO complications are
9% (in initial mixed or stromal forms of haze) and recorded more frequently in patients with certain
requires repeated surgery in not more than 3% of ophthalmic and system diseases.
cases.5,36,53 This was the base for determination of the
2. Neurotrophic epitheliopathy (NE), according to following risk factors for KRO complications.
different authors, is found in 11.2-48% of cases. – Long-term application of contact lenses;
Some authors do not distinguish NE as separate – Preceding surgeries on the cornea;
complication but include it into complex of – Aggravated ophthalmic anamnesis (particularly,
symptoms of secondary dry eye induced by KRO infectious keratoconjunctivitis);
on the basis of the fact that the rate of NE is – Age before 18 years and after 40 years;
significantly higher in the group of patients with – Long-term hormone substitutive therapy;
impairment of lachrymation. However, in some – Inclination to keloid formation;
cases, signs of secondary dry eye do not – Allergic and autoimmune diseases (bronchial
accompany NE. The cause of more frequent asthma, neurodermatitis, psoriasis, atopic
detection of NE in this group of patients is dermatitis, rhinitis, etc.)
common etiology of complications: Development Due to different mechanisms, these risk factors
of both NE and secondary impairments of
interfere in general and local (in eye tissue) metabolic,
lachrymation are caused by mechanical damage
hormonal, and immune processes. This decreases
to intrastromal corneal nerves in the course of
significantly compensatory abilities of the organism
KRO. The difference is that NE is mainly caused
to restore homeostasis after the influence of
by failure of neurotrophic function of intrastromal
exogenous destabilizing factors such as surgery or
nerves, while development of secondary dry eye
trauma. Initiation and persistence of metabolic and
is mainly caused by separation of neuronal
connections of receptor areas and glands, which immune misbalance cause development of certain
produce lachrymal fluid.9,54,59 postoperative complications of KRO.1,4,14,31,40
3. Transitory secondary dry eye forms in 8.2-45% Many authors have shown that excimer laser
of cases after LASIK and somewhat rarely after ablation of the cornea is accompanied by
PRK (up to 17% of cases).18,39,44 development of surgically induced oxidative stress (SIOS)
4. Non-specific diffuse lamellar keratitis (DLK) – at the level of tissue. It aggravates the course of post-
syndrome “Sahara sands” develops in 1.3-1.9% traumatic inflammatory reaction and is one of the
of cases. Till now, there is no generally accepted main pathophysiological mechanisms of disre-
concept of DLK etiology, it is supposed to be generative postoperative complications.16,21,28
caused by powder from surgical gloves, metal SIOS is the impairment of balance between pro-
microparticles from cutting edge of micro- and anti-oxidative systems in tissues of the anterior
keratome, lipid and mucin secrets of conjunctival eye segment. Among causes of SIOS, the main one is
glands, autoimmune reactions, and recently there generation of free radicals and active forms of oxygen
are some papers about failure of local metabolic under the influence of excimer laser.
processes induced by KRO as important factor of Besides, influence of excimer laser leads to
DLK development.33,55,60 inhibition of glutathione-dependent antioxidative
As a rule, complications, listed above, are rather system of the cornea. In the case of insufficient
successfully cured but they require long-term activation of other chains of anti-oxidative protection,
application of drugs, which are not indifferent for an it leads to aggravation of SIOS.16
18 Mastering Advanced Surface Ablation Techniques
SIOS is intensified by chronic psychoemotional The factors mentioned above indicate that SIOS
tension and unbalanced nutrition with deficiency of plays the main role in formation of certain
bioantioxidants typical of urbanization. postoperative complications of photorefractive
SIOS produces multifactor pathological influence surgery.8,58
on eye tissues. Impairment of protein metabolism with prevalence of
1. Intensification of lipid peroxidation (LPO) leads catabolic reactions over anabolic ones is another factor
to increased cell membrane permeability, ion induced by KRO and aggravated by secondary
misbalance, separation of tissue respiration and alteration by SIOS. This leads to impairment of the
oxidative phosphorylation in mitochondria, and, balance between cytolysis and cellular regeneration,
as a result, to decrease of ATP production. synthesis and inactivation of enzymes and other
Energetic starvation interferes into all energy- protein-containing substances playing an important
dependent processes. Impairment in function of role in cellular metabolism.13,24,48
transport protein aquaporin-5, which provides Thus, KRO has multifactor influence, which causes
energy-dependent trans-membrane transpor- the development of the complex of alternative-
tation of water molecules, results in long-term regenerative processes. They are reflected in deep
aseptic edema of the corneal flap. Regeneration
biochemical reconstructions at the regional level, first
of quickly renewing tissues is affected that is
of all in the cornea. They are specific and precede the
accompanied by retarded re-epithelialization of
development of clinical picture of postoperative
corneal erosions, long-term neurotrophic
complications.
epitheliopathies, etc.
Lachrymal fluid is an available diagnostic medium
2. Oxidative modification of DNA causes abnormal
regeneration of corneal cells with altered for evaluation of metabolic processes in the eye as it
cytophysical and antigenic properties. This initiates is constant, dynamically renewing micro-medium of
cascade of autoimmune reactions, which play the the anterior sector of the eye. It is tightly connected
role in formation of DLK. Besides, altered with local metabolic processes. On the other hand,
keratocytes synthesize abnormal collagen, which non-invasion method of lachrymal fluid collection is
is deposited chaotically and is visualized as the an important advantage.
component of early Haze. Besides, objective evaluation of dynamics of
3. Lipoperoxidation of proteins of cytoplasmic regenerative processes after KRO and search for
membranes and direct cytotoxic influence of LPO subclinical signs of postoperative complications are
induces cytolysis of epithelio- and keratocytes impossible without precise methods of visualization
that is manifested by retardation of re- of corneal ultrastructure. Confocal microscopy, which
epithelialization and formation of so called is recently widely introduced into different fields of
acellular zone along both sides of interface lacking ophthalmology, provides valuable assistance in
in keratocytes. This phenomenon was first
examination of corneal morphology in vivo.30,52
diagnosed with the help of confocal microscopy.
Confocal microscopy allows examination of
There are hypothesis that long-term existence of
biological tissues at the cellular level at the state of
acellular zone alters biomechanical properties of
physiological activity and demonstration of results
the cornea and may be the cause of iatrogenic
keratectasia. in three dimensions–height, width, depth, and time.25
4. Irreversible conformation of glycosaminoglycans For the first time, principle of confocal microscopy
molecules, for example, increase of number of was described by Minsky in 1957.47 He proposed the
cross-links in hyaluronic acid, causes alteration in system, where the lenses of illuminator and objective
mucin layer of lachrymal film that leads to focused in one point (had common focal points) that
alteration of its stability and induces development gave the name of “confocal” microscopy (Figure 3.1).
of special form of secondary dry eye. Confocal microscopy allowed significant increase of
 Regenerative Aspects of Excimer Laser Ablation 19
axial (5-10 μm) and lateral (up to 1-2 μm) resolution Lately, number of papers on this topic increases,
of microscopy due to exclusion from focal points of however, there are no integrative studies connecting
information from adjacent areas. This makes possible histomorphological alterations in the cornea of
600 times magnification of image without the lost of patients in vivo with metabolic processes in eye tissues
contrast and clearness.30,43 in the course of reparation after KRO and during the
development of complications.
All facts mentioned above, and twenty years
experience of active scientific and surgical activity in
the field of excimer laser surgery gave us an ides to
study morphological and metabolic features of typical
and pathological regenerative process in the cornea
after different keratorefractive interventions, to
develop objective methods of evaluation of individual
reaction of eye tissues on surgical intervention, and
to propose algorithm of diagnosis, prophylaxis, and
correction of disregenerative complications.

MATERIALS AND METHODS

Figure 3.1: Schematic presentation of the principle of confocal
microscopy. White light passing through the first perforation in the disk Clinical Characteristics of Examined Patients
is focused on the focal plane in the cornea with the help of collecting
(convex) lens. Reflected ray is refracted on the lens of the objective We studied 213 patients (394 eyes) with myopia to
and, passing through the outlet in the disk, achieves camera-detector.
All rays, which are focused above and under the focal plane, are cut solve different tasks of this study (Table 3.1).
off with the help of perforations in the disk and do not achieve the Table 3.1: Characteristic of groups of observed patients
camera Group Criteria of Number of Mean age, Type of
inclusion patients M+σ ametropia
(number of correction
Increasing interest to KRO and successes in the eyes)
study of histomorphology of the cornea in vivo using Control Uncomplicated 20 (40) 24.0+1.8 Spectacles
group myopia
confocal microscopy open wide prospects for the The main 1a – myopia, 50 (100) 23.5+1.9 LASIK
study of the cornea after different types of surgery: group 1 Initially unaltered
cornea, uncomplicated
Evaluation of cellular reactions related to healing postop period
1b – myopia, initially 30 (60) 26.2+2.4 PRK
process, migration of different types of cells and unaltered cornea,
cornea remodeling, process of re-innervation of the uncomplicated
postop period
cornea, formation of Haze, and cicatrization of the The main 2a – myopia, initially 37 (49) 24.7+2.2 LASIK
group 2 unaltered cornea,
cornea, reasons of formation of iatrogenic keratectasia dismetabolic
in the case of preservation of sufficient thickness of complications
2b – myopia, initially 26 (45) 27.1+3.4 PRK
residual stroma and several other questions that can unaltered cornea,
be answered by confocal microscopy.15,30,34,35 dismetabolic
complications
Modern confocal microscopes allow one to The main Myopia, initially 50 (100) 31.2+4.2 LASIK
group 3 altered cornea
visualize cellular composition of different corneal (because of preceding
surgeries or long-term
layers, to measure thickness of the corneal valve and use of contact lenses)
residual stroma, to determine localization and length
of subepithelial fibroplasia, to measure thickening of There were the following principles of formation
the cornea, which causes regress of refractive effect of groups:
after PRK, and to analyze the type of inclusions in 1. Control group included patients with myopia who
the interface.22,49,50,56 used spectacles for optic correction.
20 Mastering Advanced Surface Ablation Techniques
2. The first main group was formed to study specific 1. Schirmer test 1: Evaluation of total (basal and
features of typical postoperative course of different reflexive) tear production. The test is based on
KRO. It comprised patients with myopia, initially moistening of standard sterile strips of filter paper
unaltered cornea, and uncomplicated during the certain time. We used ready-to-use test
postoperative period. Based on the type of strips “Bausch&Lomb” (USA). Results were
surgical correction, the group was divided into evaluated in millimeters of moistened part of the
two subgroups: strip during five minutes.
We used the following criteria to interpret the
- 1a – patients with myopia, who have undergone
data obtained: More than 25 mm during 5 minutes
LASIK;
– hypersecretion;
- 1b – patients with myopia, who have undergone
15-25 mm during 5 minutes – normosecretion;
PRK. 10-15 mm during 5 minutes – intermediate
3. We formed the second main group to study condition; less than 10 mm during 5 minutes –
specific features of atypical postoperative period hyposecretion of lachrymal fluid.
of different types of KRO. This group comprised 2. Schirmer test 2 (modification by Jones): Examination
patients with myopia, initially unaltered cornea, of value of basal tear production.
and disregenerative postoperative complications Method of testing: After preliminary instillation
recorded three days to four months after surgery. of anesthesia, lacrimal fluid and residual
Based on the type of surgical correction, the group anesthetics were accurately absorbed by cotton
was divided into two subgroups: tampon from inferior fornix of conjunctiva. Then
- 2a – patients with myopia, who have undergone filter paper strip was placed under the lower lid
LASIK; of the patient for 5 minutes (as in Schirmer test-
- 2b – patients with myopia, who have undergone 1). Moistening of more than ten millimeters of
PRK. standard test strip during five minutes was
considered to be normal.
4. We formed the third main group to prove
3. Test for evaluation of tear film break-up time (Norn’s
effectiveness of the algorithm of prediction,
test): Examination of tear film stability indicating
diagnosis, and correction of dismetabolic
condition of its mucin and lipid layers.
complications of KRO, developed in the course of Method of testing: 0.2% sodium fluorescein
the study. It comprised patients with myopia and solution was instilled into conjunctival cavity with
initially altered cornea because of long-term subsequent examination of patient’s eye using slit-
history of contact lenses with development of lamp with cobalt filter. Time interval between the
neovascular keratopathy or KRO in anamnesis, last blinking and appearance of first chaotic dry
who were intended for LASIK. spots was evaluated. Parameters for evaluation
5. Additionally, we examined healthy volunteers of results: norm – from 15 to 45 sec., 10-15 sec. –
with emmetropia (to develop the method of intermediate values, less than 10 sec. – instability
examination and to determine normal biochemical of tear film. In cases of intermediate or decreased
parameters of lachrymal fluid). values of break-up time test the probe was
repeated three times, accepting the average
Screening System for Studying Functional Tear meaning as a result.
Complex 4. Evaluation of the cornea condition is based on
the ability of fluorescein solution instilled into
Lately in refractive surgery, much attention is paid conjunctival cavity to indicate epithelial defects
to examination of condition of functional tear Figure 3.2.
complex (FTC), which is implied to consist of eye Method of testing: Condition of the corneal
surface, tear-producing organs, and their epithelium is evaluated after instillation of 0.2%
neuroreflexive interactions. We used the following sodium fluorescein solution into conjunctival
diagnostic tests to evaluate condition of FTC: cavity using biomicroscopy with cobalt filter. For
 Regenerative Aspects of Excimer Laser Ablation 21
quantitative evaluation of epithelial damage, the To exclude influence of drugs on composition of
cornea was divided into five zones. Staining in lachrymal fluid, samples were collected at the same
each zone is evaluated using four-points scale: time in all patients (from 8.30 to 9.00 am).
1. Dotted defects (to ten spots); Biochemical examination of LF was performed
2. Moderate; using automatic analyzers “Express Plus” (Bayer,
3. Average; USA), “Hitachi-912” (F. Hoffmann-LA Roche LTD,
4. Severe alteration. Then marks for each zone are France), and spectrophotometer. The following
summarized. Maximal mark is twenty. parameters were studied: Parameters of free-radical
oxidation (malonic dialdehyde), anti-oxidative
protection (superoxide dismutase), protein synthetic
activity of cells (total protein), and activity of protein
degradation (urea).
To evaluate severity of damage to the cornea after
KRO, in all patients pre- and postoperatively, we
calculated values of earlier developed biochemical
coefficients of SIOS and degree of impairment of
synthesis/degradation of protein (SDP) using the
following formulas:
1. K1 – coefficient of evaluation of SIOS degree in
tissues of the anterior eye segment:
Figure 3.2: An example of calculation of the corneal epithelium MDA × 100
K1 = – 54.0 where
P
condition: zone 1 – intact (0 points); in zones II, III, IV, and IV one can SOD
see average alteration (corresponds to three points). Totally, it is 12
U points MDA – content of malonic dialdehyde, parameter
of activity of free-radical oxidation;
Method of Investigation of Biochemical SOD – activity of superoxide dismutase, the most
Composition of Lachrymal Fluid (LF) active enzyme of anti-oxidative protection of the
LF was collected from inferior fornix of conjunctiva cornea;
using laboratory micropipette with disposable sterile 54 is mean ratio MDA × 1000/SOD in healthy
tips or glass microcapillar without preliminary people.
If K lower than 8 corneal damage is absent,
stimulation of lachrymation (Figure 3.3).
K is from 8 to 38 – light damage of the cornea,
K is from 38 to 55 – average damage,
K is from 55 to 75 – severe damage,
K is from 75 and higher – extremely severe
damage.
2. K 2 – coefficient of evaluation of degree of
impairment in the system of SDP:

K2 = 4.9 – where

P – content of the protein, an indicator of protein-

synthetic activity of cells;
U – content of urine – the product of
biodegradation of proteins,
4.9 – average value of ratio P/U in tears of healthy
Figure 3.3: Method of LF collection people;
22 Mastering Advanced Surface Ablation Techniques
If K lower than 0.7, corneal damage is absent,
K is from 0.7 to 1.4 – light damage of the cornea,
K is from 1.4 to 2.8 – average damage,
K is from 2.8 to 4.1 – severe damage,
K is from 4.1 and higher – extremely severe damage.

Method of Confocal Microscopy of the Cornea

We used confocal microscope Confoscan 4 (Nidek,
Japan) with the following parameters: lens for
examination through immersion gel – 40x, NA 0.75,
WD 1.98, Zeiss; examined zone of the cornea was
460x345 um, image obtained was 768x576 pixel, lateral
resolution – 0.6 um/pixel, and speed of scanning was
25 images per second. We used automatic mode for Figure 3.4: Excimer laser device “MicroScan”
examination of the whole thickness of the cornea,
manual mode for visualization of certain corneal The corneal flap was formed by microkeratome
structures, automatic calculation of density of “Zyoptix” (Bausch and Lomb, USA) with head “120”,
endothelial cells with evaluation of polymorphism which allows one to form the flap 100±20 μm thick,
and size of cells, and optic pachymetry (using Z-ring). according to data of producing company. Our
Examination was performed after one instillation previous studies on flap thickness with different
of local anesthetic through immersion gel. microkeratomes performed with the use of optic
Complex of special examinations was performed in all coherent tomograph “OCT Visante” (Carl Zeiss
patients before surgery and one hour to 12 months Meditec Inc., Germany) showed that thickness of the
postoperatively. corneal flap, which is formed by keratome “Zyoptix”
with the head “120” is 105.3 um, on average (95 to
Technology of Keratorefractive Surgeries
110 um) (Figure 3.5).
Leading ophthalmosurgeons of excimer laser
refractive department of the Center of Laser Surgery
of Eye Microsurgery Complex operated all patients
of main groups.
Standard preoperative preparation in all types of
KRO was identical and consisted in antibiotic
installations three times a day two days prior operation.

Technology of LASIK Procedure

LASIK procedure was performed using standard
technology accepted in Eye Microsurgery Complex with
the use of modern home excimer ArF laser “MicroScan”
created in collaboration with the Center for Physic
Instrument-making Industry of the Institute of General
Physics of Russian Academy of Sciences. The device
functions at frequency of 100 Hz, it is equipped by Figure 3.5: Measurement of thickness of the corneal flap and residual
formation system according to the technology of “flying stroma using optic coherent tomograph OCT Visante in the patient
after LASIK
spot” with diameter of 1.0 mm and highly sensitive
system of control over the movements of patient’s eye, Standard postoperative therapy consisted in
‘eye tracking system’ Figure 3.4. regular instillations:
 Regenerative Aspects of Excimer Laser Ablation 23
– Antibiotics three times a day up to seven days that corneas were intact in all patients. This indicates
postoperatively (3-5 days, on average); homogeneity of groups and gives grounds for further
– Corticosteroid medicines during 2-3 weeks correct comparison and interpretation of results.
postoperatively according to decreasing scheme
Table 3.2: Results of FTC analysis in patients of control group and
beginning with three times a day. the first main group at first examination (M+σ)
Control 1st Main group
Technology of PRK Operation group 1a 1b

PRK was also performed using excimer laser Shirmer-1 Test, in mm 20,5±1,5 21,0±1,2 20,7±0,9
for 5 min (M±σ)
“MicroScan”. In all patients, we used an original Shirmer-2 Test, in mm 12,3±0,5 12,2±0,3 12,3±0,3
transepithelial technology of ablation – without for 5 min (M±σ)
preliminary scarification of epithelium. We have Break-up time test, sec (M±σ) 19,1±0,7 18,9±0,7 19,0±0,6
developed special algorithm of the first stage of PRK, Corneal Epithelium 1,9±0,5 2,1±0,4 2,0±0,3
Assessment, points (M±σ)
which allows us to achieve even removal of
epithelium on the whole area of correction (area of
Table 3.3: Results of biochemical analysis of LF in patients of
de-epithelialization zone depends on the diameter control group and the first main group at first examination (M+σ)
of transition zone of operation) The system of Control 1st Main group
interactive control over the process of epithelium group 1a 1b
ablation provides total differentiated removal of Total Protein, g/l 19,1±1,8 18,8±2,0 19,3±1,8
epithelium without refractive effect. This allows us Urea, mmole/l 3,87±0,5 3,90±0,3 3,88±0,4
to use standard nomograms of the laser for refractive Malonic dialdehyde, μmole/l 1,39±0,22 1,41±0,22 1,40±0,15
keratectomy itself at the second stage of correction. Superoxide Dismutase, Un/l 25,1±2,0 25,6±2,2 25,7±2,5
Transepithelial technology of PRK decreases the
All patients of the first and second main groups
risk of development of subepithelial fibroplasia due
underwent KRO without intraoperative complications.
to decrease of stimulating effects of products from
destroyed epitheliocytes on synthesis of non-
Results of Complex Dynamic Examination of
organized collagen by stromal fibroblasts.8,26 Patients of the First Main Group After KRO
The operation was completed by application of
bandage contact lens, which decreases postoperative Investigation of FTC
pain syndrome and stimulates re-epithelializaion. In all patients in early postoperative period (from one
Standard postoperative therapy consisted of two hour to three days), we found intensification of
stages: reflexive tear production that distorted results of
1. The first stage (before re-epithelialization of the examination of basal secretion of LF and break-up time
corneal erosion) during 3-5 days: antibiotic – three test, and different degree of damage to corneal
times a day; -non-steroid anti-inflammatory drug epithelium (from 4.9 points after LASIK to 12.3 points
– three times a day. after PRK according to twenty points scale). Later on,
2. The second stage – up to two months we noted general tendency to decrease of total
postoperatively: corticosteroid medicines (Schirmer test-1) and basal (Schirmer test-2) tear
according to decreasing scheme. production (maximally pronounced after LASIK)
accompanied with decrease of stability of tear film
RESULTS AND DISCUSSION (break-up time test) (also maximally pronounced after
LASIK) with gradual normalization of parameters by
At first examination, parameters of FTC and 6 (after PRK) and 8 months (LASIK) postoperatively.
biochemical tests of LF of control group and the first Degree of damage to epithelium after all types of KRO
main group did not differ significantly (p < 0.5) gradually decreased and reached initial values by
(Tables 3.2 and 3.3). Confocal microscopy showed month 1-3 of postoperative period (Figures 3.6 to 3.9).
24 Mastering Advanced Surface Ablation Techniques

Figure 3.6: Results of examination of total tear production according to Schirmer test-1 in patients of main group 1
in dynamics of postoperative period after KRO

Figure 3.7: Results of examination of basal tear production according to Schirmer test-2 in patients of main group 1 in
dynamics of postoperative period after KRO
 Regenerative Aspects of Excimer Laser Ablation 25

Figure 3.8: Results of examination of tear film stability according to break-up time test in patients of main group 1
in dynamics of postoperative period after KRO

Figure 3.9: Results of examination of epithelium condition according to twenty-points scale in patients of main group
1 in dynamics of postoperative period after KRO

The study showed that analysis of FTC allows Investigation of biochemical coefficients of degree
quick (to 15 minutes) evaluation of severe alterations of corneal damage in dynamics of postoperative
of eye surface but has low specificity and does not period of KRO was mostly interesting for us. It was
meet the requirements of subclinical diagnosis of noted that acquisition of reliable data on metabolic
postoperative complications. status of the anterior eye segment is possible from
26 Mastering Advanced Surface Ablation Techniques
the second day after LASIK and third day after PRK degree, impairments of SDP were of average
(i.e. after cessation of pronounced reflexive tear degree. Values of coefficients reached norm by
production, which coincide with re-epithelialization eight (K1) and six (K2) months postoperatively.
of the area of surgery). 2. After LASIK, alterations of metabolic status (K1
Results of dynamical coefficients in patients with and K2) are minimal, and achievement of initial
uncomplicated postoperative period after KRO are level was observed by eight months
presented on Figures 3.10 and 3.11: postoperatively (Figures 3.10 and 3.11).
Dynamic study of coefficients in patients after
Confocal Microscopy
KRO showed the following:
1. In uncomplicated course of PRK, values of Confocal microscopy in dynamics of uncomplicated
coefficient evaluating SIOS (K1) in early postoperative period allowed us to visualize the
postoperative period were within ranges of severe following features of corneal regeneration.

Figure 3.10: Dynamics of changes of coefficient K1 of the degree of corneal damage in patients of the main group 1
with uncomplicated postoperative period after KRO

Figure 3.11: Dynamics of changes of coefficient K2 of the degree of corneal damage in patients of the main group 1
with uncomplicated postoperative period after KRO
 Regenerative Aspects of Excimer Laser Ablation 27
After LASIK, foreign inclusions of different origin abnormal branching of newly formed nervous fibers
were visualized in the interface of 97% of eyes (in and abundant anastomoses did not allow one to
91.2% of cases they were metal, in 33.4% - lipid and consider it to be full (Figures 3.15A and B).
mucin, and in 12.3% there were inflammatory Quantitative and qualitative analysis of
macrophage-like cells and erythrocytes) (Figure 3.12). endothelium revealed cell loss within 2.2-2.6%
without alteration of cellular morphology.
After PRK, epithelial defect was substituted by
migration of wing-shape epitheliocytes from intact
zone of the cornea (Figure 3.16).
Thickness of newly formed epithelium was
significantly higher (76.3+9.8 μm) as compared to
intact cornea (52.1+6.5 μm).
Length of acellular zone was less (to 68 μm) than
that after LASIK (to 160 μm), and re-innervation of
the central optic zone occurred earlier (by 5-6
months). Loss of endothelial cells was 2.5-2.7% by
one year postoperatively.
Figure 3.12: Characteristics of foreign inclusions in the interface Complex dynamic examination of patients with
after LASIK disregenerative KRO postoperative complications
By days 10-14 of postoperative period, acellular (main group 2) gave the following results Table 3.4:
zone began to form along both sides of the interface. 1. Study of FTC parameters allowed us only to
It represented the area lacking differentiated cells, register complications but did not have essential
which gradually decreased in length and disappeared prognostic value.
by 6-8 months postoperatively (Figure 3.13). 2. Calculation of values of biochemical coefficients
In 78% of cases, microstrias of the corneal flap of corneal damage degree showed their
were visible (Figure 3.14). significant difference from values typical of
Re-innervation of the central zone of the cornea uncomplicated postoperative period: coefficient
occurred by 8-12 months postoperatively. However, of SIOS (K1) was increased in 97.9% of cases,

Figures 3.13A to C: Dynamics of ultra-structural changes in corneal stroma after LASIK

A. hypercellular stroma due to inflammatory cells migration first postoperative days
B. acellular intrastromal zone since 10-14 days up to 6-8 months after surgery
C. rarefied fibrocellular stromal net after 8 months postoperatively
28 Mastering Advanced Surface Ablation Techniques

Figure 3.16: Substitution of epithelial defect with wing-shape

Figure 3.14: Microstrias of Bowmen’s membrane of the corneal flap epitheliocytes

coefficient of SDP (K2) – in 84.0% of cases, both

coefficients (K1+K2) – in 76.6% of cases, that
confirms important role of these patho-
physiological mechanisms in pathogenesis of
disregenerative complications of KRO. Besides,
we noted that in all cases, increase of these
coefficients preceded clinical manifestation of
complications that allowed us to include them in
predicting system of disregenerative complica-
tions of KRO.
3. Almost in all cases, confocal microscopy of the
cornea in patients with disregenerative
complications revealed specific pathomorpho-
logical signs of the forming complication at
subclinical stage (Figures 3.17 to 3.19).

Figures 3.15A and B: Restoration of nervous fibers of

subepithelial plexus damaged by cutting corneal flap
A. “scraps” of the nerve fibers of the superficial nerve plexus
(arrow) damaged by microkeratome during corneal flap creation Figure 3.17: Confocal microscopy of the cornea of the patient with
B. re-innervation of the central corneal optical zone aseptic edema of the corneal valve (day 3 after LASIK)
 Regenerative Aspects of Excimer Laser Ablation 29
Table 3.4: Specific features of complex examination in patients with
disregenerative complications of KRO as compared to uncomplicated
course (printed in blue)
Complication Eye Time K1/K2 Specific Specific features of
N of (average) features confocal
finding of FTC microscopy
(average)

K1/K2 FTC in
(uncompli- uncompl.
cated course) course
(average) (average.)
Neurotrophic 22 Day 7-14 59,6 / 2,6 Epithelium ↓ number of basal
epitheliopathy condition epitheliocytes,
(NE) (EC): 5,7 local defects of
points epithelium
21,7 / 1,04 2,9 points

Figure 3.18: Confocal microscopy of the cornea of the patient with Aceptic edema 2 Day 3 59,0 / 1,4 EC: 4,1 Diffuse edema of all
neurotrophic epitheliopathy (day 7 after LASIK) of corneal flap points layers of the cornea,
28,8 / 1,05 3,6 points thickening of the
flap to 150 um
Dry-eye 19 Day 7 62,3 / 1,8 Schirmer Increase of number
syndrome – one month test-1 of inflammatory
(DES) (ST-1): 8,2 cells
14,1 / 0,8 17,4
NE+DES 13 Day 7-14 64,3 / 2,5 EC / SÒ-1: Local defects of
6,2/ 9,5 epithelium + many
21,7 / 1,04 2,9 / 16,8 inflammatory cells
in stroma
Subepithelial 38 1-3 months 69,2 / 2,6 No specific There is an
fibroplasia features additional pike on
of the cornea 13,3 / 0,7 4,4 points the curve of optic
density (behind
epithelium), ↑
reflective ability of
extracellular
matrix, ↑ of cell
number in stroma

Figure 3.19: Confocal microscopy of the cornea of the patient with

subepithelial fibroplasia (one month after PRK) We selected group of patients (50 patients – 100
eyes) with myopia who were intended for LASIK
4. Based on pathophysiological mechanisms (main group 3). To increase probability of signs of
revealed, we include the following medicaments atypical postoperative course, patients with initially
into complex therapy: altered cornea because of long-term use of contact
– Antioxidants in patients with high values of lenses (neovascular keratopathy) or previous KRO
coefficient of evaluation of SIOS; were included into the group. Patients were divided
– Reparative drugs in patients with high into two equal subgroups. LASIK was uncomplicated
coefficient of evaluation of SDP evaluation; in all patients.
– Antioxidants + reparative drugs in patients with Design of the study: In all patients, pre- and
combined increase of both coefficients. postoperative examination was performed according
In all patients, we recorded quick regress of to the proposed algorithm but in patients of the first
clinical signs of complications accompanied by subgroup, drug therapy was carried out in standard
decrease of biochemical coefficients. way and in patients of the second subgroup, we
Analysis of results obtained proposed the carried out differentiated correction of revealed
following diagnostic algorithm of early detection of lesions (scheme 2).
complicated postoperative course (scheme 1). Results of the study represent at the schemes 3
Final section of the study is a clinical proof of effectiveness and 4.
of the proposed algorithm of predicting and correction of Thus, in the first subgroup with initially altered
excessive lesion of the cornea resulted from KRO. cornea, average degree of corneal lesion revealed by
30 Mastering Advanced Surface Ablation Techniques

Scheme 1

Scheme 2
Regenerative Aspects of Excimer Laser Ablation 31

Scheme 3

Scheme 4
32 Mastering Advanced Surface Ablation Techniques
calculation of biochemical coefficients on day 2 young socially active patients with ametropia who
postoperatively was accompanied by development decide to get rid of spectacles or contact lenses with
of complications in 83.3% of cases, while severe the help of excimer laser correction.
degree of corneal lesion – in 100% of cases. In all
cases, confocal microscopy confirmed the diagnosis. REFERENCES
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microscopy 95.
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corneal damage (even in Compilations Hard Cover. 2000;624.
absence of clinical signs – 12. Buratto L, Ferrari M, Rama P. Excimer laser intrastromal
metabolic correction keratomileuses. Am. J. Ophthalmol 1992;113:291-5.
13. Cintron C, Hassinger LC, Kublin CL, Cannon DJ.
Thus, the study revealed morphological and Biochemical and ultrastructural changes in collagen during
metabolic features of uncomplicated course of PRK corneal wound healing J. Ultrastruct. Res. 1978;65:13-22.
14. Cobo-Soriano R, Beltran J, Baviera J. LASIK outcomes in
and LASIK and specific subclinical markers of patients with underlying systemic contraindications: a
excessive corneal damage causing disregenerative preliminary study. Ophthalmology 2006;113(7):1124.e1.
postoperative complications. Algorithm of prediction Epub 2006;27.
15. Corbett MC, Prydal JI, Verma S, et al. An in vivo
and correction of postoperative disregenerative investigation of the structures responsible for corneal
complications of KRO, developed on the basis of these haze after photorefractive keratectomy and their effect
markers, will improve quality of rehabilitation of on visual function. Ophthalmology. 1996;103:1366–80.
 Regenerative Aspects of Excimer Laser Ablation 33
16. Costagliola C, Balestrieri P, Fioretti F, et al. ArF 193 nm a new classification system. J. Cataract. Refract. Surg. 2001;
excimer laser corneal surgery and photo-oxidation stress 27(10):1560-6.
in aqueous humor and lens of rabbit: one-month follow- 34. Kachalina G, Maychuk N, Mushkova I, et al. In vivo
up. Curr. Eye Res. 1996;15(4):355-61. Confocal Microscopy of the corneal regenerating
17. Dausch D, Klein RJ, Schroeder E. Ophthalmic Excimer processes after Laser Thermokeratoplasty. Intraocular
Laser surgery. Straugsburg: Du Signe (Ed), 1994;156. Implant and Refractive Society, India 3, N 2.14-8.
18. De Paiva CS, Chen Z, Koch DD, et al. The incidence and 35. Kauffmann T, Bodanowitz S, Hesse L, et al. Corneal
risk factors for developing dry eye after myopic LASIK. reinnervation after photorefractive keratectomy and laser
Am J Ophthalmol 2006;141(3):438-45. in situ keratomileusis: an in vivo study with a confocal
19. Duffey RJ, Leaming D, Robin J. Trends in refractive surgery videomicroscope Ger. J. Ophthalmol 1997;N5:508-12.
J Refract. Surg. 1999;15: N1.15. 36. Kim JH Some problems after photorefractive
20. Durrie DS, Lesher MP, Cavanaugh TB. Classification of keratectomy. J. Refract. Corneal Surg 1994;10, ¹ 2:226-30.
variable clinical response after phothorefractive 37. Kitano S, Goldman JN. Cytologic and histochemical
keratectomy for myopia J Refract. Surg. 1995; 11:N 5. changes in corneal wound repair Arch. Ophthalmol
341-7. 1966;76:345-54.
21. Erb C, Nau-Staudt K, Flammer J, Nau W. Ascorbic Acid 38. Knorz MC. Complications of refractive excimer laser
as a free radical scavenger in porcine and bovine aqueous surgery Ophthalmologe 2006;103(3):192-8.
humor. Ophthalmic Res. 2004;36(1):38-42. 39. Kourenkov VV, Sheludchenko V.M., Kashnikova OA,
22. Erie JC, Patel SV, McLaren JW, et al. Keratocyte density Polunin G.S. Tear hypoproduction diagnostics after laser
in vivo after photorefractive keratectomy in humans in situ keratomileusis. Congress of the European Society
Trans. Am. Ophthalmol. Soc 1999;97:221–40. of Cataract and Refractive Surgeons, XVIIIth: Abstracts.
23. Farah SG, Azar DT. Laser in situ keratomileusis: literature Brussels, 2000;141.
review of a developing technique. J. Catcract Refract. 40. Loewenstein A., Lipshitz I., Levanon D., et al. Influence
Surg 1998;24(7): 989-1006. of patient age on photorefractive keratectomy for myopia,
24. Fitzsimmons T, Fagerholm P, Schenholm M, Harfstrand J. Refract. Surg. 1997; ¹1:23–6.
A. Hyaluronic acid in the rabbit cornea after superficial 41. Lui MM, Silas MA, Fugishima H. Complications of
keratectomy with excimer laser. Invest. Ophthalmol Vis. photorefractive keratectomy and laser in situ
Sci., 1991;32:1247. keratomileusis. J. Refract. Surg 2003;19(2 Suppl):S247-9.
25. Furrer P, Mayer JM, Gurny R. Confocal microscopy as a 42. Malychev V, Gorodetski BK, Chtchouko AG.
tool for the investigation of the anterior part of the eye. Rehabilitation system in excimer laser surgery. Abstract
J. Ocul. Pharmacol. Ther 1997;N13:559–78. book of XIX Congress of the ESCRS – Amsterdam,
26. Fyodorow SN, Semenow AD, Magaramow DA et al. Using Netherlands, 1–5;2001;238.
an absorbing cell delivery system for correction of myopia 43. Maurice DM. A scanning slit optical microscope. Invest.
from 4 to 26 D in 3251 eyes. Refract. Corneal. Surg Ophthalmol 1974;13:1033-37.
1993;9(Suppl.):123-24. 44. McDonald M. Dry eye complication after LASIK. Euro
27. Gartry DS, Kerr Muir MG, Lohmann CP, Marshall J. The Times 2001;6:24-27.
effect of topical corticosteroids on refractive outcome and 45. Melki SA, Azar DT. LASIK complications: etiology,
corneal haze after photorefractive keratectomy Arch. management, and prevention. Surv Ophthalmol
Ophthalmol 1992;110:944-52. 2001;46(2):95-116.
28. Giasson CJ, Bleau G, Brunette I. Short-term oxidative 46. Mezcaros L. Many successful contact lens wears consider
status of lens and aqueous humor after excimer laser refractive surgery, study finds. Ophthalmol. Times.
photorefractive keratectomy. J. Refract. Surg 1999;15, N 1996;21:N 26.22.
6:673-78. 47. Minsky M. Memoir on inventing the confocal scanning
29. Gimbell H., Probst L. The LASIK complications OSN, 2001; microscope.1988;10:128-38.
54. 48. Mohan RR, Hutcheon AE, Choi R, et al. Apoptosis,
30. Guthoff RF, Stave J. In vivo micromorphology of the cornea: necrosis, proliferation, and myofibroblast generation in
confocal microscopy principles and clinical applications. the stroma following LASIK and PRK. Exp. Eye Res. 2003;
In: Reinhard T., Larkin F. (eds). Essentials in 76(1):71-87.
Ophthalmology – Cornea and External Eye Disease. Berlin, 49. Mustonen R.K., McDonald MB, Srivannaboon S, et al.
Heidelberg, New York: Springer-Verlag, 2006;173-208. Normal human corneal cell populations evaluated by in
31. Halkiadakis I, Belfair N, Gimbel HV. Laser in situ vivo scanning slit confocal microscopy. Cornea.
keratomileusis in patients with diabetes. J. Cataract. 1998;17:485-92.
Refract. Surg 2005; 31(10):1895-8. 50. Oliveira-Soto L, Efron N. Morphology of corneal nerves
32. Iskander NG, Peters NT, Penno EA, Gimbel HV. using confocal microscopy. Cornea 2001;20:374–84.
Postoperative complications in laser in situ keratomileusis. 51. Pallikaris IG, Papatzanaki M, Stathi E. et al. Laser in situ
Curr. Opin. Ophthalmol 2000;11(4):273-9. keratomileusis. Lasers Surg. Med.1990;10:463-8.
33. Johnson JD, Harissi-Dagher M, Pineda R, et al. Diffuse 52. Petroll WM, Cavanagh HD, Jester JV. Clinical confocal
lamellar keratitis: incidence, associations, outcomes, and microscopy. Curr. Opin. Ophthalmol.1998;N:59-65.
34 Mastering Advanced Surface Ablation Techniques
53. Quurke A, Schmidt–Petersen H, Seiler T. Complications 57. Trockel S, Shrinivasan R, Braren B. Eximer laser surgery
in photorefractive keratectomy for myopia correction, of the cornea. Amer. J. Ophthalmol1983;96:710-15.
Ophthalmologe, 1998;¹10:734-40. 58. Wachtlin J, Blasig IE, Schrunder S, et al. PRK and LASIK—
54. Savini G, Barboni P, Zanini M, Tseng SC. Ocular surface their potential risk of cataractogenesis: lipid peroxidation
changes in laser in situ keratomileusis-induced neurotrophic changes in the aqueous humor and crystalline lens of
epitheliopathy. J. Refract. Surg 2004;20(6):803-9. rabbits, Cornea, 2000;¹1:75-9.
55. Schallhorn SC, Amesbury EC, Tanzer DJ. Avoidance, 59. Wilson SE, Ambrosio R. Laser in situ keratomileusis-
recognition, and management of LASIK complications. induced neurotrophic epitheliopathy. Am. J. Ophthalmol
Am. J. Ophthalmol 2006;141(4):733-9. 2001;132(3):405-6.
56. Slowik C, Somodi S, Richter A, Guthoff R. Assessment of 60. Wilson SE, Ambrosio R. Jr. Sporadic diffuse lamellar
corneal alteration following laser in situ keratomileusis keratitis (DLK) after LASIK. Cornea. 2002;21(6):560.
by confocal slit scanning microscopy. Ger. J. Ophthalmol. 61. Wilson SE Role of apoptosis in wound healing in the
1997;¹ l5:526-531. cornea, Cornea, 2000;¹3:7–12.
 CHAPTER

4 Different Techniques to
Change the Corneal Surface

Jes Mortensen (Sweden)

INTRODUCTION We have several different ways of looking at the

human eye. We can consider it to be one single strong
In this chapter techniques of modifying the corneal
plus lens, or we can consider it to be an optical system
surface and the refraction of the eye will be discussed.
comprising of a series of refracting surfaces.
The techniques can be surgical or non-surgical, tissue
In the early 1900s Professor Allvar Gullstrand
can be removed or added, and the structure of the
described the eye globe using representative values
cornea can be changed thermally or chemically. The
for the curvatures and indices of refraction for the
techniques to be discussed are:
various parts of the eye. The result is what is the
1. Nonsurgical
schematic eye.1
a. Contact lens
The eye can be described as a camera with two
b. Orthokeratology
lenses, the cornea and the crystalline lens. The
2. Surgical
essential function of the optic system is to form an
a. Removing tissue
image of objects on the retina, which is developed as
• Keratomileusis
a part of the brain. The retina will process the image
• ALK
and send it further through the visual nerve and
• LASIK
further via the visual path to the occipital cortex to
• Excimer Laser Intrastromal Keratomileusis
• PRK the visual center.
• PTK Change of the surface curvature of the cornea is the
• LASEK most efficient way to change the refraction of the eye
b. Adding Tissue as the cornea is the most refractive part of the eye.
• Keratophakia The cornea comprises 1/6th of the surface of the
• Epikeratoplasty eye, the average horizontal and vertical diameter
• Lamellar keratoplasty being 12.6 mm and 11.7 mm respectively. The central
c. By heat: Thermal Keratoplasty (Laser Ho: YAG zone of the cornea is about 4 mm, and also called the
laser, diode laser, Holmium laser, RF optical or apical zone. Classically, the apical zone is
(radiofrequency wave known as Conductive defined as the area of the central cornea with a
Keratoplasty (CK) variation of less than one diopter.
d. By weakening the cornea The cornea is flatter in the periphery and flattens
• RK. gradually from the center making the surface aplanar.
36 Mastering Advanced Surface Ablation Techniques
This form partly corrects spherical aberration ameter about 25 nm aligned in parallel lamellae, each
together with the crystalline lens structure. fibril has a coating of proteoglycans with special
Even small changes of the curvature of the cornea water-holding properties.3 The lamellae are arranged
have a significant effect on the refraction of the eye. parallel to the corneal surface, but often communi-
The radius of curvature is 7.8 mm in the central 4 mm cating with adjacent layers by their fibrils. That com-
axial zone of the anterior surface of the cornea, the munication is especially seen in the periphery of the
posterior radius of curvature is 6.7 mm. The cornea, building a stronger corneal tensile strength
difference in curvature of refraction between the in the periphery than in the centre of the cornea.
anterior and the posterior surface of the cornea is a The keratocytes form a three-dimensional
function of the difference of thickness of the cornea network, building a continuous syncytium with the
in the axial area and the corneal periphery. The other keratocytes.
thickness is about 520 microns in the axial area and The organization of the stromal extracellular
660 microns in the periphery. matrix is very precise. This exact structure is believed
The refractive power of a normal cornea is to be crucial for the transparency of the cornea.
43 diopters, that figure is the sum of the refractive Two theories try to account for transparency of
power of the anterior surface, 49 diopters and the cornea:4 the lattice model; saying that the light scatter
refractive power of the posterior surface, minus 6 by individual fibrils is cancelled by destructive
diopters. interference from the scatter light from other
To make calculations easier a semiempirical individual fibrils.5 If the wavelength of light is long
constant, the keratometric index, 2 is used in compared with the fibril spacing, as it is the cornea,
keratometry. The index is, 1.3375 which gives the the material would be transparent, and if the vacuum
dioptric power of a cornea with a radius of 7.8 mm wavelength is on the order of the fibril spacing, as in
the value 43.3 diopters. A simple calculation will show the sclera, it would be opaque. The spacing of the
that an increase respectively decrease of the radius of neighbouring collagen fibrils must be less than
curvature of the cornea by one milimeter causes a shift 200 nm to allow transparency.
of refraction of plus respectively minus 6 diopters. Descement’s membrane is a thin layer serving as
the base membrane for the endothelium.
ANATOMY OF THE CORNEA The endothelium consists of a monolayer cells
essential for the solute transport between the anterior
Before we proceed we shall look at the anatomy of
chamber and the corneal stroma. The endothelium is
the cornea:
the pump that preserves the exact hydration of the
The cornea is anatomically described as consisting
stroma, which secures the exact structure essential
of three tissue layers. From the anterior to the posterior:
for the corneal transparency.
Corneal epithelium is a multi-cellular, stratified layer
There are no blood vessels in the cornea; the
of fast growing and easily regenerated cells. The cells
nourishment is by the aqueous humour in the anterior
get progressively flattened approaching the surface and
chamber and from the limbal blood vessels. The cornea
are, as the cells of the skin, desquamated from the
is innervated by 70-80 long and short ciliary nerves
surface, but that is a very slow process.
ending in unmyelinated nerve ends making the cornea
Between the first and the second tissue layer is
one of the most sensitive tissues in the body.
Bowman’s layer, often referred to as a basement
membrane, which is incorrect as it consist of a NONSURGICAL TECHNIQUE
condensed layer of collagen fibres densely interwoven
to form a felt-like sheet, and is stromal in origin. Contact Lens
Corneal stroma has a unique three dimensional
The contact lens was the first technique mentioned.
network consisting of thin uniform fibrils with a di-
It might be argued that the surface or the curvature
 Different Techniques to Change the Corneal Surface 37
is not actually changed by the contact lens, but I think surface of the cornea. The eldest techniques use a
that the capability of the hard contact lens to treat keratome or knife; the other techniques use an Excimer
irregularity of the corneal surface and high laser for the removing of corneal tissue. To give the
astigmatism seen after PK or in keratoconus justify history and technique of the automated lamellar
its position in the chapter. The invention of the contact keratoplasty the excellent chapter by Professor I
lens dates back before 1877, when Adolf Fick, Eugene Pallikaris and Professor T Papadaki: “From
Kalt and August Müller made the first contact lens Keratomileusis in situ to LASIK: The Evolution of
from glass. The universal genius, Leonardo da Vinci, Lamellar Corneal Procedures,’’ shall be used as
as early as 1508 created sketches describing the source.6
concept of a covering for the eye. Professor Jose Barraquer of Colombia is the
The history and capability of the modern soft and inventor of the initial lamellar refractive techniques.
rigid contact lenses is very well-known to all The basics of the technique are raising a corneal flap
ophthalmologists why further presentation should and removing tissue from the residual stromal bed
not be required. or adding tissue. The classification chosen in this
Orthokeratology chapter: removing tissue or adding tissue will not
give the correct evolutionary description of the
In orthokeratology a hard contact lens is used to lamellar technique, the intention is to give an easily
temporally change the curvature of the surface of the understood summary and not a historical evolution.
cornea. The technique goes back to the 1960s; the
orthokeratology has become more popular in the last Removing Tissue
years in spite of the new refractive techniques. That
is due to the developing of the new high oxygen Keratomileusis in Situ
permeable rigid contact lens and the use of modern Jose Barraquer developed the technique in the
corneal topography to assist manufacturing the 1940s.7,8 A free-hand flap was dissected by a Paufique
individually fit rigid contact lens. knife or by a keratome in the anterior half of the
The best patient is a low myopic with refraction cornea; a second pass by the knife or the keratome
–1.0 to –4.0 diopters. The rigid contact lens was used for the refractive cut under the flap. Due
compresses the centre of the cornea; and due to the to technical difficulties the method was abandoned
viscoelastic properties the cornea will first regain its until the technological development of the keratome
original shape after several hours. Typically is the
made it possible to get better predictability. The great
rigid contact lens used during sleep and the patient
contribution by Jose Barraquer was the development
can experience a perfect vision or reduced myopia
of the suction rings of various diameters, various
during day time.
mikrokeratome heights and the applanator lenses,
The advantage of the orthokeratology is that it is
which made it possible to make a flap of predictable
a reversible technique and very seldom can inflict
thickness and diameter.
any harm to the cornea, so you can wonder why it
has not overrun the competing refractive techniques.
Freeze Myopic Keratomileusis
The answer is probably that many patients find it
very tedious to sleep with the rigid contact lens, To refine the “refractive cut” Jose Barraquer
which is not always experienced as very comfortable; developed the contact lens lathe to sculpture the
many also experience low quality of vision due to frozen lamellar corneal cap. The technique was
halo caused by the small optic zone. intended to be used correcting myopia and
hyperopia, but Jose Barraquer found the myopic
SURGICAL TECHNIQUES
corrections more successfully. The technique was
The first groups of techniques are all characterized abandoned as the cryolathe was too expensive and
by removing tissue to change the curvature of the the learning curve to steep.
38 Mastering Advanced Surface Ablation Techniques
Automated Lamellar Keratoplasty (ALK) An excellent preservation of normal corneal stromal
microstructure near to the ablation zone was found.
Ruiz introduced automated lamellar keratoplasty
The first approaches to excimer laser refractive
(ALK) in the late 1980s. The use of an automated
surgery attempted to build on the strategies
keratome to perform the cuts made the procedure
developed for radial keratotomy. Growing concerns
safer and easier to do. The corneal cap was first
about the width of the linear incisions that would be
sutured back to the cornea, very soon it was seen
expected to fill with an epithelial plug that might
that the cap would adhere without suturing making
persist for months to years directed the investigators
the procedure even faster. The advantages of the
to ablation of the superficial central cornea.
technique were: easy to perform, fast recovery,
In 1983, Dr Munnerly refined the use of excimer
stability of refraction and efficacy to correct high
lasers to alter the refractive power of the cornea. He
myopia. Disadvantages were: high rate of irregular
presented a mathematical formula to calculate the
astigmatism (2%) and poor predictability of the
depth of ablation, diameter and edge angles of the
intended refraction (within 2D). The technique is still
treatment.
available in the USA.
In July 1988, Dr Marguerite MacDonald, MD,
Photorefractive Keratectomy (PRK) performed Excimer Laser PRK on the first sighted
eye thus giving the longest follow-up in the world.
The most important break through in refractive In 1989, in Germany, Dr Theo Seiler did the first
surgery was the use of the excimer laser. bilateral Excimer Laser PRK for myopia.
In 1976, Dr Dave Muller, PhD, former President To induce corneal flattening, the most tissue must
of Summit Technology, Inc. built Cornell University’s be removed centrally, with progressively less
first Excimer Laser. The excimer laser was initially removed toward the periphery. Several laser delivery
used for etching silicone computer chips in the 1970s. systems accomplish that goal.
Excimer laser emission is inherently short pulsed, Perhaps the most precise term for this approach
typically around l0 nsec, with a repetition rate is laser anterior keratomileusis. More commonly, it
between 1 and 50 Hz. is known by the less specific term photorefractive
The ArF excimer laser emission is 193 nm. Research keratectomy (PRK). The FDA in USA 1996 approved
in the early 1980s showed that excimer laser the PRK and has the last decade totally changed
generated UV light can precisely etch a variety of refractive surgery to become the most performed
polymers. procedure in ophthalmology in developed countries.
Dr Srinivasan9 micro-etched, or photo ablated, The different types of excimer laser refractive surgery
patterns on human hairs. He was impressed as to have even obtained a broad acceptance in less
how sharply defined the edges were and how the developed countries.
micro-etched hair retained its cylindrical shape. This
information was also published, and in 1983, Dr Steve
Laser in Situ Keratomileusis (LASIK)
Trokel, MD, saw the picture of the micro-etched hair
and visited Dr Srinivasan at his IBM laboratory in In LASIK a corneal lamella is created by the
July 1983.10 automated keratome leaving a hinge so the flap can
Dr Srinivasin noticed that you could remove tissue be raised allowing tissue to be removed from the
with the laser without causing any harm to the residual bed. The flap can then be repositioned in a
neighboring material due to heating. very exact way and the flap will adhere practically
In 1983, Professor Stephen Trokel and co-workers after few seconds. The patient, who will have an
first reported the precise and controlled etching of almost perfect correction of the refractive failure
the cornea by an argon-fluorine (ArF) excimer laser. already next day, experiences very little pain.
 Different Techniques to Change the Corneal Surface 39
The LASIK technique was first presented 1989 at technique was abandoned due to the introduction of
the Seventh European Congress of the ESCRS in the IOL.
Zurich by Professor Ioannis Pallikaris from Greece.11
The LASIK technique has become widespread and Epikeratophakia (Epikeratoplasty)
is today more or less the standard in refractive In 1979, Professor Kaufmann and Professor Werblin
surgery. Some drawbacks have been seen why introduced the epikeratophakia or epikeratoplasty.17
photorefractive keratectomy (PRK) has experienced The technique is like the freeze myopic Keratomileusis
a certain renaissance. The drawbacks are flap technique of Professor Jose Barraquer. A stromal
complications and ectasia of the cornea. Professor lamellar disc is removed by a keratome and replaced
Theo Seiler reported October 1999 in the Journal of by a donor cap, which has been frozen and lathed
Cataract and Refractive Surgery on three patients who into a concave or convex lens. The lens was ordered
had developed ectasia after LASIK.12,13 It lead to a from a laboratory where the corneal lens already had
discussion and new guidelines for the screening of been cryolathed, lyophilized and stored for later use.
patients whom should fulfill certain criteria. It is The lens could be made for with a range of dioptric
especially important to exclude the with forme fruste powers as IOLs today. The technique was intended
keratoconus, and to leave at least 250 microns of to treat myopia, hyperopia, aphakia and keratoconus.
residual bed after laser ablation of the cornea. The predictability was poor and other major
complications were seen such as poor re-
Laser Assisted Subepithelial Keratectomy (LASEK) epithelialisation of the donor cap and acute or late
Three articles on laser-assisted subepithelial melt down of the donor cap. Modifications were
keratectomy (LASEK) vs PRK, concluded tried to improve the technique but in spite of that
postoperative pain is reduced, significantly quicker the technique is not available today.
visual recovery is achieved and there is lens haze in
Lamellar Keratoplasty
the eyes with low to moderate myopia.14-16
The technique involves removing the epithelium Lamellar keratoplasty was the first grafting technique
by alcohol, or by a modified keratome. The and held that position until the 1950-60s when new
epithelium is put back after laser ablation and a trephines and 10:0 prolene sutures were developed,
contact lens is installed. Professor Ioannis Pallikaris which made PKP a much safer procedure in corneal
has developed the Epi-Lasik technique, which grafting. From the 1980s when viscomaterial, healon
involves the mechanical removal of the epithelium was introduced and revolutionised anterior segment
from Bowman’s membrane. The advantage vs LASEK surgery, the PKP totally replaced the lamellar
is that you have not killed the epithelium with the technique in developed countries.
alcohol, so the epithelium you put back after ablation The lamellar keratoplasty was superseded, as the
of the surface is still viable. The superiority of the optical quality of the graft was often poor due to the
method vs LASEK is still to be determined. technical problem of free hand dissection of the
lamella on the recipient and on the donor.
Adding Tissue In South America the lamellar keratoplasty
survived due to Dr Barraquer´s creation of the
Keratophakia
“Refractive Lamellar Technique”.18-20 He designed a
In 1961, Jose Barraquer introduced keratophakia. The new keratome with a suction ring that by flattening
purpose of the technique was to treat aphakia after the cornea enabled the keratome to cut a lamella with
cataract extraction. The technique involved a disc of the same thickness in the periphery as in the centre.21
donor tissue placed under the lamellar cap thus The success of the refractive surgery meant a
steepening the central curvature of the cornea. The renaissance for lamellar techniques when Ionnas
40 Mastering Advanced Surface Ablation Techniques
Pallikaris, in Greece, introduced the LASIK operation. By Heat
Research and capital were ready to develop the
Conductive Keratoplasty (CK)
surgical technique of lamellar keratoplasty.
The technique involves a lamella cut from the Conductive keratoplasty imposes a central steepening
donor cornea using an artificial anterior chamber. of the cornea due to thermal contraction of the
Often an anterior lamella is cut from the patient’s peripheral cornea. The contraction is due to shrinkage
eye if the cornea has the sufficient thickness. of the collagen fibrils. A radio frequency probe
At the start we used three techniques: Superficial delivers the thermal effect. The FDA approved the
lamellar keratoplasty, deep anterior keratoplasty and technique in USA April 2002. The approval was for
endolamellar keratoplasty. As time goes by the the Viewpoint Ck System the technique was approved
techniques have changed especially in lamellar in persons of the age of 40 years and older with
grafting of keratoconus, the most frequent diagnosis hyperopia from +0.75 diopters to +3.00 diopters.
and in eyes that already have had a PKP, but have
high astigmatism or/and irregularity of the surface Laser Thermal Keratoplasty (LTK)
of the transplant and for that reason no help from Laser thermal keratoplasty (LTK) uses an infrared
the graft. laser to induce the thermal contraction of the corneal
If the pachymetry is less than 300 microns the periphery using 16 laser spots. The LTK technique
Hessburg-Baron vacuum trephine is used to make a was approved on June 2000 in the USA by the FDA,
circular partial penetration of about 180 microns. A for treating persons from 40 years and older with
pocket of the size of 0.5 mm is created to allow the hyperopia from +0.75 diopters to +2.75 diopters and
donor lamella to be tucked into the pocket minimizing astigmatism less than 0.75 diopters. Different lasers
the risk of epithelial undergrowth. Actually the best are used, e.g. diode laser, Holmium laser.
remedy against epithelial undergrowth is using tissue Laser thermal keratoplasty, sunrise, has shown
glue, Tisseel. Since we started using this glue we have inferior results concerning predictability and stability.
only seen two cases of epithelial undergrowth. Treatment with the conductive keratoplasty has been
Initially 16 single sutures were used, later a running found safe, giving reliable results in the majority of
suture; today 8 single sutures and one running suture treated patients. The technique is popular in
are used. correcting presbyopia especially in monovision.
If the corneal thickness is more than 300 microns
a lamella is cut from the patient’s cornea with the By Weakening the Cornea
130-micron keratin head. From the donor cornea a
Radial Keratotomy (RK)
lamella is cut with the 250-micron keratome head.
The lamella is placed and sutured with the same The Norwegian ophthalmologist Schiotz was the first
technique as above. to perform a relaxing incision in the steep meridian
The technique used in endolamellar keratoplasty of the cornea to treat astigmatism after cataract
is that a lamella is cut with the 130 micron head on surgery.
the patient’s cornea leaving a “LASIK” hinge nasally. Professor Tsutomu Sato in Japan, found that
A trepanation is made with a sharp keratome (the breaks in the descemets membrane seen in
majority with a 7 mm keratome). The donor cornea keratoconus flattened the curvature of the cornea
is cut in the same way but without a hinge. A graft when the breaks healed. Experiments in rabbits
0.25 mm bigger is cut and placed in the hole of the showed that surgery on the inside of the cornea was
recipient cornea without sutures. The flap is put back more effective in changing the curvature. This
and sutured with a double running suture. The (DSAEK) initiated the treatment of myopia by radial incision
descement automatic stripping endokeratoplasty has starting in Japan in beginning of the 1950s. The
replaced that technique to day. development of radial keratotomy was driven by
 Different Techniques to Change the Corneal Surface 41
ophthalmologists in former Soviet Union. First by a very short period in the mid 1990s. After the advent
Yanaliev 1969 to 1977 and later by Durnev and the of PRK and LASIK, the RK era has ended.
world famous Professor Fyodorov in Moscow. They Limbal relaxing incisions are still in use after
found that the most important factors for the cataract surgery and penetrating keratoplasty.
procedure was the length, the distance and not least
the depth of the incisions, between 4 or 8 incisions, DISCUSSION
the higher myopia the more incisions.
In this chapter different techniques of modifying the
During the 1970s and 1980s The Fyodorov Institute
corneal surface have been discussed. The form and
became the Mecca for all refractive surgeons of the
the regularity of the surface of the cornea have the
world who went on pilgrimages to learn, especially
greatest significance of the function of the eye.
from the USA. Patients traveled to the Fyodorov
Irregularity of the corneal surface is the biggest
Institute to have RK performed, which was carried
threat to that function are seen in different corneal
out in an almost industrial scale using an assembly
dystrophies, keratoconus and corneal scars. Most
line with eye doctors sitting at different positions
treatments today are not for therapy of the diseased
doing differerent parts of the surgery.
cornea, but for changing the curvature of the surface
The radial keratotomy is performed with a
of the cornea to treat different refractive errors,
guarded micrometer knife in a spoke-like pattern
allowing the individual to live without the need for
through 90-95% of the corneal thickness. A central
correction by glasses or contact lenses.
area of 3-4 mm is left untreated. The incisions will
permanently weaken the cornea and let the periphery REFERENCES
bulge out and so flattening the central part of the
cornea. The radial scars will be permanent. The best 1. Marina Storani de Almeida and ‡Luis Alberto Carvalho.
results were seen in myopia from –1.5 diopters till Different schematic eyes and their accuracy to the in vivo
eye: a quantitative comparison Study. Brazilian Journal
–6.0 diopters. of Physics, 2007;37(2A).
RK become the most popular refractive technique 2. Gobbi PG, Carones F, Brancato R. Keratometric index,
for treating myopia in the United States during the videokeratography, and refractive surgery. J Cataract
1980s until to the beginning of the 1990s when the Refract Surg 1998;24(6):730.
3. Hedbys BO. The role of polysaccharides in corneal
PERK study (The Prospective Evaluation of Radial swelling. Exp. Eye Res. 1961;1:81-91.
Keratotomy) gave reason for concerns about the 4. David B Ameen, Marilyn F Bishop, Tom McMullen. A
safety of the RK technique. The 10-year follow-up Lattice Model for Computing the Transmissivity of the
Cornea and Sclera. Biophys J, 1998;75, No.5: 2520-31.
PERK study results showed that RK could reduce
5. Benedek, GB. Theory of transparency of the eye. Appl.
myopia but the predictability was low22; worse was Optics. 1971;3:459-73.
the instability of the refraction both during day time 6. Professor I Pallikaris and Professor T Papadaki. From
and over time. In the myopic group with moderate Keratomileusis in situ to LASIK: Ashok Garg et al (Eds).
The Evolution of Lamellar Corneal Procedures shall be
myopia (–1.50 to –4.0 diopters) the results were
used as source. Mastering the Techniques of Corneal
acceptable. A hyperopic change was seen in 43% of Refractive Surgery 2006;13-19.
the eyes by +1.0 diopter or more from 6 months to 7. Barraquer JI. Safety technique in penetrating keratoplasty.
10 years. The hyperopic shift showed a progression Transactions of the Ophthalmol Soc of the UK 1949;69-
77.
in some eyes which later required complementary 8. Barraquer JI. Lamellar Keratoplasty (Special Techniques);
surgery to correct the refractive errors, which could Annals of Ophthalmol 1972;437-69.
disable the patient so he/she could not maintain their 9. Srinivasan R, Leigh WJ. Ablative photodecompensation
on poly(ethylene terephthalate) films. J Am Chem Soc
professions.
1982;104:6784.
Radial keratotomy by and large not performed 10. Trokel SL, Srinivasan R, Braren B. Excimer laser surgery
today in the USA. In Sweden RK was performed for of the cornea. Am J Ophthalmol 1983;96:710.
42 Mastering Advanced Surface Ablation Techniques
11. Pallikaris I, Papatzanaki M, Stathi EZ, et al. Laser in situ 17. Werblin TR, Kaufman HE. Epikeratophakia: the surgical
keratomileusis. Laser Surg Med 1990;10:463-8. correction of aphakia. II Primary results in a non-human
12. Theo Seiler. Iatrogenic keratectasia:Academic anxiety or primate model. Current Eye Res 1981;1:131-7.
serious risk? J Cataract Refract Surg. In the “guest 18. Barraquer JI. Safety technique in penetrating keratoplasty.
editorial” in 1999;25. Transactions of the Ophthalmol Soc of the UK 1949; Vol
13. Seiler T, Quurke AW. Iatrogenic keratectasia after LASIK
69,77.
in a case of forme fruste keratoconus. Universitats-
19. King JH Jr. Variations in technique in Lamellar
augenklinik, Dresden, Germany, J Cataract Refract Surg.
Keratoplasty—An Inst Barraquer 1966;7:365-85.
1998;24(7):1007-9.
14. Autrata R, Rhurek J. Laser-assisted subepithelial 20. Barraquer JI. Lamellar Keratoplasty (Special Techniques):
keratectomy for myopia:two-year follow-up. J Catarct Annals of Ophthalmol 1972; 437-69.
Refract Surg 2003;29(4):661-8. 21. Haimovici R, Culbertson WW. Optical lamellar
15. Lee JB, Seong GJ, Lee JH, Seo KY, Lee YG, Kim EK. keratoplasty using the Barraquer Microkeratome. Refract
Comparison of laser epithelial keratomileusis and Corneal Surg 1991;7:42-5.
photorefractive keratectomy for low to moderate 22. Waring GO, Lynn MJ, McDonnell PJ. Results of the
myopia. J Cataract Refract Surg 2001;27(4):565-70. prospective evaluation of radial keratotomy (PERK) study
16. Anderson NJ, Beran RF, Schneider TL. Laser assisted 10 years after surgery. Arch Ophthalmol 1995;
subepithelial keratectomy vs PRK. J Cataract Refract Surg 113(10):1225-6.
2002;28(8):1343-7.
 CHAPTER

5 Resurgences of
Surface Ablations

D Ramamurthy (India)

INTRODUCTION information was also published, and Dr. Steve Trohel

MD, saw the picture of the microetched hair and
Writing about surface ablation is nostalgic business
invited Dr Srinivasan at his IBM lab in July 1983. This
since after dominating in the early 1990s as the
was the start of the whole era of excimer laser
principal mode of laser vision correction, it almost
photokeratectomy.
disappeared but it now seeing a renaissance as glaring
concerns about problems and limitations in lasik PHOTO REFRACTIVE KERATECTOMY (PRK): THE
surgery are becoming more and more apparent. What INITIAL PHASE
follows is partly from the literature but mostly from
our personal experience with excimer laser surgery. In early days in PRK, the epithelium was scraped off
To talk about the present and future one needs to with a knife and broad beam lasers were used to
first mention the past, the history. Though not achieve the desired correction. Inspite of patching
directly relevant to the subject I would like to and bandage contact lenses immediate postoperative
emphasize the invaluable contribution made by a pain and discomfort (bilaterally in young individuals
person of Indian origin to the development and who had normal eyes except for the Refractive error)
application of excimer laser technology in eye was something disconcerting to both the patient and
treatment. The excimer laser was initially used for surgeon. More importantly haze and regression which
etching silicone computer chips in 1970s. Dr Srinivasan interfered with the visual outcome and sometimes
micro-etched or photoablated patterns on human hair lead to loss of BCVA were matters of graver concern.
(his own hair). He was impressed with how sharply The broad beam lasers of that era with their lack of
defined the edges were and how the micro-etched tracking, iris registration, slow speed, tendency to
hair retained its cylindrical shape. produce central islands, added to the compromised
Dr Srinivasan observed that the ablated substrate outcomes which at times were uncharitably attributed
is broken into small fragments that are ejected into to the debridement of the epithelium.
the surrounding atmosphere. They called the process
ablative photodecomposition, now referred to as LASIK
photoablation. He observed that you could remove Lasik with its preservation of the epithelium and
tissue with the laser without causing any harm to the Bowman’s membrane and direct treatment at the mid-
neighbouring material due to heating. The stromal level seemed to be the answer to the ills of
44 Mastering Advanced Surface Ablation Techniques
PRK. Postoperative corneas were clear on day 1, of extreme grades of refractive errors does increase
higher powers could be treated and haze was the chances of this complication. But even more
considered history. Regression especially when low importantly, as we understand corneal biomechanics
and moderate refractive errors were treated was it is obvious that the corneal flap seems to reduce
minimal. The oft repeated “wow effect” of modern corneal resistance and hysteresis and predispose
refractive surgery become a part of ophthalmic patients to keratectasia even when all the rules have
lexicon. The “Lasik take over” coincided with rapid been observed.
advances in excimer laser technology – Scanning and
flying spot lasers, much faster laser delivery systems, PRK: The Second Coming
algorithms which consumed less tissue for the same
While lasik had occupied center stage there was a
correction, better tracking and iris registration and
small group of surgeons who continued to practice
the concept of wave front ablation.
PRK, inspite of the disapproval of their peers. All the
We seemed to have a winner in lasik, a panacea
improvements of the laser systems earlier mentioned
for all refractive errors till the limitations and
also had a positive impact on the PRK outcomes.
complications of lasik became more established as
Various peer reviewed literature has shown that
more and more patients underwent treatment in the
upto a power of –6 D the long term outcomes of lasik
hands of more and more surgeons. Till date it is
and PRK were comparable. PRK was confined to
estimated that 17 million lasik procedures have been
lower levels of refractive errors (arbitrary cut off for
performed worldwide. Flap complication have been
many surgeons being –5 Diopters and +3 Diopters).
overcame with advances in microkeratome
When used for these smaller powers in conjunction
technology and Femtosecond laser flap binding but
with mitomycin-c haze and regression seemed to be
they still are encountered. DLK, epithelial ingrowth,
much less of a problem. Though iatrogenic kerate-
displaced flaps, flap micro and macro striae,
ctasia has been reported after surface ablations the
persistent dry eye and rarely infections are still
incidence is significantly lower compared to post-
encountered frequently enough to be a matter of
lasik cases. Wavefront treatment is believed to be
concern for large volume refractive surgeons. As
more compatible with a surface ablative procedure
Wavefront ablation took firm roots the concept of
and this may primarily become the reason for an
carrying out extremely fine and precise treatment at
interest in surface ablation procedures in the years
the mid stromal level and covering with a thick flap
to come.
and expecting the impact of the treatment to reflect
at the corneal surface itself seemed to be illogical to
LASEK
some. Further the very process of flap making could
induce refractive errors and higher order aberrations Laser assisted subepithelial keratomileusis (Lasek)
which could compromise the ultimate refractive was introduced by Massimo Camellin in 1999. Here
outcome. 20% ethanol in distilled water is used for a period of
So far, only 180 cases of postlasik ectasia has been 30 seconds to create a detachment of the epithelium
documented in published literature but this is a and creating an epithelial flap that is then repositioned
complication which is obviously under reported. after the laser ablation. The modification of the
Experts believe that from 5000 to 112000 cases of surgical technique as compared to the conventional
iatrogenic keratectasia might have gone unreported. PRK was the separation of the corneal epithelium as
It might be impossible to arrive at the exact frequency a sheet rather than its scrapping prior to the
of this complication but it is large enough to be a photoablation. The epithelium regenerates itself in a
matter of serious concern to all refractive surgeons. few days and in the mean time the existing flap
Thin corneas and the treatments where the residual protects the ablated surface. The technique has the
stromal beds were less than 250 microns, treatment potential to eliminate or reduce many disadvantages
 Resurgences of Surface Ablations 45
of PRK, i.e. postoperative pain, slow visual recovery first postoperative day. It was initially thought that
and corneal haze and at the same time avoid the afore the epithelial flap created survived but now it is
mentioned potential complications of lasik. Early established that the epithelial cells in the flap are not
studies suggest that refractive and visual results, dead but damaged and in the initial 3-5 days the
stability and safety of Lasek are comparable to those epithelial flap acts as a mechanical barrier preventing
of PRK and Lasik. Visual recovery appears to be the cytokines in the conjunctival sac coming in contact
relatively faster after Lasek compare to PRK though with the lasered stroma and thus reducing haze and
it takes significantly longer than Lasek. A bandage regression. The extremely regular surface that is left
soft contact lens is of critical importance to keep the after creating a flap and the uniform gutter in the
epithelium in place after the surgery. This contact periphery after epilasik are further said to contribute
lens can be removed on the third postoperative day. in rapid and uniform reepithelialisation. There is, at
Topical medications would consist of antibiotic drops, this point of time, some debate as to whether the
nonpreserved lubricants and steroids tapered over a epithelial flap should be repositioned or discarded
period of one month. with both groups claiming good results with their
results.
Epilasik There are still certain grey areas as far as surface
Ioannis G Pallihaus (Greece), who originally coined ablations are concerned. Clear cut guidelines have
the term “Lasik” came up with the concept of Epilasik not been established as to what should be the
in 2003. In order to avoid the probable toxic effect of minimum corneal thickness (400 or 450 microns),
alcohol on the epithelium and the underlying stroma what should be the residual bed (300 or 400 microns),
the epithelial sheet is separated mechanically with upto what power can be treated and can cases of
the use of customized device very similar to the minimal corneal irregularity be subjected to surface
microkeratome used for Lasik. Epilasik is derived ablation procedures because of its lesser tendency to
from the Greek word “Epipalis” that means superficial alter the corneal biomechanics. The pain, haze,
and lasik. regression have been reduced by Lasek and Epilasik
In epilasik the flap is created by a blunt separator compared to PRK but they still are a problem when
which passes the path of least resistance and creates compared to PRK.
a laminar separation between the Bowmans CONCLUSION
membrane and the basement membrane of the
epithelium. The thickness of the flap created does Lasik is still the king as for laser vision correction is
not depend on the microkeratome but the thickness concerned and this is likely to continue in the years
of the epithelium in the individual eye which varies to come. However, judiciously performed surface
between 45-60 microns. Histologicaly intracellular ablation procedures act as an adjunct to lasik and
organelles and intracellular desmosomal connections, enable us to treat about 10% of the cases which may
as well as hemidesmosomal connections with the not qualify for lasik but can be treated on the surface.
basement membrane appeared close to normal with In two decades millions of patients have
only focal disruptions. undergone surgery with excimer laser all over the
Mechanical separation with epilasik appears to world. The many scientific articles written and still
have the advantage of a deeper cleavage plane over being produced on this subject are the best guarantee
alcohol assisted separations thus being expected to that the evolution of excimer keratactomy will
provide better control of corneal healing with the continue.
46 Mastering Advanced Surface Ablation Techniques

CHAPTER

6 Pearls of Surface Ablation:

When and How?

Ramiro Salgado, António Marinho (Portugal)

INTRODUCTION scarification. Another method is to perform the

desepithelization with the excimer laser following the
Surface ablation techniques are presently gaining new pattern of a phototherapeutic profile. The technique
thrust as flap-related complications in Lasik become of the above combined methods in sequence is
more apparent.1,2 Featuring surgical options are PRK, another option, performing a 40-45 micra depth
LASEK and epi-LASIK. The main reasons for ablation with the laser excimer as a first step,
returning to the surface include the reduced risk of concluding with the epithelium removal with the
corneal ectasia3, elimination of flap complications,4 spatula. Finally, the chemical removal of the
and the belief shared by some surgeons that surface epithelium can be achieved by means of diluted
ablation may actually provide superior quality of ethanol (15-20%). The dilution of alcohol can be
vision.5 Of these three reasons, the complications accomplished in BSS, physiologic solution or sterile
inherent to the flap including free caps, incomplete water, with no definite advantage of a specific
pass of the microkeratome, flap wrinkles, epithelial formulation in various studies.6 The photoablation is
ingrowth, flap melt, interface debris, and diffuse performed as in Lasik, after which a bandage contact
lamellar keratitis, outstand amongst the others. The lens is placed and kept for the following days until
downside to surface ablation previously was the full reepithelization.
significant pain associated with the early postoperative The main indications are low pachimetry,
recovery period and the potential for visually important dry eye and anatomical peculiarities, such
significant haze later in the healing process. Time will narrow palpebral fissures.
tell if surface ablation will supplant LASIK as the The postoperative care involves a careful (first visit
predominant method for refractive error correction. at day 5 postop, the latest) follow-up until full
reepithelization, keeping the patient under topical
TECHNIQUES NSAID and antibiotic regimen, four times a day.
PRK After contact lens removal, a topical mild steroid drug
should substitute for the NSAID, being that steroid
Photo Refractive Keratectomy (PRK) is a refractive eyedrops should be kept for 3 months.
surgical technique in which the corneal curvature is Moderate postoperative pain in the first 24-
modified after epithelial removal. This is 48 hours (the “day after” pain is associated with this
traditionnaly achieved manually, 6 by means of technique, and dry eye last up to a few weeks.
 Pearls of Surface Ablation: When and How? 47
As to the functional recovery, 7 it is normaly
achieved between 3 and 7 days, whilst refractive
stability occurs from 3 weeks to several months.8
The major complications are haze formation and
corneal scarring, happening, in large series, in 1-2%
of the cases.9

LASEK
Laser Subepithelial Keratomileusis is a technique in
which, instead of removing the epithelium, dilute
alcohol is used to loosen the epithelium adhesion to
the corneal stroma. The loosened epithelium is then
Figure 6.1B
moved aside from the treatment zone as a hinged
sheet, with return to the original position after laser The surgeon then uses the instrument of his choice,
ablation. The first LASEK procedure10 was performed such as a microhoe, to gently debride the epithelium,
by Azar in 1996 and since then, it has come more gather it and fold it off to the hinge side of the cornea.
popular. He then performs the ablation.
The procedure is normally performed under Once the treatment is complete, the surgeon uses
topical anesthesia. The surgeon seats a trephine a spatula to spread the epithelium back over the
(usually 8 mm in diameter) over the cornea, cutting stroma. The patient goes home wearing a therapeu-
about 70 μm deep into the tissue. tic contact lens, which he leaves on until it is
The trephine is blunt for 80 degrees in one section reepithelialized. The surgeon instills antibiotic and
so as to leave a corneal hinge when it is lifted off the nonsteroidal anti-inflammatory drops.
eye. The surgeon then places an 8.5-mm well over Some surgeons11 subtract 10 percent from the PRK
the cornea and pours an 18 or 20% alcohol solution nomogram for corrections up to –8 D. The nomogram
into it. The alcohol is left on for about 30 seconds, advises to subtract 15 percent for errors between –8D
then soaked up with a surgical sponge (Figures 6.1A and –10 D, and 20 percent for anything over –10 D.
and B). The well is removed and the eye is thoroughly There is probably an ideal concentration of alcohol
irrigated with BSS. and a duration of instillation.
Though many surgeons continue to create their
epithelial flaps in LASEK the conventional way, a few
are working with alternative methods.
A possible technique is epithelial flap
hydrodissection (Figures 6.2A and B). The technique
was first introduced at the 2001 meeting of the
International Society of Refractive Surgery, at which
time only BSS was being used for it. It involves first
scoring the epithelium with the trephine and applying
alcohol. Sometimes, hydrodissection cases can work
without alcohol. BSS, GenTeal or GenTeal Gel
(Novartis Ophthalmics) is injected beneath the flap
with a Slade cannula to gently dissect the epithelium
Figure 6.1A away from the stroma.
48 Mastering Advanced Surface Ablation Techniques
steroid) and NSAID (such as flurbiprofen) q.i.d. for
four days, and artificial tears and an over-the-counter
oral NSAID as needed. It is imperative that the
bandage contact lens remain on the eye for three to
four days to minimize pain, “especially the pain that
can occur on day two”.
Though there have been not many rigorous, long-
term studies comparing LASEK with other surgeries
A
on haze,15 surgeons have studied it in their practices.
Acuities after LASEK appear to be similar to those
after PRK and LASIK,16 though the visual recovery
rate can vary.

Epi-LASIK
Also designated Lamellar Epithelial Debridement, is
a version17 of surface ablation like PRK that is more
similar to LASEK with some distinct advantages over
Lasik and IntraLasik. A microkeratome with a blunt
blade is utilized to mechanically cleave the epithelium
B
from the Bowman’s membrane (Figures 6.3A to C),
Figures 6.2A and B leaving an expose area for excimer laser ablation. Epi-
Lasik preserves the structural integrity of the stroma
Vinciguerra, MD, has also developed a new flap- and is heralded as minimizing patient discomfort
making technique. 12 In his method, called the when compared to PRK and LASEK, shorten the
butterfly, he creates two sections of epithelium which length of time before visual recovery, and reduce
he spreads apart. He first makes a linear abrasion on the incidence of corneal haze associated with other
the cornea slightly off center with a spatula, then surface ablation procedures, such as PRK and LASEK.
instills 20% alcohol in a 9 mm corneal marker for 5- Laser refractive surgery has gone through an
30 seconds. He uses the same spatula to lift the evolution beginning in the early 1990s with PRK. PRK
epithelial edges, separate the epithelium from uses an excimer laser was fired directly through the
Bowman’s membrane and nudge the two epithelial Bowman’s layer and into the stromal layer of the
sections toward the limbus. After the ablation, he cornea to reshape its curvature effecting the refraction
joins the flap edges, with one edge slightly of the patient. PRK tended to be more uncomfortable
overlapping. To help minimize the risk of haze because of the eye’s wound response. Discomfort
formation postoperative, some surgeons will treat continues until the epithelium grew back over the
the stromal bed prophylactically with the powerful ablated area. Newer techniques limit patient
antimetabolite mitomycin-C immediately after the discomfort, but rarely eliminate discomfort
ablation. 13 Though the protocols for using this completely. Additionally, because of corneal haze due
controversial agent vary from surgeon to surgeon, it to wound response, some autors advocate that the
is usually used in a concentration of 0.02% or 0.03% safe refractive change with PRK is limited to
for 15-45 seconds, then washed off with copious approximately +3 D to –6 D correction.18 Let alone,
amounts of BSS. There is still some question as to corneal haze is still an issue that needs to be
mitomycin-C’s long-term effects, however.14 accommodated.
The standard postoperative regimen is topical Lasik was the next evolution in laser refractive
antibiotic (quinolone alone or association with surgery. Lasik involves a precise incision into the
 Pearls of Surface Ablation: When and How? 49
knowing that it has surgery, so the procedure is
virtually painless and given the control of the depth
of flap. While Lasik solved many of the issues
surrounding PRK, it has its own set of complications
and refractive issues. The majority of the
complications relate to the flap itself and the optical
aberrations, which are attributed to it.
Ever in search of a better procedure, ophthal-
mology returned to surface ablation solutions,
primarily LASEK. The primary methodology around
this procedure was to attempt to separate the
A
epithelial layer from the top of the cornea, ablate the
underlying tissue with the excimer laser and replace
the epithelium on top of the cornea making it act as a
biological bandage contact lens. This greatly reduced
the pain seen in PRK and eliminated the flap-related
issues plaguing Lasik. Although LASEK reportedly
improved patient comfort and reduced the probability
of corneal haze, the alcohol solution required to
release the epithelial cells from the underlying cornea
mortally wounds all cells, delaying vision recovery
and creating an unstable epithelial layer until the cells
B are replaced.
Epi-Lasik attempted to provide the best of both
Lasik and PRK/LASEK. By using a blunt blade to lift
the epithelium in a single sheet, it was thought that
the this structure would be a much more viable entity18.
Actually, the repositioned epithelium will die, acting
as a bandage while the underlying cornea heals.
Although current studies are inconclusive if patient
outcomes are better with Epi-Lasik when compared
to PRK or LASEK,19 many studies have shown that
the surface ablation class of Epi-Lasik, LASEK, and
PRK provides better outcomes than Lasik.20

AA-PRK
Indications
C
Figures 6.3A to C Since 2004, our department in Hospital da Arrábida,
Porto, has been using a modified PRK technique, in
which a 20% alcoholic solution is employed to remove
stromal layer of the cornea, creating a flap. The flap the epithelium.
is lifted exposing the stroma, where the excimer laser In our series, the main indication was a too low
ablates the tissue, reshaping the curvature from pachimetry value for conventional Lasik (below
within. Lasik effectively fools the cornea into not 490 micra), being that in one case the indication was a
50 Mastering Advanced Surface Ablation Techniques
too narrow palpebral fissure for employing a suction
ring.

Surgical Technique
Our technique involves the following steps:
• Topical anaesthaetic (oxybuprocaine)
• Placement of cup 9.5 φ on cornea (preferred
diameter)
• Usage of the trephine (apply light pressure)
• Filling of the cup with a 20% alcohol solution
(ethanol in bidestiled water) while keeping the
cup in place
• Keep the solution for 35 seconds
• Soak up the solution with a cotton-tipped surgical Figure 6.4
sponge
• Irrigate the cornea and conjunctiva with saline
• Proceed to subtotal desepithelization with a
surgical sponge, leaving an outer perimeter of
epithelium (around 1-1.5 mm)
• Perform laser ablation as in normal Lasik
• At the end of the ablation place contact lens
Our postoperative regimen is: contact lens +
topical non-steroidal anti-inflammatory drug
(flurbiprofen) + atb (ofloxacin) for 6 days (until full
reepithelization) and removal of contact lens and
replacement of NSAID for steroidal anti-
inflammatory drug (fluorometholone) for 3 months.

Results
Figure 6.5
The surgery was performed in 54 eyes with myopia
or myopic astigmatism (sphere between –0.25 and
– 6.00D and cylinder from –0.25 to –4.50D) (mean:
–1.97 ± 1.15D of sph.equi.); 6 eyes had mixed
astigmatism (sphere from +1.00 to +3.00 and cylinder
between –1.50 and –5.00D) (mean: +0.42 ± 0.41D of
sph.equi.). The BSCVA was 20/20 in all patients. The
mean pachimetry was 471 ± 31 μm. The age was
between 21 and 30 years old (mean: 25.50 ± 3.39).
The follow-up was from 3 to 9 months (mean: 6
months). In all patients the corneal ablation was
performed with Bausch&Lomb’s Technolas 217.
High refractive performance regarding accuracy,
safety and stability were achieved (Figures 6.4 to 6.6).
Full reepithelization (Figure 6.7) occurred, in 54
eyes (90%), at day 6 postoperative, being that 6 eyes Figure 6.6
(10%) achieved that status at day 10 postoperative.
 Pearls of Surface Ablation: When and How? 51
All patients were submited to surgery one eye at
a time, being that, in spite of the associated pain
experienced with the first eye surgery, the importance
of this symptom, for all of them, did not act as a
factor for refusal of a second eye surgery.
As to haze, we registered “trace haze” in 3 eyes
ino our series, with no clinical significance.

CONCLUSION

With surface ablation techniques, the high standards

of refractive surgery performance in terms of
Figure 6.7
refractive results such as efficacy, safety and accuracy
As to the endothelium status (study performe with are achieved. The complications associated with
Konan Noncontact Endothelial Microscope), there LASIK (mainly corneal ectasia flap-related) are not
was no significant change in cell form or number (with present. In spite of a longer visual recovery period,
observed positive variation of 0.4%) (Figure 6.8). the final results are similar.
Amongst the various surface ablation techniques
the final outcome, all being characterized by
postoperative pain and the possibility of haze. The
latter has been addressed to by use of mytomicin C,
whose long-term effects are not it yet reassuring,
and by modifications of the techniques. Several recent
studies show no significant difference in visual or
refractive outcomes amongst the different surface
ablation techniques. In our experience with AA-PRK,
both postoperative pain and haze although not
erradicated, were within acceptable levels in clinical
significance, furthermore considering the high patient
Figure 6.8 satisfaction, notwithstanding the pain and the longer
recovery time compared to a standard ablative
Complications procedure such as LASIK.
Pain is present postoperatively in the first 48 hours. Hence, as to AA-PRK, we believe it can be
The presence of the bandage contact lens and considered a valid alternative to Lasik as a modified
adequate postoperative regimen greatly reduces the PRK (epithelium removal through alcoholic solution)
magnitude of the discomfort. indicated mainly in cases of low pachimetry value
In our series, all patients (60 eyes) had pain up to for conventional technique or anatomical peculiarities
48 hours, with a peak at day 1 postoperative (day- (such as a too narrow palpebral fissure for employing
after pain), which subsided onwards, with no a suction ring).
medication required for 90% of the patients; in 10% of
the patients, there was need of clonidine, one tablet, REFERENCES
per os, to control the discomfort at day 1 postoperative.
All patients characterized the pain as moderate 1. Knorz MC. Complications of refractive excimer laser
surgery. Ophthalmologe 2006;103(3):192-8.
during the first 48 hours, somewhat different from 2. Melki SA, Azar DT. LASIK complications: etiology,
the intensitiy mentioned in other studies, 21 and management, and prevention. Surv Ophthalmol 2001;
possibly related to the subtotal desepithelization. 46(2):95-116.
52 Mastering Advanced Surface Ablation Techniques
3. Reinstein D, Srivannaboon S, Archer T, Silverman R, 12. Vinciguerra P, Camesasca FI, Randazzo A. One-year
Sutton H, Jackson Coleman D. Probability Model of the results of butterfly laser epithelial keratomileusis. J Refract
Inaccuracy of Residual Stromal Thickness Prediction to Surg 2003;19(2 Suppl):S223-6.
Reduce the Risk of Ectasia After LASIK Part I: Quantifying 13. Argento C, Cosentino MJ, Ganly MJ. Comparison of
Individual Risk. Journal of Refractive Surgery 2006;22: laser epithelial keratomileusis with and without the use
No. 9. of mitomycin C. Refract Surg 2006;22(8):782-6.
4. Schallhorn SC, Amesbury EC, Tanzer DJ. Avoidance, 14. Camellin M. Laser epithelial keratomileusis with
recognition, and management of LASIK complications. mitomycin C: indications and limits. J Refract Surg 2004;
Am J Ophthalmol 2006;141(4):733-9. 20(5 Suppl):S693-8.
5. Schallhorn S. US Naval Study: wavefront-guided PRK 15. Long Q, Chu R, Zhou X, Dai J, Chen C, Rao S, Lam D,
versus wavefront-guided LASIK. Paper presented at: The MD. Correlation between TGF-β1 in tears and corneal
XXIII Congress of the ESCRS; September 13, 2005; Lisbon, haze following LASEK and Epi-LASIK. Journal of
Portugal. Refractive Surgery 2006;No. 7.
6. Lee HK, Lee KS, Kim JK, Kim HC, Seo KR, Kim EK. 16. Pirouzian A, Thornton J, Ngo S. One-year outcomes of a
Epithelial healing and clinical outcomes in excimer laser bilateral randomized prospective clinical trial comparing
photorefractive surgery following three epithelial
laser subepithelial keratomileusis and photorefractive
removal techniques: mechanical, alcohol, and excimer
keratectomy. J Refract Surg 2006;22(6):575-9.
laser. Am J Ophthalmol 2005;139(1):56-63.
17. Pallikaris IG, Kalyvianaki MI, Katsanevaki VJ, Ginis HS.
7. Hashemi H, Fotouhi A, Foudazi H, Sadeghi N, Payvar S.
Epi-LASIK: preliminary clinical results of an alternative
Prospective, randomized, paired comparison of laser
surface ablation procedure. J Cataract Refract Surg 2005;
epithelial keratomileusis and photorefractive keratectomy
31(5):879-85.
for myopia less than –6.50 diopters. J Refract Surg 2004;
20(3):217-22. 18. Katsanevaki V, Naoumidi I, Kalyvianaki M, Pallikaris I.
8. Bedei A, Marabotti A, Giannecchini I, Ferretti C, Epi-LASIK: Histological Findings of Separated Epithelial
Montagnani M, Martinucci C, Barabesi L. Photorefractive Sheets 24 Hours After Treatment. Journal of Refractive
keratectomy in high myopic defects with or without Surgery 2006;22: No. 2.
intraoperative mitomycin C: 1-year results. Eur J 19. Dai J, Chu R, Zhou X, Chen C, Qu X, Wang X. One-year
Ophthalmol 2006;16(2):229-34. outcomes of epi-LASIK for myopia. J Refract Surg 2006;
9. O’Connor J, O’Keeffe M, Condon P. Twelve-year follow- 22(6):589-95.
up of photorefractive keratectomy for low to moderate 20. Charters L. Advanced surface ablation: future of refractive
Myopia. Journal of Refractive Surgery 2006;22:No.9. surgery? Ophthalmology Times 2006;31;9:41-2.
10. Taneri S, Zieske JD, Azar DT. Evolution, techniques, 21. Blake CR, Cervantes-Castaneda RA, Macias-Rodriguez
clinical outcomes, and pathophysiology of LASEK: review Y, Anzoulatous G, Anderson R, Chayet AS. Comparison
of the literature. Surv Ophthalmol 2004;49(6):576-602. of postoperative pain in patients following
11. Camellin M. Laser epithelial keratomileusis for myopia.J photorefractive keratectomy versus advanced surface
Refract Surg 2003;19(6):666-70. ablation. J Cataract Refract Surg 2005;31(7):1314.
 CHAPTER

7 Advances of Solid-State
Ophthalmic Laser Technologies

J T Lin (Taiwan)

INTRODUCTION Table 7.1 summarizes the ophthalmic lasers

currently in the market and the major manufacturers
Since the first ruby laser was developed in the early
(Table 7.2). The vision correction technologies (both
1960, lasers and the related technologies such as
laser and non-laser) are summarized in Table 7.3 and
optical fibers, optical and ultrasound image and
also illustrated by Figure 7.1.
diagnostic devices have been used for medical,
industrial and military applications. The development Table 7.1: Summary of ophthalmic lasers
of medical lasers also stimulated by the basic research Laser (wavelength, pulse width) Applications
in medicine, light-tissue interaction and the surgical 1. Excimer ArF (193 nm, 5-20 n.s.) PRK, LASIK, LASEK
techniques related to a wide areas of dermatology, 2. Excimer XeCl (308 nm, 200 n.s.) Glaucoma (ablation)
3. Argon Ion (488/514 nm, cw) Coagulation
cosmetology, microsurgery, physiology and 4. HeCd (695 nm, cw) Coagulation
ophthalmology. 5. Diode laser (810 nm, cw) TTT (thermal for CNV or
(1.4 to 2.1 micron, cw) AMD) DTK (hyperopia)
This chapter will cover the currently used modern 6. Nd:YAG (1064 nm, pulsed) Posterior capsulotomy,
solid-state laser systems for ophthalmic applications phaco
7. Doubled Nd:YAG (532 nm, PDT (for CNV or AMD)
including: 3-10 n.s.)
• Photodynamic therapy (PDT) lasers 8. UV solid-state (213-266 nm, LASIK, presbyopia
• Lasers for phacoemulsification (Laser phaco) 3-20 n.s.)
9. Ho:YAG (2.1 micron, 200 us) LTK (hyperopia)
• Lasers for glaucoma treatment 10. Er:YAG and Er:YSGG LAPT (presbyopia),
• Technologies for refractive surgery (LASIK, (2.8-2.94 micron, 200 u.s) phaco, blepharoplasty
11. CO2 (10.6 micron, ultrapulsed) Coagulation, blepharoplasty
LASEK, LTK, DTK, CK, etc.) 12. Ultrashort laser (1064, 532, Photodisruption,
• Solid-state 213 nm system for LASIK. 780 nm, f.s. ps) LASIK-flap
This Chapter will emphasize on the laser system
Table 7.2: Laser candidates for laser phaco or photodisruption of
parameters, applications and Comparing the ocular lens
advantages and disadvantages. The new diode- Laser type Wavelength (pulse width) Energy/pulse
pumped UV-laser at 213 nm will be compared with Nd:YAG 1064 nm (n.s. and p.s.) (1.0 - 20) mJ
the ArF excimer system in LASIK. New directions Nd:YLF 1053 nm (n.s., p.s. and f.s.) (0.01 - 10) mJ
Ti:sapphire 780 nm (p.s. and f.s.) (0.01 - 0.1) mJ
for improved outcome of existing procedures or new Ho:YAG 2100 nm (μs) (10 - 20) mJ
applications will also be discussed. Er:YAG 2940 nm (μs) (10 - 20) mJ
54 Mastering Advanced Surface Ablation Techniques

Table 7.3: Comparison of laser candidates for glaucoma treatment

Argon-ion Excimer IR (Er:YAG) UV-266 Diode laser

Laser CW gas Gas (XeCl) Solid-state Solid state Solid state
Wavelength 488/514 nm 308 nm 2940 nm 266 nm 800-830 nm
Pulse width CW 200 ns 500 microsec 5 ns CW
Operation mode CW Long-pulse Long-pulse Q-switched CW
Energy/pulse Varies 4-5 mJ 10-15 mg 5-8 mj varies
Average power Few W 0.3 - 0.4 W 0.1 - 0.2 W 0.1 - 0.2 W 0.2-2.0 W
Ablation efficiency Low Medium High High Low
Thermal effects All thermal Partial Partial Minimal Partial
Beam delivery Fiber/contact Same Same Non-contact Fiber/contact
Beam spot size Fixed Fixed Fixed Adjustable 0.3-0.5 mm
Treating area Trabeculum Trabeculum Sclera Sclera, Sclers
Cornea, Ciliary

which can cause the recurrence of the neovascular

tissue. However, a short-pulse (about 3 ns) green
laser, the doubled-YAG at 532 nm, has been
successfully used for the treatment of open-angle
glaucoma, a procedure called selective laser
trabeculoplasty (SLT) which shows advantages over
the conventional system using an argon cw laser.
PDT for the treatment of subfocal choroidal
neovascularization (CNV) using verteporfin as the
phtosensitizer has been proven for subfoveal CNV
in both AMD and in pathologic myopia (or non-AMD)
Figure 7.1: Summary of various technologies for vision correction
patients. CNV may be also treated by a procedure
called transpupillary thermotherapy (TTT) using
diode laser at 810 nm, where PDT drug is not needed.
To overcome the low specificity of the
PHOTODYNAMIC THERAPY (PDT) photosensitizer in single-photon PDT, a 2-photon
excitation with ultra-fast IR laser at about 850 nm
Retinal photocoagulation has been reported by using
(where the 1-photon contribution was negligible)
various visible and IR lasers such as argon blue-green
using photofrin. Due to the nonlinear interaction
laser (488/514 nm), double-YAG green laser (at 532
mechanism, the 2-photon PDT with a focused beam
nm), krypton laser (at 647 nm) and diode lasers (at
is localized in and allows the treated area localized
800-830 nm). Photocoagulation process was also used
within the focused laser beam spot size about few
to seal leak blood vessels for the treatment of age-
microns. However, new photosensitizer with higher
related macular degeneration (AMD) consisting of
2-photon cross section on the photofrin for IR lasers
two types, the choroidal neovascular (“CNV,” wet)
excitation may be required for further improvement.
and nonneovascular (dry). In the wet AMD, the
vascular ingrowth causes photoreceptor destruction, LASER PHACOEMULSIFICATION
or bleeding with extensive loss of vision.
The major drawback of photocoagulation to Table 7.2 shows a variety of ophthalmic lasers for
destroy the vascular growth beneath the retina is the laser-phaco including Nd, Ho and Er:dopped YAG
nonselective necrotic damage to the adjacent normal laser with long and short pulse duration have been
retina and the thermal damage in the subfocal area proposed as alternatives for the conventional
 Advances of Solid-State Ophthalmic Laser Technologies 55
ultrasound phaco. The possible advantages of laser Laser phaco may be an alternative for conventional
phaco, or laser disruption of lens nuclei include: less ultrasound phaco under certain cataract conditions.
invasive, more efficient and might be used for both However, deeper understanding of the biophysical
soft and hard cataracts. However, as of today, none aspect of the laser-lens interaction and the system
of the laser methods have been FDA approved, other design aspect are required, in addition to longer term
than the conventional Nd:YAG laser for posterior clinical studies. The new application for presbyopia
capsulotomy. using the short-pulse IR lasers to modify the elasticity
Furthermore, some remaining technical and clinical of the lens showed certain initial safety progress.
issues still remain and limit the use of IR lasers for However, the efficacy remains unknown. Combining
lens nuclei disruption. Nd:YAG laser with 200 to 400 ultrasound and laser device may be explored for
ns pulse duration was first proposed for phaco potential new applications or for clinical advantages.
procedure (the “Dodick Photolysts” using laser- Laser phaco represents one of the examples of
induced shockwave) which, however, was abandoned selective tissue (matter) interaction by a focused beam
due to its inefficiency limited to soft cataracts (less at a specific spectrum for strong absorption
then +2) comparing to the conventional ultrasound (interaction). Figure 7.2 shows focused laser for (A)
phaco (USP). Dr Sunita Agarwal proposed the use of for retina coagulation and AMD and (B) laser-phaco
combining USP and Ho:YAG laser for faster and capsulotomy using ablation process.
procedure, particularly for soft cataracts. The use of
IR laser has been recently shifted to new application
for presbyopia treatment by photophaco “modulation”
of the crystalline lens to be discussed as follows.
One of the critical issues in laser photo-
disruption (LPD) of lens nuclei for the increase of
accommodation is how to modify the lens without
forming a cataract. The early work of LPD was
conducted with rabbit eye experiment and showed
that the postoperative lenticular opacity with a laser Figure 7.2: Focused laser for: (A) retina coagulation and PDT (for
AMD) and (B) selective capsulotomy, phaco and photodisruption
of nanosecond duration was absent when a shorter
picosecond laser was used. Experimental increase
GLAUCOMA LASERS
of accommodation in animal lens was also
conducted by using a femtosecond Nd:YAG laser In addition to the conventional surgical methods,
of Ti:sapphire laser (at 780 nm wavelength) laser based minimally invasive glaucoma surgery
showing no cataract formation after 3 months. The (MIS) becomes the new direction for glaucoma
concept of modulating the elastic properties of the treatments. The following lasers include those on the
crystalline lenses by a low energy short pulse laser market and prototypes in trials (see Table 7.3).
may be an alternative for the long-pulse Er:YAG • Excimer laser of XeCl (at 308 nm) or ArF (at 193 nm)
laser modification of the scleral tissue for the (Takhchidi, Russia) to ablate pores in the trabecular
treatment of presbyopia. Scleral tissue elasticity meshwork for open angle glaucoma. It reduces the
may be also modified by a UV laser ablation as risk of perforating the trabeculodescemetic
proposed by Lin (2005). In comparison, scleral membrane with minimal thermal effects
ablation method (using IR or UV laser) has the • Ti:sapphire laser at 760 nm (Simon, Spain)
advantages over femtosecond laser method being absorbed by pigmented trabecular meshwork
low system cost and noninvasive to the lens. It, cells with minimal thermal damage
however, is more invasive to the eye involving • Selective laser trabeculoplasty (SLT) using a pulsed
scleral ablation. (about 5 ns) green laser (at 532 nm) as a better
56 Mastering Advanced Surface Ablation Techniques
alternative for argon laser. The system was first of the fiber in the contact mode thus reducing the
developed by Coherent, Inc. and used by Latina. efficiency of subsequent ablation. A comparison of
It selectively target the trabecular meshwork cells various glaucoma lasers is shown in Table 7.4.
rather than the complete coagulation of the Table 7.4: Summary of technologies for vision corrections (laser
trabework meshwork and non-laser methods, see also Figure 7.1)
• Solid-state UV laser (at 266 nm) proposed by Lin Method Features
and Kadambi for NPDS procedure (greater detail 1. PRK, LASEK Corneal surface ablation with epithelium
will be shown later) removed preserved; suitable for low diopter
corrections (<3.5D).
• Er:YAG laser (at 2.94 um) for trabecular ablation 2. LASIK Stroma ablation by laser after a “flap” is
to avoid conjunctive scarring and postoperative prepared by microkeratome.
hypotomy. More ablative efficiency than 308 nm 3. LASA, LACA Presbyopia treatment by laser scleral ablation
(LASA) to increase accommodation via ciliary
excimer or CO2 laser with minimal thermal like body contraction; combining effects of lens
that of UV-266 nm laser. curvature change and anterior chamber shift.
Efficiency may be improved by deeper laser
• CO2 laser (at 10.6 um) for ablation of dried sclera ciliary-body ablation (LACA).
tissue and protected from perforation system was 4. LZT, LCT Laser zonules thermal (LZT) stimulation for
made by Optomedic Medical Technology (Israel). presbyopia; non-invasive method using gona
lens and focused laser. Laser ciliary-body
• Diode laser (at about 810 nm) using a G-probe for thermal shrinkage (LCT) for presbyopia.
contact cyclocoagulation (made by IRIDEX) 5. SEB Scleral expansion band implanted in scleral
layer: major regression.
• Krypton laser (at 647 nm) absorbed by the 6. ACS Anterior ciliary sclerotomy by diamond knife
pigmented epithelium for cyclocoagulation. It is incision; major regression which may be
also a standard device for retinal photo- reduced by silicon expansion plug.
7. CK Conductive keratoplasty using radio
coagulation. Both visible laser (at 532, 630, 647 frequency wave for monovision correction;
nm) and diode laser (at 810 nm) have better treated eye to see near but losing its far vision.
8. LTK and DTK Laser thermal keratoplasty (LTK) using
absorption in the pigmented tissue of the ciliary Ho:YAG (at 2.1 um) or diode laser (1.45 to
body than the near IR Nd:YAG (at 1064 nm). 2.1 micron) (DTK).
In argon laser trabeculoplasty (LTP), focal burns 9. BFCR Bifocal corneal reshaping by excimer LASIK
for pseudoaccommodation.
with an argon laser beam (about 50 micron spot size 10.AIOL Accommodative IOL implanted to lens
and 1.0 W power) for 0.1 second causes contraction capsule; forward movement for accom-
modation; could be single or dual-optics IOL.
of the meshwork tissues. This causes separation of 11.Phakic IOL IOL implanted in the anterior, posterior
the adjacent trabecular sheets to increase the outflow chamber, or lens capsular bag.
12.MIOL Multifocal IOL implanted for patient with
of aqueous. Additionally, the laser burns induce high refraction errors.
alteration in phagocytic activity of the trabecular cells. 13.ICRS Intracorneal ring segments for low myopia
and astigmatism.
LTP does succeed in lowering the IOP in 70 to 75% 14.Advanced CL Advanced contact lens having multifocal or
of patients with open-angle glaucoma. However, over designed for the correction of high-order
aberration.
time the effectiveness decreases so that 5 years after 15.Super vision Customized LASIK combined with wave-
treatment only 30% to 60% of patients maintain good front technology; flying-spot scanning laser
with eye tracking is required for customized
intraocular pressure control. and irregular corneal reshaping.
Excimer laser sclerostomy and trabeculectomy has 16.Bionic eye Microchip implanted in the eye to stimulate
not gained wide acceptance due to poor scleral either the retina or directly the optical nerves.
17.Bifocal lenses Liquid-crystal diffractive lenses with
ablative properties and the non-availability of a autofocusing.
suitable delivery system through a hand piece. Pulsed *Major technologies (inventors): Broad beam Excimer (L’Esperance,
Erbium:YAG laser was used to ablate scleral and Blum, Tsuboda); LTK (Sand); SEB (Schachar); Flying-spot LASIK
corneal tissue layer by layer to create filtration (Lin); LAPR & LACA (Lin), LZT (Lin, Martinez); Eye-tracking (Lai);
Solid-state UV Laser for LASIK (Lin, Lai); BFCR (Ruitz). Most of the
channels. It is believed that the Er:YAG laser did above technologies have been patented (1988-2004) by various
produce significant co-lateral thermal damage. This inventors and greater details may be found in US patent No: 4718418,
would often lead to formation of coagulum at the tip 5484432, 5520679, 5144630, 6263879, 6258082, 5533997, 5354331.
 Advances of Solid-State Ophthalmic Laser Technologies 57
The PR-270 UV laser (made by New Vision, Inc., hyperopia (farsightedness), astigmatism and
Taiwan) uses Nd:YAG laser and nonlinear crystals presbyopia (aging eye). These corneal reshaping
to generate the 4th harmonic at a UV wavelength of procedures can be performed via several mechanisms
266 nm. It is very efficient in ablating tissues with including:
high water and protein content such as cornea and 1. Corneal surface ablation (PRK, LASEK),
sclera. The laser is delivered through a specifically 2. Cornea stroma ablation (LASIK, Epi-LASIK),
designed articulated arm with a hand-piece which 3. Corneal collagen tissue thermal shrinkage (LTK,
delivered the UV laser energy by a focusing lens. DTK, CK).
The 5-nanosecond short pulsed laser is focused to a The earlier refractive surgery procedure known
spot size about 0.2 to 0.8 mm on the treated area as photorefractive keratectomy (PRK) using an argon
with energy per pulse of 5 to 7 mJ and operated at 10 fluoride (ArF) excimer laser (at the 193-nm) and for
to 20 Hz (both are adjustable). We note that this 5 ns large area corneal surface ablation. During 1990s, PRK
laser is much shorter than the typical excimer laser has been the only procedure recognized as having a
(about 20 - 100 ns), or Er:YAG (about 500 micro- high clinical success rate and predictable diopter
seconds). Therefore, it offers minimal thermal damage corrections for myopia, astigmatism, and hyperopia.
with effective tissue ablation. Furthermore, the Alternative methods such as intrastroma
focused UV laser spot may be as small as 0.2 mm if photorefractive keratectomy (IPK, using Nd:YLF and
needed, which is not available in other IR lasers. The doubled YAG), conductive keratoplasty (CK) and
laser spot size is adjustable by varying the distance X laser thermo keratoplasty (LTK using Ho:YAG or
of the attached end tip which contacts the treated diode-laser DTK at 1.4 to 2.1 micron) have also been
surface. The laser is a noncontact cold laser and hence proposed.
there is no concern about collateral thermal damage, The more recent procedure laser in situ
or problems resulting from the fiber-tip damage in a keratomileusis (LASIK) has replaced the PRK with
contact IR laser of Ho:YAG or Er:YAG. advantages such as no epithelial removal, minimal
corneal would healing, reduced haze and regression,
REFRACTIVE LASERS and quicker recovery of vision. LASIK, however,
requires investments in a microkeratome and also in
Lasers in UV, visible and IR spectrum have been
doctor training. An alternative procedure called
widely used in various ophthalmic applications such
LASEK, similar to PRK without the use of
as glaucoma, cataract (or phaco emuleification) aged-
microkeratome, has been used for thin cornea or low-
related macular degeneration (AMD) and most
diopter correction.
importantly, for refractive corrections as summarized
The success of LASIK using UV scanning lasers
in Table 7.4. Presbyopia resulting from age may be
(either excimer or solid-state lasers) is mainly
treated by restoring or improving the accommodation
attributed from the following unique features:
via several means: the scleral expansion band (SEB)
(Figure 7.3 for scanning laser system schematics).
method by Schachar, the ciliary scleratomy by • Minimal tissue thermal damage due to the short
Fukusaku and the laser scleral ablation by Lin (2005). wavelength used;
Alternatively, accommodation may be improved by • Tissue bond-breaking of corneal collagen by high
direct modification of the modulus (or elasticity) of photon energy;
the aging lenses, or reduction of the lens volume • Precise corneal tissue surface ablation (on the
proposed by Gwon (1995) and Krueger et al (2005). order of 0.2 to 0.4 um per pulse) achieved by using
Thermal shrinkage of the lens by lasers was also small laser fluence of 150 to 200 mJ/cm2.
proposed by F. O’Donnell (US Patent) to reshape the • Use of computer programmed algorithm for
lens surface for refractive power change. ablation profile control;
Refractive surgical lasers have been used to correct • Use of eye tracking to minimize off-center ablation
the refractive errors including myopia (near-sighted), caused by eye movement;
58 Mastering Advanced Surface Ablation Techniques

Figure 7.3: Schematics of a scanning LASIK system

• Use of flying spot scanning for customized In contrast to the first-generation broad-beam
ablation; technology, which used industrial-type, high-power
• Use of advanced topography device and (about 300 mJ from the laser or 30 mJ on the corneal
wavefront technology for super-vision, where surface) excimer lasers, the recent generation systems
high order surface aberration may be minimized. use high-repetition-rate (100-500 Hz) excimer laser
New UV lasers for refractive surgery were also
operated at a much smaller beam spot size of 0.8 to
explored (1992 – 1998) as potential substitutes for the
1.5 mm in a scanning mode. It only requires a laser
first-generation ArF excimer lasers, which is bulky,
energy per pulse of only 0.8 to 2.0 mJ on the corneal
heavy, and high gas and maintenance costs. These
new UV lasers include: surface to achieve the same range of fluence (or
energy per unit area, 160 to 200 mJ/cm2) as that of
a. The Laser-Harmonic-1 (flash-lamp pumped) using
the fifth harmonic of and the high-power broad-beam excimers which require
Nd:YAG at 213 nm, and the LaserHarmonic-2 about 35 mJ per pulse.
diode-pumped Nd:YLG (or YLF) at 213 (or 209) Ultra-short-pulse lasers were also proposed for
nm, both patented by J T Lin (1992); LASIK procedures. These include picosecond and
b. The Ti:sapphire (fourth-harmonic) UV solid-state femto-second Ti:sapphire, Nd:YLF, or Nd:YAG
laser at 208 nm, made by Lai (Novatec, 1994). lasers, in which the wavelengths are not required to
At the 1991 ARVO and 1992 SPIE conferences, Lin be in the UV range. A “plasma-assisted” ablation
reported the first flash-lamp pumped, solid-state UV mechanism occurs in these short-pulse lasers. A mid-
(at 213 nm) PRK laser, where tissue ablation was IR laser generated from optical parametric oscillation
performed in collaboration with the groups at Emory (OPO) and Er:YAG was also proposed for LASIK
University (Waring) and the University of Miami (Ren procedures (Lin, US Patent, 2001). Various beam
et al). At the 1993 SPIE Biomedical Optics Meeting
delivery devices have been used, including the broad-
(Los Angeles, California), Lin reported the first diode-
beam laser with diaphragm and the small beam laser
pumped UV solid-state laser (at 209 nm). At the 1992
with computer controlled scanning mirrors, so called
American Academy of Ophthalmology (AAO)
meeting, Lin introduced the first miniexcimer laser the flying-spot technology invented by Lin. A list of
for PRK using a scanning scheme, which is currently major ophthalmic systems manufacturers is shown
sued by all LASIK systems. in Table 7.5.
 Advances of Solid-State Ophthalmic Laser Technologies 59
Table 7.5: List of major manufacturers of ophthalmic systems produce the UV 213 nm at about 3-5 mJ. This system
Applications Manufacturers shows an overall efficiency about (8-12%) from 1064
LASIK VISX/AMO, Coherent/Lumenis to 213 nm conversion. In comparison, the system made
Meditec/Zeiss, Nidek, Wavelight,
Alcon, Bausch & Lomb, LaserSight, by CustomVis (Australia) has a much lower energy
66-Vision, New Vision per pulse at 213 nm (up to a maximum of 1.0 mJ), where
AMD, glaucoma Lumenis, Nidek, Bausch & Lomb, Alcon
Retina, cataract IRIDEX, 66-Vision, MedLight a much higher repetition rate of 300 Hz is needed,
Microkeratome Alcon, Bausch & Lomb, Lumenis, since a smaller spot of 0.6 mm is used in this system
Zeiss/Meditec, Nidek, etc.
Wavefront device Alcon, Bausch & Lomb, Nidek, Topcon (spot size is limited by the available energy). The
Tracey, Wavefront Science CustomVis system, due to the limited energy and spot
Laser flap IntraLase (femto second Nd:YLF)
LTK, DTK, CK Refractec, Prolase, New Vision size, suffers slow procedure, about 2 times slower than
Laser presbyopia SurgiLight, New Vision Scan-213 model made by New Vision Inc.

Ablation Rates
SOLID-STATE 213-NM LASIK SYSTEM
The reported laser ablation rate in porcine eyes by
Generation of UV-213 nm Dair et al (1999) is based on the Q-switched, flashlamp
The use of UV laser at 213 nm for corneal reshaping pumped Nd:YAG laser, model Surelite II (made by
was first proposed and patented by Lin (US Continuum, CA) producing up to 660 mJ of energy
patent,1991). As shown in Figure 7.4, the fifth per pulse at a wavelength of 1064 nm. The duration
harmonic generation (at 213 nm) may be achieved by of the 1064-nm pulses was 5 nsec with a rather low
the mixing of the UV at 266 nm and the fundamental repetition rate of 10 Hz. The second harmonic (532
at 1064-nm in BBO crystal, where the green was nm) was produced using the crystal BBO (provided
produced from the first doubling crystal (KTP, LBO by Casix Inc., Fuzhou, China). The fourth (266 nm)
or BBO) and the UV-266 was produced by the fourth and fifth harmonics (213 nm) were produced using
harmonic generation crystal (BBO). One may also the new crystal called CLBO crystals (provided by
obtain the UV-213 by mixing the green (532-nm) and Crystal Associates, Waldwick, New Jersey). The
the third harmonic generation UV (at 355-nm). conversion efficiencies obtained were 60%, 25%, and
40% respectively, for each stage, resulting in an overall
conversion efficiency of 6%. The maximum fifth
harmonic output energy was 20 mJ per pulse for a
fundamental input energy of 330 mJ. The drawback
of this flash-lamp pumped system is the low repetition
rate of 10 Hz, which will result a very slow
procedure, say longer than 150 seconds for a typical
5 diopter myopic correction, versus 15 seconds in a
100Hz system.
As shown in Figure 7.5 (for porcine cornea), a
fluence in the region of 200 mJ/cm2 was found to be
Figure 7.4: Schematics of solid-state UV-213 laser the most efficient for ablation. The efficiency in this
region was approximately 0.35 mm 3/J, and the
Currently, there are only two companies ablation rate was found to be 0.6 μm/pulse. The
manufacturing the 213-nm system for LASIK. The ablation threshold in porcine corneas was about
Scan-213 made by New Vision, Inc. (Taiwan), a diode- 50 mJ/cm2. In the region of highest efficiency, the
pumped system consisting of 40 mJ, 8 ns, 100 Hz peak varied slightly in the fluence range between 150
fundamental Nd:YAG (at 1064 nm) was used to and 250 mJ/cm2.
60 Mastering Advanced Surface Ablation Techniques
environment, no sudden patient movement as
laser starts
• Accurate overlap of true Gaussian spots without
the need of beam uniforming optics which is
required in ArF system having a much less efficient
in producing uniform beam profile from a
multimode, hot-spot gas discharge
• Less patient pain-level due to lower temperature
increase (Table 7.6).
It was reported by Garimoldi et al in ESCRS
(Barcelona, Spain, Jan. 23-25, 2004) that cooling of
cornea reduce pains tissue damage and reduce haze.
The temperature increase in solid-state 13-nm laser
is (mean 0.8 C, max 1.3 C) versus excimer of (mean
5.3 C, max. 7 C), hence the pain level is reduced in
213-nm system (Table 7.6).
Figure 7.5: Comparison of ablation rates of UV laser at 213 nm and
193 nm (on porcine cornea) Table 7.6: Pain-level comparison (based on N = 48 and 26
cases, Garimoldi et al, ESCRS, 2004)
Also shown is the ablation rate of 193 nm excimer
Solid-state (213) Excimer(193)
laser which is about 55% of that of 213 nm laser due
Severe 14% (5 cases) 46% (12% case)
to the lower corneal tissue ablation and the higher Medium 14%, (12) 15.4% (4)
absorption of water (or the BSS on the corneal Light 33% (12) 31% (8)
Absent 39% (14) 8% (2 cases)
surface).
It was also reported that the absorption of BSS
(with 90% NaCl) in 213 nm laser is much lower than NEW DIRECTIONS
that of 193 nm. Therefore, the 213 nm laser is much Improvements of the existing systems or new systems
stable in response to surgeon’s BSS control of the for new ophthalmic procedures would rely upon
corneal surface during the LASIK procedures. certain new R&D directions proposed as follows.
• For PDT applications
The Advantages of 213 nm Laser
PDT offers clinically proven treatments in
Comparing to the ArF excimer system, the solid-state dermatology and ophthalmology. For the
213 system (particular the diode-pumped system) treatment of cancer or tumor tissues,
offers the following benefits: improvements may be achieved by:
• All solid-state, long life-time, low maintenance and – Enhancement transport of PDT drugs, such as
compact the use of aminolaevulinic acid (ALA);
• No toxic gas or gas bottles handling and storage – Enhancement drug delivery to tumors by low-
• No specific room requirements to prevent
dose PDT;
potential leaking toxic argon-fluoride gas
– Multi-wavelength of tunable lasers which may
• Very long lifetime cavity using crystals and no
be absorbed by multiple photosensitizers;
gas refill needed
• Surgical performance with reduced variability due – Increase clinical efficacy by deeper penetration
to lower BSS absorption of the laser at near-IR;
• Ablation with significcntively reduced stress – Increase localized (volume) excitation using IR
• Ablation or laser firing generates no audible laser sensitive drugs, where IR laser with ultra-
sound and treatment is done in a silent short pulse would be needed.
 Advances of Solid-State Ophthalmic Laser Technologies 61
For ophthalmic applications of PDT, mainly the BIBLIOGRAPHY
treatment of CNV of AMD or pathologic myopia,
1. Fleck BW, Chew PTK, Lim ASM et al. Q-switch Nd:YAG
PDT is the preferred process over photo- laser photodisruption of rabbit lens nucleus. Laser Light
coagulation. However, the closure of leaking Ophthalmol 1990;3:227-32.
blood vessels in wet AMD may be temporary and 2. Gailitis, P, Ren, Q, Thompson, KP, Lin, JT, Waring, GO.
re-treatments may be needed. Therefore, Solid state ultraviolet laser (213 nm) ablation of the
cornea and synthetic collagen lenticules Lasers Surg Med
improvements based on new photosensitizers 1991; 556-62.
and/or new laser sources are required. 3. Geoffrey T Dair, Wayne S Pelouch, Paul P van Saarloos,
• For laser phaco Darren J Lloyd. Investigation of corneal ablation efficiency
using ultraviolet 213-nm solid state laser pulses. Invest.
– Improve the safety and ablation efficiency using
Ophthal Visual Science 1999;40:2752-6.
new flexible fibers 4. Gwon A, Fankhauser F, Puliafito C, et al. Focal laser
– Optimize laser parameters in UV or mid-IR lasers photophacoablation of nomicel and cataractous lenses
– Combine laser phaco and ultrasound in rabbits. J Cataract Refract Surg 1995;21:282-6.
5. Krueger RR, Kuszak J, Lubatschowski H, et al. First safety
• For glaucoma treatments
study of femtosecond laser photodisruption in animal
– Improve clinical techniques for minimal invasive lenses: tissue morphology and cataractogenesis. J Cata-
– Combine laser and non-laser methods ract Refract Surg 2005;31:2380-94.
– Potential use of PDT 6. Lin JT. Critical review on refractive surgical lasers. Opt
• For refractive surgeries Engineer 1995;34:668-75.
7. Lin JT. Mini-excimer laser corneal reshaping using a scan-
– All solid-state UV lasers (replacing the gas ning device. SPIE 1994;2131:228-36.
excimer laser) 8. Lin JT. Multiwavelength solid state laser for ophthalmic
– Combined topography and wavefront devices applications. SPIE 1992;1644:266-75.
– Integrated real time customized procedures 9. Lin JT. Scanning laser technology for refractive surgery.
In. Garg et al, (Eds). Mastering the techniques of corneal
– New software (nomogram) for new applications refractive surgery. India Jaypee Brothers, New Delhi;
– All laser (blade-less) procedure for LASIK 2005; 20-36.
– Combined with IOL or accommodative IOL for 10. Lin JT. The new mechanism of laser presbyopia reversal
postcataract surgery and accommodation. In Agarwal A. (Ed):Presbyopia, a
surgical textbook. Thorofare, NJ, SLACK 2002; Chapt.
– New parameters (system and clinical) designed 6: 63-70.
for young patients or pediatric eyes after cataract 11. Myers RI, Krueger RR. Novel approaches to correction
surgery of presbyopia with laser modification of the crystalline
– Integrate multi-function system for myopic, lens. J Refract Surg 1998;14:136-9.
12. Ren Q, Lin JT et al. Ultraviolet solid-state laser (213 nm)
hyperopic, astigmatism and presbyopic patients
photorefractive keratectomy. Ophthalmology
from age 20 to 65. 1993;100:1828-34.
13. Ren, Q, Gailitis, P, Thompson, KP, Lin, JT. Ablation of the
CONCLUSION cornea and synthetic polymers using a uv (213 nm) solid-
state laser IEEE J Quantum Electron 1990;26:2284-8.
Many of the modern laser systems have been 14. Ren, Q, Simon, G, Legeais, J–M, et al. Ultraviolet solid-
approved for market, whereas some are in their clinical state laser (213 nm) photorefractive keratectomy: in vivo
study Ophthalmology 1994;10:1883-9.
trials. Improvements of existing systems or innovative 15. Ren, Q, Simon, G, Parel, J. Ultraviolet solid-state laser
new systems are always the continuing R&D efforts (213-nm) photorefractive keratectomy Ophthalmology
of researchers and manufacturers. Medical systems are 1993;100:1828-34.
integrated technologies of electro-optics and image 16. Ren, Q, Simon, G, Parel, J–M. Ultraviolet solid-state la-
ser (213 nm) photorefractive keratectomy: in vitro study.
device, in addition to the clinical technologies and
Ophthalmology 1993;100:1828-34.
methods. This chapter provides an overview of the 17. Seiler T et al. Laser thermokeratoplasty by means of a
existing systems for ophthalmic applications and also pulsed holmium:YAG laser for hyperopic correction.
addresses some new directions. Refract Corneal Surg 1990;6:335-9.
62 Mastering Advanced Surface Ablation Techniques
18. Sher NA. Surgery for hyperopia and presbyopia. Will- 21. Trokel SL et al. Excimer laser surgery of the cornea. Am
iams and Wilkins:1997. J Ophthalmol 1983;92:741-8.
19. Srinivasan R. Ablation of polymers and biological tissue 22. Yap, YK, Inagaki, M, Nakajima, S, Mori, Y, Sasaki, T.
by ultraviolet lasers. Science 1986;234:559-65. High-power fourth- and fifth-harmonic generation of a
20. Srinivasan, R, Sutcliffe, E. Dynamics of the ultraviolet laser Nd:YAG laser by means of a CsLiB6O10 Opt Lett 1996;
ablation of corneal tissue Am J Ophthalmol 1987;130: 470-1. 21:1348-50.
 CHAPTER
New Techniques for Improving
8 Laser Ablation Efficiency and
Accuracy

J T Lin (Taiwan)

INTRODUCTION This chapter will address the following issues

affecting the efficiency or accuracy of the LASIK
Scanning (flying-spot) laser has been widely used in
procedures:
almost all of the LASIK procedures. However, it has • Laser parameters (including optimal scanning
been over 15 years since the first system called overlap, ablation rate calibration in PMMA and
scanning mini-excimer was designed, invented and tissue, etc.) affecting the procedure time and
patented by J. T. Lin (U.S. Pat. 5,144,630; 5,520,679, accuracy
1992). Integrated with an eye tracking (first • Spherical ablation algorithm (first order, high
introduced by S. Lai in 1993), scanning laser offers order, keratometry power, etc.)
the unique feature for customized corneal ablation. • Aspherical algorithm (the Q-value).
Elevation-type corneal topography and wavefront
devices offer additional advantages over the non- KEY FACTORS
scanning laser for minimal optical aberration to
Following factors are the main issues affecting the
improved image quality.
outcomes of LASIK (see also Table 8.1):
Three main refractive surgical procedures, LASIK,
• The UV (193 or 213 nm) wavelength used in LASIK
LASEK and epi-LASEK have become the choice of
provides minimal tissue thermal damage (few
vision corrections for myopia, hyperopia and
microns) by tissue bond-breaking of corneal
astigmatism, whereas other methods such as laser
collagen by high photon energy
sclera ablation (LSA), bifocal-LASIK and mono-vision
• Precise corneal tissue surface ablation (on the
correction (using CK or LTK) have been used for
order of 0.2 to 0.4 um per pulse) achieved by using
presbyopia. However, some critical issues still remain small laser fluence of 150 to 200 mJ/cm2
and limit the performance of the procedures. As • The use of eye tracking to minimize off-center
summarized in Table 1, the issues affecting the ablation caused by eye movement
procedure outcomes are governed by laser • The use of flying spot scanning for customized
parameters, system design, ablation algorithms, ablation
preoperative calibrations and microkeratomes, in • The use of topography and/or wavefront guided
addition to the clinical aspects relating to the technology for supervision, where high order
surgeon’s techniques, stroma hydration, corneal surface aberration may be minimized.
surface condition and management of the flap, The clinical issues of LASIK include patient
complications and postoperative medications. centration, operative eye motion, corneal haze, night
64 Mastering Advanced Surface Ablation Techniques
Table 8.1: Technical and clinical issues affecting LASIK outcomes is the adjustable effective zone diameter in multizone
LASER SYSTEM method, or H = (6.8 to 14.1) microns per diopter.
• Spot size (0.5–2.0 mm)
• Repetition rate (100–500 Hz) Another possible issue relates to mis-matching of
• Energy per pulse (1.0–4.0 mJ) the microkeratome cutting edge which may be
• Laser fluence (120–250 mJ/cm2)
• Eye tracking (50–5,000 Hz) alternated by the laser ablation “transition zone”. The
healing of the mis-matched flap might affect the
MICROKERATOME
• Flap size (8.5–10.5 mm) effective zone (Weff) postoperatively, in addition to
• Flap thickness (120–200 um) its surface quality. In this regard, a new method using
• Flap orientation
• Stroma surface quality ultra short pulse IR laser (made by Intralase) was
ABLATION ALGORITHM also on the market as an alternative of microkeratome.
• Ablation zone (5.0–7.5 mm) Better surface quality is expected, however, the flap
• Transition zone (1.0–1.5 mm)
• Beam overlap (for smoothness)
thickness uncertainty may be greater in the laser-flap
• Multi-zone (for reduced ablation depth) method.
• High-order ablation depth
• Corneal asphericity (Q-factor)
Smooth ablation boundary transitions should
• Random scanning (for minimal thermal) reduce the regression particularly in high diopter
• Customized profiles (for minimal aberration) corrections, where epithelium filling of the ablated
PREOPERATIVE CALIBRATION area may be triggered by a “deep” transition edge
• Keratometry power (K-reading)
• Corneal surface radius (r1, r2) on the ablated zone. A “shallow” transition can be
• Ablation rate (PMMA-reading) easily achieved in the scanning mode. In addition, a
CLINICAL ASPECTS final “polishing” of the ablated area can also be easily
• Surgeon’s techniques conducted to further reduce the haze effect. Shock-
• Stroma conditions (hydration level)
• Flap management wave-induced tissue damage and central islands
• Postoperative management occurred in the high-power excimers have not been
• Retreatment and enhancement
found in the scanning mode. Figure 8.1 shows a
typical schematics of flying-spot scanning laser
halo and power regression effects, pain, wound
system, where the rotating layers provide smooth
healing (reepithelizlization time), and procedure time.
ablation surface.
These clinical issues are directly correlated to
engineering aspects that involve laser parameters LASIK ACCURACY
(beam energy/pulse, spot size, homogeneity, and
fluence on the ablated corneal surface) and delivery Other than the semi-scanning broadbeam system
methods (diaphragm, scanning, mask, fiber). In (used in Visx system), almost all the existing LASIK
addition, nonexcimer solid-state lasers without systems have used the flying-spot scanning method
fluorine gas may be preferred for their ease of (patented by Lin in 1996) which uses a typical spot
operation and low maintenance. size of 0.5 to 2.0 mm. For low repetition rate (R)
The existing microkeratomes are designed to cut systems (20 to 50 Hz), a larger spot size about 1.5 to
a flap thickness about 120 to 180 um with about 5% 2.0 mm would be required to achieve a reasonable
uncertainty resulting from the conditions of preparing procedure rate of about 3 to 5 seconds per diopter of
the flap such as vacuum pressure and initial corneal correction. For system with high R = (300 to 500) Hz,
surface curvatures. Stroma bed margin thickness of spot size of 0.5 to 0.8 mm may be the optimal for
about 200 to 250 um is recommended. Therefore the both procedure time and ablation precision.
120 to 130 um setting would be preferred for high It should be noted that spot size larger than 1.5
diopter corrections, considering that the central mm may speed up the procedure and obtain smoother
ablation depth (H) is about Weff2/3 microns per 1.0 surface, however, it would lose the accuracy in
diopter of correction, where Weff = (4.5 to 6.5) mm ablating “fine profile” having structure smaller than
 New Techniques for Improving Laser Ablation Efficiency and Accuracy 65

Figure 8.1: Schematics of a scanning patterns in LASIK system

1.0 mm, or for the correction of localized high-order Weff results in about 20% errors in the correction
surface aberration or irregularity in customized diopter (D). We will first discuss the optimal
procedures. A system with adjusted spot size method parameters, then the ablation rates described by a
(Lin, patent pending) was proposed to overcome the thermal model.
above drawbacks, where large spot (about 1.5 to
Optimal Scanning Parameters
2.5 mm) is proposed for regular large area profile,
whereas small spot (0.2 to 0.5 mm) for irregular or Smooth PMMA profiles of myopic correction may be
surface aberration corrections. generated and used as the calibration at various
The ablation rate is very sensitive to the hydration overlap parameters (L) defined by L = 1-d/R, with d
level of the ablated stroma (for LASIK) or corneal being the displacement between each scanning spot
surface (for LASEK). A possible uncertainty of 10% and r being the diameter (or spot size) of the beam.
to 20% could occur under a non-controlled condition. For a spot size of 1.0 mm and d = 0.2 mm, L = 0.8 or
However, this may be overcome by adjusting the 80% overlap. It should be noted that given a spot
PMMA calibration which translates the “actual” tissue size, smaller beam displacement d (or larger beam
ablation rate to the PMMA by empirical factor. Greater overlap) always gives a smoother ablation surface in
detail will be discussed in the Calibration Section. which, however, the thermal effect may also increases
The new solid state 213 nm system provides a more accordingly.
stable, consistent results than the 193 nm excimer due Another important issue is beam uniformity. A
to the much lower BSS absorption in 213 nm compact scanning laser system did not include
wavelength. Greater detail comparing 213 and 193 complicated optics for beam uniformity. Instead, the
laser may be found in another Chapter of Lin in this beam overlap technique is used to minimize the need
book. of beam uniformity. A smooth overall ablation surface
The accuracy of LASIK procedure is also affected was achieved by enough beam overlap (typically, L =
by the accuracy of the effective ablation zone (Weff) 60 to 80%), which is, however, limited by the minimal
which is influenced by the non-normal incidence of procedure speed required. Typical LASIK preferred
the laser, surface reflection loss and biotissue related procedure should be completed within 15 to 20
regressions. By the relation of d (ablation depth) ~ seconds for a –5 diopter correction at an ablation zone
D(Weff),2 we may easily see that each 10% error of of 6.5 mm. In addition to the beam overlap, a uniform
66 Mastering Advanced Surface Ablation Techniques
profile may also be achieved by beam “spinning” (or which is proportional to the tissue absorption
rotation by a so-called K-mirror) or by beam coefficient (B) and may be approximated by A ~ Bln(F-
orientation when it is linearly scanned such as in F*), where F = (E/R2) is the fluence (or the energy
Nidek system. per unit area of each scanning spot having a radius
Yet another important issue is the ablation profile, of R); F* is a threshold fluence for stroma tissue to be
which must match the theoretical curve in order to removed. The currently used systems use a typical
achieve the desired diopter correction. In the fluence of F = (120 to 250) mJ/cm2. Higher F would
scanning mode approach, unlike the diaphragm mode, speed up the procedure, however, it also slightly
the profile is software-driven with profile accuracy suffers the ablation accuracy , lower fluency suffers
limited by the beam spot size, that is, a small spot more sensitive ablation rate change resulted form
size of 0.5 to 0.8 mm is preferred. A smaller spot size laser energy stability. It should be noted that A is
takes a longer time to scan over the entire ablation governed only by the fluence (F-F*) rather than E
zone, although it is easier to achieve an accurate (the laser energy per pulse). Therefore, one would
profile. Therefore, the third optimization rule is the expect the similar ablation rate for a spot size of
spot size and procedure speed at a given average 2.0 mm having E = 5.2 mJ and a smaller spot of 1.0
power P. Given an optimized spot size, higher mm with E = 1.3 mJ, assuming the threshold
average power will always speed up the procedure F* = 20 mJ/cm2 or E* = 0.3 mJ (for a 1.0 mm spot) and
without losing the accuracy of ablation profile. E* = 1.2 mJ (for 2.0 mm spot).
Yet another issue is the increase of thermal effects By defining T* = T/D, or the procedure time (in
in high repetition rate laser, say 200 Hz. This seconds) per diopter correction (D), one may obtain
accumulated thermal effect from the spatially the following overall scaling law:
overlapped pulse may be minimized by a so called T * ~ W2/[AHPR2], (1.a)
2
“random scanning” such that pulse to pulse or F = (E/R ) (1.b)
scanning layer to layer may be separated for minimal Relationships based on above equation are shown
thermal effects although the UV laser is considered in Figures 8.2 Shown in Figure 8.3 are the ablation
to be a “cold” laser. rate vs. fluence (F) and T* vs. A. The following
examples may be obtained from above equation.
Optimal Parameters for Procedure Time For a typical system parameters of W = 6.0 mm,
H = 100 Hz, P = 100 mW, E = 1.0 mJ/pulse and spot
The key issue for LASIK procedure is to optimize size of R = 1.0 mm (diameter) and ablation rate of
the scanning parameters of d, L and the procedure A = 0.5 microns/pulse, we define a typical T* = 5.0
time (T). It should be noted that laser average power seconds in myopia correction. The procedure time
(P) rather than the energy (E) is the determining (per diopter) T* is determined by (P,H, R, W) as
parameter of the procedure time (T), assuming the follows (Figures 8.2 and 8.3).
laser fluence is above the ablation threshold. 1. For fixed (A,H, R, W), T* is linear propositional
Furthermore, a smaller energy per pulse (E) and/ to 1/P, that is T* = (2.5, 10) seconds for P = (200,
or lower fluence(F) will achieve a smoother ablation 50) Hz. Therefore for H<100 Hz, a larger spot
surface. However, the procedure time (T) is inverse size of R > 1.2 mm would be needed for
proportional to the ablation rate (A) and the laser reasonable T*.
repetition rate H. Therefore, the second optimization 2. For fixed (A,P,R,W), T* ~ W2, therefore, T* = (3.5,
is to adjust the parameters of E (or F), A, and H in 5.8, 6.8) seconds, for W = ( 5.0, 6.5, 7.0)mm, in
addition to d and L. single-zone method. The procedure is faster in a
The procedure time (T) is governed by the ablation multi-zone method which has a smaller effective
rate (A) defined as tissue depth removed per laser inner zone size.
pulse. Basically, T is inverse proportionally to A 3. For fixed (A,P,H,W), T* ~ R2. Therefore,
 New Techniques for Improving Laser Ablation Efficiency and Accuracy 67
for lower H,100 Hz, larger spot of >1.2 mm is
needed.
4. For a limited available energy/pulse, say <1.0 mJ,
a small spot is required in order to have
F >150 mJ/cm2.
If none of the laser parameters are limited, then
the sole limiting parameter determining T* is the laser
power (P) and T* ~ P, where typical P is 200 mW to
340 mW. On the other hand F value can not be too
for the sake of ablation depth precision, say 0.2 to
0.5 micron/pulse. This is another limiting factor for
A
T*, even laser power is not limited. The current
systems in the market having H = (100-500) Hz, and
unlimited laser power (>500 mW), the typical range
of T* = (3.5–7.0) seconds have been used based on
the issues discussed above.

Thermal Model of Laser Ablation

It was proposed by Pursikov et al (1990), that the
LASIK ablation rate may be modeled by a laser
induced evaporation which defines the ablation rate
(A), or the laser ablation/penetration depth per pulse
B (A) given by
Figures 8.2A and B: Procedure time (per diopter) T* as function of
the ablation diameter (W, in mm), laser power (P, in mW), laser repetition
A = b In (F/F*), (2.a)
rate (R, in Hz) and laser spot radius/size (R, in mm) b = (0.616/n) (λ/a)1/2 (2.b)
F* = (ΔT/a1/2 ) [π m3 C3K tp]1/4 (2.c)
where F, F* are the true and threshold fluences,
ΔT is the temperature increase needed for tissue
thermal destruction per laser pulses, a is the linear
absorption coefficient, m is the density, C is the heat
capacity, K is the thermal conductivity, λ is the
wavelength, and n is the refractive index (n = 1.52 at
193 nm) and tp is the laser pulse duration. For a square
pulse the maximum surface temperature increase is
given by an analytic form of (Lin & George, 1983).
ΔT = 2Io (1-Re) tp1/2 (π m CK) 1/2, (3)
where, Io is the laser intensity, Re is the surface
Figure 8.3: Ablation rate (A) vs laser fluence (F) and procedure
time (T*) vs ablation rate
refection loss. Combining Eq. (2) and (3.), one further
obtains F* ~ tp3/4 that is for a given laser energy (or
T* = (20, 13.9, 3.47) seconds, for R = (0.5, 0.6, 1.2) intensity) longer pulse requires a higher threshold
mm. This is the major reason that a small spot fluence to achieve the temperature needed for
system such as a diode-pumped laser system made thermal destruction/evaporation of the corneal tissue.
by CustomVis having a small energy/pulse about One may also re-write Eq. (2) as following
1.0 mJ and spot size of 0.6 mm, requires a very F = F* exp (A/b) (4.a)
high repetition rate of >500Hz. On the other hand, F = F* exp [A a1/2 /(0.616/n) λ1/2], (4.b)
68 Mastering Advanced Surface Ablation Techniques
which implies that for a given laser fluency, the
ablation rate (A) is inverse proportional to the
absorption coefficient (a); and to achieve the same
ablation rate, high fluence (F) is needed for a higher
absorption coefficient (a). The relationships of A, F
and F* are presented in the normal scale and in the
natural log (In) linear scale, where, A = 0, when F = F*.
It was known that the cornea stroma consists of
80% water and 20% protein. The measure absorption
coefficient (A) in bovine cornea as about 2700 and
210 cm–1 at 193 and 248 nm, respectively. As shown
in Figure 8.4 the ablation rate (depth in microns) in
bovine cornea at various wavelengths. Figure 8.5 and
Figure 8.6 show the feature of wavelength
Figure 8.6: Measured ablation rate (A) vs laser fluence (F) in
dependence of the ablation rates at 193 nm, 213 nm bovine cornea at 193 nm and 248 nm
and 248 nm, in which lower absorption coefficient
shows higher rates. The influence of corneal surface
BSS or water absorption is shown in Figure 8.7 for
dry eye (higher rate) and wet eyes (lower rate).

Figure 8.4: Ablation rate (A) vs laser fluence in the normal and log Figure 8.7: Measured ablation rate (A) vs laser fluence (F) in dry
scales defined by the threshold value F* and wet human cornea at 193 nm and 223 nm

Aberration Rate Calibration

Clinical factors causing variations of ablation depth
include the re-absorption of laser energy by the
ablated plume nearby the corneal surface and the
hydration (BSS) levels on the treated surface. Surface
reflection loss and the non-normal incidence of the
laser beam (with increased effective zone size) may
also contribute to about 8% to 10% reduction. For
example, it was measured by Lin that the central
ablation depth on a PMMA was reduced by about
25% for a testing without air blowing on the surface
due to the re-absorption of the PMMA plume. It was
Figure 8.5: Ablation rate (A) vs. laser fluence (F) in porcine cornea known that the BSS absorption in 193 nm is much
at 193 nm and 213 nm higher than that of 213 nm laser.
 New Techniques for Improving Laser Ablation Efficiency and Accuracy 69
Another error comes from system manufacturers CF value would suffer inevitable errors, where only
provided conversion factor (CF) or the ablation rate the theoretically defined CF value and a refined
ratio between corneal stroma tissue and PMMA. The algorithm could provide the accurate outcomes.
CF value, 2.8 to 3.5 empirically defined in various
systems and based on statistical average may be the ABLATION ALGORITHMS
major source of error in determining the actual
High-order Term
ablation depth. The “apparent” CF value is clinically
adjusted by individual surgeons such that the errors A new formula for the corneal central ablation depth
of about 10% to 15% are “smeared” and compensated. (H) in a myopic three-zone LASIK is given by Lin:
The “true” CF value depends on accurate H = (RF) (DW2/3) (1+ C) (5)
measurement of tissue ablation rate, which is where, H in microns, LASIK correction power D
influenced by laser energy re-absorption and corneal in diopters, and the ablation zone diameter W in mm.
surface hydration conditions, and is hard to measure RF is a reduction factor when a 3-zone-ablation is
accurately from patient to patient. used in comparing to single-zone depth. C is a high-
The above PMMA calibrated CF value had been order correction term. Depending on the software
suggested by the manufacturers. However, depending design of manufacturers, RF ranges from 0.75 to 0.85.
on the control of corneal conditions and the feedback For example, in a 3-zone distribution design of: 100%
from treated cases, some surgeons had further ablation within 0.5W, 50% within 0.75W and 25%
adjusted these CF values by 5% to 15% based on my within the transition zone of 0.25W, RF = 0.78.
knowledge. The other factors may also influence the The high-order correction term C is introduced
ablation rate include: how the ablated plume is to account for the effect of preoperative corneal
removed (by air blower, or by a vacuum); control of anterior radius of curvature (r1) which is related to
microscope illuminating light and the number of stops the measured preoperative keratometry reading
made by the surgeon in each procedure. All these (Kpre) by Kpre = 337/r1, therefore
factors would affect the BSS level on the ablated stroma C = 0.19 (W/r1) 2 = 0.19 [W(Kpre/337)]2 (6)
surface and therefore the ablation rate for a given laser The above correction term is important particularly
fluence or energy per pulse. for high-myopic (or steep cornea with r1<7.5 mm)
Most of the current algorithms perform good and when large ablation zone is used (with W > 6.5
outcomes even they had used the first order mm). Lin’s calculation shows that the commonly used
approximation and ignored the high-order correction. first-order formula (with C = 0) underestimates the
It may be fair to state that the major reason is that ablation depth by 10 to 16% in comparing to the
the errors resulting from the ignorance of the high- new formula. For examples: for r1=7.8 mm (or
order term, the surface reflection loss and other bio- Kpre = 43.2 D), C = (11.2, 13.2, 16.4)% for W = (6.0,
mechanical related factors had been “balanced” by 6.5, 7.0) mm; for W = 7.0 mm, C = (16.4, 13.2, 11.1)%
the manufacturer-provided and surgeon-adjusted CF for r1 = (7.0, 7.8, 8.5) mm or Kpre = (48.1, 43.2, 39.6)
values. These values are clinically (empirically) D. That is the high-order correction becomes
adjusted for accurate (at least in the average sense) significant (about 16% deeper than the first-order
refractive outcome based on the paraxial formula) for steeper cornea (Kpre > 45D) and large
approximated (PA) algorithms and ideal spherical ablation zone.
corneal surface. It should be emphasized that the Therefore, a refined ablation algorithm should
empirically defined CF value may compensate most include the following as the “input” parameters:
of the uncertainties due to algorithms or ocular a. The preoperative K-reading (Kprep) for
conditions and therefore, provide good outcomes for individual eye, particularly for those having
normal populations. For individual subjects deviating Kprep values substantially different from the
from the normal (average) conditions, the empirical mean value of 43 D.
70 Mastering Advanced Surface Ablation Techniques
b. If the personalized Kprep is not available, then would be reduced by about 3 um when # 4 profile is
the mean value may be used. used; or increased by 2.4 um in #5 profile. The # 6
However, Eq.(1) must be used to include the high- and # 7 profiles offer larger EOZ but also required
order correction (C). larger ablation depth. They also found that
For a fixed LASIK ablation depth, the first-order significantly less change of corneal asphericity after
approximation (FA) will causes an over-correction OTZ than the conventional method.
(OC), comparing to the high-order formula, an
amount of OC = 3CH/ (RF)W2. For example, a 5.0 Corneal Asphericity Change
diopter myopic correction with a zone size of 7.0 mm It was reported by Marcos et al, Jimenez et al and
and RF = 0.78, OC = 0.66 diopters; and ablation depth Lin that the corneal asphericity (Q) increases
error of (10.4, 8.4) microns for r1 = (7.0, 7.8) mm. The (decrease) after myopic (hyperopic) LASIK.
new formulas show central ablation depth (per According to Lin’s formula, the postop (Q2) and
diopter correction) of 14.42 micron versus 12.74 preop (Q1) asphericity are related by:
micron in FA for the case of W = 7.0 mm, r1 = 7.8 mm Q2 = a (Q1 + 1) -1, (7)
and RF = 0.78 (in 3-zone design). These values may where a = 1.23 for -5.0 D myopic and a = 0.826
also be compared with the single-zone (or when for +5.0 D hyperopic LASIK. For example, an initially
RF = 1.0) which are 28% deeper in the above example. prolate cornea (with Q1 = –0.1) will become oblate
We also note that the ablation depth (H) is (with Q2 = +0.11) after a myopic-LASIK. In
proportional to the square of the ablation zone comparison, an initially prolate cornea (with Q1 = –
diameter (W) and 10% reduction of W will cause 19% 0.26) will become more prolate (with Q2 = –0.39) after
reduction in ablation depth for a given refraction a hyperopic-LASIK, which may also change an initially
correction. oblate cornea (with Q1 = +0.1) will become slightly
The true corneal refraction power (Dpost) after prolate (with Q2 = –0.09).
LASIK may be calculated by Dpost = 1.117Kpost – In general, the factor a in Eq.(3) is given by a = (R’/
41/r2, which requires the measurements of the post- 2
R) , where R and R’ are the corneal preop and postop
LASIK K-reading (Kpost) and the corneal posterior surface radius, respectively. For myopia, R’>R, a>1
radius of curvature (r2). The prior work of Hamed and Q2 > Q1 or increase of asphericity after LASIK.
et al using a mean value r2 = 6.8 mm in above For hyperopia R’<R, and Q2<Q1, a decrease of Q. R’
calculation will cause a refraction error of 1.1 and 1.4 and R are related to the refractive error (D) by
diopters for individual patient with r2 = 8.0 and 5.5 D = 377(1/R’ – 1/R). (8)
mm, respectively. The above theoretical prediction providing the
consistent trends with measurements by Chen et al,
Optimized Transition Zone (OTZ)
however, underestimated the actual change of corneal
It was reported by Hori-Komai et al that using a new asphericity which may be further changed by the
ablation algorithm called OTZ may offer larger proposed factors of: reflected/absorbed energy loss
effective optimal zone (EOZ) and decrease the and nonnormal incidence angle of the laser; the
postoperative halo, glare and reduced night vision, asphericity induced by wound healing and
in comparing to the conventional multizone method. biomechanical response of the cornea.
Seven types of OTZ are available (in NIDEK EC 5000 As proposed by Lin and others, the post-LASIK
system) defined by the inner/outer zone size of 4.5/ corneal asphericity may be controlled to meet the need
8.5 mm. For example, a myopia profile of -5.0 D has a for minimal high-order optical aberration (HOA) where
central ablation depth (H) of about 69 um, for a the postop corneal Q-value is required to balance the
conventional method having an inner optical zone of lens Q-value for minimal HOA. Greater details may be
6.0 mm and transition zone of 7.0 mm. The depth found in another Chapters by Lin in this book.
 New Techniques for Improving Laser Ablation Efficiency and Accuracy 71
Q-factor Customized Ablation will ablate too much corneal tissue with the high risk
of corneal weakening and is limited only to
Preoperative wave-front analysis may be used to
symmetric-type corrections. Therefore, the existing
create individualized ablation to compensate for
systems having input parameters based on the surface
preexisting aberrations. However, this analysis is time
diopter cannot correct localized irregularity of the
consuming and may not be necessary for majority of
surface which requires the EM data as well as the
the eyes, as pointed out by Koller et al. Therefore a
calculated profile difference between the desired
new algorithm based on aspheric non-individualized
regular profile and the initial irregular profile.
profile was proposed to improve the visual outcomes.
In addition, all the existing LASIK systems using
Manns et al reported that a target Q value of –0.4
a fixed laser beam spot size limit the accuracy of
would create a minimum spherical aberration.
corrected profile, particularly when the localized
Gatinel et al reported that for an intended value
irregularity is smaller than the laser spot size, typically
change of –0.6 (within optical zone of 6.5 mm) would
about 0.8 to 1.5 mm. It should be noted that smaller
require about 28.5 um more central tissue removed.
beam spot provides more accurate ablation profile
Therefore, for stronger attempted asphericity
but slower procedure, whereas larger spot gives
correction with Q change larger than –1.0 (in myopia
faster procedure with poor accuracy. Current excimer
correction) or +1.0 (in hyperopia correction), requiring
laser technologies can only offer up to about 250 Hz
extra central ablation depth greater than about 60
repetition rate which also limits the procedures speed
um, would not be recommended.
to be about 3.0 seconds per diopter. Therefore, the
Limitations of CCR ultimate solution for accurate and fast procedure
would require a system having an adjustable beam
Laser manufacturers have claimed the use of spot size. For example, one may use 0.3 mm laser
customized corneal reshaping (CCR), however, they spot to correct smaller or irregular profile, whereas
did not address the technical difficulties which have a 2.0 mm spot for large area and smoother profile. A
not yet been overcome for a true, realtime CCR. two-step CCR with adjustable spot size has been
The scanning lasers currently used for LASIK were recently proposed accordingly. (Lin, JT. US pending
designed with the intent for customized surface patent, 2005).
ablation. However, they are all based on average To conclude, the current technologies combining
corneal surface data for “approximate” large area scanning beam, eye-tracking, elevation map and
correction. A localized, small area correction for CCR wave-front device may offer a customized corneal
based on the EM has not yet been developed since reshaping (CCR), but is only limited to large area
the concept was first presented by Lin in 1999 (Fall averaged correction, such as off-center correction. A
World Refractive Surgery Symposium, Oct. 1999, true, real-time CCR, particularly for high-degree,
Orlando, FL). preoperative small-scale irregularity, will remain
Most of the systems on the market (made by technically impossible, until the surface smoothness
Nidek, LaserSight, Alcon, Bausch and Lomb and and irregular beam overlap issue addressed above
others claiming the capability of customized reshaping can be resolved.
are simply misleading without mentioning the
limitations. For example, in correcting a post-PRK off-
CONCLUSION
centered eye, a portion of the off-centered corneal
surface was ablated and followed by another The outcomes of LASIK, LASEK or epi-LASIK
correction on the resultant refractive error, where procedures depend not only on the system
“symmetry” ablation profiles were typically used and parameters, ablation algorithm, microkeratome, but
the correction power is defined by an averaged also on surgeon’s technique in handling the ocular
surface diopter. This procedure, most of the time, conditions, preoperatively and intraoperatively. Laser
72 Mastering Advanced Surface Ablation Techniques
spot size, fluency and repetition rate affect the ablation calibration and the vacuum device (or blower) to
rate and the thermal effects. For improved visual avoid the reabsorption of the plume.
outcomes, high order aberration of the cornea must
be optimized by controlling the postoperative corneal BIBLIOGRAPHY
asphericity (the Q-factor) for minimum overall 1. Furzikov N. P., Lekhtsier E. N., Semyenov A. D., “Model
aberration by compensating the pre-existing lens and description of UV laser ablation of the cornea”, SPIE
Proceeding, 1990;1202:286-98.
aberration. The personalized preoperative overall Q 2. Lin JT, George TF. Laser-Generated Electron Emission from
value should also include the age effect on the lens. Surfaces: Effect of the Pulse Shape on Temperatureand
To improve the overall visual outcome, the Transient Phenomena. J. Appl. Physics 1983;54:382-7.
3. Lin JT. A new formula for ablation depth in 3-zone
improved algorithm should also consider the
LASIK. J Refract Surg 2005;21:413-4.
following extra information, in addition to the 4. Lin JT. Critical review on refractive surgical lasers. Opt.
conventional input parameters of refractive error (D) Engineer. 1995;34:668-75.
and the ablation zone (W): 5. Lin JT. Mathematical handbook of LASIK. In Garg A.,
Rosen E, Lin JT et al, (Eds): Mastering the techniques of
• Optimal procedure time (T) based on multi-factor corneal refractive surgery. India, Jaypee Brothers; New
of (A,H,P,R,W) Delhi 2007;86-92.
• Preoperative K-reading (Kpre) and/or the corneal 6. Lin JT. Multiwavelength solid state laser for ophthalmic
anterior surface radius (r1) applications. Proc SPIE 1992;1644:266-75.
7. Lin JT. Scanning laser technology for refractive surgery.
• Preoperative corneal and lens asphericity (the Q In: Garg et al, Ed. Mastering the techniques of customized
values) LASIK. New Delhi, India, Jaypee Brothers; 2005;20-36.
• Adjusted effective ablation zone (Weff) to include 8. Lin JT: Mini-excimer laser corneal reshaping using a scan-
the laser energy loss due to extra hydration on ning device. Proc SPIE 1994;2131:228-36.
9. Puliafito C. A., Wong K., and Steinert R. F., “Quantita-
the treated surface, reflection loss, non-normal tive and ultrastructural studies of excimer laser ablation
incidence and other biomechanical effects of the cornea at 193 and 248 nanometers”, Lasers Surg.
• Re-adjust the manufacturer provided PMMA Med., 1987;7:155-9.
calibration conversion function (CF) based on 10. Ren Q, Lin JT et al. Ultraviolet solid-state laser (213 nm)
photorefractive keratectomy. Ophthalmology.
surgeon’s experience and the empirical data obtained. 1993;100:1828-34.
The CF value may be affected by surgeon’s handling 11. Srinivasan R. Ablation of polymers and biological tissue
of the treated corneal surface, the material used for by ultraviolet lasers. Science. 1986;234:559-65.
 CHAPTER

9 The Genetic Effect on Anterior

Corneal Aberration

Lung-Kun Yeh, I-Jong Wang (Taiwan)

OPTICAL ABERRATIONS IN HUMAN EYES The Zernike coefficients can be used to represent the
amount of each individual’s aberrations, and the total
The quality of an image on the retina is determined
wavefront errors and root mean squares (RMSs) of
by the optics of the eye and is degraded by scatter,
the wavefront aberrations can describe the overall
diffraction, and wavefront aberration. In most eyes,
index of aberrations.6
wavefront aberration causes greater degradation of
the retinal image than scatter or diffraction. 1 CAUSES OF ANTERIOR CORNEAL ABERRATIONS
Therefore, ocular aberrations of the human eye play
a major role in optical quality.2 The air to cornea It is now understood that several components
interface provides the greatest optical power of the contribute to corneal wavefront aberrations, including
ocular system due to the large difference in refractive the population distribution, aging and the genetic
index.3 Thus, anterior corneal aberrations greatly factors.8 Wang et al. reported that anterior corneal
influence ocular wavefront aberrations.4 The optical aberrations varied greatly among subjects, and
aberrations were first reported by Tscherning in moderate degree symmetry existed between right
1894,5 and they can be divided into anterior corneal, and left eyes.11 Whether the corneal aberrations is
posterior corneal, and lenticular aberrations. genetically or environmentally determined has been
the subject of much debate. It is interesting to know
ANTERIOR CORNEAL ABERRATIONS that the heritability of the anterior corneal aberrations
and their relationship with the ocular refraction
Previous studies have introduced that computerized
errors.
videokeratoscopes (CVK) have enabled the
measurement of corneal shapes and the
THE TWIN STUDY OF ANTERIOR CORNEAL
determination of wavefront aberration of the anterior ABERRATIONS
corneal surface. 6-8 The normalized Zernike
polynomials, which are a set of functions that are Twin studies have been regarded as the “perfect
orthogonal over the unit circle describing the shape nature experiment” to study the relative importance
of an aberrated wavefront in the pupil of an optical of genetic and environmental factors.12 Monozygotic
system, has been recommended as the standard (MZ) twins share the same genes and dizygotic (DZ)
method for specifying the eye wavefront errors.9,10 twins on average share only half their genes. Any
74 Mastering Advanced Surface Ablation Techniques
greater similarity between MZ twins can therefore right eyes in MZ and DZ twin pairs and the mean
be attributed to this additional gene sharing. 9 value of RMSs of spherical aberration (SA) and coma
Genomic DNA was collected by buccal swabs were shown in Table 9.1 and the intrapair correlations
biosampling methods for polymerase chain reaction of Zernike coefficients and RMS of anterior corneal
(PCR)-based genotyping assays to determine twin aberrations between right and left eyes of each subjects
zygosity.13 Corneal topographies were obtained from in twin pairs were shown in Table 9.2. In MZ twins,
Computer-Assisted Videokeratography (Orbscan II, ).14 vertical coma (Z3-1), secondary vertical coma (Z5-1),
CTView program which can calculate and display spherical aberration (Z40), and secondary spherical
Zernike coefficients from 0 up to 27th order was used aberration (Z60) were moderately correlated (Pearson’s
to compute anterior corneal aberration from corneal correlation coefficients r = 0.43, 0.51, 0.41, and 0.65,
elevation data.9 The topographic maps were centered respectively). In DZ twins, vertical coma (Z 3-1 ),
around the entrance of the pupil, and wavefront secondary horizontal coma (Z 5 1 ), and spherical
aberrations were calculated for the central 6.0 mm aberration (Z40) were moderately correlated (Pearson’s
zone by the method of converting elevation data to correlation coefficients r = 0.44, 0.65, and 0.34,
corneal aberrations described by Wang et al., 8 respectively). The RMSs of higher order aberrations
Aberrations associated with Zernike coefficients (HOAs, 3rd to 6th orders), spherical aberrations, and
between the 3rd and 6th orders were grouped as coma were moderately correlated between right and
higher-order aberrations (HOAs) and used to left eyes (in MZ, Pearson’s correlation coefficients
calculate the root mean square (RMS) wavefront r = 0.45, 0.62 and 0.28, respectively; in DZ, Pearson’s
errors: total RMS of 3rd through 6th orders, RMS of correlation coefficients r = 0.73, 0.54 and 0.50,
spherical aberrations (SA) (square root of the sum of respectively; all p<0.05). Among Zernike coefficients,
the squared coefficients of Z40 and Z60), RMS of coma the spherical aberrations (Z40) and secondary spherical
( square root of the sum of the squared coefficients aberration (Z60) were moderately correlated at the
of Z3-1, Z31, Z5 and Z5-1) and RMS of 3rd-, 4th-, 5th-, same right eyes in MZ twin pairs (Pearson’s correlation
and 6th-order aberrations as previously described. 8 coefficients r = 0.46 and 0.53), whereas horizontal coma
Pearson’s correlation analysis was performed to (Z31) and secondary spherical aberration (Z60) were
investigate the symmetry of the refractive errors, highly to moderately correlated at the right eyes in
corneal curvatures and corneal aberrations between DZ twin pairs (Pearson’s correlation coefficients r= 0.79
twins. Heritability (h 2 ) was calculated from the and 0.42) (Table 9.3). In particular, there was a
equation ”(rMZ-rDZ)×2” which “r” is correlation significant difference in the spherical aberration (Z40)
coefficients, MZ is monozygotic twins and DZ is between MZ and DZ groups (0.46 vs 0.18).
dizygotic twins. This estimate is nearer to the broad Interestingly, the RMSs of HOAs, SA and coma were
sense-sense heritability than it is to the narrow-sense moderately correlated at the same right eyes within
heritability.15 both twin pairs (in MZ, Pearson’s correlation
Zernike polynomial coefficients (Z3-1, Z31, Z40 Z51, coefficients r = 0.45, 0.62, 0.28, respectively; in DZ,
Z5 , and Z60) between right eyes and left eyes in MZ
-1
Pearson’s correlation coefficients r = 0.40, 0.40, 0.30,
and DZ twin pairs were presented in Table 9.2. respectively; all p<0.05). In particular, there was a
Vertical coma (Z3 -1), horizontal coma (Z 3 1 ), and significant difference in the RMS of spherical aberration
spherical aberration (Z40) were the major components between MZ and DZ groups (0.62 vs 0.40).
of the higher-order aberrations. From the Zernike
coefficients, the values of root mean squares (RMS) of COMPARISON OF ABERRATIONS BETWEEN BOTH
anterior corneal aberrations within MZ, DZ twin pairs EYES
were calculated, the values were highest for 3rd order
terms and progressively decreased up to the 6th order. In 2001, Porter et al. studied monochromatic
The mean value of total HOAs (3rd to 6th order) at aberrations in 109 normal human eyes and found that
 The Genetic Effect on Anterior Corneal Aberration 75
Table 9.1: Values of root mean squares (RMS) of anterior corneal that there are significant correlations of 3 rd and
surface aberrations within MZ and DZ twin Pairs
4th orders between right and left eyes.8 Except for
Order Eye MZ DZ
3rd order Right 0.17±0.10 (0.15-0.20) 0.19±0.20 (0.11-0.27)
spherical power, total astigmatism, mean corneal
Left 0.18±0.073 (0.16-0.20) 0.20±0.12 (0.15-0.25) curvatures and cornel astigmatisms, our data also
4th order Right 0.084±0.027 (0.077-0.091) 0.110±0.121 (0.060-0.164)
Left 0.085±0.039 (0.076-0.095) 0.088±0.033 (0.074-0.102) demonstrated the existence of mirror symmetry of
5th order Right
Left
0.012±0.0079 (0.010-0.014)
0.013±0.011 (0.010-0.016)
0.021±0.042 (0.0034-0.039)
0.021±0.026 (0.010-0.032)
spherical aberration (Z40) and secondary spherical
6th order Right 0.0034±0.0023 (0.0029-0.0039) 0.0042±0.0047 (0.0022-0.0062) aberration (Z60), total HOAs, 3rd-, 4th-, 5th-, and 6th-
Left 0.0033±0.0021 (0.0028-0.0038) 0.0046±0.0040 (0.0029-0.0063)
RMS of Right 0.27±0.13 (0.23-0.30) 0.33±0.37 (0.18-0.48) order aberrations, RMS of SA and RMS of coma
HOA Left 0.28±0.10 (0.25-0.37) 0.32±0.17 (0.38-0.24)
RMS of Right 0.068±0.029 (0.061-0.075) 0.070±0.027 (0.059-0.081)
between right and left eyes of each individual
SA Left 0.068±0.030 (0.061-0.075) 0.074±0.030 (0.061-0.087) (Pearson’s correlation coefficients from 0.28 to 0.84).
RMS of Right 0.140±0.085 (0.12-0.16) 0.13±0.10 (0.088-0.17)
Coma Left 0.142±0.074 (0.12-0.16) 0.14±0.07 (0.11-0.17) Therefore, the datas also demonstrated the symmetry
Values are means± SD, (95%CI (ìm)) of refractive variables, corneal curvatures, and
anterior corneal aberrations.
Table 9.2: Intrapair correlations of Zernike coefficients and RMSs of
anterior corneal HOAs between right and left eyes of each subject of PREVIOUS STUDIES OF HERITABILITY ON
twin pairs
REFRACTION
Order MZ p value DZ p value
-1
Z3 0.43 <0.001 0.44 0.043 Heritability, defines as the proportion of phenotypic
Z 31 -0.20 0.111 -0.35 0.113
Z 40 0.41 0.001 0.34 0.116 variance attributable to genetic variance, was
Z5-1 0.51 <0.001 -0.60 0.003 described as one of standard quantitative genetic
Z 51 -0.53 <0.001 0.65 0.001
Z 60 0.65 <0.001 0.28 0.210 methods by Neale and Cardon.15 Due to heritability
3rd order 0.33 0.006 0.70 <0.001 is a proportion, its value ranges from 0.0 ( no genetic
4th order 0.65 <0.001 0.63 <0.001
5th order 0.47 <0.001 0.84 <0.001
factor contributed to phenotype) to 1.0 (only genetic
6th order 0.37 0.002 0.78 <0.001 factor contributed to phenotype). Usually, the
RMS of HOA 0.45 <0.001 0.73 <0.001
RMS of SA 0.62 <0.001 0.54 0.010
estimates of heritability are in the moderate range of
RMS of Coma 0.28 0.019 0.50 0.017 0.30 to 0.60. Previous studies of ocular refraction and
its component have shown a high degree of
Table 9.3: Intraclass correlations of Zernike coefficients and RMSs
heritability.12,18 Based on the hypothesis of the equal
of anterior corneal HOAs at right eyes between twin pairs
Order MZ p value DZ p value
environment influences on the twin study, we applied
Z3 -1
0.079 0.666 -0.21 0.529
the equation ”(rMZ-rDZ)×2” which r is correlation
Z 31 -0.37 0.036 0.79 0.004 coefficients, MZ is monozygotic twins and DZ is
Z 40 0.46 0.008 0.18 0.595
dizygotic twins to estimate heritability (h 2 ). In
Z5-1 -0.18 0.323 0.72 0.012
Z 51 -0.23 0.208 -0.48 0.140 previous our study, we have shown that disruption
Z 60 0.53 0.002 0.42 0.210 of the tear film increases anterior corneal higher order
3rd order 0.32 0.006 0.35 0.002
4th order 0.65 <0.001 0.49 <0.001 aberrations, especially for coma and trefoil. 196
5th order 0.47 <0.001 0.45 <0.001 Therefore, we reason why the negative heritability
6th order 0.37 0.002 0.35 <0.001
RMS of HOA 0.45 <0.001 0.40 <0.001 of 3rd order and RMS of coma may be due to
RMS of SA 0.62 <0.001 0.40 0.010 unpredictable change in tear film.
RMS of Coma 0.28 0.019 0.30 0.017
For Zernike coefficients, negative correlations
there was a random variation in aberrations from were found in vertical coma, horizontal coma,
subjects to subjects.16 Aberrations in the right eye were secondary vertical coma and secondary horizontal
significantly correlated with counterparts in the left coma. Therefore, heritability was not applied to these
eye. In addition, Castejon-Mochon and colleagues Zernike conefficients due to improper assumption on
found a slight tendency for mirror symmetry between the calculation of heritability. Spherical aberrations
both eyes.17 In the report of Wang et al. they found (Z40) showed a significant heritability (h2 =0.58) after
76 Mastering Advanced Surface Ablation Techniques
excluding the negative correlations of other Zernike diameter.17 The Orbscan II system is a Placido-based,
terms (Table 9.4). Although only RMS of 4th order slit scanning instrument that projects 20 slits from
aberration and spherical aberration showed a genetic the right and 20 slits from the left during each
predisposition (h2 =0.32 and 0.44), other anterior 2.1 second scan at a fixed angle of 45 degrees onto
corneal aberrations did not present genetic effects in the cornea. Each slit was captured by video camera
our results. Since RMS of spherical aberration and used to construct mathematical representations
represented the combination of two aberration of the ture topographic surfaces. Cairns et al showed
modes (Z40 and Z60), and both of them were located that in comparison with Talysurf analysis as the “gold
in the central part of wavefront plane. It suggests standard”, anterior elevation differed by less than
that genetic factors may have stronger effect on these 0.2 μm ± 0.32 (SD) centrally and 0.7 ± 0.41 μm in the
modes and the central part of wavefront plane is periphery.20,21 Cairns’s study highlights the extreme
predominantly affected by genetic factors. Spherical accuracy of Orbscan II in test surface. Carvalho also
aberration (Z40) is the major component of RMS of clearly indicated that conventional Placido-based
4th order aberration and spherical aberration. VKS systems are sufficiently precise (given corneal
Therefore, both RMS of 4th order aberration and profile algorithms with precisions in the order of
spherical aberration showed meaningful indices of 0.5 μm) for determination of wave-front aberrations
heritability. associated with the corneal surface, even the skew
Table 9.4: The correlations and heritability (h2) of refractive errors, ray ambiguity and the skew ray error.11 However,
Zernike coefficients and anterior corneal aberrations the ability of Orbscan II to accurately map the surfaces
Measure MZ DZ Heritability of human cornea remains unknown due to uncertain
(correlations) (correlations) (h 2 )
variances like microsaccades, light scatter, tear
Z3-1 0.079 -0.21 -
Z 31 -0.37 0.79 - instability and surface irregularities.
Z 40 0.46 0.18 0.56 In conclusion, the twin study suggest genetic
Z5-1 -0.18 0.12 -
Z 51 -0.23 -0.48 - predisposition toward the corneal spherical
Z 60 0.53 0.42 0.22 aberrations. These results offer exciting prospects in
3rd order 0.32 0.35 -0.06
4th order 0.65 0.49 0.32
the understanding of the mechanisms and gene-
5th order 0.47 0.45 0.04 environment interactions in the distribution of
6th order 0.37 0.35 0.04
anterior corneal aberrations.
RMS of HOA 0.45 0.40 0.10
RMS of SA 0.62 0.40 0.44
RMS of Coma 0.28 0.30 -0.04 REFERENCES
2
h =(rMZ-rDZ) × 2
1. Liang J, Williams DR. Aberrations and retinal image quality
of the normal human eye. J Opt Soc Am A 1997;14:2873-
LIMITATIONS OF MEASUREMENTS ON ANTERIOR 83.
CORNEAL ABERRATIONS 2. Liang J, Williams DR. Aberrations and retinal image quality
of the normal human eye. J Opt Soc Am A Opt Image Sci
Videokeratoscopes, based on the Placido disk Vis 1997;14:2873-83.
3. Patel S, Anderson L, Cairney K. The refractive index of
principle, is important to estimate the corneal
tears in normals and soft lens wearers. Adv Exp Med Biol
aberrations. One of the major limitations on the 1994;350:417-20.
precision of the corneal wave aberration is accuracy 4. Applegate RA, Hilmantel G, Howland HC, et al. Corneal
of videokeratoscope devices to measure the surface first surface optical aberrations and visual performance. J
Refract Surg 2000;16:507-14.
elevation. Therefore, the height resolution is very 5. Tscherning M. Die momochromatischen aberrationen
important in studying wavefront aberrations with desmenschlichen Auges. Z Psychol Physiol Sinne
VKC instrument. Guirao et al. have shown the efficacy 1894;6:456-71.
6. Guirao A, Artal P. Corneal wave aberration from
of corneal aberration estimation for commercial
videokeratography: accuracy and limitations of the
Placido-based videokeratography (VKS) with an procedure. J Opt Soc Am A Opt Image Sci Vis 2000;17:955-
accuracy of 0.05-0.2 μm for a pupil 4-6mm in 65.
 The Genetic Effect on Anterior Corneal Aberration 77
7. Ahlbom A, Lichtenstein P, Malmstrom H, et al. Cancer in 14. Carvalho LA. Absolute accuracy of Placido-based
twins: genetic and nongenetic familial risk factors. J Natl videokeratographs to measure the optical aberrations of
Cancer Inst 1997;89:287-93. the cornea. Optom Vis Sci 2004;81:616-28.
8. Barbero S, Marcos S, Merayo-Lloves J, Moreno-Barriuso 15. Falconer DS, Mackay TFC. Introduction to Quantitative
E. Validation of the estimation of corneal aberrations from Genetics. 4th ed. Essex, England: Longman; 1996:172.
videokeratography in keratoconus. J Refract Surg 16. Porter J, Guirao A, Cox IG, Williams DR. Monochromatic
2002;18:263-70. aberrations of the human eye in a large population. J Opt
9. Thibos LN, Applegate RA, Schwiegerling JT, Webb R. Soc Am A Opt Image Sci Vis 2001;18:1793-803.
Standards for reporting the optical aberrations of eyes. J 17. Castejon-Mochon JF, Lopez-Gil N, Benito A, Artal P.
Ocular wave-front aberration statistics in a normal young
Refract Surg 2002;18:S652-S660.
population. Vision Res 2002;42:1611-7.
10. Schwiegerling J, Greivenkamp JE. Using corneal height
18. Sorsby A, Sheridan M, Leary GA. Refraction and its site
maps and polynomial decomposition to determine
components in twins. Vol. 303. London, UK: Medical
corneal aberrations. Optom Vis Sci 1997;74:906-16.
Research Council, Special Report Series, HMSO; 1962.
11. Wang L, Dai E, Koch DD, Nathoo A. Optical aberrations 19. Lin YY, Carrel H, Wang IJ, et al. Effect of tear film break-
of the human anterior cornea. J Cataract Refract Surg up on higher order aberrations of the anterior cornea in
2003;29:1514-21. normal, dry, and post-LASIK eyes. J Refract Surg
12. Hammond CJ, Snieder H, Gilbert CE, Spector TD. Genes 2005;21:S525-S529.
and environment in refractive error: the twin eye study. 20. Cairns G, McGhee CN, Collins MJ, et al. Accuracy of
Invest Ophthalmol Vis Sci 2001;42:1232-6. Orbscan II slit-scanning elevation topography. J Cataract
13. Walker AH, Najarian D, White DL, et al. Collection of Refract Surg 2002;28:2181-7.
genomic DNA by buccal swabs for polymerase chain 21. Cairns G, McGhee CN. Orbscan computerized
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Perspect 1999;107:517-20. Cataract Refract Surg 2005;31:205-20.
78 Mastering Advanced Surface Ablation Techniques

CHAPTER Comparative Profile of Methods

10 for IOL Power Calculation After
Incisional and Photoablative
Refractive Surgery

Antonio Calossi, Massimo Camellin (Italy)

CORNEAL POWER AFTER KERATOREFRACTIVE according to the different manufacturers) 15 that

SURGERY considers the refractive effect of the corneal posterior
surface of an average eye, provides the dioptric power
With the advent of keratorefractive surgery, more
of the measured cornea. After refractive surgery, two
and more patients undergoing cataract surgery with
phenomena occur that render this method inapplicable:
intraocular lens (IOL) implantation have previously
(1) the corneal asphericity is considerably modified:
undergone some type of refractive surgery. In these
e.g. in myopic correction, asphericity is often
cases, no particular technical difficulty exists when
reversed, in a more or less accentuated way,
performing cataract surgery; however, the IOL power
depending on the type of surgery, and the central
is usually inaccurate.1-13
part of the cornea is flatter than the one measured
The problem is that after keratorefractive surgery,
by the keratometer; and (2) in laser ablative surgery,
conventional keratometry provides incorrect corneal
the ratio between the modified anterior corneal
power values. In the specific case of refractive surgery
surface curvature and the unaltered posterior surface
for myopic correction, keratometry readings
changes, making the commonly utilized keratometric
overestimate the corneal power. In this case, by using
refractive index no longer valid.
conventional measuring methods and calculation
formulas, the resulting IOL power is too low and an Change of Corneal Asphericity
unintentional postoperative hyperopic refraction After keratorefractive surgery for myopic correction,
results. In hyperopic refractive surgery, the reverse the optical zone of the cornea becomes flatter. Usually,
occurs, i.e. corneal power is underestimated and IOL inside the pupillary area the central cornea becomes
power is higher than necessary with the consequence flatter than the portion of cornea that lies over the
of induced myopia after cataract surgery.14 marginal zone of the pupil, so its prolate shape
The origin of the error lies in a series of becomes oblate (with reverse asphericity) (Figures
approximations made in the measurement of corneal 10.1 and 10.2). In hyperopic correction, the cornea
power. Usually this value is an outcome of only the becomes even more prolate and asphericity increases.
anterior corneal surface measured by a keratometer. This phenomenon increases with the amount of
This instrument measures the sagittal curvature in a surgical correction and is more evident in incisional
small paracentral area and, by using a fictitious surgery or laser ablative surgery with a small optical
refractive index (variable from 1.3315 to 1.3375, zone.16-22
 Comparative Profile of Methods for IOL Power Calculation After Incisional 79

Figure 10.1: In a prolate cornea the marginal radius of curvature is longer than the
central one, while in oblate shape the marginal radius is shorter than the central one

Figures 10.2A: The graph shows the sagittal (axial) curvature profile of an unoperated normal cornea

Figures 10.2B: Postmyopic LASIK sagittal curvature profile. As usually in conventional treatments, inside the
pupillary area the central cornea has become flatter than the portion of cornea that lies over the marginal zone
of the pupil
80 Mastering Advanced Surface Ablation Techniques
Keratometers measure a portion of cornea that
does not include the pupillary central area. The
measured area is limited to the portion of cornea that
reflects the keratometric targets; it is constituted by
a circular crown with a diameter that varies between
approximately 2 and 4 mm and a width that varies
between 0.1 and 0.4 mm according to the constructive
characteristics of the keratometer and to the measured
surface curvature.23-25 (Figure 10.3) With the same
keratometer on a steeper cornea, a portion of cornea
closer to the center is measured, whereas on a flatter
cornea a more peripheral zone is measured. Due to
the Stiles-Crawford effect (SCE) of the first kind,25-27
Figure 10.3: The colored area represents the zone of the cornea
the area of the cornea that covers the central pupillary utilized for keratometry measurements and for computerized
zone gives a brighter image than the one formed by videokeratography Sim-K index. As we can see, the central pupillary
area is not measured
the portion of the cornea that covers the marginal
zone of the entrance pupil: if the central ray is
perceived as having a brightness of 100%, a ray 1
mm off-center appears 93% as bright, 2 mm off-center
it appears 71% as bright and 3 mm off-center only
41% as bright (Figure 10.4), so the central cornea,
which is not measured, has a more dominant role in
the formation of the foveal image in respect to the
portion of cornea that is usually measured by
keratometers. In a normal cornea with an average
asphericity this phenomena is of little impact because
the sagittal curvature varies slightly from the center
to the keratometer measuring area, 23 but when
asphericity has high absolute values, differences
between central and paracentral curvature cannot be
neglected (Figures 10.5 to 10.7). In our opinion, it is Figure 10.4: The area of the cornea that covers the central pupillary
zone gives a brighter image than the one formed by the portion of the
for these reasons that the measurement of the corneal cornea that covers the marginal zone of the entrance pupil. The graph
curvature for optical purposes should provide the represents the relative efficiency of the entrance pupil. (After Stiles
WS and Crawford BH, 1933)25
average value, weighted according to SCE (i.e. a
gaussian weighing), of the whole corneal area that lensmeter does for ophthalmic lenses, but only the
covers the entrance pupil. For the reasons we have curvature of its anterior surface, from which the
just described, this measurement cannot be dioptric power of the whole cornea is derived.
performed by conventional keratometers, but can be Instruments such as keratometers, autokeratometers
obtained by computerized videokeratographs. and computerized videokeratographs based on the
Placido principle follow the same concept: the anterior
Change of Ratio between Anterior and Posterior curvature of the cornea is measured, then the radius
Corneal Surfaces is converted into diopters by using the following
Clinical measurement of corneal power usually is paraxial equation:
performed by instruments that do not measure the n–1
P= (1)
corneal power directly, in the same way that a r
 Comparative Profile of Methods for IOL Power Calculation After Incisional 81

B
Figure 10.5: Instantaneous, axial, altimetric and refractive corneal maps and sagittal curvature profile of a cornea post a high myopic PRK
treatment. In this case the average simulated keratometry (sim-K) is 36.56 D, while the mean pupil curvature is 32.25 D
82 Mastering Advanced Surface Ablation Techniques

B
Figure 10.6: Instantaneous, axial, altimetric and refractive corneal maps and sagittal curvature profile of a cornea post a hyperopic
LASIK treatment. In this case the average simulated keratometry (sim-K) is 45.38D, while the mean pupil curvature is 46.50D
 Comparative Profile of Methods for IOL Power Calculation After Incisional 83

B
Figure 10.7: Instantaneous, axial, altimetric and refractive corneal maps and sagittal curvature profile of a cornea post a radial
keratotomy treatment with a high central flattening effect. In this case the average simulated keratometry (sim-K) is 35.74, while the mean
pupil curvature is 32.75
84 Mastering Advanced Surface Ablation Techniques
where P is the corneal power (in diopters) For simplify, we shall try to reason following Gauss’s
r is the corneal radius (in meters) paraxial approximation, where the rays from the object
1 is the air refractive index to the image lie close to the principal axis and form
n is the corneal refractive index. small angles with the axis. If we accept this
Because the principle of all current instruments is approximation, we can apply to the cornea the
to consider the cornea as a single refractive surface, paraxial equation of the spherical diopters:
to compensate the effect of the posterior surface and
corneal thickness, instead of using the real refractive P= (3)
index of the corneal tissue, a fictitious keratometric where P is the power of the dioptric surface (in
index (lower than the one of the epithelium and of diopters)
the stroma) is used. The keratometric refractive index r is the power of the dioptric surface (in diopters)
usually is considered constant for all cases and is n1 is the refractive index of the first medium
obtained by calculating the average ratio between n2 is the refractive index of the second medium
the anterior and posterior corneal surface of an We can, therefore, calculate the power of the
average schematic eye. 28 This approximation is anterior surface, of the posterior surface and,
acceptable for an average normal eye but may cause following the laws of paraxial optics, vertex and
intolerable errors in some cases. effective corneal powers.29 In the Gullstrand “exact”
Schematic Eye No.1,28 the cornea is schematically
THEORY reproduced as a system formed by two spherical
Gullstrand’s Schematic Eye surfaces 500 μm apart, the anterior face has a
curvature of 7.70 μm and the posterior surface of
As in all dioptric compound systems, corneal power 6.80 mm; the refractive index of the air (n1) is 1.000,
is function of the curvature of the surfaces that the one of the cornea (n2) is 1.376, and the one of the
separate its optical media and of their refractive index. aqueous (n3) is 1.336. The tear film is ignored, since
The optical media that condition the corneal dioptric it is like a thin lamina with parallel surfaces with
system are: air, tear film, corneal tissue, and aqueous power equal to zero. Applying formula (3) we obtain
humor. In order to have an accurate study of corneal an anterior corneal power (P1) of +48.83 D and a
dioptrics, we should perform a complete ray tracing posterior power (P2) of –5.88 D. When two dioptric
applying Snell’s law: surfaces of power P1 and P2 separated by a distance t
are combined, we can calculate the equivalent power
= (2)
by applying the following formula:
where i is the angle of incidence of a light ray
Pe = P1 + P2 = – P 1 P2 (4)
r is the refraction angle
n 1 is the refractive index of the incident ray In this case the corneal equivalent power is +43.05 D.
medium If we subsequently simplify our corneal model
n 2 is the refractive index of the refracted ray approximating it to a single surface system, by
medium. resolving the inverse formula of (1) we can calculate
In order to apply Snell’s law, we must know the the keratometric refractive index in order to obtain
refractive indexes of the various optical media, the the same equivalent power of the two-surface model:
profile of the separating surfaces, and the distance n=rP+1 (5)
between the surfaces. Since it is not possible to Being r = 7.70 mm and P = + 43.05 D we obtain an
measure directly all these quantities in a living eye, equivalent refractive index (n) of 1.3315.
we can use a geometric model. This model should This keratometric refractive index value is purely
represent with sufficient precision the real eye, but fictitious and does not represent any real optical
for a simple model some approximations are needed. medium present in the eye, so Gullstrand proposed
 Comparative Profile of Methods for IOL Power Calculation After Incisional 85
a simplified Schematic Eye No.2, 28 with a single cornea, we must consider the dioptric effect of the
corneal surface and as refractive index the one of the anterior surface only, i.e. for ablation calculations and
aqueous: 1.336. In order to maintain the same dioptric variation estimates due to laser ablation
equivalent power of the exact Schematic Eye No. 1, refractive surgery, the refractive index of the corneal
Gullstrand modified in this model the corneal epithelium or stroma of 1.376 should be used in
curvature radius from 7.70 to 7.80. Normally, when converting radius to optical power values.34-36
we perform a keratometry, we do not compensate
the radius in this way, so by using a keratometric The Real Eye
index of 1.336 we cause an average error of 0.59 D What we have until now described is true for a real
(Table 10.1). eye only if the relation between its posterior corneal
If in Gullstrand exact Schematic Eye No.1, instead curvature and anterior one is equal to 6.80/7.70. In
of considering the effective power (Pe) of (4), we this case, utilizing a keratometric index of 1.3315 we
calculate the back vertex power (P v ), with the can approximate the cornea to a model with an only
following equation: surface and obtain the same power equivalent to a
n two surface model without adjusting the radius.37
Pv = P2 + –— (6)
n Between the real eyes there are individual variations
–— – t in corneal thickness and ratio between posterior and
P1
anterior corneal curvature,38-41 when this relation
We obtain a corneal power of +43.83 D. In this between the two curvatures changes in a significant
case, applying again (5) we obtain an equivalent way, we cannot use a constant keratometric index to
refractive index of 1.3375. This keratometric convert millimeters in diopters.
refractive index was initially proposed by Javal and A particular case is the cornea treated with laser
Schjötz30 and is still nowadays probably the most ablative refractive surgery. In this case only the
diffused one. This value is very close to the real anterior curvature of the cornea is modified, while
aqueous humor and tear film index and furthermore the posterior surface remains ideally unchanged
it yields the simple relation 7.50 mm = 45.00 D. (Figure 10.7). This way the relation between posterior
Nevertheless, we must consider the focal distances curvature and anterior curvature is changed, so a
from the posterior surface of the cornea and not from keratometric index that would have been valid before
its anterior vertex otherwise, in an average eye, we surgery cannot be valid after the treatment. Our
have an error of 0.78 D (Table 10.1). purpose was to verify possible differences in the
Table 10.1: Keratometric power for radius = 7.70 mm and various dioptric power.
keratometric refractive indexes for the Gullstrand “exact” Schematic
Eye. Delta K is the difference in power in comparison with the real one
calculated with index = 1.3315. KERATOMETRIC REFRACTIVE INDEX AFTER
Corneal radius (mm) 7.70 7.70 7.70 7.70 LASER ABLATIVE REFRACTIVE SURGERY
Keratometric index 1.3315 1.3360 1.3333 1.3375
Corneal power (D) 43.05 43.64 43.29 43.83 In order to calculate the variations of refractive index
Delta K (D) 0.59 0.24 0.78
necessary to maintain a correct equivalent power, in
In some cases a keratometric index of 1.333 has the Gullstrand Schematic Eye, we have calculated the
been proposed.31-33 This value is equivalent to 4/3 curvature change of the corneal anterior surface
and consents more simple calculations. This value is needed to obtain a certain amount of refractive
relatively close to the equivalent refractive index; in correction on the spectacle plane, so, given a constant
an average eye creates an overestimate of the real optical zone, we have calculated the change of corneal
corneal power of 0.24 D. thickness consequent to curvature change due to laser
We must remember that when, instead of ablation; maintaining the corneal posterior surface
evaluating the absolute dioptric power of the whole unvaried, we calculated the equivalent corneal power,
86 Mastering Advanced Surface Ablation Techniques
and then finally obtained the equivalent refractive
index as a function of the surgical induced refractive
change (SIRC).
Since with this type of surgery only the anterior
surface of the cornea is modified, 34 in order to
calculate the change of curvature necessary to obtain
a certain dioptric effect by laser ablative surgery, we
considered the stroma refractive index (n = 1.376)
and, by subtracting the SIRC from the pre-operative
anterior corneal power, by means of (1) we obtained
the post-operative curvature radius. The change of Figure 10.8: Schematic relationship between the anterior and posterior
corneal curvature in a normal unoperated cornea and after different
thickness (Δz) has been calculated with the following types of corneal refractive surgery. After RK and CK we observe an
equation42 which is the basis of the non approximate indirect change of the central anterior corneal curvature. Since no
tissue is removed, it is assumed that the anterior and posterior surface
Munnerlyn formula:34 of the cornea react in an analogous way, and the ratio between the
anterior and posterior corneal curvature remain almost the same. The
a2(ΔP)
Δz = ——— (7) asphericity of the cornea changes proportionally to the curvature
2(n–1) changes. After the laserablative procedures, although the central
anterior curvature changes, the posterior surface should remain
where a is the half diameter of the optical zone, unchanged.
ΔP is the variation of power, and n is the stroma
refractive index. With these values, using (4), we
calculated the effective corneal power, then using (5) Results are reported in Figures 10.8 and 10.9. After
the equivalent refractive index. Finally, we calculated corneal laser ablative surgery, the equivalent
the differences between the corneal power obtained keratometric refractive index approximately
by utilizing a fixed refractive index and the real decreases of 0.001 units per diopter of myopic
corneal power as a function of the SIRC. correction and increases of the same amount in case

Figure 10.9: Keratometric refractive index in function of surgically induced refractive change (SIRC). The
regression curve equation reported on the graph shows that the equivalent keratometric refractive index varies
approximately of 0.001 units per diopter of correction
 Comparative Profile of Methods for IOL Power Calculation After Incisional 87

Figure 10.10: Difference (delta K) between corneal power calculated by using a constant keratometric refractive index and the real
equivalent power calculated in function of surgically induced refractive change (SIRC)

of hyperopic correction. By using a constant refractive index for all cases. This matter has a
keratometric index, in corneas treated with myopic considerable clinical importance in calculating the
laser ablation we have an overestimate of the corneal power of IOL in eyes that have been previously
power, which increases with the operated correction. treated with refractive surgery. Corneas that have
Vice versa, in hyperopic correction, the tendency is been treated with laser ablative refractive surgery
to underestimate. By utilizing a keratometric are a particular case in which errors may become
refractive index = 1.3315, for a surgical correction of particularly significant. After this type of surgery,
–4.00 D, we have an error of 0.50 D, for an SIRC of the anterior surface of the cornea is modified while
–9.00 D the error is 1.00 D and reaches an2.00 D error the posterior surface ideally remains unchanged (even
for a correction of –20.00 D. If, as it usually happens, if bio-mechanic effects may induce a slight posterior
we use a greater keratometric refractive index, the corneal change). In this case, the ratio between
error increases in case of a myopic correction, i.e. anterior and posterior curvature is changed, so a
with a keratometric index = 1.3375 the error is 1 D keratometric refractive index that could have been
for a correction of –2.00 D and goes up to 2.00 D for valid before surgery may not be the same after
a correction of –13.00 D. surgery. 48 Conventional keratometric refractive
Our calculations show that differences between index, after a myopic laser ablation causes an
real corneal power and the power estimated using overestimation of the corneal power, whereas in
conventional keratometric procedures cannot be hyperopic correction, it causes an underestimation.
neglected. The possibility that corneal refractive index Unfortunately, errors due to corneal asphericity
varies through its thickness43, 44 and in relation to changes and those caused by variations in ratio
stroma hydration45-47 could further increase the value between anterior and posterior corneal surface
of the errors we reported. These aspects are usually curvatures always go in the same direction and their
ignored when using a constant keratometric effects are cumulative.
88 Mastering Advanced Surface Ablation Techniques
THE EFFECTIVE LENS POSITION: ANOTHER
SOURCE OF ERROR

Until recently, the attention of cataract surgeons for

the post-keratorefractive eye has mainly been focused
on accurately determining the central corneal power. It
is now becoming more widely understood that a
flattened or steepened central cornea not only renders
keratometry inaccurate, but also causes problems with
many IOL power calculation formulas that in normal
eyes work well.49, 50 When it is entered into a standard
IOL power formula, the post-keratorefractive surgery
Figures 10.11A: The 3 main variables utilized by an IOL power
K readings are not only used as a measure of the corneal calculation formula: corneal power (K), axial length (AL), and the
power but also to calculate the effective lens position effective lens position (ELP). The effective lens position (ELP) is the
estimated postoperative distance between the anterior corneal surface
(ELP) which is the estimated postoperative distance and of the principal plane of the IOL
between the anterior corneal surface and of the principal
plane of the IOL (Figure 10.11A). This measurement is
also referred to as the pseudophakic anterior chamber
depth. Modern, 2-variable IOL power calculation
formulas51-55 use different methods to calculate the
effective lens position; however, except for the Haigis
formula,56, 57 which does not use corneal power readings
to predict postoperative ELP, they all use the
keratometric values in their calculations. In normal
cases, a flatter corneal measurement signifies a shallower
anterior chamber depth. With a low central corneal
power the formula makes the assumption that the IOL
following cataract surgery will end up sitting closer to Figures 10.11B: If the ELP is incorrectly assumed falsely shallow, a
deeper postoperative ELP occurs that induced a hyperopic error
the cornea than normal and call for less power (Figure
10.11B). The contrary occurs with a high corneal power
(Figure 10.11C). After keratorefractive surgery, the
anterior corneal surface is flattened for myopic
correction, or steepened for hyperopic surgery, but the
effective lens position is unaltered. And the flatter or
steeper the cornea, the bigger a problem this
becomes.49, 50, 58, 59 Unless a correction is made for this
situation, the artifact of centrally altered Ks following
keratorefractive surgery will have these formulas
incorrectly assume a falsely shallow or deep post-
operative ELP. The end result is that without a special
correction, 2-variable formulas following kerato-
Figures 10.11C: If the ELP is incorrectly assume falsely deep, a
refractive surgery will recommend less IOL power after shallower postoperative ELP occurs that induced a myopic error
myopic surgery and more IOL power after hyperopic
surgery than is actually required. Furthermore, its effect power estimation. The Aramberri double-K method49
is cumulative to the error produced by the corneal was established specifically to correct for this problem.
 Comparative Profile of Methods for IOL Power Calculation After Incisional 89
INTRAOCULAR LENS POWER CALCULATION the refractive procedure from the keratometric
AFTER REFRACTIVE CORNEAL SURGERY diopters measured before refractive surgery:
K = Kpre + Rxpre – Rxpost
Several methods have been proposed for calculating
where, K is the actual value to be used; Kpre is the
corneal refractive power in patients who have
preoperative keratometry; Rxpre is the preoperative
undergone corneal refractive surgery, including
spherical equivalent refraction; Rx post is the
(1) empirical adjustment;4,60 (2) refraction-derived
postoperative spherical equivalent refraction. The
method;50, 61 (3) clinical history method;62-64 (4) contact
refractive change must be calculated at the corneal
lens overrefraction; 63,64 (5) computerized video-
plane with correction for the vertex distance from
keratography (CVK); 65-72 (6) consideration of
the spectacle plane. Both Holladay and Hoffer
posterior corneal curvature;48, 73, 74 (7) method based
recommend against vertex-correcting the refractive
on correlation between axial eye length and corneal
errors due to published reports of improved results
radius correcting factor; 75 (8) method based on
without it. In their clinical series, Odenthal et al 88
correlation between axial eye length and a theoretical
also found not vertex-correcting more accurate.
variable keratometric refractive index;76 (9) method
However, Seitz et al published a case report of
based on correlation between actual corneal curvature
cataract surgery after a PRK for excessive myopia of
and corneal power correcting factor;50 (10) calculating
–24 D in which they demonstrated that pure
IOL power in a standard fashion and modifying the
subtraction of the spherical equivalent change at the
final value of the IOL as a function of the SIRC;14, 77, 78
spectacle plane (without vertex correction) from the
(11) using a variable keratometric refractive index
corneal power value before refractive surgery has to
that is a function of SIRC; 79-83 (12) and aphakic
be avoided because it results in a far too small corneal
intraoperative refraction techniques.84-87
power.89 In this case, they found that subtraction of
24% of the refractive change at the spectacle plane
Empirical Method
from the actually measured corneal power before
On patients that have previously undergone radial cataract surgery gave the best IOL power prediction
keratotomy, Lyle and Jin 4 have proposed the with the Haigis56,57 formula.
subtraction of a fixed value of 1 D from usual In theory, this method is formally correct;
keratometric readings (adjusted K) however, sometimes it cannot be adopted because
Kadj = K – 1 D the required data are not always available. The
where Kadj is the adjusted keratometric reading required information is the pre-operative refractive
and K is the average of keratometric reading, and keratometric data and post-operative refraction
moreover to use an average result between the data unaffected by change in lens power due to
Binkhorst and Holladay formulas. Jin et al60 proposed cataract. Each diopter of error in evaluating variations
the same approach for eyes with previous myopic of refraction due only to refractive surgery causes
LASIK. 1D of refractive error after IOL implantation. 90
Although this approach may reduce the chance of Furthermore, in the time between refractive surgery
post-operative hyperopia, we believe it is over- and cataract, there should be no change in axial length.
simplified and does not allow calculation of individual A variant of the clinical history method was
differences due to the type and amount of surgery. described by Ladas and Stark,91 Walter et al92 and by
Sambare et al.93 Following this approach, one simply
Clinical History Methods calculates IOL power as if the patient had not had corneal
This method, first published by Guyton 62 and refractive surgery, targeting the patient’s original
Holladay 63 and later termed as ‘clinical history refractive error. Therefore, if the patient was spherical
method’ by Hoffer, 64 consists of subtracting the equivalent -8.00 before refractive surgery, simply use
changes in spherical equivalent refraction induced by –8.00 as the post-implant refractive target. The results
90 Mastering Advanced Surface Ablation Techniques
in their small series are excellent. This variant of clinical Topographic Data
history method is, probably, more simple and do not
Several authors report that analysis of corneal
affect the estimation of ELP described by Aramberri.49
topography describes the changes in corneal
The limitations of this approach are the same described
curvature due to keratorefractive surgery better than
above: (1) pre-refractive surgery data may not be
keratometry.65-72 Modern and up-to-date computer-
available or accurate and (2) the patient’s outcome from
ized video-keratographers allow us to measure the
corneal refractive surgery prior to developing the
anterior surface of the cornea in thousands of points
cataract may not be known or accurate.
in a wide area, and after being computed, all these
data give us many keratometric indices: sim-K, min-
Contact Lens Method K, K at 3, 5 and 7 mm, Kc (central keratometry), ACP
This method, first described by Frederick Ridley of (average corneal power), etc. Therefore, the question
the UK and later by Thomas Soper in the USA, becomes: which of these is the most adequate for
determines the difference between the manifest calculating IOL power? As we have mentioned
refraction with and without a hard contact lens of previously, our opinion is to consider the average
known base curve and subtracts this difference from curvature of the corneal area that covers the entrance
that base curve plus the power of the lens:63, 64 pupil weighted on the SCE. Nevertheless, if we
K = BCcl + Pcl + ORx – Rx convert the corneal curvature in such a way, by using
where, K is the actual outcome keratometric value; a conventional constant refractive index, this analysis
BCcl is the contact lens base curve in diopters; Pcl is may be sufficient for incisional types of surgery,
the lens dioptric power, ORx is the spherical whereas in laser ablative corneal surgery, errors due
equivalent of the over-refraction over the contact lens to variation in ratio between corneal anterior and
and Rx the spherical equivalent of the refraction posterior curvatures still remain.13
without the contact lens. The spherical equivalent of
Consideration of Posterior Corneal Curvature
refraction and over-refraction must be calculated at
the corneal plane with correction for the vertex To accurately determine the total keratometric
distance from the spectacle plane. Recently, a variant diopters of the cornea, the keratometric diopters of
of this method was proposed by Haigis.94 the anterior and the posterior surface of the cornea
From a theoretical point of view, this method is must be known. Seitz and Langenbucher74 proposed
correct, however, in practice, it is a difficult application two methods: (1) Consideration of posterior corneal
due to the inevitable difficulties of performing curvature without measurement of posterior
accurate refractions with and without contact lenses, curvature. In this case, the first step is to calculate
in eyes affected by cataracts. Even with this method, the keratometric diopters using the real refractive
each diopter of error in measurement of refraction index of the cornea (n = 1.376) and add –5.90 D, which
and over-refraction causes 1 D of refractive error after is the theoretical posterior surface power according
IOL implant.90 Zeh and Koch95 analyzed this method to Gullstrand’s model eye, or add –6.20 D, which
in patients with normal corneas and found that the has been found to be the mean keratometric diopters
accuracy decreased with increasing media opacity but of the human posterior surface in vivo assessed
was still acceptable with Snellen acuity of 20/70. though the scanning slit topography technique.96 (2)
Following all forms of ablative keratorefractive Consideration of posterior corneal curvature with
surgery (LASIK, PRK, etc.) a review of the literature measurement of posterior curvature by scanning slit
now suggests that the hard contact lens method may topography device potentially improves accuracy. As
be less accurate than originally thought. For this reported by the same authors, the first method may
reason it is no longer recommended.59 be a cause of error for inter-individual variability in
 Comparative Profile of Methods for IOL Power Calculation After Incisional 91
posterior surface keratometric diopters ranging from radius that gave the same IOL power found before
–2.10 to –8.50 D. Therefore, adding only the mean surgery was calculated for each patient. Then, they
value of the posterior surface keratometric diopters calculated the ratios between the calculated radius
may cause a considerable error in a given patient. and the measured postoperative radius for each
For the second method, the accuracy of presently patient and correlated them with the axial eye length.
available commercial devices to measure the corneal They found quite a good correlation (r2 = 0.4597)
posterior profile by means of scanning split between axial eye length (x) and these ratios (y) with
topography is still not completely validated.97-101 In a linear correlation formula:
a recent paper Cheng and Lam102 reported that after y = 0.0276 x + 0.3635
LASIK the K-value obtained from the Gaussian optics They propose this linear regression formula, or a
formula (CalK) based on postoperative corneal subdivision into classes derived from it, to calculate
topography by Orbscan II (Bausch and Lomb, the correcting factors which, when multiplied by the
Rochester, NY) correlated closely (R=0.967) to that measured postoperative radius, gave the new
obtained from the clinical history method. The limits adjusted radius to use in the SRK/T formula. In our
of agreements using two standard deviations were experience, 79 this method induced a significant
–1.37 D and +1.63 D. Oculus Pentacam (Oculus degree of myopic error. Probably, we observed this
Optikgeräte GmbH, Wetzlar, Germany), which lack of accuracy because the SIRC is not necessarily
images the anterior segment of the eye by a rotating correlated with axial length, though we could expect
Scheimpflug camera, would seem to increase the a greater photoablation in more myopic eyes. In two
accuracy of this method.103, 104 eyes with the same ametropia, the axial length may
Other authors have proposed ultrasound be significantly different. Moreover, preoperative
pachymetric methods for deducing the curvature of ametropia may be the same and the postoperative
the posterior surface of the cornea by measuring the refraction may be different for intentionally planned
curvature of the anterior surface and by taking a ametropia, or overcorrection, undercorrection or
series of measurements of the corneal thickness with regression that may occur. In our group of patients,
an ultrasonic pachymeter.39, 40, 105, 106 We propose this the variance of Rosa’s method is two times greater
method when the patient clinical history is completely than conventional formulas without corneal power
unknown (i.e. no data about the SIRC), or in eyes adjustment, and three times greater than the
that underwent lamellar keratoplasty (LK) or Camellin-Calossi formula; this aspect underlines the
phototerapeutic keratectomy (PTK).79 Emergent very unpredictability of refractive outcome obtainable only
high-frequency (VHF) ultrasound pachymetry 107 correlating corneal power with axial length.
might further increase the accuracy of this method.
Method Based on Correlation between Axial Eye
Method Based on Correlation between Axial Eye Length and a Theoretical Variable Keratometric
Length and Corneal Radius Correcting Factor Refractive Index
Rosa et al75 proposed a method, based on correlation Following a similar way, Ferrara et al76 proposed a
between axial eye length and corneal radius correcting theoretical variable keratometric refractive index
factors to find a way of calculating IOL power that (TRI) that is correlated to axial length as the following
may be independent of preoperative data, in eyes regression formula:
that have developed a cataract after refractive TRI = –0.0006 × AL 2 + 0.0213 × AL + 1.1572
surgery. Prior to, and 1 month after PRK, the SRK/T53 where AL is the axial length. The corneal power
formula was used to calculate IOL power in 88 eyes is calculated with: P = (TRI–1)/r (r = corneal curvature
of 65 patients. IOL power was calculated by using in m). Using this keratometric corrected power, they
the spherical equivalent refraction as target both suggest to calculated IOL power with SRK/T formula
before and after PRK. The mean postoperative corneal similar to that for emmetropia.
92 Mastering Advanced Surface Ablation Techniques
Also for this method, in our experience we observed in a sample of cases. The correlation formula is:
a large unpredictability of refractive outcome.108 As Kc.cd = –5.1625 × RCpost + 82.2603
for Rosa approach, probably, we observed this lack of Where RCpost is the currently measured corneal
accuracy because the SIRC is not necessarily correlated radius with the IOLMaster. Haigis combined this
with axial length, though we could expect a greater regression formula with a correction factor to
photoablation in more myopic eyes. compensate a small residual error, obtaining an
algorithm – the Haigis-L formula – that allows IOL
Method based on Correlation between Actual calculation after myopic laser surgery solely based
Corneal Curvature and Corneal Power on present IOLMaster measurements.
Correcting Factor The advantage of these methods is that they
Shammas et al50 described a method to calculate a require no historical data and have been reported to
corrected keratometric value after myopic LASIK have a low variance when used with either the
when the amount of myopic correction achieved by Holladay II114 and Haigis56, 57 formulas or a 2-variable
the refractive surgery is completely unknown. This formula combined with an Aramberri double K
clinically-derived method uses a regression equation method correction nomogram published by Koch and
to modify the measured post-LASIK K reading. The Wang.109 The drawback of these methods is that they
calculated corneal power is labeled Kc.cd: do not relate to the amount of treatment obtained
Kc.cd = 1.14 × Kpost – 6.8 by LASIK; in other words, a –10.00 D and a –1.00 D
Where Kpost represents the post-LASIK Sim-K value treatment with the same measured postoperative K
obtained from a videokeratograph. readings would have the same adjustment.
Another method of post-LASIK corneal power It must be emphasized that the regression
estimation was originally described by Robert formulas reported here should be applied only in eyes
Maloney and subsequently modified by Koch and that have had laser photoablation, not those that have
Wang.109, 110 Using this technique, the central corneal had prior RK.
power is estimated by placing the cursor at the exact
center of the axial map of the corneal topographer. Modifying the Final Value of the IOL as a Function
of the SIRC
This value is then converted back to the anterior
corneal power by multiplying the axial map central Feiz et al 14 described an IOL power adjustment
topographic corneal power by 376.0/337.5, which is method that one can apply when good historical data
the same as 1.114. An assumed posterior corneal is available. Using this technique, first the IOL power
power of 6.1 D is then subtracted from this product. is calculated using the pre-LASIK keratometry as
Kc.cd = 1.114 × CCP – 6.1 though the patient had never undergone
Where CCP is the corneal power with the cursor keratorefractive surgery. There is no special formula
in the center of the refractive map of the Zeiss correction that needs to be employed for the Feiz et
Humphrey Atlas topographer (Carl Zeiss Meditec, al method. This calculated pre-LASIK IOL power is
Jena, Germany). then increased by the amount of refractive change at
The results of these formulas are similar to that the spectacle plane divided by 0.7. This approach is
of the first method of Seitz and Langenbucher 74 outlined as follows:
described above. IOLpost = IOLpre – (Δ D × 0.7)
Haigis111-113 has proposed a similar method based Where IOLpre is the power of the IOL using pre-
on current Zeiss IOLMaster keratometry. He derived LASIK keratometry, and Δ D is the stable refractive
corneal power from the correlation of the actual change after LASIK at the spectacle plane, then IOLpost
corneal power derived from the refractive history is the estimated power of the IOL to be implanted
method with the measured radii after myopic LASIK following LASIK.
 Comparative Profile of Methods for IOL Power Calculation After Incisional 93
This is the method that is least likely to result in a sometimes result in an under-correction. Ks are
post-operative hyperopic surprise, as the Feiz et al provided by simulated keratometry. The IOL power
method will frequently produce a myopic over- is calculated without a double K method correction.
correction.59 These techniques takes advantage of the fact that
Latkany et al 77 described two methods: (1) there appears to be a linear relationship between the
Calculate IOL power using mean keratometry readings spherical equivalent of the total amount of the stable
obtained using the Javal keratometer and modify it laser vision correction (SIRC) and the over- or under-
by -0.46x + 0.21, where x equals the surgically induced estimation of central corneal power by keratometry.
change in refraction, or (2) calculate IOL power using This works for myopic and hyperopic laser-ablative
the flat K and modify it by -0.47x + 0.85. Masket78 procedures. It must be emphasized that these
proposed a formula that is similar in approach and regression formulas should be applied only in eyes
structure to 2 formulas devised by Latkany: that have had laser photoablation, not those that have
IOL Power Adjustment = –0.326 × LSE + 0.101 had prior RK. The chief weakness of this method is
Where LSE is the total prior laser treatment (SIRC), that the amount of prior laser vision correction must
adjusted for vertex distance, in spherical equivalent. be known.
With these formulas one calculates IOL power in
a standard fashion and simply modifies the final value Refraction-derived Method
of the IOL as a function of the laser ablative-induced
refractive change. The differences between these 3 Shammas et al 50 described a simple method to
formulas are relatively small, and comparisons are calculate a corrected keratometric value after myopic
subject to error since K-readings were obtained LASIK. The calculated corneal power is labeled Kc.cd:
differently in each (IOLMaster for Masket and Javal Kc.cd = Kpost – 0.23 × CRc
keratometer for Latkany et al). However, it is Where Kpost represents the post-LASIK Sim-K value
interesting to look at the values they calculate. For obtained from a videokeratograph and CRc is the
example, for a 3.0 D laser ablative-induced change, amount of correction obtained by the refractive
the modification of IOL power would be 0.87 D with surgery. Shammas suggests decreasing the K reading
Masket’s formula, 1.17 D with Latkany et al’s by a factor of 0.23 for each diopter of myopia
average-K formula, and 0.56 D with Latkany’s flat-K corrected by the refractive surgery. Half of this error
formula. For 8.0 D, the respective values are 2.48, is attributed to changes in the net corneal index of
2.91, and 3.47. An advantage of this method is that refraction after LASIK and the remainder error is
there is less reliance on historical data as the laser ascribed to sampling in the periphery of an aspherical
ablative-induced change is multiplied by a factor that oblate corneal surface.48, 50, 61, 115, 116 Shammas et al
is 0.326 following Masket, and 0.46 or 0.47 following propose to use this method when the pre-LASIK K
Latkany formulas. Therefore, if there is a 1.0 diopter readings are not available but the amount of refractive
(D) error in the historical data regarding the correction is known.
refractive change, this translates to only a 0.32, 0.46 Hill59 proposed a similar regression formula where
or 0.47 D error in IOL selection. the Sim-K suggested by Shammas was replaced by
Hill59, 104 proposed a similar, but slightly different the adjusted effective refractive power (EffRPadj) of
regression formula: the Holladay Diagnostic Summary of the EyeSys
IOL Power Adjustment = –0.4385 × LSE + 0.0295 Corneal Analysis System (EyeSys Technologies,
By this method, the IOL power is calculated using Houston, TX) or the central corneal power value
the Holladay I formula for axial lengths greater than (CCP) obtained averaging the 1, 2, 3 and 4 mm power
23.0 mm and the Hoffer Q formula for axial lengths values of the numerical view of the Zeiss Humphrey
less than 23.0 mm. The SRK/T formula is generally Atlas topographer:
not recommended as the artifact of very flat Ks may Post-LASIK adjusted corneal power = CCP – ΔD × 0.19
94 Mastering Advanced Surface Ablation Techniques
Where CCP = the EffRPadj, or the averaged Zeiss flattening is usually transient, it can be as much as
Atlas central corneal power, and ΔD is the refractive +4.00 D, and is further accentuated by greater than
change after LASIK at the spectacle plane. eight incisions, an optical zone of less than 2.0 mm,
As with the Latkany, Masket, and Hill methods, or incisions that extend all the way to the limbus.59
this technique takes advantage of the fact that there Ahmed and Toufeeq87 described a variant of this
appears to be a linear relationship between the method using intraoperative retinoscopy with high plus
spherical equivalent of the total amount of the stable soft contact lens in estimating corneal power and the
laser vision correction (SIRC) and the over-estimation axial length. A +10 D disposable soft contact lens was
of central corneal power by keratometry after myopic applied on the cornea to minimize retinoscopic error.
correction. It must be emphasized that also the They conclude that intraoperative retinoscopy with a
regression formula reported here should be applied high plus soft contact lens after phacoemulsification is
only in eyes that have had laser photoablation, not useful but not accurate in estimating corneal power or
those that have had prior RK. The chief weakness of axial length of the eye. It should be used cautiously in
this method is that the amount of prior laser vision IOL power calculation as a substitute for standard
correction must be known. keratometry or biometry machines when either of these
is not available or in error.
Aphakic Intraoperative Refraction Techniques As is always the case when there are several
solutions to a problem, none is perfect. Fortunately,
Mackool et al84, 85 described a technique in which the
new methods continue to improve accuracy and, in
cataract is removed and the patient is refracted 30
some cases, reduce the complexity of these
minutes later. Using a nomogram developed by the
calculations.117
authors, the power of the IOL is calculated and the
IOL is then implanted. Ianchulev et al86 described a THE CAMELLIN-CALOSSI FORMULA
similar approach using intraoperative automated
refraction. Both Mackool and Ianchulev et al To minimize the various difficulties mentioned above,
multiplied the measured refractive error by a fixed, we have developed a new formula for calculating
albeit different, value: 1.75 for Mackool and 2.01 for the power of intraocular lenses in eyes that have
Ianchulev et al. A disadvantage of this approach, of previously undergone keratorefractive surgery.79-81
course, is the need to return to the operating room The details of this formula have been described
for IOL implantation. Although this approach may elsewhere.79 Our formula originates from a theoretical
reduce the chance of post-operative surprise when one that we empirically adjusted in two parameters:
keratometry and ultrasonic or optical biometry are 1) the corneal power (Dc); 2) and the prediction of
unreliable, we think that it use over-simplified effective lens position (ELP).
refractive formulas. More sources of error may be The variable ELP is a function of the anterior
the vertex distance dependence of a high aphakic error chamber depth previous to cataract surgery (ACDpre),
and the instability of refraction immediately after of the lens thickness (LThick), of the axial length (AL),
cataract surgery. The instability of post-operative and of the A constant (Aconst) of the IOL. In a different
refraction is particularly important in prior incisional way from other third-generation formulas that often
refractive surgery.6 Patients with previous 8-incision use keratometry as one of the predictors to estimate
radial keratometry will commonly show variable the ELP of the IOL, we have chosen a method
amounts of transient hyperopia in the immediate independent of K,79 since an eye with a 37 D cornea
post-operative period following cataract surgery. This without keratorefractive surgery would not be
is felt to be due to stromal edema around the radial expected to be similar to an eye with a 37 D cornea
incisions, producing a temporary enhancement of with keratorefractive surgery.58 As described above,
central corneal flattening. While this central corneal Aramberri proposed a method in which the SRK/T
 Comparative Profile of Methods for IOL Power Calculation After Incisional 95
formula was modified to use the pre-refractive power calculation compared with keratometric data;
surgery K-value for the ELP calculation and the post- however, clinical experience teaches us that
refractive surgery K-value for IOL power calculation repeatability of measurements is lower with
by the vergence formula. 49 The K pre value was computerized videokeratographs compared with
obtained by keratometry or topography and the Kpost, keratometers and that the possibilities of error
by the clinical history method. Double-K modification increase in short distance CVK.120 For this reason,
of the SRK/T formula improved the accuracy of IOL we suggest an accurate verification of the instrument
power calculation after LASIK and PRK, but it is calibration; we also suggest taking more
sometimes impossible to adopt because the pre- measurements of the same eye, eliminating the
refractive surgery K-value is not always available. extremes and calculating the average of the central
To estimate the real corneal power, we propose values. If the conventional keratometric targets have
to use the average curvature, weighted according to a regular appearance, it is useful to compare
SCE, of the corneal area that covers the entrance keratometric readings with CVK sim-K, and if these
pupil. Then we calculate the real corneal power values greatly differ, new measurements should be
adopting a relative keratometric refractive index that obtained. In our opinion, after radial keratotomy
is a function of the actual corneal curvature (r), of the (RK), conventional keratometric readings should only
kind of keratorefractive surgery, and of the surgically be used when reliable topographic measurements are
induced refractive change (SIRC). not available, because after RK the measurement of
Our formula follows two different procedures the corneal radius with a keratometer is affected by
according to the type of refractive surgery performed errors, due to great variations of corneal asphericity
on the eye for which we must calculate IOL: in and the possibility that the keratometric targets are
incisional surgery, keratometers perform an incorrect reflected out of the optical zone, in an irregular and
measurement of the corneal curvature; whereas in curved area. 72,74,119 After RK, when using
laser ablative surgery, the prime cause of error is the keratometric readings, precision can be improved by
conversion from curvature radius to dioptric power following this procedure: consider the average of the
of the cornea.118 conventional keratometric readings (R), then calculate
the real corneal power according to equation (1) using
Incisional Refractive Surgery an adjusted keratometric refractive index (nadj), which
If the eye for which IOL power is being calculated is a function of the surgical induced refractive.
has undergone incisional refractive surgery or any
Laser Ablative Refractive Surgery
other type of surgery that does not modify the ratio
between anterior and posterior corneal surface, the When the eye for which we must calculate IOL power
average curvature is considered as the radius (r), has previously undergone laser ablative refractive
weighted according to SCE, of the corneal area that surgery or any other kind of surgery that modifies
covers the entrance pupil. This value can be measured the ratio between anterior and posterior corneal
with a corneal topographer that allows this possibility, surfaces, the real corneal power is calculated with
e.g. CSO (CSO Ophthalmic, Florence, Italy), EyeSys equation (1) using a relative keratometric refractive
(EyeSys Technologies, Houston, TX), Keratron index obtained as mentioned above.
(Optikon 2000, Rome, Italy), TMS (Tomey, Japan), The methods described above cannot be used
etc. Then, the real corneal power is calculated using when the patient clinical history is completely
equation (1) adopting a keratometric refractive index unknown (i.e. no data about the SIRC), or in corneas
(n) of 1.332. Our opinion, in accordance with other that have undergone lamellar keratoplasty (LK) or
authors,65, 72, 119 is that in eyes that have previously phototerapeutic keratectomy (PTK). To solve these
undergone incisional refractive surgery, the use of particular cases, we suggest obtaining the curvature
topographic data allows the greater precision of IOL of the posterior surface of the cornea using the
96 Mastering Advanced Surface Ablation Techniques
Camellin Formula.105 As already stated, with this postoperative refraction with the actual measured
formula it is possible to calculate the radius of the postoperative refraction. The postoperative
curvature of the posterior corneal surface on the basis measurements were obtained as part of a routine
of the measurement of the curvature radius of the follow-up, after manifest refraction had stabilized.
anterior corneal surface, central pachymetry and a In the group of laser ablative cases we obtained a
series of pachymetries performed in a 3-mm circular small average hyperopic error (mean +0.28, SD 0.66)
zone. All these measurements are critical and only a not significantly different from zero (p = 0.1274); 60%
few microns can affect the precision of the calculation. of absolute refractive prediction errors were within
Once the radius of the anterior (rant) and posterior 0.50 D, 80% within 1.00 D and 93% within 1.50 D. In
(rpost) curvature (in mm) is known, the real corneal the group of RK cases (n=5) with our formula the
power can be calculated. average error was +0.22 D (range: –1.25 to +1.49 D),
To eliminate the tediousness of the calculations two absolute refractive prediction errors were within
for our formula, a computer program was 0.50 D, and three within 1.00 D. Without adjustment
developed.80,81 of the corneal power, the conventional formulas
demonstrated a significant degree of hyperopic
CLINICAL DATA prediction error.79 (Figure 10.12)
We used our formula to calculate the IOL power in
20 eyes from 12 patients (7 male, 5 female, ranging in
age from 29 to 62 years) that have previously
undergone refractive surgery for myopia: 6 PRK, 6
LASIK, 3 LASEK, and 5 RK. The axial length (ranging
from 25.37 to 32.10 mm, mean 28.60, SD 2.02), the
anterior chamber depth (ranging from 2.00 to 3.90
mm, mean 3.13, SD 0.53) and the lens thickness
(ranging from 3.00 to 5.16 mm, mean 4.21, SD 0.59)
were measured with an ultrasound 10 MHz A-scanner
with a solid transducer probe. The corneal curvature
(ranging from 28.31 to 40.76 D, mean 36.55, SD 3.20)
was measured with a computerized video- Figure 10.12: Comparison of mean spherical equivalent prediction
keratographer EyeTop (CSO Ophthalmic, Florence, error for each formula split by refractive surgery procedure (error
bars: 95% confidence interval). This comparison shows the entity of
Italy), or Keratron (Optikon 2000, Rome, Italy) as the errors we could have obtained using conventional formulas
described above. All eyes underwent cataract (empirical, theoretical, and 2-variable 3rd generation ones as well)
without adjustment of corneal power
extraction and posterior chamber intraocular lens
implantation (A constant ranging from 117.4 to 119.0, As with other published experience,1-13 our results
mean 118.45, SD 0.57). For the majority of our confirm that conventional methods, with whatever
patients, we were not able to calculate the IOL power formula, do not accurately calculate the IOL power after
by utilizing the historical method because at least one keratorefractive surgery. With the Camellin-Calossi
of the three necessary parameters-preoperative formula in eyes that had undergone refractive surgery,
corneal power, preoperative and postoperative we obtained refractive outcomes similar to the ones
refraction before cataract onset- was unknown. The reported by Murphy et al121 in normal eyes with normal
final refractive result was used as a criterion to judge cornea with no previous keratorefractive surgery.
the accuracy and predictability of our approach. With the Camellin-Calossi formula, it has been
Because we did not always aim for emmetropia, we possible to calculate the power of an IOL even in
evaluated the formulas by comparing the predicted those cases in which we did not have all the necessary
 Comparative Profile of Methods for IOL Power Calculation After Incisional 97
data to follow the clinical history method, because may be employed in general even on non-operated
we did not have keratometries previous to refractive eyes. In this last case, a SIRC = 0 neutralizes the
surgery or because we did not know with sufficient personalization of the keratometric index, while the
precision the entity of the surgical induced refractive personalization of ACD remains. In this case, our
change. Following our approach, the keratometric formula becomes similar to the other third-generation
data before refractive surgery are not necessary, theoretical formulas 51-53, 56 whose higher accuracy,
whereas even for our formula, when possible, the in comparison to the previous theoretical or empirical
use of the SIRC value is recommended. formulas, is attributed to their improved prediction
In the Camellin-Calossi formula an error in the of pseudophakic anterior chamber depth, i.e. the
estimate of SIRC produces an error in the refractive effective lens position (ELP).54, 122
outcome lower than the one produced by the clinical The issue of IOL calculation after refractive
history method, because this datum is not directly surgery is becoming an ever-increasing one, as more
used to calculate the corneal power but is used to refractive patients are presenting for cataract surgery.
obtain a relative keratometric index. In this way the Up to now, intraocular lens power calculation after
error in refractive outcome will be only a fraction of corneal refractive surgery has remained
the error in the estimate of SIRC. In one of our cases, challenging.117, 123 Ophthalmologists are significantly
we knew the complete clinical history: the refraction challenged by the expectations of patients associated
pre PRK was: –8.75 –2.00 × 20°, BCVA 20/25, spectacle with any form of refractive surgery; the challenge
spherical equivalent –9.75 D; keratometry: 46.25 / becomes even greater when former refractive
44.25 @ 5°. Twelve months post PRK the refraction surgery patients require cataract surgery. The
was: –0.25 –0.50 × 180°, BCVA 20/25; K 39.25 / 39.75 paradox is that, as a group, postrefractive surgery
@ 180. Two years later he developed the cataract; patients may have unrealistic goals for the exactness
the refraction became: –2.00 –1.00 × 10°, BCVA 20/ of the optical results after cataract surgery, although
30; K 39.25 / 39.50 @ 10°; biometry was: axial length their outcomes have been less predictable than in
26.70, ACD 3.10, and lens thickness 3.00 mm. routine eyes.78 We believe that in our first series of
Considering the refraction post PRK, before cataract, cases, we have obtained encouraging results. With
the SIRC was –9.25 D and with the clinical history follow up of a greater number of cases, we will be
method applied to Binkhorst formula the IOL power able to perform further statistical empirical
was +17.67, while with the Camellin-Calossi formula adjustments relative to the different types of
a similar IOL power of +17.29 resulted. The implanted refractive surgery in order to better improve the
IOL was +17.00, A const 117.5. At the four months accuracy of calculations. The number of cataract
follow-up the refractive outcome was +0.50 +0.25 × surgeries after corneal refractive surgery is
150, BCVA 20/25. The prediction error of the history anticipated to increase. As more and more refractive
method was +0.13 D, and +0.41 D for our formula. If patients will present for cataract surgery, more and
we had not known the real SIRC and we had more cases will be analyzed. In the future, it would
considered the refraction with the cataract, the SIRC be useful if a central data bank could be established
would have seemed –7.25 D: 2.00 D less than the real for all eyes that had keratorefractive surgery so that
one. In this case, with the history method the IOL details and records of previous laser treatment
power would have been +15.21 and with the would be available. In this way, we shall be able to
Camellin-Calossi formula +16.96; with a prediction perform further statistical empirical adjustments, in
error of +1.90 D for the history method and +0.65 D order to better correct patients who, by their original
for our formula. decision to have vision correction surgery, have
Our formula was conceived primarily for eyes that demonstrated that they have above-average
have previously undergone refractive surgery but refractive demands.
98 Mastering Advanced Surface Ablation Techniques
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102 Mastering Advanced Surface Ablation Techniques

CHAPTER
Update on IOL Power
11 Calculations After Corneal
Refractive Surgery

Srinivas K Rao (India), Arthur Cheng, Dennis SC Lam (China)

INTRODUCTION to review the methods described to overcome these

problems.
Cataract surgery has evolved tremendously in the
The two most important measurements that aid
past few decades and most patients expect excellent
accurate IOL power calculation are the axial length
unaided vision following the procedure. Present day
of the eye and the corneal curvature. Their importance
techniques of phacoemulsification, which disturb the
is highlighted by the fact that an error of 1.0D in
corneal contour minimally and ensure in-the-bag
keratometry would result in an equivalent error in
intraocular lens (IOL) placement in a consistent
IOL power, while a 0.33 mm error in axial length
fashion, have contributed considerably to such results.
determination would cause a 1.0D error in IOL power
An improved understanding of the methods used
in an eye of average axial length. In eyes shorter than
for IOL power calculation and the precision of current
22 mm, the magnitude of the error in IOL power
technologies used to measure axial length and corneal
estimation would increase.
curvature have also contributed to the increased
Another factor that has recently been recognized
accuracy of cataract surgery refractive outcomes.
as important is the postoperative position of the IOL
Another procedure which has gained tremendous
within the eye — this has been termed as the effective
popularity in recent years is excimer laser corneal
lens position (ELP). Previously termed the anterior
refractive surgery and it is currently the second most
commonly performed ocular surgical procedure. chamber depth, this factor allows the surgeon to
Although laser in situ keratomileusis (LASIK) is the personalize the lens constant for his surgical
most advocated procedure, a large number of patients technique, by using data from a series of patient
have undergone photorefractive keratectomy (PRK) undergoing cataract surgery with IOL implantation,
and radial keratotomy (RK) in the past. Most of these and using the postoperative outcomes. Factors such
refractive procedures have been performed in as the retinal thickness have also been incorporated
patients in the second to fourth decades of life, and in more recent IOL formulae and while these do
as these individuals age they will need cataract improve the accuracy of refractive outcomes, in
surgery as well. However, initial attempts resulted general, they have less of an impact compared to the
in poor refractive predictability following cataract factors mentioned earlier. After corneal refractive
surgery in these eyes. The purpose of this article is surgery, the most important change is in the corneal
to highlight the reasons for such poor outcomes, and shape — the site of the surgery. Thus, any inaccuracies
 Update on IOL Power Calculations After Corneal Refractive Surgery 103
in IOL power calculation in this situation arise in is assumed to represent the power distribution within
large part from these changes — axial length tends this area and at the corneal apex. Since keratometers
not to contribute much to these changes. use the first Purkinje image of the reflection target
In this chapter, the effects of corneal changes on from the anterior corneal surface, what is measured
IOL power calculation inaccuracies during cataract is the curvature of the anterior corneal surface.
surgery are explored. A better understanding of these Refraction at the posterior corneal surface results in
changes and their resultant effect on the calculations a negative power, and the overall power of the cornea
has resulted in the evolution of many methods to try is the algebraic sum of these two components. Since
and counter these inaccuracies and these are the posterior corneal power cannot be measured
described as well. Since it is important to understand using standard keratometric techniques,
the actual changes that occur in the cornea and the manufacturers use a correction in the refractive index
eye after refractive surgery, these are first described. of the cornea to account for this factor. Hence, most
In RK, deep incisions in the peripheral cornea keratometers use a corneal refractive index of 1.3375
allow the intraocular pressure to shift the peripheral instead of the true value of 1.376. This allows a
cornea outwards, resulting in a flattening of the conversion of the measured radius of curvature of
central corneal curvature. There is thus, no tissue the anterior surface to the total power of the cornea.
removal in this procedure, unlike in PRK and LASIK, For this assumption to be valid however, a constant
in which the excimer stromal ablation results in tissue relationship between the anterior and posterior
removal from the central cornea. In the latter corneal surfaces is assumed. This assumption is
procedures, tissue removal would depend on the violated in excimer refractive surgery, in which tissue
amount of myopic correction attempted. Based on a is removed from the anterior corneal surface. This
rule-of-thumb that 1.0D of refractive correction would therefore, further affect the accuracy of
requires the removal of 10 μm of central corneal tissue, conversion of the measured anterior radius of
a 12.0D correction would require the removal of curvature into corneal power in such eyes.
about 120 μm of corneal tissue. Axial length Since the shape of the cornea after refractive
measurement using non-contact ultrasound surgery, be it RK or excimer surgery, is oblate –
techniques and the IOL master which uses the meaning that there is a negative shape factor, or a
principle of optical coherence would detect this central flattening, using a reflection-based system
amount of tissue loss, when measuring the axial (standard keratometer or Placido topographer)
length. Contact ultrasound techniques may not have results in errors. This is because the flattened anterior
the sensitivity to detect this change and hence may corneal surface reflects a larger image of the object
be a source of error in IOL power calculations. This in the measuring device, and hence what is used for
should lead to a 0.30 to 0.50D error in IOL power calculation is the measurement from the paracentral
estimation. Studies of IOL power calculation in eyes cornea, and this results in an erroneously steeper
that have undergone corneal refractive surgery have value for the central corneal power. Thus, after RK
however indicated that most of the error that occurs and excimer surgery for myopia, the measured
results from inaccurate estimation of the corneal corneal power in the 3 to 4 mm zone is steeper than
power. that in the central cornea which the patient uses for
Standard keratometry makes certain assumptions image formation. This results in an underestimation
regarding corneal shape. The cornea is considered a of the IOL power and a postoperative hyperopic
regular sphero-cylindrical surface, and the refractive error.
measurement of its curvature is derived from points In addition to this problem, in eyes that have had
situated on a central circle which is about 3 mm in excimer surgery, tissue has been removed from the
diameter. Since the central cornea within this zone is anterior cornea. This results in a change in the
considered to be a spherical surface, this measurement relationship between the anterior and posterior
104 Mastering Advanced Surface Ablation Techniques
corneal surfaces–with a lessening of the distance Calculations
between them. This causes a further inaccuracy, when Refractive error corrected = 7.0 D
the measured anterior radius of curvature is Hence, post-LASIK keratometry = (44.0 – 7.0)
converted into total corneal power by using the = 37.0D
effective refractive index. This reduction in the This method uses the post-treatment refractive
separation between the surfaces can actually result error of the patient, prior to the development of the
in reduced corneal power — although this is much cataract. This is usually obtained one month after
less in magnitude compared to the change resulting LASIK, or when refractive stability has been attained.
from the anterior surface change. In conjunction with Since the change in refractive error is the direct result
the initial measurement error, this conversion error of the corneal alterations produced by the surgical
can contribute further to the inaccuracy in IOL power procedure, it is logical to derive the final corneal
calculations in eyes that have undergone PRK and power by subtracting the refractive change attained,
LASIK. from the pre-treatment refractive error. Although this
In both RK and excimer surgery, there is a method works fairly well, it requires access to patient
posterior shift in the effective and true position of data in the pre- and early post-treatment periods.
the anterior corneal surface. However, the position Details of the surgical procedure, including the
of the crystalline lens remains unchanged and since correction attempted are also important. It is also
this determines the location of the IOL after cataract vital that the post-refractive surgery refractive error
surgery, it is important that IOL power calculations is recorded before the development of the cataract
take into account the altered position of the anterior as nuclear sclerotic cataracts often cause a myopic
corneal surface. Failure to do so would result in the shift in refraction.
use of an underpowered IOL and a hyperopic Whether to use the patient refraction at the corneal
refractive error after cataract surgery. plane or the spectacle plane has been a point of
Recognition of the various factors that contribute discussion — since the changes in power are at the
to the postcataract refractive shift has spawned a corneal surface, some authorities argue that it is best
number of strategies that try and address these issues. to use the spectacle power converted for vertex
In this chapter, these strategies are addressed under distance. In the example provided, let us see the
two headings — those that can be used when the power calculation when this approach is used.
surgeon has access to the pre-refractive surgery data
Example
of the patient, and those that can be used when the
Preoperative refraction = – 8.0D (–7.3D at
patient presents with no prior data.
corneal plane;
vertex, 12 mm)
STRATEGIES TO BE USED WHEN PRIOR DATA IS
AVAILABLE Preoperative keratometry = 44.0D
Refractive correction attempted = – 8.0D
The History Method1 Post-LASIK refraction = – 1.0D (–0.99D
This method derives the post-refractive surgery at corneal plane)
keratometric value from the pre- and postsurgery Calculations
refractive data of the patient. This can be explained Refractive error corrected = – 6.31D
with the help of an example, Hence, post-LASIK keratometry = (44.0 – 6.31)
Example = 37.69D
Preoperative refraction = – 8.0D Hence, this results in a higher value for the
Preoperative keratometry = 44.0D postoperative corneal power, and as the IOL power
Refractive correction attempted = – 8.0D calculations are best performed with the lowest
Post-LASIK refraction = – 1.0D corneal value, it may be preferable to use the
 Update on IOL Power Calculations After Corneal Refractive Surgery 105
refractive errors at the spectacle plane. However, current), and the central corneal power measured
when correcting very high errors, viz. more than 10D, from the Holladay Diagnostic Summary of the system.
it has been suggested that corneal plane refractions This value is the calculated mean refractive power of
may be more accurate, although data supporting this the central 3 mm of the cornea, accounting for the
are lacking. Stiles Crawford effect. In their study, the authors
noted that the EffRPpost (effective refractive power
The DBR Method2 after surgery), tended to overestimate corneal power
In this approach, preoperative patient data are and this increased significantly with increasing change
essential. When the patient presents for refractive in refractive equivalent (SE). Hence, they proposed
surgery, in addition to refraction and keratometry, the following regression equation to improve the
the axial length is also measured and the IOL power accuracy of corneal power estimation.
required for emmetropia is calculated. Following EffRPpost-adj = EffRPpost – 0.15 (SEpost – SEpre) – 0.05
refractive surgery, the stable refractive error prior EffRPpost-adj – adjusted postoperative effective
to onset of cataract is determined and the change in
refractive power of the cornea
refraction effected by the surgical procedure is
calculated. This can be explained with the aid of the SEpost – post–LASIK spherical equivalent refractive
following example, error
Example SEpre – pre-LASIK spherical equivalent refractive
Preoperative refraction = – 5.25D error
Preoperative keratometry = 46.2D
Refractive correction attempted = – 5.25D The Double K Method4
Post-treatment refraction = Plano
In third and fourth generation IOL calculation
Axial length = 25.0 mm
formulae that use corneal power values to predict
IOL power for emmetropia = 16.8D
the effective lens position (ELP), tissue removal from
(A constant 118.0)
the anterior corneal surface and the lesser
Since there has been a 5.25D change in refraction
keratometry value result in an erroneous anterior
at the spectacle plane following surgery (12 mm
calculated ELP — this will result in underestimation
vertex distance), the IOL inside the eye should have
of the IOL power and resultant hyperopic error
its power increased by an equivalent amount for the
postoperatively.
post-refractive surgery eye to attain emmetropia. It
To overcome this fallacy, it has been suggested
is also calculated that for every diopter of change in
that the pre-refractive surgery keratometry be used
IOL power, only 0.7 D of change in refraction at the
to determine ELP. The postrefractive surgery
spectacle plane will be achieved.
keratometry is then used with the previously
Example determined ELP to calculate the IOL power. As
5.25D change at the spectacle plane = 5.25 / 0.7 described by Aramberri, the postoperative
= 7.5D change at keratometry value is calculated using the Clinical
the IOL plane History method. He describes in detail his method
IOL power for emmetropia = 16.8D + 7.5D of programming the SRK/T formula into a
= 24.3D spreadsheet so that ELP calculation algorithms used
the preoperative keratometry and the vergence
Using Corneal Topography3 formula algorithms used the postoperative
This method depends on the use of a specific keratometry and interested readers are advised to
topographic unit — the EyeSys device (which is not refer to his article.
106 Mastering Advanced Surface Ablation Techniques
This insight of Aramberri has been incorporated the values are correlated with the amount of change
by Holladay into his Holladay 2 formula. In this in SE achieved after refractive surgery.
formula, the corneal power before refractive surgery They caution however, that while this may be an
can be entered for the calculation of the ELP. For appropriate method for eyes that have had PRK and
patients who do not have such data available, this LASIK, after RK, the Sim K value may be the most
formula offers the option of using a standard value appropriate. They also suggest the use of modern
of 44D for the corneal power. In an editorial, Koch keratometers with a large number of measurement
and Wang provide a table with precalculated values points (360-420) to obtain the postrefractive surgery
for modifying the IOL power according to the double measurement.
K method. 5 However, these are based on the
assumption that the pre-refractive surgery Back Calculated IOL Power8
keratometry is 43D and the IOL implanted is the In this method, the authors used pre-LASIK
SA60AT (Alcon). keratometry readings and axial length to derive the
IOL power calculations. They then chose the IOL power
Theoretical Formula 20046
that would provide the pre-LASIK SE refraction.
This formula was proposed to calculate the In another method the pre-LASIK SE refractive
postoperative power of the cornea after refractive error and the post LASIK flattest keratometric
surgery and requires knowledge of the preoperative measurement were used to adjust the power of the
keratometry and the postoperative radius of IOL calculated using the flattest keratometry value.9
curvature of the corneal surface (calculated using an
autokeratometer) Example
Kpostop = Kpreop – [(Nc – 1) × (Ra-postop – Ra-preop) / If a patient underwent LASIK for – 6.5D (SEQ), then
(Ra-postop × Ra-preop)] the adjustment for the IOL power obtained using the
flattest keratometry would be –
Kpostop – Keratometry reading after LASIK
Adjustment = [ – (0.47 SEQ) + 0.85]
Kpreop – Keratometry reading before LASIK = [ – (0.47 × 6.50) + 0.85]
Nc – Index of refraction of the cornea (1.376) = + 2.20D
Hence, if the IOL power calculated using the
Ra-postop – Postoperative radius of curvature of the
flattest keratometry was 17.76D, then the IOL power
anterior corneal surface to be used should be 17.76 + 2.20 = 19.96D.
Ra-preop – Preoperative radius of curvature of the In another variation of this approach, the IOL
anterior corneal surface power adjustment was performed using the following
correction factor.10
Modified Keratometry Method3 IOL power adjustment = LSE × (–0.326) + 0.101
If the amount of refractive correction is known, Sim K LSE – Total prior laser treatment, adjusted for
or keratometry readings obtained after refractive vertex distance in SE.
surgery can be reduced by 0.24D per diopter of
Example
refractive correction obtained after surgery.
- Post refractive surgery, SRK T formula suggests
Corrected Keratometry7 16.0D IOL for emmetropia
The authors describe the correction factor necessary - Prior laser correction (SE) = – 6.0D
to correct the corneal power overestimation that - Adjustment = – 6.0D x (–0.326) + 0.101 = + 2.057D
occurs when keratometry is measured after PRK and - IOL power calculated as – 16.0 + 2.0 = 18.0D for
LASIK. The table is described in their article, and emmetropia
 Update on IOL Power Calculations After Corneal Refractive Surgery 107
Nomogram Based Adjustment of IOL Power11 If the pre-LASIK refractive error is known, they
suggest the following new refractive indices.
Based on analysis of data using method #2, a
theoretical formula was determined that allowed the Pre-LASIK refractive error New refractive index (rN)
estimation of IOL power underestimation, using the < –4D 1.3355
–4 to –8D 1.3286
change in SE induced by the refractive surgery. –8 to –12D 1.3237
IOL power underestimation = –0.231 + (0.595 × > –12D 1.3172
SEchange-spectacle plane) The new keratometry reading is obtained by using
Using this formula, they developed a nomogram the equation
that provided the adjustment factor for IOL power K = [rN – 1 / Ra]
based solely on post-LASIK keratometry and Ra = anterior corneal curvature in meters,
refractive change induced by LASIK without the need measured after refractive surgery, using an automated
for pre-LASIK keratometry. The derived values are instrument.
detailed in a table in their paper referenced above, The authors also describe an alternate formula to
and the example they have provided explains the determine rN for eyes in which the change in
method. refraction after LASIK is known,
rN = 0.0014SEc + 1.3375
Example SEc – Spherical equivalent change after LASIK
Pre-LASIK refraction (spectacle) = – 13.38D
Spherical equivalent (corneal plane, = – 11.27D STRATEGIES TO BE USED WHEN PRIOR DATA IS
vertex – 12,5 mm) NOT AVAILABLE
Post-LASIK refraction (spectacle) = – 2.50D
Corneal Topography13
Post-LASIK SE (corneal plane, = – 2.50D
vertex – 12,5 mm) The reasons why standard keratometry results in
Pre-LASIK keratometry = 41.75/43.00D poor refractive outcomes after IOL implantation in
Post-LASIK keratometry = 35.90/33.40D eyes that have had corneal refractive surgery, have
Axial length = 30.38 mm already been described. Most of the currently
Desired postcataract refraction = Plano available computerized videokeratography units
Step 1: The change in refraction at the spectacle provide color-coded maps of corneal power
plane = 10.88D distribution. The basic principles adopted by the
Step 2: The IOL power based on the axial length Placido-based devices remain very similar to those
and post-LASIK keratometry with the SRK T formula in manual keratometers. Hence, they are subject to
is determined, aiming for plano = 13.06D the inaccuracies described earlier. However, in post-
Step 3: The IOL power is adjusted according to RK eyes, some degree of accuracy can be attained by
the nomogram provided in their article, ignoring the simulated keratometry values provided
13.06 + 6.31 = 19.37D by the machine (measured from a 3 mm zone), and
The IOL chosen according to this method is deriving the value from the center of the zone of
19.50D (SA60AT). flattening indicated in the topographic map. This is
more accurate since these devices use data from more
Corrected Refractive Index Method12 points on the corneal surface including the cornea
The authors derived a correction factor for the within the 3 mm zone measured by the keratometer.
effective refractive index of the cornea and suggest This method would not however be useful in eyes
the use of this method to derive the postrefractive that have had excimer surgery, due to the inaccuracy
surgery keratometry value. in conversion mentioned earlier.
108 Mastering Advanced Surface Ablation Techniques
To further improve the accuracy of this method, corneal surgery. However, in eyes that have had
Maloney suggested the following modification to the corneal surgery, the formula may lead to
power obtained from the center of the corneal overestimation of keratometry.
topographic map.14 To overcome this, he suggests the use of the
Adjusted central corneal power = [Measured following formula
central topographic power × (376/337.5)] – 4.9 PCe – 1.119 × PCLO – 5.78
Koch et al, using data from 11 eyes suggested the PCe – Equivalent corneal power
use of 6.1D instead of 4.9D as the value for the PCLO – Power from the contact lens over-refraction
posterior corneal power. method

The Hard Contact Lens Method15 Regression Derived Clinical Method17

In this technique, a hard contact lens of known base The authors used a dataset of eyes undergoing LASIK
curve is placed on the eye with lens changes, and to derive the following equation using regression
refraction is performed. The subjective refraction with equations.
the contact lens in place is compared with the Kc.cd = 1.14Kpost – 6.8
refraction obtained without the contact lens. These Kc.cd = Clinically derived post refractive surgery
values are used to derive the corneal power, using
keratometry
the following relationship.
Kpost = Measured postrefractive surgery
Keratometry (D) = Contact lens base curve (D) +
keratometry
contact lens power (D) + (refraction with the contact
lens) – (refraction without the contact lens) Example

Example If the measured post refractive surgery keratometry

is 40.0D.
If refraction without the contact lens (base curve 38.0D)
The value according to the above equation would
is – 5.0D, and with the contact lens in place is plano, it
be = (1.14 × 40) – 6.8 = 38.8D.
means that the cornea underlying the lens is steeper
than the contact lens by 5D. Hence, the corneal power
Intraoperative Retinoscopy18
would be contact lens power plus 5D (assuming that
the contact lens power was zero). Thus, Keratometry In this technique, cataract surgery is completed and
= 38 + 0 + (0) – (– 5) = 38 + 5 = 43.0D. retinoscopy is performed intraoperatively in the
This method is advantageous because it does not aphakic eye. From the aphakic refraction, the IOL
require access to patient data. However, it is accurate power can be determined. Alternatively, the IOL
only if the cataract allows refraction and the patient chosen can be implanted and then retinoscopy is
has have a best-corrected visual acuity of at least performed, although IOL exchange would be necessary
6/18 (to ensure that the refraction is accurate). If the if there was a significant error. It would also be
cataract is very dense or total, and accurate refraction necessary to consider the loss of aseptic technique that
is not possible, or if the visual acuity in the cataractous may occur during this intraoperative maneuver.
eye cannot be improved beyond 6/24, then the These issues were addressed in a recent study
accuracy of this method is open to question. and the authors derived a regression equation to help
More recently, the contact lens over-refraction determine the IOL power required using the
method was reviewed and modified by Haigis.16 He intraoperative aphakic automated refraction obtained
explains that the formula described above may during surgery.19
provide a clinically acceptable estimate of the corneal Predicted final adjusted IOL power = 2.01449 ×
back vertex power in normal eyes without previous intraoperative SE refraction.
 Update on IOL Power Calculations After Corneal Refractive Surgery 109
In another similar approach, the authors suggest With techniques that require access to pre-
performing a manifest aphakic refraction 30 minutes refractive surgery patient data, it is important that
after cataract surgery and using the following such data be accurate. 24 Especially with post-
equation to calculate the IOL power.20 refractive surgery refractive error, it is vital that this
Predicted final adjusted IOL power = 1.75 × be obtained before the onset of cataract alters the
manifest SE refraction. value. With methods such as the contact lens over
refraction, the degree of cataract and visual function
The Gaussian Optics Formula21 affect the accuracy of the outcome, as also the contact
This is a theoretical approach that uses the values for lens fit and centration.
anterior and posterior corneal curvatures measured Finally, even if all these are accurate, the quality
after refractive surgery—using the Orbscan or the of the refractive ablation is very important in
Pentacam, with the pachymetry – to derive the corneal determining the outcomes of these calculation
power. The values obtained are used with the techniques. If there has been a very small, irregular
formula described below or decentered ablation zone, the outcomes can still
Corneal power = P1 + P2 – [d / n1] × P1 × P2 be suboptimal.
P1 = [1 / r1 (n1 – n0)] Thus, in dealing with these patients, it is important
P1 = [1 / r2 (n2 – n1)] to have access to as much of the available pre-
P1 = Power of the anterior corneal surface refractive surgery data as possible, perform a careful
P2 = Power of the posterior corneal surface preoperative examination of the eye and corneal
n0 = refractive index of air (1.0) profiles, use as many of the methods described as
n1 = refractive index of cornea (1.376) possible, choose the least keratometry value obtained
n2 = refractive index of aqueous humor (1.336) (ensuring that it is fits with the data available),
d = corneal pachymetry calculate the IOL power required using the third and
r1 = anterior corneal radius of curvature (mm) fourth generation formulae, choose the highest IOL
r2 = posterior corneal radius of curvature (mm) power determined (for eyes that have had myopic
refractive surgery), and aim for a slight postoperative
Theoretical Variable Refractive Index Method22 myopia of 0.75 to 1.0 D. Despite all this, it may be
necessary also to discuss with the patient the issues
The authors used a dataset of post PRK eyes to derive
involved and explain the possible need for some
a theoretical variable refractive index correlated to axial
further procedures, should the desired result not be
length. This was used to derive the corrected value for
obtained. Finally, it is important to keep a database
post PRK keratometry using the measured value.
of these patients, to help improve our ability to
Theoretical refractive index (TRI)
improve refractive outcomes after cataract surgery.
= [–0.0006(AL × AL) + (0.0213 × AL) + 1.1572]
Corneal power = (TRI – 1)/r REFERENCES
AL – Axial length in mm
R – Corneal curvature in mm 1. Holladay JT. Consultations in refractive surgery. Refract
Corneal Surg 1989;5:203.
The availability of these various techniques has
2. Feiz V, mannis MJ, Garcia-Ferrer F, Kandavel G,
resulted in improved accuracy in IOL power Darlington JK, Kim E, Caspar J, Wang JL, Wang W.
calculations for eyes that have had refractive Intraocular lens power calculation after laser in situ
surgery. 23 However, there is still scope for keratomileusis for myopia and hyperopia. Cornea
improvement. Concerns exist with some of the 2001;20:792-7.
3. Hamed HA, Wang L, Misra M, Koch DD. A comparative
methods described — especially those that are analysis of five methods of determining corneal refractive
theoretical derivations, which require verification power in eyes that have undergone myopic laser in situ
with actual patient datasets. keratomileusis. Ophthalmology 2002;109:651-8.
110 Mastering Advanced Surface Ablation Techniques
4. Aramberri J. Intraocular lens power calculation after 14. Wang L, Booth MA, Koch DD. Comparison of intraocular
corneal refractive surgery: Double K method. J Cataract lens power calculation methods in eyes that have
Refract Surg 2003;29:2063-8. undergone LASIK. Ophthalmology 2004;111:1825-31.
5. Koch DD, Wang L. Calculating IOL power in eyes that 15. Hoffer KJ. Intraocular lens power calculation for eyes
have had refractive surgery. J Cataract Refract Surg after refractive keratotomy. J Refract Surg 1995;11:490-3.
2003;29:2039-42. 16. Haigis W. Corneal power after refractive surgery for
6. Jarade EF, Tabbara KF. New formula for calculating myopia: Contact lens method. J Cataract Refract Surg
intraocular lens power after laser in situ keratomileusis. J 2003;29:1397-1411.
Cataract Refract Surg 2004;30:1711-15. 17. Shammas HJ, Shammas MC, Gabaret A, Kim JH,
7. Stakheev AA, Balashevich LJ. Corneal power Shammas A, LaBree L. Correcting the corneal power
determination after previous corneal refractive surgery measurements for intraocular lens power calculations
for intraocular lens calculation. Cornea 2003;22:214-20. after myopic laser in situ keratomileusis. Am J Ophthalmol
8. Walter KA, Gagnon MR, Hoopes PC, Dickinson PJ. 2003;136:426-32.
Accurate intraocular lens power calculations after myopic 18. Seitz B, Langenbucher A. Intraocular lens power
laser in situ keratomileusis, bypassing corneal power. J calculation in eyes after corneal refractive surgery. J
Cataract Refract Surg 2006;32:425-9. Refract Surg 2000;16:349-61.
9. Latkany RA, Choksi AR, Speaker MG, Abramson J, 19. Ianchulev T, Salz J, Hoffer K, Albini T, Hsu H, LaBree L.
Soloway BD, Yu G. Intraocular lens calculations after Intraoperative optical refractive biometry for intraocular
refractive surgery. J Cataract Refract Surg 2005;31:562- lens power estimation without axial length and
70. keratometry measurements. J Cataract Refract Surg
10. Masket S, Masket SE. Simple regression formula for 2005;31:1530-6.
intraocular lens power adjustment in eyes requiring 20. Mackool RJ, Ko W, Mackool R. Intraocular lens power
cataract surgery after excimer laser photoablation. J calculation after laser in situ keratomileusis: Aphakic
Cataract Refract Surg 2006;32:430-4. refraction technique. J Cataract Refract Surg 2006;32:435-7.
11. Feiz V, Moshirfar M, Mannis MJ, Reilly CD, Garcia-Ferrer 21. Cheng ACK, Lam DSC. Keratometry for intraocular lens
F, Caspar JJ, Lim MC. Nomogram-based intraocular power calculation using Orbscan II in eyes with laser in
lens power adjustment after myopic photorefractive situ keratomileusis. J Refract Surg 2005;21:365-8.
keratectomy and LASIK. Ophthalmology 2005;112:1381- 22. Ferrara G, Cennamo G, Marotta G, Loffredo E. New
7. formula to calculate corneal power after refractive
12. Jarade EF, Abi Nader FC, Tabbara KF. Intraocular lens surgery. J Refract Surg 2004;20:465-71.
power calculation following LASIK: Determination of the 23. Cheng AC, Lam DS. Correcting the corneal power
new effective index of refraction. J Refract Surg measurements for intraocular lens power calculations
2006;22:75-80. after myopic laser in situ keratomileusis. Am J Ophthalmol
13. Celikkol L, Pavlopoulos G, Weinstein B, Celikkol G, 2004;137:970.
Feldman S. Calculation of intraocular lens power after 24. Cheng AC, Rao SK, Tang E, Lam DS. Pachymetry
radial keratotomy with computerized videokerato- assessment with Orbscan II in postoperative patients with
graphy. Am J Ophthalmol 1995;120:739-50. myopic LASIK. J Refract Surg 2006;22:363-6.
 CHAPTER
Advanced Surface Ablation
12 Techniques: Current Scenario

Ashok Garg (India)

INTRODUCTION b. Complication rate in ASA is far less than lasik

which has complications from bad flaps, slipped
Since the inception of photorefractive keratectomy flaps, diffuse Lamellar Keratitis, epithelial in
(PRK) in early ninties the Laser Refractive Surgery has growth and posterior corneal changes.
gone full circle. For last one decade lasik has been the c. In ASA when wavescan is performed before
standard and most popular refractive surgery procedure surgery, the laser can treat all these components
worldwide. Due to severe postoperative complications however in lasik when flap is cut, higher order
of lasik specially corneal ectasia there is renewed aberrations can occur certainly ASA is safe and
interest in Surface Ablation Technique among Refractive more accurate.
Surgeons. There is Resurgence of surface Ablation Advanced Surface Ablation Techniques are
procedures with a bang in recent time. classified in following categories:
Clinically, Advanced Surface Ablation (ASA) is I. PRK.
defined as Surface Ablation Techniques in which II. Epi-LASIK
epithelium (the outermost) layer of the cornea is III. Lasek (E-LASIK)
removed either temporally or permanently in order IV. Transpithelial PRK (No touch–one step
to reach corneal stroma. Computer controlled excimer procedure).
laser then reshapes the front surface of corneal V. SBK.
stroma. Then epithelium is either replaced or assisted VI. Custom Surface Ablation: Wavefront guided
in healing back over the corneal surface underneath PRK, epi-LASIK and LASEK.
a bandage contact lens. ASA is indicated instead of Here I shall discuss in brief the salient features of
lasik in patients with thin corneas. ASA is indicated these techniques. The details of individual technique
to treat Myopia, Hyperopia and Astigmatism. is prescribed in different chapters of this book.
Advanced Surface Ablations shows excellent visual
PHOTOREFRACTIVE KERATECTOMY (PRK)
results with less postoperative pain. It shows
following advantages over LASIK. It is a standard ASA technique in which corneal
a. It is certainly a safe procedure. Cutting the flap epithelium is removed and then Excimer Laser is used
in lasik weakens the cornea and with treatment as it would be in lasik. In this technique instead of Intralase
tissue is removed and corneal thickness is laser or micro Keratome a special brush is employed to
further reduced. remove the epithelium. This brush leaves a smooth
112 Mastering Advanced Surface Ablation Techniques
surface with well-defined epithelial edges that appears is an Avanced Surface Ablation procedure also known
to enhance healing. In this ASA technique the corneal as E-Lasik or thin flap LASIK. In this technique
nerves are not cut as in Lasik, the tear film is not affected Excimer Laser Ablation is performed under a hinged
which often leads to postoperative dry eye. flap of corneal epithelium. In lasek alcohol solution
In PRK when treating Myopia Excimer Laser is is used to soften the epithelium and it is removed
used to remove central corneal tissue in a circular manually. The Excimer Laser than sculpts the cornea
pattern thereby flattening the cornea and weakening and epithelium is placed back into position. After the
the focusing power of the eye. While in Hyperopia procedure a transparent bandage contact lens is
laser is used to remove peripheral corneal tissue placed on the cornea to promote healing. In this
thereby steepening the central cornea to increase the technique no micro Keratome is used and no stromal
focusing power of the eye. Lamellar cut is made. The advantage of Lasek is
In Astigmatic correction the Excimer Laser is safety. All of the complications associated with
programmed to remove tissue in an elliptical pattern, stromal flaps are eliminated.
selectively reshaping some portions of the cornea to
form a smooth symmetrical surface. This procedure TRANSEPITHELIAL PRK
requires the correct preoperative Astigmatism
This is relatively a new No Touch Technique. Here
evaluation so that correct amount of Laser Energy is
the corneal epithelium is ablated (vaporized) with
delivered to the appropriate areas of the cornea.
the same Excimer Laser that is used to treat corneal
PRK is certainly a better option than lasik in
stroma. C-TEN (Custom Transpithelial No touch)
peoples whose occupation makes it more dangerous
procedure is a single step transpithelial approach
to have a flap as it can be dislodged accidentally.
which eliminates mechanical touching of cornea.
EPI-LASIK C-TEN eliminates any mechanical or Laser Keratome
induced aberrations that are unmeasured for with
It is a refractive procedure used for patients with thin lasik in addition to safety concerns with the use of
corneas who are not fit candidate for the conventional inicrokeratomes.
lasik procedure. Epithelial lasik is indicated to treat
Myopia, Hyperopia and Astigmatism. SBK
In this technique a special type of micro keratome
Sub-Bowman Keratomileusis is a new surface
known as epi-keratome is used. This separator
Ablation Technique combining the best of both PRK
precisely separates thin epithelial layer (much thinner
and Lasik. SBK is hybrid of PRK and LASIK and it is
than lasik flap) from the rest of corneal layers. Once
designed to provide a superior method for
the epithelium is separated from the rest of the
performing corneal refractive surgery. This technique
cornea, the thin sheet of epithelium cells is lifted to
involves the use of a customized corneal flap of
one side. Laser is used to treat the cornea than thin
between 90 to 110 mm with the diameter that is closely
epithelial sheet is moved back into the place. Where
matched to ablation zone of the Excimer Laser being
it will self adhere. After the completion of refractive
used typically 8.5 mm or less. SBK has a number of
procedure, a transparent bandage contact lens is
advantages specially predictable thin flap, quicker
placed over the cornea to promote healing. Epilasik
visual recovery with minimal pain and discomfort.
is certainly a safe and effective procedure with
Minimal biomechanical changes with fewer higher
excellent visual outcome.
order aberrations and reduced incidence of
LASEK (E-LASIK) postopertive dry eye and decrease in loss of corneal
sensitivity. Certainly SBK is a better technique which
Laser assisted sub-epithelial Keratectomy (Lasek) was has definitely changed the way we perform refractive
first introduced by Dr Massimo Camellin in Italy. It surgery.
 Advanced Surface Ablation Techniques: Current Scenario 113
CUSTOM SURFACE ABLATION (CSA) Custom wavefront guided PRK, Epilasik and
Lasek are promising techniques in the correction of
Custom Surface Ablation techniques include wavefront
ametropia. It avoids mechanical variations due to the
guided PRK, epi-LASIK and LASEK. CSA is indicated
creation of the Lamellar Flap (Lasik) which has
to treat non-standard refractive errors or to correct
potential benefits when dealing with the micron level
errors induced by previous refractive surgery. CSA is
of accuracy demonstrated by wavefront diagnostic
required based on topography/wavefront
and therapeutic modalities.
examinations CSA has following advantages.
a. Wavefront guided preoperative examination Corneal Interactive Programmed Topographic
provides a relatively accurate data of corneal Ablation (CIPTA) provides multiple laser surgical
shape so that preoperative accurate Keratometry planning. CIPTA includes corneal lower and higher
readings can be calculated as comparison to order aberrations. Recently, Corneal Lamellar
traditional methods. Accurate topography data Ablation for Transplantation (CLAT) has come as a
helps the treatment planning software to boon for Keratoconus patients. With CLAT the
algorithmically determine parameters for precise surgeon may choose to utilize a fully automated
visual results. custom lamellar transplantations of the cornea. CLAT
b. Pricise topography data can incorporate advanced creates a uniform thickness receiving bed. This
techniques to account for corneal asphericity. eliminates the serious residual irregularities of the
Preoperative asphercity can be measured from Keratome prepared bed thus improving corneal optics.
topography exam. It provides a mean of With the resurgence of interest in advanced
generating a treatment plan designed to
surface ablation techniques there is steady increase
maintain preoperative asphericity thereby
in the percentage of surface ablation procedures
reducing the induction of spherical aberrations.
performed due to safety, better results and improved
c. With accurate topography data about pre-
operative corneal surface, the all corneal medical regimes.
irregularities can be corrected effectively Advanced surface ablation techniques are
specially irregular corneal surface due to injury continuously evolving in order to achieve faster visual
or previous surgery resulting in an ideal recovery and less pain ASA certainly holds great
postoperative corneal shape. future in coming decade.
114 Mastering Advanced Surface Ablation Techniques

CHAPTER

13 My Journey with
Surface Ablation

Christopher J Rapuano (USA)

INTRODUCTION manual debridement of the epithelium with a blunt

or sharp blade. In the early part of the clinical trials,
My experience with excimer laser surgery began in
the eyes were fixated by the surgeon using a suction
1992. Interestingly, this was the exact same time that
ring. Later in the trials, patients were encouraged to
radial keratotomy (RK) was enjoying a resurgence
self-fixate by focusing on the red blinking fixation
of popularity in the United States. RK would suffer
light in the laser unit, as it was thought that ablation
greatly with the publication of the 10-year Prospective
centration was actually better with patient self-
Evaluation of Radial Keratotomy study in 1994, which
fixation in most cases. If a patient could not self-fixate,
demonstrated a significant hyperopic shift in many
the surgeon could always use the suction ring. The
patients over 10 years. Soon after, the number of RK
ablations were accomplished using large broad beam
procedures performed in the United States decreased
laser spots. The spots started out small (and were
dramatically.
very quiet) and increased in size (and loudness) during
I was a co-investigator for the VISX FDA Phase
the treatment. The ablation zone was 6.0 mm.
III clinical trials for excimer laser photorefractive
keratectomy (PRK) and phototherapeutic keratec- Postoperatively patients were treated with topical
tomy (PTK) at Wills Eye Hospital. The excimer laser antibiotics and steroids, and either a soft contact lens
model was the VISX 2020B. The PRK trials were or a pressure patch.
divided into low myopia (up to –6D), moderate The results were quite good. Most patients had a
myopia (–6 to –8D), and high myopia (–8 to –12D). significant amount of pain for several days after
Wills had the moderate myopia cohort. In these trials, surgery, despite oral pain medications. The epithelial
cylinder wasn’t treated, and patients could only have defect generally healed between 4 to 5 days post-
a low degree of refractive astigmatism. Patients could operatively, at which point the comfort was good,
only have one eye treated at a time; the fellow eye but the vision was mediocre. Over the years of the
could be treated 6 months later, if the trials were FDA study, improvements in the protocol included
continuing. I, and the other investigators at Wills, the ability to use non-steroidal anti-inflammatory
treated a large number of moderate myopes with (NSAID) drops postoperatively, which significantly
very good results. improved the comfort postoperatively. We learned
The FDA trials required the surgery be performed that you needed to use steroid drops along with the
according to a strict protocol. The technique involved NSAID or there was a high risk of developing sterile
 My Journey with Surface Ablation 115
inflammatory infiltrates. The protocol steroid was with no defined endpoint, and were often
fluorometholone 0.1% qid for 1 month, tid for 1 moderately myopic. They were generally detected
month, bid for 1 month, qd for one month and then within the first post-operative month, when the vision
discontinue. If steroids were stopped early, there was wasn’t improving as expected and a topography
a higher chance of regression and anterior stromal measurement was performed. Fortunately, the vast
haze. One of my patients moved 2000 miles away to majority improved and eventually disappeared on
a location where there is intense sunshine and their own, but it could take 3–6 months. Before this
stopped his steroid drops about 1 month after PRK. entity was widely appreciated, some patients
He returned to see me about a month later underwent retreatments for moderate degrees of
complaining of poor vision. He had developed myopia, and occasionally ended up quite
significant regression (initially –7D, plano one month overcorrected. VISX later developed “anti-central
postoperative, now –3D two months postoperative, island’’ software which significantly reduced the
yielding 20/70 BCVA) and haze (2+) (Figure 13.1). incidence of this problem.
He was treated with prednisolone acetate 1% 6xday The FDA approved PRK for the treatment of up
which was then tapered, and his regression, haze and to –6D of myopia for Summit in 1995 and VISX in
BCVA all improved (–1D, 20/25, trace haze). While 1996. While the results were very good and disasters
we blamed the lack of steroid drops for his problems, were rare, the popularity of PRK did not increase
we were beginning to realize that ultraviolet exposure nearly as much as many people in the business and
might also be playing a part. Not only did we stress medical community had predicted. The reason for
the need for using the steroid drops as prescribed, this was widely believed to be because of post-
but also avoiding UV exposure by using sunglasses operative pain and the slow recovery of vision. At
and hats for at least 3–6 months postoperatively. this very time, because of these very issues, laser in-
situ keratomileusis (LASIK) was becoming more and
more popular and gaining widespread acceptance.
LASIK involves the creation of a hinged, anterior
corneal flap, including epithelium, Bowman’s and
superficial stroma. The flap is moved to the side, the
underlying stroma is ablated with the excimer laser
and the flap is replaced in its original location. The
primary advantages of LASIK over PRK are much
less pain, faster visual recovery and less corneal haze.
And the visual results are comparable to PRK. For
these reasons, LASIK quickly became the refractive
surgery procedure of choice for the vast majority of
Figure 13.1 : 2+ corneal haze two months after PRK for –7D. The patients (and surgeons), and PRK almost disappeared.
patient had discontinued his steroid drops about one month prior
In fact, at that time, many beginning refractive
The other problem we encounternot infrequently surgeons didn’t bother to learn PRK at all, and just
was central islands. Central islands are small areas performed LASIK on all their refractive patients. I
of central steepening seen on computerized corneal started LASIK in 1997, reserving it for my patients
topography. They are typically about 2–3 mm in who were over – 6D where I felt the risk of haze
diameter with about 2–4D of steepening compared after PRK was somewhat increased. I also avoided it
to the surrounding cornea. Patients would complain in eyes where the residual stromal bed would be less
of poor quality of vision. Their uncorrected vision was than 250–275 microns and eyes with anterior basement
often in the 20/30–20/40 range, but it would not dystrophy, where I felt ectasia or flap complications
correct much better. Refractions were very variable, were more likely to occur.
116 Mastering Advanced Surface Ablation Techniques
Now, of course, we have since learned that LASIK the excimer laser ablation is performed and the
isn’t perfect and it certainly isn’t for everyone. epithelial flap is replaced and covered with a soft
Complications such as shredded flaps, free caps, contact lens. This procedure tended to work better
buttonhole flaps, diffuse lamellar keratitis, flap striae, than LASEK, but often the epithelium sloughed over
traumatic flap dislocation, epithelial ingrowth and several days, delaying return of comfort and vision.
ectasia were unknown with PRK. Certain eyes are I began epi-LASIK several years ago, first with
higher risk for some of these complications and it the Visi-Jet/Norwood epi-LASIK unit and later with
was learned to avoid LASIK is such patients. Most the Moria epi-LASIK unit. On one of my early epi-
refractive surgeons currently perform some form of LASIK patients, I was unable to get good suction with
surface ablation in selected patients. In fact some the epi-LASIK unit in one eye, so I simply debrided
surgeons perform only surface ablation in order to the epithelium mechanically and performed PRK. The
completely avoid the LASIK flap issues. fellow eye underwent successful epi-LASIK where I
Improvements in excimer laser technology replaced the epithelium. The early and late results
including larger ablation and transition zones, were quite similar for the two eyes. The patient did
scanning lasers, tracking systems and custom not have significantly less pain in the epi-LASIK eye,
wavefront treatments over the years have improved leading me to question whether replacing the
outcomes for both PRK and LASIK. epithelium was worth it. Other surgeons were using
While I continue to perform LASIK in appropriate the epi-LASIK microkeratome to remove the
patients, I am always looking for ways to improve epithelium and then simply discarding it, as they felt
the PRK procedure, especially to decrease the post- it actually impeded reepithelialization and didn’t
operative pain, speed the visual recovery and decrease pain. I then started discarding the epithelium
decrease the chance of haze. About 7 years ago, a after epi-LASIK and feel that patients reepithelialize
technique termed laser subepithelial keratomileusis about 12–24 hours faster, on average, than my
(LASEK) was described that purportedly mechanical debridement PRK patients. I feel the
accomplished these goals. It involved placing 20% slightly smaller epithelial defect and the very smooth
alcohol in a well on the corneal surface for 20–30 edges lead to the faster reepithelialization. While not
seconds to loosen the epithelium. The epithelium was a huge difference, it is step closer to the rapid recovery
then moved to the side, but remained attached at a of LASIK.
small hinge. The excimer laser ablation was The pain during the first few days after surgery
performed and the epithelium was replaced, attached is still an issue with surface ablation. Surgeons have
at its hinge, and covered with a soft contact lens. developed many techniques to minimize this pain.
Ideally the replaced epithelium reattached under the A bandage soft contact lens and NSAID drops for
contact lens and remained clear, resulting in minimal several days after surgery help tremendously. Oral
pain and rapid visual recovery, with negligible post- pain medications, such as narcotics, NSAIDS and
operative haze. In my experience, and in the other pain medications are very effective. Some
experience of many others, these outcomes simply surgeons prescribe a short course of perioperative
did not occur, and most surgeons eventually oral steroids. In my experience, cooling the cornea
abandoned LASEK. immediately after the laser ablation has done
The next iteration of surface ablation was epi- wonders to decrease postoperative pain. I have used
LASIK. This procedure involves using a micro- an iced cellulose sponge and also iced saline for 20-
keratome with a blunt blade, that separates the 30 seconds with great success. Using these techniques,
epithelium from Bowman’s layer. Since no alcohol is pain after surface ablation is generally mild.
used, the epithelial cells are theoretically more viable Haze can still occur after surface ablation, although
than after LASEK. Here too, the epithelial flap it seems to be occur much less with the newer excimer
remains attached at a hinge. It is moved to the side, lasers which use smaller spot sizes and more
 My Journey with Surface Ablation 117

advanced ablation patterns. Mitomycin C, a potent CONCLUSION

chemotherapeutic alkylating agent which decreases Excimer laser surface ablation continues to be a very
scarring, has been used for many years to improve viable technique for laser vision correction. It avoids
the success rate of glaucoma surgeries. It has also the complications of a stromal flap and carries
been used to decrease recurrences and scarring after significantly less risk of ectasia than LASIK. There is
pterygium surgery. About 6-8 years ago, it became also no worry of traumatic displacement of the stromal
a popular adjunctive therapy with surface ablation flap, either soon after surgery or years later. Techniques
to decrease the risk of significant postoperative haze.1 to minimize postoperative pain, speed the visual
I currently use MMC 0.02% (0.2 mg/ml) on a cellulose recovery, decrease the risk of haze are continuing to
sponge for 12 seconds at the end of surgery in patients advance and will certainly improve in the future. Epi-
who are over approximately –6D, as they are at LASIK, removing the epithelium, is my current surface
increased risk of postoperative haze. I then irrigate ablation procedure of choice but that may change over
the cornea with 30 cc of cold saline. I also discuss the time. I believe, however, that surface ablation will
pros and cons of MMC and have patients sign a specific continue to hold a prominent position in the field of
MMC consent form before surgery. In my experience, laser vision surgery for years to come.
MMC does not slow down reepithelialization and I
REFERENCE
know of no significant complications from single
application of MMC 0.02% for 12 seconds. 1. Majmudar PA, Forstot SL, Dennis RF, Nirankari VS,
Damiano RE, Brenart R, Epstein RJ. Topical mitomycin-C
Perioperative oral vitamin C can act as an antioxidant for subepithelial fibrosis after refractive corneal surgery.
and may also decrease postoperative haze. Ophthalmology 2000;107: 89-94.
118 Mastering Advanced Surface Ablation Techniques

CHAPTER Advances in
14 Refractive Surgery:
Surface Ablation

Ronald Singal (USA), Mikhail Pojaritsky, Dimitrii Dementiev (Italy)

INTRODUCTION reduce astigmatism. The techniques quickly spread

Refractive surgery has emerged as a vital and safe around the world and introduced millions of people
specialty within ophthalmology. In just a few years to the possibilities of refractive surgery. Due to
many techniques and new technologies have been advances in laser correction, RK has lost its primary
developed to allow for modification of the refractive role in the refractive surgery field. It is still used
errors of the human eye. Safety, cost effectiveness, however as an adjunct procedure.
and reproducibility of outcomes have each been a The 1990’s saw the introduction of photorefractive
driving force in the field. Although Laser-Assisted keratotomy (PRK) which employed the excimer laser
in situ Keratomileusis (LASIK) has become the leading to ablate surface tissue on the anterior cornea to
technique for carrying out refractive surgery, other effect not only a flattening of the cornea for correction
techniques have established themselves. All refractive of myopia and astigmatism, but also to effect a
layers of the cornea and lens have been utilized at steepening of the central cornea for the correction of
various times in this process. Each successive surgical hyperopia. PRK was not epithelial sparing and healed
has strived to improve on its predecessors. Each new relatively slowly. It was associated with moderate
technique not only exhibited indications and a unique pain and visual blur lasting several days. Outcomes
safety profile, but also limitations and complications. were quite good in eyes requiring low to moderate
A comparative discussion of these techniques is in degrees of correction. Newer techniques of laser
order (see Table 14.1) with an emphasis on the two surface ablation have developed which seem to allow
most prominent, LASIK and epi-LASIK. for higher dioptric corrections, faster healing, and
After a few false starts, the era of refractive less discomfort (LASEK and epi-LASIK) Epi-LASIK
surgery began in Moscow in the 1980’s with the is fast becoming the second most employed refractive
introduction of Radial Keratotomy (RK) by Fedorov. surgery technique.
The discovery was made that the myopic cornea could The late 1990’s saw the introduction of the
be flattened by creating radial incisions from the microkeratome and the LASIK procedure. The
papillary zone of the cornea to the limbus of microkeratome allowed for sub-surface ablation of
predetermined number, length, and depth. Low to corneal stroma with preservation of the corneal
moderate myopia could be corrected to a high degree surface by creating a corneal flap containing
of accuracy. Arcuate incisions were later added to epithelium, Bowman’s Membrane, and a thin layer
 Advances in Refractive Surgery: Surface Ablation 119

of superficial stroma. Reflection of the flap to the side the patient, although most are correctable. In an effort
gave the excimer laser access to the stroma for to prevent flap creation problems, advanced
ablation purposes. After laser ablation, the intact flap microkeratomes have been designed with a better
containing the corneal surface was replaced. Visual understanding of the dynamics of microkeratome
recovery was fast with minimal discomfort. Safety function. The most advanced of the microkeratomes,
and reproducibility of results was high. LASIK has the Horizon™ by Refractive Technologies has
remained the primary mode of refractive visual reduced flap creation problems to almost zero. In
correction to this day. flat to moderately curved corneas. No micro-
Multiple refractive surgical techniques give the eye keratome, however, is 100% safe when used on steep
surgeon a variety of choices in approaching the corneas, due to intrinsic forces that are generated
correction of vision. Certain techniques may be more during the cutting of a flap. Flaps created on steep
appropriate for one patient than for another. As in corneas tend to be thinner and some tend to perforate
any surgery, some risks and limitations apply to any during the cutting process. For this reason, many
technique. Listed in Table 14.1 are some of the major surgeons choose to perform epi-LASIK or LASEK on
limitations or complications associated with each steeply curved corneas.
technique. New interest in surface ablation emerged with
Table 14.1: Complications of various refractive surgery techniques the introduction of the LASEK procedure. Rather than
RK: Limited Range, Perforations, and disposing of epithelium as in PRK, LASEK tries to
Structural Instability preserve the central epithelium and use it as a
With Regression and/or Progression of
effect. bandage after surface ablation.
PRK: Initial Discomfort, Haze, and Relatively The bandage effect of the epithelial sheet seems to
Slow Visual improvement.
LASIK: Flap Complications, DLK, Striae, Thin increase post-op comfort for the patient and lessen the
Stromal Beds, chance of corneal haze, a problem with some PRK cases.
Late Ectasia and Induced Higher Order
Aberrations. Unfortunately, the alcohol employed to disrupt epithelial
EPI-LASIK: Stromal incursion, mild discomfort attachments in LASEK also kills limbal epithelial cells,
LASEK: Alcohol Toxicity, Relatively Painful, and
Slow Healing. slowing the ingrowth of new central epithelium.
CORNEAL INSERTS: Limited Dioptric Range; Mostly Limited
to Special Uses (Keratinous).
REFRACTIVE LENS Invasive, retinal complications.
Epi-LASIK
EXCHANGE:
LASER KERATOMES: Requires Expensive Equipment and Bed Epi-LASIK is a technique that uses a mechanical epi-
issues. keratome to separate the central epithelium with its
REFRACTIVE IOLs: Invasive, Costly, Endophthalmitis,
centration
basement membrane from the underlying Bowman’s
membrane in a sheet that can be used after corneal
Since LASIK and surface ablation (primarily PRK, ablation to cover the open cornea, much like a flap is
epi-Lasik, and LASEK) now account for more than used in LASIK. No toxic alcohol is used and no
80% of all refractive procedures, LASIK and surface epithelial cytotoxicity occurs. The epi-keratome has
ablation will be discussed in detail. a dulled plastic blade instead of metal, so no cut is
planned through Bowman’s membrane. A smooth
LASIK
Bowman’s Membrane is exposed for laser ablation
LASIK makes use of a mechanical microkeratome in and viable limbal epithelial cells remain intact to
producing a thin superficial flap of corneal tissue initiate ingrowth of new central epithelium. The
which is reflected to the side by the surgeon before a epithelial regrowth seen in epi-Lasik is more rapid
corrective ablation of the cornea is performed. Flap than in LASEK, and the vital epithelial flap seems to
creation complications occur at a rate of 1-2% in the moderate postoperative discomfort. The difference
best of hands. Spoiled flaps can be vision limiting for from the LASIK flap is that the epi-LASIK epithelial
120 Mastering Advanced Surface Ablation Techniques

sheet only serves as a bandage while the cornea heals Second generation devices such as the Horizon
by central reepithelialization. (In LASIK, the flap is much System™ safely produce an Epithelial “flap” without
thicker and the epithelium and Bowman’s Membrane stromal intrusion.
are retained, only to heal in at the periphery.) The flap is created by separating epithelial
First generation epi-keratomes mirrored their basement membrane from Bowman’s Layer of the
microkeratome cousins, substituting dulled plastic cornea with a non-metallic, automated separator.
blades for the sharp metal blades. As with their early
The unique edge design of the Horizon mechanical
microkeratome cousins, some problems existed with
separator cleanly incises the epithelial edge and
the design and some results were unfavorable. Failure
pushes epithelium forward without stretch. The
to remove a total epithelial sheet, sheet destruction,
stromal incursions, and epithelial stretch were some resultant epithelial flap replaces easily over the
of the noted problems. treated stromal bed, without overlap or wrinkling.
A newer Second Generation epi-keratome is now The separator edge has a soft edge™ design with a
available which has incorporated advanced separator compound curve that will not cut Bowman’s and
design to overcome these problems. intrude into the stroma. The LASIK related risks
The Horizon epi-keratome by Refractive (while low) of ectasia, buttonhole, DLK, scarring, flap
Technologies, Inc. is an excellent example of a second striae, and severe postoperative dry eye are markedly
generation epi-keratome and will be used as the reduced, if not eliminated entirely in epi-LASIK.
model for this discussion.
Overall, epi-LASIK offers the following:
• Increased safety profile over LASIK in steep
corneas.
• Higher degree of patient comfort than in PRK and
LASEK.
• Ease of procedure and low complication rate.
• Excellent postoperative results. Visual outcomes
comparable to LASIK. No induced higher order
aberrations.
• Very cost effective.
• Predictability of visual outcome.
• Leaves a THICKER residual corneal stromal bed
for structural stability.
• Indicated for thin corneas, steep corneas, and
higher myopic corrections. Figure 14.2: Transferent epi-Lasik separator

Epi-Keratomes strip both epithelium and basement

membrane from Bowman’s membrane by pressing an
oscillating blunt edged separator onto the cornea and
moving forward at a constant rate. The histological
specimens below (Palikaris) demonstrate this.
Comfort levels approaching that of LASIK are
being achieved with epi-LASIK. Preserving the
epithelium as a vital sheet and replacing it over the
ablated stromal bed increases postoperative comfort,
perhaps by reducing chemical mediators of pain.
Figure 14.1: Horizontal epi-keratome. Note, clear PMMA Vital limbal epithelial cells (undamaged by alcohol)
construction and plastic separator are available for immediate ingrowth over the stromal
 Advances in Refractive Surgery: Surface Ablation 121

Linear and rotational microkeratomes can create

thin stromal flaps centrally, especially when a steep
corneal curve exists at the 90° axis. Rotational
microkeratomes also can produce ragged and thin
inferior stromal flap edges. Epi-Lasik is the safer
option for use on steep corneas, as no stromal cut is
made. Epithelial flaps are sharp edged and retain a
wide “hinge”. Central flap thinning is not a problem.
Epi-Lasik also allows for treating higher myopic
corrections and/or thinner corneas, while all the while
retaining a thicker residual stromal bed. epi-Lasik
seems to provide the following advantages:
• No induced Higher Order Aberrations as
sometimes seen in LASIK
• More rapid re-reepithelialization with less haze
and pain as compared to PRK
• Compatible with mitomycin C use if desired in
higher corrections.
• Visual results comparable to LASIK in the near
term and long term,
Figures 14.3A and B: Arows indicate basement membrance
LASIK has the advantage of a faster visual rebound
and somewhat less discomfort in the immediate
postoprative period.
The Horizon System was designed as a dual use
system. Both LASIK and epi-Lasik can be performed
with the same system. Switching from epi-Lasik to
LASIK takes less than a minute. The console is pre-
programmed for either function and changes over
with the push of a button. The drive cable supports
either an epi-Lasik hand piece or a LASIK handpiece.

Figure 14.4: Horizon epi-keratome, translucent, single use injection

molded. No compression plate sterile handpiece, sterile head, pre-
assemblen

bed. Bandage soft contact lenses such as the Vistakon

Oasis® add to comfort and protect the healing Figures 14.5 A: Epi-keratome, B: Microkeratome
epithelium.
“Steep” corneas have always presented a The following questions then arise: When is Epi-Lasik
challenge to LASIK refractive surgeons. Mechanical more appropriate than LASIK? On what basis is the choice
microkeratomes face an “uphill battle” when between the two techniques made? Several factors are
confronting steep corneas (> 45.00D). More on this later. considered.
122 Mastering Advanced Surface Ablation Techniques

Two factors almost always favor the choice of LASIK. • As the corneal volume admitted through the
These are post-op comfort and rapidity of visual microkeratome aperture increases, either by
recovery. There also is a FAST gratification factor increasing aperture size or corneal curvature,
which is highly marketable. upward force against the advancing micro-
Four factors almost always favor the choice of Epi-Lasik. keratome head will also increase.
These are the ability to treat thinner corneas, achieve • Too much generated upward force results in thin
higher corrections, retain a thicker stromal bed, and flap or buttonhole creation.
avoid thin flaps/buttonholes. • Controlling corneal volume controls upward force
An additional factor, SAFETY, overrides all of these and resultant flap quality.
other factors. • It’s all about Corneal VOLUME. The more corneal
volume that is exposed to the compression plate,
Safety Favors the Epi-Lasik Procedure in the greater chance for flap complications.
Steeper Eyes
LASIK microkeratomes don’t always work as well
on steep eyes as they do on flatter eyes. The origin
of this problem is the subject of many theories. What
we do know is that LASIK microkeratomes pressurize
the eye and compress the cornea, to achieve a planar
cut flap. This corneal compression generates forces
that in turn push back on the entire LASIK
Microkeratome, trying to lift it away from the eye. Figure 14.6: The volume of cornea exposed to the microkeratome
The steeper the cornea, the more the compression, can be regulated by the choice of appropriate aperture size

the more pushback, and the more lift generated. At

some critical degree of corneal steepness, the
PUSHBACK causes some tissue distortion, a slight
lift of the keratome for a microsecond, and a thin flap/
buttonhole may occur.

Newer Design Epi-Keratomes Work Better on

Steep Corneas
Second generation epi-keratomes do not use
compression plates and are less subject to this
Figure 14.7: Upward induced force on the attached microkeratome
pushback or lifting force. Epi-Lasik epithelial sheets can cause distortion of the ocular tissues and microscopic lift of the
are safer to create on steep corneas than Lasik flaps. device without suction loss, one major factor in flap thinning and
Epi-Lasik sheets are not subject to thinning. possible buttonhole creation

To understand the limitations of microkeratomes The Horizon system microkeratome is unique in

and where epi-keratomes fit into the refractive that it regulates the amount of corneal volume
surgery picture, the concept of corneal volume needs admitted through the suction plate aperture by
to be considered. matching aperture size to corneal shape.
INCREASING the Size of the Suction Ring Aperture Seven apertures are available for this purpose.
INCREASES the Corneal Volume admitted through that Larger ones for flat corneas, smaller ones for steep
aperture. corneas.
INCREASING the Corneal Curvature INCREASES If the 3 variables already mentioned are not
the Corneal Volume admitted through that aperture. enough (curvature, aperture, and corneal volume), the
 Advances in Refractive Surgery: Surface Ablation 123

cutting head advancement rate also plays a major role We know that the use of mechanical micro-
in creating additional induced upward force on the keratomes in LASIK has corneal curvature limitations.
microkeratome assembly. Slowing down the Steeper corneas are riskier to treat with LASIK
advancement rate is crucial to lowering induced microkeratomes — (Induced Upward Forces and
upward force. Higher Risk of Thin Flaps and Buttonholes.)
The induced upward force of steep corneas is The integration of epi-Lasik into the refractive
controlled by these methods up to a point. surgery spectrum expands the safety zone in regard
to treating steep corneas.
Flat and medium corneas do well with either Lasik
or epi-Lasik.
Steep corneas do better overall with epi-Lasik.
Lower induced forces rule the behavior of the epi-
keratome.
Little volume induced lift and no flap thinning
occurs in the epi-procedure.
With this in mind, the Horizon system uses a
unique predictive nomogram which serves as a guide
for the surgeon.
The nomogram ties together corneal curvature
and microkeratome plate aperture in such a way that
eyes of flat and moderately curved eyes produce
predictable LASIK flaps and steeply curved eyes are
shifted to epi-Lasik for treatment.
In summary, LASIK is still the most prominent
refractive surgery procedure with surface ablation
in the format of epi-LASIK coming in second. Both
Figure 14.8
are relatively safe techniques with certain limitations.
On what basis is the decision made as to whether Further improvements in refractive surgery
to treat with LASIK or Epi-Lasik? The answer is to techniques are to be expected as surgeons are always
use the safest method. striving to provide better care to their patients.
Section
2

Advanced
Surface Ablation
Technique I: PRK
 CHAPTER

15 PRK Patient Evaluation

Christopher J Rapuano (USA)

INTRODUCTION understood by all patients, especially those 35 years

of age and older. Pre-presbyopes should realize that
The importance of the patient evaluation prior to
within a few years they will need reading glasses for
refractive surgery cannot be overestimated. Not only
everything up close, just as they would have, had
is this examination the best way to get an idea as to
they continued in contact lenses. Early presbyopes
whether the patient’s eyes are good for refractive
should realize that they may not read as well after
surgery, but also, just as importantly, whether the
refractive surgery as they could with their glasses
patient is a good candidate or not.
before surgery and may need reading glasses. The
The evaluation consists of history, manifest and
concept of monovision should be brought up with
cycloplegic refractions, a complete ophthalmic
these patients. If interested, they might want to try
evaluation and ancillary testing. After the evaluation,
monovision contact lenses for several days to see if
a complete discussion of the refractive surgery
they are happy with this compromise.
options, benefits and risks should be performed.
Informed consent for surgery needs to be obtained HISTORY
prior to surgery. The history includes the patient’s
expectations regarding refractive surgery, a social Social History
history, medical history and ocular history.
The social history may help identify the visual needs
PATIENT EXPECTATIONS of the patient’s profession or recreational activities.
Certain occupations require the patient’s best vision
Expectations can be divided into refractive results to be a particular distance, e.g. a watch maker may
(e.g. level of uncorrected distance and near vision) want the best vision to be at 14 inches, not 20 feet.
and emotional results (e.g. improved self-confidence). Other occupations (e.g. military, police or fire fighters)
Patients should understand that their uncorrected may have specified uncorrected and best-corrected
vision after surgery is typically not better than their vision requirements. Some jobs may also have
best-corrected vision before surgery. Refractive restrictions on the types of refractive surgery they
surgery also does not prevent other ocular problems may have. The type of sports or recreational activities
such as cataract and retinal detachment. It is extremely a patient engages in may also help determine which
important that the concept of presbyopia be refractive surgical procedure may be best for them.
128 Mastering Advanced Surface Ablation Techniques
A kick boxer or wrestler may want to avoid a lamellar time to be out of lenses, but good general rules are
procedure and proceed with surface ablation. to be out of soft contact lenses for at least 3-14 days
and rigid contact lenses for at least 2-3 weeks. Any
Medical History patient with an unstable or irregular cornea should
The medical history includes systemic conditions, remain out of the lenses until the corneal topography
prior and current medications and treatments and normalizes and the refraction stabilizes.
previous surgeries. Some systemic disorders, such Anatomic history includes problems such as dry
as connective tissue diseases, can lead to difficulty eyes, blepharitis, recurrent erosions, glaucoma and
healing, while immunocompromised patients may be retinal problems such as tears or detachments. Many
at higher risk for infections after surgery. Certain patients seek refractive surgery as they have recently
medical diseases, such as diabetes, significantly become contact lens intolerant due to worsening dry
increase the risk of future ocular problems, such as eyes. Occasionally treating the dry eyes and
cataract and retinopathy, which can seriously affect modifying their contact lens regimen may be a better
the vision. Systemic corticosteroids are also associated option than refractive surgery. Patients who are
with cataracts and glaucoma. Certain other functionally monocular are not great candidates for
medications may increase the risk of problems after refractive surgery because of the risk of a poor result
refractive surgery. Isotretinoin (e.g. accutane), in their only good eye.
amiodarone (e.g. cordarone), sumatriptan (e.g.
imitrex), hormone replacements and systemic EXAMINATION
antihistamines are thought to increase the risk of poor
Visual Acuity and Refraction
corneal healing. Refractive surgery is also generally
contraindicated in pregnant and nursing women as The uncorrected distance visual acuity should be
the refraction and corneal hydration states may not measured. The patient’s current glasses should be
be stable. measured and compared to the refraction as a way
to help assess refractive stability. A manifest
Ocular History refraction should be performed. The best vision with
The ocular history can be divided into refractive and the least amount of minus (i.e. “pushing plus”) should
anatomic. The refractive issues include stability of be documented. A cycloplegic refraction should also
the refraction and the previous and present modes be performed. Make sure to wait until the full
of optical correction. Ideally the patient’s refraction cycloplegic effect has occurred before performing the
should be stable for the past several years. A contact cycloplegic refraction. The cycloplegic refraction
lens history should be taken. Important information should be used to refine the sphere but not the
includes the type of lens used (e.g. soft, rigid gas- cylinder. When large refractive errors are being
permeable, polymethylmethacrylate, hybrid), the measured (e.g. over 5D) a vertex distance should be
wearing time (e.g. daily disposable, frequent determined. Patients with a large difference between
replacement, overnight wear including number of the manifest and cycloplegic refractions may require
night worn in a row), the disinfection and enzyming a post-cycloplegic manifest refraction to achieve the
methods and exactly how old the lenses are. Any most accurate result.
new problems with contact lens wear should be
Pupillary, Ocular Motility, Confrontation Field
discussed. The patient should be out of the contact
and Orbital Anatomy Evaluation
lenses for period of time prior to the refractive
surgery evaluation and also the surgery as contact Prior to placing the dilating drops, the external and
lens wear can change the shape of the cornea and anterior segment examinations are performed. A
affect the refraction. There is no universally accepted standard pupil evaluation is done looking for pupil
 PRK Patient Evaluation 129
reactivity and a relative afferent pupillary defect. or ocular surface disease are associated with delayed
Pupil size in dim light is also generally measured as epithelial healing and poor vision after PRK and
large pupils may increase the risk of postoperative should therefore be treated preoperatively.
glare and halos. There are several techniques to The anterior chamber, iris and lens should also
measure dim light pupil size including using a near be evaluated. Eyes with significant lens opacities are
card with the pupil sizes on the edges and instruments not ideal candidates for PRK.
such as light amplification and infrared pupillometers.
Ocular motility is also evaluated as some patients with Dilated Fundus Evaluation
asymptomatic phorias or tropias may develop The lens and posterior segment should be examined
symptoms after refractive surgery. If there is a after dilation. Again, eyes with significant lens
question regarding ocular alignment or previous opacities may do better with lens replacement surgery
strabismus surgery, a trial of contact lenses prior to than PRK. The optic nerve should be examined for
surgery is often helpful. Confrontation fields should abnormalities, especially glaucomatous damage. The
also be performed. The anatomy of the orbits should retina should also be evaluated, especially the
be evaluated, as placement of the microkeratome peripheral retina, as highly myopic eyes are at
suction ring for epi-LASIK may be difficult in patients increased risk for peripheral retinal abnormalities,
with small palpebral fissures or prominent brows, retinal tears and detachments.
predisposing to a poor epithelial flap.
ADDITIONAL TESTING
Intraocular Pressure
The intraocular pressure (IOP) should be measured. Corneal Topography
Patients with a history of glaucoma should understand An assessment of the corneal curvature is needed
that if a suction ring is used to create an epithelial prior to PRK. Manual keratometry readings can be
flap, the IOP is significantly elevated for a period of helpful, but computerized corneal topographic
time, which can potentially damage the optic nerve. analysis gives much more information. A few
PRK procedures thin the cornea and often cause falsely different technologies are currently available to
low IOP measurements postoperatively. Patients evaluate corneal curvature including Placido disc,
should alert their eye doctors that they have had PRK, scanning slit beam and Scheimpflug photography.
especially if they are being evaluated for glaucoma. Whichever method is used, the best candidates for
PRK have spherical corneas or regular astigmatism.
Slit Lamp Evaluation Patients with irregular astigmatism may have mildly
A complete slit lamp evaluation should be performed to moderately decreased best corrected visual acuity.
in all patients prior to PRK. Special attention should The irregularity may be due to contact lens warpage
be directed at the eyelids looking for blepharitis and or an ectatic condition such as keratoconus or pellucid
meibomitis and other abnormalities such as trichiasis marginal degeneration (Figures 15.1 and 15.2). Other
and exposure. The tear film and tear lake should be less common causes of irregular astigmatism include
examined for evidence of dry eyes. The conjunctiva corneal scarring and significant punctate keratopathy.
should be assessed for evidence of active Patients in whom irregular astigmatism is thought to
conjunctivitis (e.g. allergic conjunctivitis) and corneal be due to contact lens warpage should be re-
scarring (which could affect microkeratome use in examined out of their contact lenses for an additional
epi-LASIK). The corneal surface should be carefully- period of time. PRK should be delayed until the
examined for abnormalities such as superficial corneal topography regularizes and stabilizes, which
punctate keratopathy, rapid tear break-up time and may occasionally take many months.
anterior basement membrane dystrophy. Other While somewhat controversial, many surgeons
corneal abnormalities such as keratoconus and Fuchs’ believe that the quality of vision deteriorates when
dystrophy should also be ruled out. Significant eyelid corneas are overly flattened or steepened. The post-
130 Mastering Advanced Surface Ablation Techniques

Figure 15.1: Placido disc computerized corneal topography of an eye with keratoconus. Note the significant irregular inferior steepening,
superior flattening and high “Sim K” values on the color map. The rings demonstrate a mild ovoid pattern

Figure 15.2: Placido disc computerized corneal topography of an eye with pellucid marginal degeneration. Note the irregular against-the-rule
astigmatism pattern and the “Sim K” values indicating high astigmatism on the color map. The rings demonstrate a grossly irregular ovoid pattern
 PRK Patient Evaluation 131
operative keratometry reading should be estimated higher order aberrations and ideally results in better
based on the preoperative measurement and the quality of vision than conventional ablations.
amount of intended correction. Corneas flatter than
approximately 34 D or steeper than approximately DISCUSSION AND INFORMED CONSENT
50 D are thought to be higher risk of poorer vision.
After the history, examination and ancillary testing,
The degree and axis of the corneal topographic
the findings should be discussed with the patient. If
astigmatism should be similar to the refraction. If
he or she is a good candidate for refractive surgery,
not, the topography and refraction should be
their surgical options and their benefits and risks
rechecked. If they are still different, then lenticular
should be thoroughly discussed. Important issues to
astigmatism is the most likely cause. Most surgeons
include in the discussion regarding PRK are post-
will treat the refractive astigmatism with the
operative pain, the delayed recovery of vision and
understanding that after cataract surgery in the future,
the possibility of corneal haze. If mitomycin C is being
some astigmatism will likely reappear.
used, its off-label status needs to be explained.
Pachymetry Expected results for both uncorrected and best
corrected vision for their particular refraction,
The corneal thickness should be measured prior to chances of needing an enhancement, chances of
surgery. While most commonly performed with decreased vision (including rare but severe vision
ultrasonic pachymetry, newer technologies can also loss), the possible need for reading glasses, chances
be used including slit-beam scanning, Scheimpflug of increased glare and halos, dry eye symptoms and
photography and ocular coherence tomography decreased “quality of vision” should be discussed.
systems. The newer methods can provide a “map” Patients should also be offered surgery on one eye
of thicknesses throughout the cornea, which can often one day and the fellow eye a different day if they
be very useful when evaluating corneas with irregular desire. Patients should be familiar with postoperative
topographies. Eyes with extremely thin corneas might medication use and follow-up visits. Patients should
not be great candidates for PRK as excessive corneal review and sign the informed consent document
thinning may increase the risk of keratectasia. Eyes which covers the above issues prior to surgery. The
with moderately thick corneas may require an surgeon should answer any questions prior to
evaluation for endothelial dystrophy, e.g. with surgery.
specular microscopy. The preoperative examination is a vital element
in the evaluation of patients prior to PRK. The history,
Wavefront Analysis
examination and ancillary testing provide the basis
Wavefront analysis is a technique that provides an for a discussion with the patient regarding the pros
objective refractive measurement that is and cons of a variety of refractive options including
individualized for each eye. Some surgeons will use PRK. After this discussion patients should understand
the wavefront refraction to refine the manifest both the benefits and the risks of PRK. If they decide
refraction. Many excimer lasers can use these to undergo surgery, they are now in a position to
wavefront measurements to create a customized partner with the surgeon to obtain the best possible
ablation pattern, which theoretically induces fewer results.
132 Mastering Advanced Surface Ablation Techniques

CHAPTER

16 PRK for Low to

Moderate Myopia

Michael O’Keefe, Caitriona Kirwan (Ireland)

INTRODUCTION disappears. There is an invasion of inflammatory cells

from the tear film.3 They activate keratocytes which
In 1983 Trokel demonstrated that the 193 NM
form new collagen and a proteoglycan matrix. 4
wavelength could precisely remove corneal tissue.1
Fibrocytes also repopulate the stroma. 5 This
Initially two laser systems existed, Visx (Santa Clara,
proteoglycan which gives rise to haze appears at one
California) and Summit Technology (Waltham
month and is maximal at three months (Figure 16.1).
Massachusetts). The technology has evolved through
It usually disappears during the first postoperative
animal and human studies to current clinical practice.
year. Sometimes it takes much longer and may remain
Much of the original data came from Europe.
indefinitely.
However, there was resistance and scepticism
particularly in academic circles as it was feared that
removing Bowman’s layer would result in loss of
corneal transparency. At the time the procedure was
considered to be mainly cosmetic and therefore the
original surgeons were pioneers in this area of
ophthalmology.
Photorefractive keratectomy (PRK) involves the
use of high energy photons produced by an excimer
laser to remove corneal tissue and alter corneal shape.
Following the application of excimer laser to the
cornea, a number of changes take place. Loss of
Bowman’s layer and the removal of stromal tissue
results in a stromal wound healing response.
Figure 16.1: Grade 4 haze following LASEK
Immediately following ablation a pseudomembrane
covers the ablated area. There is an immediate Changes in treatment profiles, ablation zones used
epithelial response with epithelialization of the and the delivery systems have improved both the
ablated area occurring in about 3 to 5 days and technique and the results of PRK. Treatment zones
initially comprising 3-5 layers.2 The new collagen and have increased from the 4 mm optical zone to 6 mm or
proteoglycan forms a pseudomembrane which soon greater and many of theses treatments include
 PRK for Low to Moderate Myopia 133
transition zones. The laser beam has changed from procedures over the last 30 years have included their
the original broad beam to the scanning or spot size transient popularity, short term problems and the
beam resulting in smoother ablation zones and lack of long term follow up. However, excimer laser
elimination of central islands. The initial problems has been the most enduring and most popular of all
encountered included overcorrection or hyperopic shift the refractive procedures that have been performed.
which in some cases times lasted up to six months We have seen a unique departure in refractive
postoperatively. Fortunately, this was followed by practice with the emergence of commercial clinics and
regression and resulted in longer term stable outcomes. clinicians are no longer the masters but the employees.
Many people experienced night visual problems The push for high volume has been responsible for
because of the small optical zones and this manifested the lack of good long term follow up data. There are
in glare and poor vision in dim light. There were no long term prospective randomized studies
corneal changes due to haze which caused permanent published in the literature.
scarring in a minority of patients. Over time, positive The retrospective 12 year study by Rajah et al 8
changes have occurred resulting in significant using 4 mm optical zones and correcting up to 7
improvement in outcome. Unwanted hyperopic shift dioptres of myopia has shown stability over time.
which was so worrisome to both surgeons and patients Corneal haze declined and there was no late haze.
is no longer a problem. Haze and myopic regression Night vision disturbance, haloes and glare was a
which were troublesome have been reduced major issue but it was not an unexpected with the
particularly in the treatment of low to moderate smaller optical zones treated. There was no ectasia
myopia. Pain after surgery which for many patients is or other long term visual threatening complications.
severe has been modified but has not been eliminated. The other longer term retrospective study by
Barraquer first described Cryolathe keratomile- O’Connor et al9 reported night visual problems in
usis to correct myopia.6 In the late 1990’s a procedure 35% of their patients and reported as severe in about
known as laser in situ keratomileusis (LASIK) grew 2%. 5 mm optical zones were used in these patients.
in popularity.7 Patients who underwent this treatment All patients who suffered these symptoms stated that
had a rapid visual rehabilitation and minimal they would undergo the surgery again. In this study,
postoperative discomfort. This new form of treatment good refractive stability was reported from 8 to 12
had greater efficacy in the treatment of higher years with an excellent level of patient satisfaction.
degrees of myopia. Therefore, PRK was only used There have been a number of other studies with
for certain specific indications such as thin cornea, shorter term follow up and all of these studies
narrow aperture, patients with surface corneal confirm the safety of PRK. Whilst there are no surgical
problems and patients who requested it (Table 16.1). risks, post-surgical complications such as infection,
Table 16.1: Indications for LASEK decentred ablations, haze, halos and glare, dry eyes,
Corneal thickness < 500 μm ectasia and ptosis are also less frequent than with
Surface corneal erosions LASIK (Table 16.2).
Anterior basement membrane dystrophies
Post LASIK flap complications Table 16.2: Complications of LASEK
Re-treatment after LASIK Infection
Younger patients Severe haze
Contact sports Regression
Economics Ectasia
Haloes/Glare
LASIK popularized and established the longer
Dry eyes
term future of refractive surgery to the point where Decentred ablation
it has become the most popular surgery in the world Wrong correction
to day. Drawbacks of many refractive surgical Ptosis
134 Mastering Advanced Surface Ablation Techniques
Laser subepithelial keratomileusis (LASEK) is a described13, whereby an epi-keratome separates the
modification of PRK and in contrast to the PRK the epithelium from the underlying stroma without the
epithelial layer is replaced after the laser ablation is use of alcohol. The epithelium is repositioned on
performed. Camellin et al 10 first described their the stroma after the ablation is complete, although
technique involving the use of an 8 mm laser corneal some surgeons chose not to and discard it. A number
trephine to create epithelial separation for removal of different mechanical instruments are now available.
in the treatment of myopia. The trephine is placed O’Doherty et al14 showed comparable visual and
on the cornea and rotated through approximately 10 refractive outcomes to the alcohol technique with
degrees. A special alcohol holding well is then placed lower postoperative pain in the first two hours using
on the cornea encircling the epithelial incision. This the epi-keratome. However, there was a high degree
is filled with a 20% alcohol solution and left in place of failure in flap creation with a 30% conversion rate
for 30 seconds. The alcohol is then absorbed with a to PRK.
wet sponge and the corneal surface is irrigated with LASIK has been a magic operation. It is
saline solution. The epithelium is peeled back to 12 characterised by rapid visual recovery, minimum
o’clock and following completion of the laser ablation discomfort and absence of postoperative pain or haze.
the epithelial layer is repositioned on the cornea. In PRK on the other hand results in pain and slower
a technique described by Azar’s11, the 7 mm, semi visual recovery and for a long time has been relegated
sharp epithelial marker serves as a trephine. This is as the procedure for patients who where unsuitable
attached to a hollow metal handle and serves as a for LASIK. These were patients with large pupils,
reservoir for an18% alcohol solution. A button is thin corneas, those who played contact sports and
pressed on the handle which releases the alcohol into those with small palpebral apertures. Over time, as
the well of the marker. After 25 seconds the alcohol the number of procedures performed has increased,
is absorbed with a dry cellular sponge. Loosened problems have emerged with LASIK such as button
epithelium is peeled as a singular sheet using a dry hole formation, free caps, incomplete caps, diffuse
cellular sponge leaving a flap of epithelium still lamellar keratitis and the increased potential for
attached to the superior part of the cornea. Following keratectesia.15 LASEK, a modified version of PRK has
laser ablation, the epithelial layer is repositioned on to some extent redressed the imbalance as there
the corneal surface. induces less discomfort, less haze and has fewer
Shah et al12 and Azar et al11 have shown that the associated severe operative complications. It offers a
plane of cleavage lies within the epithelial basement safer and improved chance of performing repeat
membrane, between the lamina densa and the lamina surgery into the future. In one of the only studies
lucida. Therefore, there is sufficient basement published, visual improvement after LASEK was
membrane present to aid in epithelial flap significantly slower than LASIK.16 However, visual
reattachment which reduces apoptosis and keratocyte outcomes at three months postoperatively was similar
activation. Bowman’s layer is not disturbed in the in both techniques.
initial process of epithelial loosening. However, many A number of agents to modulate healing have
epithelial cells are destroyed by the alcohol, even at become popular such as Mitomycin C and steroids.17
concentration of 20% and thus they do not provide a The objective of their use in LASEK and PRK is to
mechanical barrier. During procedures where the minimize regression and corneal haze. Epithelial
epithelial flap is lost resulting in PRK there is less removal activates keratocytes on the corneal stoma
haze and rapid visual recovery compared with the and this triggers the production of different collagen
older technique of performing this procedure and which is much less organized than the normal stromal
the results are comparable to LASEK. A further collagen and this may be in turn be a factor in the
modification of LASEK known as Epilasik has been creation of haze. Topical steroids sometimes work
 PRK for Low to Moderate Myopia 135
to completely or partially removing haze. In some myopia. Improved surgical technology resulted in the
eyes the reversal in only temporary and in others development of LASIK. The introduction of LASEK,
there is no effect. Why this treatment works in some a modification of PRK once again has popularized
and not in other patients is not entirely known. It treatment on the surface of the cornea. Long term
may relate to the type of collagen or indeed the outcome is one of the frequently asked questions by
intercellular matrix that is produced. Topical steroids patients contemplating laser surgery. The 12-year
have been used by most refractive surgeons but given studies show stability, safety and a high degree of
that about 20% of patients are steroid responders patient satisfaction in patients treated for low to
and may develop glaucoma, ongoing intraocular moderate myopia by PRK. There are no comparable
pressure monitoring is required. Mitomycin C is an long term studies published regarding LASIK.
alkylating agent which inhibits DNA synthesis.18 Therefore, LASEK has now established itself as an
Whilst it has other ocular indications, it has also excellent alternative to LASIK in low to moderate
established itself in refractive surgery where it is used myopia and indeed may soon challenge as an
alternative in the treatment of higher degrees of
intraoperatively during LASEK and PRK treatments
myopia. Some of the older problems such as severe
of high myopia as a prophylactic measure to prevent
haze and permanent corneal scarring are no longer
the development of postoperative haze. It is also used
an issue. We are becoming more knowledgeable and
to treat severe pre-existing haze (Figure 16.2).
experienced in the modulation of corneal healing.
Concentrations such as 0.03% and 0.02% applied for
Refinements such as the use of larger optical zones
20 seconds following ablation are used and there has
and wavefront technology are now being applied to
been no report of short term corneal complications.
PRK and LASEK. The fear of long term complications
Other medications such as ascorbic acid have been
and the emergence of ectasia, the lack of versatility
used both in vitro and in vivo. They have an anti- and the lack of long term data on LASIK have
oxidative effect and inhibit corneal hydrogenase. rekindled our interest in PRK and LASEK. However,
Patients require large oral doses and there are no the reality is that both procedures have a future.
proper studies to show that they are of definite
benefit.19 REFERENCES
1. Trokel SL, Srinivasan R, Braren B. Excimer Laser Surgery
of the Cornea. Am J Ophthalmol 1983;96:710-5.
2. Tuft SJ, Marshall J, Rothery S. Stromal Re-modelling
following photorefractive keratectomy. Ophthalmology
1987;1:177-83.
3. Campus M, Culvas K, Shuch E, et al. Corneal wound
healing after excimer laser ablation in rabbits. Refractive
Corneal Surgery 1992;8:378-81.
4. F, Hanna D, Waring GO, et al.Wound healing after
excimer laser keratomileusis (photorefractive
keratectomy) in monkeys. Arch Ophthalmol 1990;
108:665-75.
5. Tuft SJ, Zabel RW, Marshall J. Corneal repair following
keratectomy. A comparison between conventional
surgery and laser photoablation. Invest Ophthalmol Vis
Sci 1989;30:1769-77.
Figure 16.2: Significant reduction in corneal haze in eye shown in 6. Queratomileusis y Queratofaquia Bogato Columbia
Figure 1 following treatment with mitomycin c Instituto Barraquer de America 1980;405-6.
7. Pallikaris IG, Katsanevake VJ, Panagopoulou S. Laser in
situ keratomileusis – Intraoperative complication using a
CONCLUSION
type of microkeratome. Ophthalmology 2002;109:57-63.
8. Rajan MS, Jaycock P, O’Brart D, et al. Long term study of
PRK was the first universally popular refractive photorefractive keratectomy 12-year follow up.
procedure for the treatment of low to moderate Ophthalmology 2004;111:1813-24.
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9. O’Connor J, O’Keefe M, Condon PI. Twelve year follow 15. Knorz MC. Flap and interface complications in LASIK.
up of photorefractive keratectomy for low to moderate Curr Opin Ophthalmol 2002;12:242-5.
myopia. Journal Refract Surg 2006;22;871-7. 16. de Benito-Llopis L, Teus MA, Sanchez-Pina JM, et al.
10. Camellin M, Cimberle MR. LASEK technique promising
Comparison between LASIK and LASEK for correction
after 1 year experience. Ocular Surgery News 2000;18:14-7.
of low myopia. Journal Refract Surg 2007;23:139-45.
11. Azar DT, Ang RT, Lee JB, et al. Laser Sub Epithelial
keratomileusis: Electron microscopy and visual outcomes 17. Tolamo JH, Gollamudi S, Green WR, et al. Modulation of
of flap photorefractive keratectomy. Curr Opinion corneal wound healing after Excimer laser keratomileusis
Ophthalmol 2001;12;323-8. using topical Mitomycin C and steroids. Arch Ophthalmol
12. Shah S, Sarham AR, Doyle SJ, et al. The epithelial flap for 1991;109:1141-16.
photorefractive keratectomy. Br J Ophthalmol 18. Carones F, Vigo L, Scandola E, et al. Evaluation of the
2001;85;393-6.
prophylactic use of Mitomycin C to inhibit haze formation
13. Anderson NJ, Beran RF, Schneider TL. Epi-LASEK for the
after photorefractive keratectomy. Journal Cataract
correction of myopia and myopic astigmatism. J Cataract
Refract Surg 2002;28:1334-42. Refract Surg 2002;28:2088-95.
14. O’Doherty M, Kirwan C, O’Keeffe M, et al. Postoperative 19. Askinoff SA, Opalinski Y. The pharmaco therapy of
pain following epi-LASIK, LASEK and PRK for myopia. photorefractive keratectomy. Comprehensive
Journal Refract Surg 2007;23:133-8. Ophthalmol Update 2003;4:225-33.
 CHAPTER

17 The History of PRK and the

Position of PRK in
Refractive Surgery Today
Jes Mortensen (Sweden)

INTRODUCTION the future you have to first mention the past, the
history.
PRK was the leading method for refractive surgery The term excimer is a contraction of excited dimer.
during a long period, and that LASIK has taken the In 1976, Dr Dave Muller, PhD, former President
leading role, but that the PRK has begun to regain of Summit Technology, Inc., built Cornell University’s
popularity. That is even truer today where some first excimer laser. The excimer laser was initially
refractive surgeons cannot pay the insurance bills used for etching silicone computer chips in the 1970s.
demanded by the insurance companies to cover the Excimer laser emission is inherently short pulsed,
risk of performing LASIK. We perform almost 50% typically around l0 nsec, with a repetition rate
PRK today, but aim to increase that number. We between 1 and 50 Hz.
perform Laser-assisted subepithelial keratectomy The ArF excimer laser emission is 193 nm. Research
(LASEK), which we find is superior to PRK. How in the early 1980s showed that excimer laser
the results compare to the EPI LASIK technique generated UV light can precisely etch a variety of
remains to be seen. Today we give more local polymers.
anesthetic eye drops, which were not recommended Dr Srinivasan microetched or photoablated,
earlier; but we have seen no adverse effect on the patterns on human hairs (Figure 17.1A). He was
healing of the epithelium after that. The eye is always impressed as to how sharply defined the edges were
given a contact lens for 3 days, when the patient is and how the microetched hair retained its cylindrical
seen at our clinic. Visual acuity is often better than shape. This information was also published, and in
20/40 after 3 days, and most patients have a visual 1983, Dr Steve Trokel, MD, saw the picture of the
acuity after one week that allows them to drive a car microetched hair and visited Dr Srinivasan at his IBM
without correction. laboratory in July 1983.
PRK disappeared for a while but is now seeing a Drs Srinivasin and Leigh observed that the
renaissance as growing concerns about problems in irradiated substrate is broken into small fragments
LASIK surgery are becoming more and more evident. that are ejected into the surrounding atmosphere.
I shall try to cover the subject partly from the They called the process “ablative photode-
literature but mostly from my own experience from composition”. The term preferred today is
excimer laser surgery. To talk about the present and photoablation. Dr. Srinivasin noticed that you could
138 Mastering Advanced Surface Ablation Techniques

Figure 17.1B

zone was found. In 1996, the first excimer laser for

refractive use in the USA was approved by the FDA.
In 1983, Dr Munnerly refined the use of excimer
lasers to alter the refractive power of the cornea. He
Figure 17.1A presented a mathematical formula to calculate the
depth of ablation, diameter and edge angles of the
remove tissue with the laser without causing any harm treatment.
to the neighbouring material due to heating. The Munnerly´s PRK formula:
At 193 nm, a single UV photon has energy of T = S/3 (D)2
6.4 eV, which exceeds the covalent bond strength of Thickness of the removed tissue (microns)
many molecules. After bond breakage occurs, intense = Refractive change (diopters) divided by 3 ×
local pressure in a confined volume ejects the (Diameter of the ablated zone).2
molecular fragments into the surrounding The first approaches to excimer laser refractive
atmosphere. Corneal tissue effectively absorbs laser surgery attempted to build on the strategies
energy at 193 nm. developed for radial keratotomy. Growing concerns
The high photon energy may result in a purely about the width of the linear incisions that would be
photochemical process. The temperature is only expected to fill with an epithelial plug that might
increased by 5°C. Extremely short laser pulses help persist for months to years turned the investigators
to limit local heating. Photochemical and to direct ablation of the superficial central cornea.
photothermal effects of the excimer laser wavelengths In 1984, Dr Marguerite MacDonald from LSU
on the cornea are due to absorption by solid elements. started doing animal research with the excimer laser.
The excimer laser does not cut like a knife, rather it From that point on, research and development
removes tissue by ablation sending the material groups began to spring up all over the world,
ablated up in the air as a plume. That caused the especially in Western nations. The early pioneers
problems of the early broad beam excimer lasers, as include: Dr Steve Trokel, MD, USA; Dr Francis
the plume shadowed the central part of the ablation L’Esperance, MD, USA; Prof John Marshall, PhD,
zone causing the central island. England; Dr Malcolm Ker-Muir, MD, England;
Mutagenesis and carcinogenesis are always Dr Theo Seiler, MD, PhD, Germany; Dr Olivia
concerns with UV radiation. However, in several Serdarevic, MD, USA; Dr Carmen Puliafito, MD, USA;
studies no mutagenic or carcinogenic cellular Dr Roger Steinert, MD, USA; Dr Marguerite
events 9,10 were seen to be caused by 193 nm MacDonald, MD, USA; Dr Charles Munnerlyn, USA;
irradiation. and others.
In 1983, professor Stephen Trokel and co-workers In July 1988, Dr Marguerite MacDonald, MD,
first reported the precise and controlled etching of performed excimer laser PRK on the first sighted eye
the cornea by an argon-fluorine (ArF) excimer laser thus giving with the longest follow-up in the world.
(Figure 17.1B). An excellent preservation of normal In 1989, in Germany, Dr Theo Seiler did the first
corneal stromal microstructure near to the ablation bilateral excimer laser PRK for myopia.
 The History of PRK and the Position of PRK in Refractive Surgery Today 139
To induce corneal flattening, the most tissue must There were considerable problems with central
be removed centrally, with progressively less islands in the beginning, up to 26% had that problem.
removed toward the periphery. Several laser delivery The patients were unhappy, as the UCVA was low.
systems accomplish that goal. In most cases the central island would disappear
Perhaps the most precise term for this approach without further treatment, but not always.
is laser anterior keratomileusis. More commonly, it Different approaches were developed. Multipass
is known by the less specific term photorefractive multizone technique and multizone ablation in a single
keratectomy; abbreviated (PRK). pass were superior to the old single ablation zone8.
The first laser systems were: A scanning beam in Treating astigmatism was also of concern in the
conjunction with a diaphragm (Meditec, Novatec), early days. To treat astigmatism you have to
and laser systems (Summith, VISX 20/20) with a laser accomplish a toric contour of the corneal surface. Two
beam with a diameter of 4 to 6 mm. A diaphragm basic strategies were pursued. In the first, the laser
system places a moveable circular aperture in the path beam was directed through a moving aperture of
of the laser beam. The aperture can either expand or parallel slit blades that progressively closed during
contract during the exposure. In either case, the the ablation. The ablation could be performed with
central cornea will be exposed to each laser pulse, this aperture alone, or secondly in combination with
and the more peripheral cornea will be exposed to the moving round diaphragm that was used in
fewer pulses. The modern scanning laser systems we spherical myopic PRK.
see today have a scanning beam with a point size of Today the scanning laser has solved the problem,
1 to 2 mm; the laser beam is steered by a computer but pronounced astigmatism is still of some concern;
system. Modern excimer laser systems have a pulse it is possible to treat but there is a problem with
frequency of 50 to 200 Hz. regression. In my experience LASIK is superior to
The excimer laser removes 0.22 to 0.25 microns of PRK in the treatment of severe astigmatism.
the corneal tissue per pulse.
The larger the diameter of the ablation zone the CLINICAL RESULTS
deeper the ablation. A scanning laser cuts deeper than The first clinical studies were done outside the USA. It
the old broad beam lasers, which prompted VISX to was first in 1996 that the FDA approved PRK. Most
offer a combination of the two techniques. That even studies have focused on the correction of myopia in the
made the ablation faster. range of –1.5 to –6.0 diopters11-13. Two studies under
The diameter of the ablation zone was initially the Food and Drug Administration’s (FDA) investiga-
4.0 mm (Summit), but it was soon realized that many tional protocols, generated 2-year follow-up results on
patients had problems with glare and halo, disturbing 500 to 700 patients. Most ablations have been performed
the vision especially during night driving. Eyes with with 5 mm optical zones, and patients have been treated
wider ablation zones were much more unlikely to postoperatively with moderately intense doses of
develop such problems. I have never used an excimer steroids; gradually, the dose was tapered over 4 to 6
laser system with less than a 6 mm zone, so I have months. With this approach, uncorrected visual acuity
not seen a lot of patients with problems from small at 6 months was 20/40 or better in approximately 93%
ablation zones. Most problems disappeared after of patients in both trials. Six-month accuracy within
6 to 12 months. Today we know that the retina is ± 1.00 D of emmetropia was achieved in 75% of patients
able to adapt to the smaller ablation zone at least if it with preoperative myopia ranging from –1.5 to –6.00
is not less than 6 mm. D. Other investigations have looked into the use of the
Another method of reducing the depth of ablation excimer laser for the correction of higher myopia14 and
was to use multiple zones in treating moderate and astigmatism 15-18 ; these studies were performed
highly myopic eyes. multinationally.
140 Mastering Advanced Surface Ablation Techniques
In 1994, professor Björn Tengroth and co-workers 10% had retreatment due to regression. Visual
from Sweden published a study with 495 patients acuity for the whole group, 72% ≥ 20/30, and 81%
followed for 24 months19. Preoperative refraction ≥ 20/40. In the –1.0 to –4.0 group, 92% were better
ranged from –1.25 to –7.50 diopters: than 20/40.
The PRK procedures was performed by the Before treatment 30 eyes had no astigmatism, 52
Summit laser (ExciMed UV/200LA excimer laser). eyes between –0.25 to –0.75 diopters, and 36 eyes
Mean refraction after 24 months was –0.27 ± 0.74 –1.0 to –6.0 diopters. After treatment 73 eyes had no
diopters. The correction was stable first after astigmatism, 27 eyes between –0.25 to –0.75 diopters,
18 months. Subgroup analysis showed that the 18 eyes between –1.0 to –2.0 diopters.
patients with low to moderate myopia (up to –3.90 We achieved an appropriate reduction of the
diopters) had a significantly better refractive outcome astigmatism especially the high astigmatism group.
than those with high myopia. 91% of the eyes had an Unfortunately, we also saw induction of astigmatism,
uncorrected visual acuity of at least 20/40, and 81.5% particularly in cases with high myopia. Our experience
of at least 20/30. 87.5% were within ±1 diopter of was that astigmatism correction is somewhat difficult
emmetropia. to predict. We have tended to under-correct it. The
The first patient was treated at our clinic in problem with astigmatism is hitting the right axis; 5
Jonkoping in February 1992. So far 6000 patients have degrees off the axis reduces the power of the
correction by 20%. If you are 30 degrees from the
been treated, 1000 with PTK. Our first excimer laser
correct axis you get no correction of the astigmatism
was a VISX twenty-twenty B laser. In 1995, we
at all.
upgraded to a VISX Star, which served us until 2000
The second group consisted of high myopics
when we changed to a scanning laser, Chiron 217 c.
(23 patients, average 35 years), 30 eyes between
Today we have the Chiron 217 z and use the Zywave
–10.00 and –25,00 diopters. All were treated in three
technology.
zones; 4.5, 5.0 and 6.0 mm, and in one session.
In the early days we scraped off the epithelium
Astigmatism was also treated if present.
with a knife, then we used an automatic brush (we
The average spherical equivalent before treatment
liked it, the patients did not). Today we use LASEK
was: –13.44 diopters and after –1.88 diopters. We did
(20% alcohol for 20 seconds, roll off the epithelium
not go for full correction in all cases. The follow-up
from the ablation zone, after the excimer laser was 6 months. Every eye in this group showed a
ablation, carefully roll back the epithelium and put tendency to regression. At least 5 eyes have been
on a contact lens). Until we changed to the Chiron retreated. Happily there were very little problems with
excimer laser we had no eye tracker, so free fixation haze; 7 eyes showed haze +1, and 1 patient +2.
was used. Postoperatively dexametason or pred- A change in best-corrected visual acuity was seen: 11
nisone was used topically. Astigmatism > 0.75 D was unchanged, 10 better and 9 worse. One eye lost 3 lines.
corrected. Increase of IOP was seen by 10% in the low myopic
The results I shall present are all from before 1996. group; and by almost 20% in the highly myopic group.
The first reports tell about a hyperopic shift the first As mentioned this material is from 1992 to 1995.
months, we did not see that with our VISX Twenty- I shall now show you results from a group of high
Twenty B laser. myopics with 12 to 13 years follow-up. That might
The first group (89 patients, average age 27 years) give some indications of the safety of the excimer
118 eyes preoperative refraction –1.0 diopters to laser procedure.
-9.75 diopters. Six months follow-up: 80% achieved Performing reoperations we have seen that the
refraction between ±1.0 diopter. Fourteen patients pattern etched into the cornea is unchanged even after
had traces of haze. 13 years (Figure 17.1C).
 The History of PRK and the Position of PRK in Refractive Surgery Today 141
117°. Left eye had macular degeneration.
The corneas were clear, no trace of haze. Observe
the videokeratographies (Figures 17.4 and 17.5).
Left eye posterior ectasia, but no sign of anterior
ectasia.
3. Man 45 years of age. Amblyopic due to severe
myopia and astigmatism.
May 1992, full treatment: Right eye: 20/60,
refraction –14.0/–5.0 × 167°. Left eye full treatment.
August 1992, Left eye: 20/80, refraction –15.0/
–5.0 × 1°.
Due to regression retreatment right eye, August
1993: –6.0 sphere. Visual acuity: 20/60.
Last visit December 2004. Right eye: 20/60,
Figure 17.1C
refraction –5.5/–2.5 × 155°. Left eye: 20/125,
I have three patients (6 eyes) with 13 years follow- refraction –5.5/–5.0 × 170°. Clear corneas no haze.
up and 2 patients (4 eyes) with 12 years follow-up. Videokeratographies Figures 17.6 and 17.7.
Presented as the following cases: Posterior ectasia, but no sign of anterior ectasia.
All eyes were treated with the VISX Twenty- 4. Woman now 41 years of age. Both eyes poor vision
Twenty B laser, epithelium was scraped off with a due to nystagmus, amblyopia; left eye excentric
scalpel. Dexametason was given locally for at least fixation.
4 months postoperatvely, if regression or haze was June 1993, left eye full treatment. Left eye:
seen a longer period of treatment was prescribed. 20/150, refraction –10.0/–1.5 × 0°. November 1993,
1. Woman now 48 years of age. PRK performed May full treatment right eye. Right eye: 20/60,
1992. Refraction left eye: –15.75/–2.25 × 152°. refraction –4.0/–1.5 × 25°. Last visit March 2005.
Visual acuity 20/60. PRK ablation: –13.25/ –2.25 × Right eye: 20/50 without correction, emmetropia.
152°. In August 1992, the right eye was treated. Left eye: 20/125 without refraction, 20/50 with
Refraction right eye: –17.75/–1.75 × 49°. Visual –2.0/–4.0 × 145°.
acuity 20/40. PRK ablation, full treatment. No Videokeratographies show excentric ablation zone
retreatment was needed only traces of haze were left eye, surely caused by the left eyes inborn
seen. Last visit, April 2005. Right eye 20/100 excentric fixation, the patient does not complain
without correction, and 20/50 with –2.75/–1.0 × of any problems with halo or glare. She does not
113°. Left eye 20/150 without correction, and wear any correction. Videokeratographies Figures
20/30 with –5 spherical. The corneas were clear 17.8 and 17.9.
no trace of haze was seen. Observe the 5. Man now 54 years of age. April 1993, right eye
videokerato-graphies. Posterior ectasia, but no treated –11.0/–2.0 × 5°. Right eye: 20/50, refaction
sign of anterior ectasia Figures 17.2 and 17.3. –12.0/–2.25 × 5°. November 1993, left eye full
2. Woman now 55 years of age. 1992, full treatment treatment. Left eye: 20/60, refraction –12.25/–4.0
left eye: –12.0 diopters. Visual acuity left eye: × 168°.
20/50. 1994, full treatment right eye: –8.75/–0.75 Last visit March 2005. Right eye: 20/60, refraction
× 114°. Visual acuity right eye: 20/20. –4.5/–1.0 × 100°. Left eye: 20/80, refraction –5.0/
December 2001, reoperation left eye: –1.5/–3.0 –1.25 × 75°. Videokeratographies Figures 17.10
× 98°. Reoperation due to regression, haze +1.0. and 17.11. Rather nice videokeratographies. No
April 2005, right eye: 20/25, refraction –0.75/–0.75 haze was seen. Again posterior ectasia, but no sign
× 65°. Left eye: 20/50, refraction –2.75/–3.75 × of anterior ectasia.
142 Mastering Advanced Surface Ablation Techniques

Figure 17.2

Figure 17.3
The History of PRK and the Position of PRK in Refractive Surgery Today 143

Figure 17.4

Figure 17.5
144 Mastering Advanced Surface Ablation Techniques

Figure 17.6

Figure 17.7
The History of PRK and the Position of PRK in Refractive Surgery Today 145

Figure 17.8

Figure 17.9
146 Mastering Advanced Surface Ablation Techniques

Figure 17.10

Figure 17.11
 The History of PRK and the Position of PRK in Refractive Surgery Today 147
What we can learn from these cases is that it is article 1994, that except for corrections greater than
possible to treat very high myopia without getting 6 diopters, complications after PRK were rare22.
an anterior ectasia. The cornea is clear and regular. Haze is a kind of scarring taking place during the
Regression was seen in all cases; in spite of that the healing process. Regression will also occur as a part
patients were very satisfied with the reduction of of the haze process. Steroids were suggested to
the very high myopia they had from the beginning, ameliorate the haze and regression 27 . Some
none regretted the treatment. investigators however found that steroids were not
necessary28, 29.
COMPLICATIONS We have had very few problems with haze after
Where the complications that we saw the same as PRK with the VISX excimer lasers. Today we use the
the complications that we had feared? We were LASEK method and in treating higher myopes always
interested in: healing, haze, size of the ablation zone, use mitomycin C 0.02% after the ablation. The whole
regression, hyperopic shift, irregularity, keratoconus, process is described in an article by McCorbett et
postoperative infection and pain during the 2 to 3 al23. They conclude that epithelial and keratocyte
first postoperative days. disturbances only transiently affect visual function.
The worst complication I have seen was a melting The subepithelial deposits are more persistent and
of the cornea. The history: Woman early twenties can have lasting effect on the visual performance.
underwent PRK for myopia of –8 diopters one year Another concern was that a recurrent erosion would
earlier. She suffered a regression of one diopter; we occur. The opposite was seen; we actually use the
had read a paper that suggested the removal of the excimer laser ablation to cure recurrent erosions.
epithelium without further keratectomy would Phototherapeutic keratectomy is our first choice with
suffice. This was performed and the patient was recurrent erosions seen after trauma or with various
prescribed diclophenac (Voltaren) eye drops 4 times types of anterior corneal dystrophies.
a day as a painkiller. She experienced severe pain The size of the ablation zone is still a big issue
and administrated drops every half to one hour for even with LASIK. To day we use the aberrometer
three days, when she was re-examined as she (Zywave) to estimate the size of the pupil under
complained of extremely bad vision in her treated scotopic conditions using that as the size for the
eye. The slit lamp examination revealed a cornea that ablation zone. Not everyone agrees with this. As
had almost melted down with only a few microns mentioned we have had very little complaints after
left of the tissue centrally. She underwent PK the next using the 6.0 mm zone in all treatments during our
day and regained good vision but the refraction VISX period. A certain retinal adaptation takes place.
ended at –8 diopters, no one ever tried to treat this. If you have a decentred zone you might get into
Healing was a concern in the very beginning. The trouble. Decentration was a problem treating the
first eyes to be treated were from the rabbit. All highly myopic eyes, as you could get a drifting of
treated eyes developed severe scarring. When the fixation during the relatively long time the operation
monkey was used, a more controlled healing was took. Today we have a high speed eye tracker, which
seen20, 21. Reepithelialization was seen within 24 to solves the problem. Reoperating decentration is not
48 hours. Stromal reorganization was accompanied an easy task, but the Zywave technology has helped
by an initial phase of vacuolation and invasion by us to reoperate older cases (Figures 17.12 and 17.13).
keratocytes. By 6 months a return to normal was seen. Regression was a problem especially in cases with
Haze is a part of the healing response. The deeper haze. Dr Ca Gauthier et al concluded that that both
you ablate the larger the risk of getting haze. The subepithelial and epithelial layers contribute to
smoother the surface after the ablation the less risk regression in the Summit treated eyes24. Treating
for haze. Professor Theo Seiler et al. concluded in an regression after PRK we always use mitomycin C
148 Mastering Advanced Surface Ablation Techniques

Figure 17.12

Figure 17.13
 The History of PRK and the Position of PRK in Refractive Surgery Today 149
0.02% after the ablation. There are many reports in eye –2.5/–1.5 × 180º. October 1997, retreated –2.5/
the literature confirming this.25,26 –1.5 × 180º. All went well until new haze was
After the experience from the RK procedure a followed by further regression. January 1999,
progressive hyperopic shift was feared. Hyperopic refraction left eye was –0.25/–1.5 × 179º (Figure 17.12).
shift is seen after the PRK procedure, but disappears Full retreatment was done. Haze and new regression
after 3 to 6 months. retreatment number 3 was performed. April 2002,
Irregularity of the ablated zone is caused by the +1.75/–2.25 × 155º. After that treatment his VA
healing response. If we get haze and regression without correction was 20/25 and 20/20 with 0/-1.25
leading to an irregular surface with inferior visual x 140º. But the patient was still not satisfied with the
acuity, we always wait until we are sure that the quality of his vision. Last treatment was done with
healing is complete. It is not always easy to convince the help of the Zywave aberrometer and as you can
the disappointed patient that you have to wait perhaps see his PSF is very good and the patient is now very
for 1 to 2 years before retreatment can take place. satisfied. Visual acuity is 20/20 without correction
We give the patient a contact lens, which often helps. and 20/16 with 0/–0.75 × 10º.(Figures 17.13 and 17.14)
We do not use steroids for a long time as we find What we learned from this is you should never
that the potential complications are more threatening give up and never abandon the patient. The modern
than taking your time with the patient and convincing aberrometers can be very helpful.
him/her that we will find a solution in the end.
A patient with primary keratoconus is not LASER EPITHELIAL KERATOMILEUSIS LASEK
regarded as a suitable patient for PRK by most
surgeons. We treated 24 eyes of 23 patients with I started this chapter with the statement that ´PRK
primary keratoconus; all eyes were scheduled for disappered for a while but is now seeing a renaissance
penetrating keratoplasty. We concluded that: no as growing concerns about problems in LASIK
increased risk was associated with treating primary surgery are becoming more and more evident‘.
keratoconus with excimer laser PRK. We found that During the autumn of 1999 we started performing
excimer laser surgery could improve vision and the LASIK at my clinic. After half a year almost every
ability to wear contact lenses, and it did not interfere procedure was LASIK. We even successfully
with subsequent corneal transplantation surgery30. reoperated some difficult cases with regression after
Do we still treat primary keratoconus? Yes but not PRK with the LASIK procedure. However we stopped
as often. If we find that the odds for postponing the treating eyes with very high myopia; the limit was
PK operation are good we consider treatment if the set to –10 to –12 diopters. We had very few problems
patient agrees. Today we operate the young people with the flaps using the Hansatom. Then 2 years ago
with keratoconus with lamellar keratoplasty. I saw my first case with post-LASIK ectasia. I studied
We are starting to treate the lamellae with the all the available material I could find about this
excimer laser, especially after lamellar keratoplasty subject. We use the Orbscan videokeratograph and
for post LASIK ectasia. We hope that it will be possible the Zywave aberrometer. We look especially for eyes
to restore a normal vision to the patient. The first with forme fruste keratoconus and of course with
patient is scheduled for operation autumn 2005. pachymetry less than 500 microns.
To illustrate what has been said I will tell the story This experience caused a revival of the older PRK
about my patient BL born 1957. August 1996, he technique which was modified (LASEK). The
underwent PRK left eye –6.50/–1.75 × 145º. Visual advantage of LASIK over PRK (LASEK) is the absence
acuity (VA) was preoperatively 20/20. Haze of pain in the post-operative period, rapid visual
developed, and regression followed. February 1997, recovery and very little response in the wound
VA left eye: 20/25, refraction left eye –1.5/–1.0 × 145º. healing, minimizing haze. The problems are well
August 1997, regression had continued refraction left known: Flap problems and risk of developing ectasia.
150 Mastering Advanced Surface Ablation Techniques

Figure 17.14

To the associated flap problems I would even add LASEK was performed in one eye and the fellow
the impact of higher order aberrations. This potential eye had PRK. Preoperative mean spherical equivalent
problem could even become the major cause of the (MSE) was –4.65 diopters (range –1.75 to –7.50 D)
revival of the surface ablation techniques. With the after two years the MSE in the PRK group was –0.18
new technology of treating higher order aberrations ±0.53 D, in the LASEK group –0.33 ± 0.46. No LASEK
you cannot perhaps give the patient “ the vision of eye lost a line of BSCVA31.
an eagle”, but restore the same quality of vision as We often find that the eyes in the high myope
the patient had before the operation; however group are candidates for LASEK . We use mitomycin
postoperative problems with contrast sensitivity and C 0.02% and after we started with this we have not
night vision are still a concern. seen any problems with haze.
In three articles about Laser-assisted subepithelial Another sign of this shift to the surface ablation
keratectomy (LASEK) vs PRK, a reduction in techniques is that the inventor of LASIK, professor I
postoperative pain , significantly quicker visual Palikaris, is now promoting the EPI LASIK technique,
recovery and reduced haze in the eyes with low to which involves the mechanical removal of the
moderate myopia was seen31-33. In a two year follow epithelium from Bowman´s membrane. The
up study by Autrata et al 92 patients were operated. advantage vs LASEK is that you have not killed the
 The History of PRK and the Position of PRK in Refractive Surgery Today 151
epithelium with the alcohol, so the epithelium you 6. Trokel SL, Srinivasan R, Braren B. Excimer laser surgery
of the cornea. Am J Ophthalmol 1983;96:710.
put back after ablation of the surface is still alive. 7. Seiler T, Wollensack J. Myopic photorefractive
The advantages of the method over LASEK is still to keratectomy with the excimer laser. One-year follow-up.
be determined. Ophthalmology 1991;98(8):1156-63.
8. Carones F et al. Ophthalmic Surg Lasers 1996;27
(5 Suppl):S458-65.
SUMMARY 9. Kremer F, Blumenthal M. Myopic keratomileusis in situ
combined with VISX 20/20 photorefractive keratectomy.
Dr Steve Trokel, MD, saw the picture of microetched J Cataract Refract Surg 1995;21:508-11.
hair in July 1983, and visited Dr Srinivasan at his IBM 10. Pallikaris IG, Siganos DS. Excimer laser in situ
laboratory; that was the start of the whole era of keratomileusis and photorefractive keratectomy for
correction of high myopia. J Refract Corneal Surg
photorefractive keratectomy. Never before has a new 1994;10:498-510.
surgical technique been brought to the benefit of 11. Maguen E, Salz JJ, Nesburn AB, et al. Results of excimer
patients so quickly. The dream of changing the laser photorefractive keratectomy for the correction of
myopia. Ophthalmology 1994;101(9):1548-56.
refraction of the eye is very old; different techniques 12. Talley AR, Hardten DR, Sher NA, et al. Results one year
have been tested. Radial keratotomy (RK) was after using the 193-nm excimer laser for photorefractive
developed by the famous Russian eye surgeon, keratectomy in mild to moderate myopia. Am J
Ophthalmol 1994;118(3):304-11.
Professor Fydorov; the RK was the leading technique
13. Dutt S, Steinert RF, Raizman MB, Puliafito CA. One year
until the excimer laser came onto the market -today results of excimer laser photorefractive keratectomy for
it has disappeared. low to moderate myopia. Arch Ophthalmol 1994;
In two decades millions of patients have 112:1427-36.
14. Sher NA, Hardten DR, Fundingsland B, et al. 193-nm
undergone surgery with excimer laser keratectomy excimer photorefractive keratectomy in high myopia.
all over the world. The results are very good; but no Ophthalmology 1994;101(9):1575-82.
one should forget that it is a surgical method; you 15. Hersh PS, Patel R. Correction of myopia and astigmatism
using an ablatable mask. J Refract Corneal Surg 1994;10
can never promise the patient that complications will Supplemental:250-4.
not happen. This is even more important to bear in 16. Cherry PM, Tutton MK, Bell A, Neave C, Fichte C.
mind as excimer keratectomy today in many countries Treatment of myopic astigmatism with photorefractive
keratectomy using an erodible mask. J Refract Corneal
is marketed as a procedure without any risks. The Surg 1994;10(2 Suppl):S239-45.
many scientific articles written, and still being 17. Taylor HR, Kelly P, Alpins N. Excimer laser correction of
produced, on this subject are the best guarantee that myopic astigmatism. J Cataract Refract Surg 1994;
20(Suppl):S243-51.
the evolution of excimer keratectomy will continue.
18. Pender PM. Photorefractive keratectomy for myopic
astigmatism: phase IIA of the Federal Drug
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on poly(ethylene terephthalate) films. J Am Chem Soc 19. Epstein D, Fagerholm P, Hamberg-Nystrom H, Tengroth
1982;104:6784. B. Twenty-four-month follow-up of excimer laser
2. Srinivasan R, Mayne-Bayton V. Self-developing photorefractive keratectomy for myopia. Refractive and
photoetching of poly(ethylene terephthalatate) films by visual acuity results. Ophthalmology. 1994;101(9):1558-
far-ultraviolet excimer laser radiation. Appl Phys Lett 63;discussion 1563-4.
1983;41:576-8. 20. Marshall J, Trokel SL, Rothery S, Krueger RR. Long.term
3. Burlamacchi P. Laser Sources. In: Hillenkamp F, Pratesi healing of the central cornea after photorefractive
R, Sacchi CA (Eds). Lasers in Biology and Medicine. New keratectomy using an excimer laser. Ophthalmolohy
York: Plenum, 1980;1-16. 1988;95(10):1411-21.
4. Puliafito CA, Stern D, Krueger RR, Mandel ER. High- 21. Fagerholm P, Hamberg NH, Tengroth B. Wound healing
speed photography of excimer laser ablation of the human and myopic regression following photorefractive
cornea. Arch Ophthalmol 1987;105:1255. keratectomy. Acta Ophthalmol (Copenh) 1994;72(2):229-34.
5. Kahle G, Stadter H, Seiler T, Wollensak J. Gas 22. Seiler T, Holschbach A, Derse M, Jean B, Genth U.
chromatograph/mass spectrometer analysis of excimer Complications of myopic photorefractive keratectomy
and erbium-YAG laser ablated human corneas. Invest with the excimer laser. Ophthalmology 1994;101(1):153-
Ophthalmol Vis Sci 1992;33(7):2180-4. 60.
152 Mastering Advanced Surface Ablation Techniques
23. Corbett MC, Prydal JL, Verma S, Oliver KM, Pande M, 28. Gartry D, Kerr Muir M, Lohmann CP, Marshall J. The
Marshall J. An in vivo investigation of the structures effect of topical corticosteroids on refractive outcome and
responsible for corneal haze after photorefractive corneal haze after photorefractive keratectomy: a
keratectomy and their effect on visual function. prospective, randomized, double-blind trial. Arch
Ophthalmology 1996;103(9):1366-80. Ophthalmol 1992;110:944-52.
24. Ca Gauthier, Ba Holden, D Epstein, B Tengroth, P 29. O’Brart DP, Lohmann CP, Klonos G, et al. The effects of
Fagerholm, H Hamberg. Nystrom. Role of epithelial topical corticosteroids and plasmin inhibitors on refractive
hyperplasia in regression following photorefractive outcome, haze, and visual performance after
keratectomy. British Journal of Ophthalmology 1996;80, photorefractive keratectomy. A prospective, randomized,
545-8. observer-masked study. Ophthalmology 1994;101(9):
25. Porges Y, Ben-haim O, Hirsch A, Levinger S. 1565-74.
Phototherapeutic keratectomy with mitomycin C for 30. Jes Mortensen, MD, Kent Carlsson, MD, Arne Öhrström,
corneal haze following photorefractive keratectomy for MD, PhD. Excimer laser surgery for keratoconus. J
myopia. J Refract Surg 2003;19(1):40-3. Cataract Refract Surg 1998;24:893-8.
26. Vigo L, Scandola, Carones F. Scraping and mitomycin C 31. Autrata R, Rhurek J. Laser-assisted subepithelial
to treat haze and regression after photorefractive keratectomy for myopia:two-year follow-up. J Catarct
keratectomy for myopia. J Refractive Surg 2003;19(4):449- Refract Surg 2003;29(4):661-8.
54. 32. Lee JB, Seong GJ, Lee JH, Seo KY, Lee YG, Kim EK.
27. Fagerholm P, Hamberg NH, Tengroth B, Epstein D. Effect of Comparison of laser epithelial keratomileusis and
postoperative steroids on the refractive outcome of photorefractive keratectomy for low to moderate
photorefractive keratectomy for myopia with the myopia. J Cataract Refract Surg 2001 Apr;27(4):565-70.
Summit excimer laser. J Cataract Refract Surg 1994; 33. Anderson NJ, Beran RF, Schneider TL. J Catract Refract
20(Suppl):212-5. Surg 2002;28(8):1343-7.
 CHAPTER
The Excimer Laser as
18 Instrument in
Phototherapeutic Laser
Treatment
Jes Mortensen (Sweden)

INTRODUCTION The irregularity of the corneal surface is often the

cause of reduced visual acuity after corneal scars and
From more than 15 years experience of photo- different corneal dystrophies. The hope for a system
therapeutic treatment I will describe treatments that for treating higher orders aberrations has not yet
have stood the test of time and new therapeutics been fulfilled. The manual polishing is still the best
possibilities coming up. Recurrent corneal erosion is and only alternative as the higher order measuring
still the largest group, and the results are good, systems will not function with pronounced
especially if the exact point of erosion is marked at irregularity. We use LaserVis ® as our preferred
the corneal surface, so the diseased area can be treated masking agent when polishing with the laser beam.
properly. The results seen with the dystrophies are often
Keartoconus is a very little group today, especially very good and long lasting.
after we started to perform lamellar keratoplasty The exact edging capability of the excimer laser
almost 5 years ago. The risk of rejection after lamellar has been found useful in treating superficial corneal
keratoplasty is much less than with the penetrating opacities, corneal scares, dystrophies and
keratoplasty, the procedure even gives a irregularities. This part of the excimer laser use is
strengthening of the cornea, so the patient can go commonly referred to as phototherapeutic
back to his job after one to two weeks. keratectomy (PTK).
The correction of high astigmatism after This chapter is based on the author’s experience
penetrating keratoplasty has shown very variable in treating PRK and PTK for over 11 years. More
results not leading to a steady refraction, as the than 5000 patients have been treated at my clinic and
astigmatism very often will return. The new cross- at least 600 PTK cases among those. Until January
linking with riboflavin is very promising in treating 1998 I have been using the VISX B 2020 (Figure 18.1)
early keratoconus and might even allow PTK laser and after January 1998 the VISX Star laser,
treatment of the cross-linked cornea. followed by the Technolas 217 c, now Technolas 217
In high astigmatism and irregularity after PKP we z. The VISX B 2020 laser is a broad beam laser which
first perform a lamellar keratoplasty. That often is able to treat PTK and myopia with or without
reduces irregularity and astigmatism to a degree that astigmatism. The VISX Star is able to treat PTK,
can be treated by PTK or to allow the patient to myopia, astigmatism and hyperopia using a scanning
tolerate contact lenses. mode. The Technolas 217 c and z are flying spot
154 Mastering Advanced Surface Ablation Techniques
Now I will give a little menu, so to speak, of the
diagnoses I have been treating and further on I will
try to tell you more thoroughly about the results for
each group.
It has not been easy to decide how to group the
different treatments. I have chosen to group them
according to the different diagnoses, but you could
even choose to group them according to what
symptoms the patients have exhibited.
Back to my database: Bandkeratopathy, primary
keratoconus, recurrent erosion, pterygium,
Figure 18.1: VISX B 2020 dystrophies (lattice, geographic, fingerprint, Reis
lasers, which can treat the forthmentioned and even Bückler, Groennow), astigmatism, anisometropia,
use custom ablation. I believe that the function of the corneal scars.
excimer laser is so well known that I will not
penetrate deeper into that aspect; instead I will RECURRENT EROSION
proceed to tell you about my own experience.
First described by Hansen in 1972, causes episodes
As I mentioned, about 600 patients have been
of acute pain, lacrimation and photophobia on
treated by PTK at my clinic during the last eleven
waking. There may be a history of previous ocular
years. 382 eyes have had a follow-up time, which can
trauma, or it may occur spontaneously - probably in
give some indication of the achieved results.
association with some base membrane degeneration
Before you start treating with the excimer laser
and often seen with different dystrophies.
you have to remember that it is a surgical device and
The recurrent erosion group is the largest and
that you can only remove tissue, you can never add
includes 116 eyes. We found the results very good
tissue. So you really have to be sure what you intend
and consider PTK as a cure for that disease today.
to do; therefore, do a thorough investigation, not
After one treatment 81% were cured and after
only with a slit lamp, but also with videokerato-
repeated treatment, our success rate was 100%. Today
graphy and pachymetry, especially if you are to treat
LASEK is used. Success rate after LASEK has been
thin corneas. Of course, you should also try to arrive
83% after one treatment.
at the right diagnosis so that you can fully discuss
Many of the patients have had a long history for
the prognosis for the achieved result with the patient.
several years with problems that more or less have
As I have said, you can only remove tissue, never
disabled them for long periods. Today we find that
add. The cornea has a given thickness. The more you
PTK at our clinic is the preferred choice of treatment
treat the cornea - and it is especially worth giving a
with recurrent erosion, and as we have not seen any
thought to this when you are to treat diseases that
complications we treat very liberally.
you are not able to cure, and diseases that might recur
as dystrophies and bandkeratopathies - the less you
How we Treated?
will be able to repeat the treatment in the future.
Irregularities of the surface remain irregularities after If the patient did not have any epithelium defect we
treating if you are not using a masking technique to chose to treat transepithelially, 45 to 50 my followed
smooth the surface. Custom ablation is improving by 5 my. If the patient had any erosion or we found the
but still far from perfection. Do be very careful when epithelium very loose we scraped the epithelium away
you are to treat very dry eyes, postherpeutic eyes or from the affected area and treated 5-8 my through the
eyes with some blinking defect, and never treat a Bowman membrane. Today LASEK is used: in a ring
de-enervated cornea. with a diameter of 8 to 9 mm, 30% alcohol is placed for
 The Excimer Laser as Instrument in Phototherapeutic Laser Treatment 155
21 seconds, increasing time with one second for each Treatment
decade over 20 years. The epithelium is carefully rolled
The group was treated as a PRK group. First we
off, and after ablation of 5 microns replaced, a contact
scraped off the epithelium with a knife and then we
lens is placed for 4 to 5 days.
used a brush, which we liked but the patient did not
A thing you should be very careful about is not to
like. Today we use LASIK or LASEK. Much discussion
treat too much especially if you have an emmetropic
has been if LASIK could be used on eyes, which had
or hyperopic patient, or you might end up with
an operation for retinal detachment. We do not find
unintended hyperopia and not a very satisfied patient.
any contraindication to that.
Videokeratography can often help you if you are not
able to localize the erosion at the moment of healing, Conclusion
as it will often show irregularity of the afflicted area.
If the erosions are near the visual axis the treatment Anisometropia due to iatrogenically produced
should always be properly centred to omit any refractive errors is not uncommon, but it is a
irregularity of the surface that could disturb the visual decreasing group, which can easily be treated with
acuity or visual quality of the eye. Postoperatively the the same good results as you get after PRK or LASIK.
patients were given painkiller orally and antibiotic In this group, we have not included patients with
eyedroppers as recommended treatment. high astigmatism after PK; that group will be
evaluated later.
Conclusion
KERATOCONUS
PTK is safe treating recurrent erosion. After repeated
treatment, our success rate was 100%; after one Treating keratoconus with the excimer laser has been
treatment 81% cured. Success rate after LASEK has regarded as contraindicated until we started treating
been 83% after one treatment. The risk of inducing primary keratoconus in 1992. In the two articles * see
hyperopia can be minimised if the ablation depth is References 5 and 6( (1) Mortensen J, Öhrström A.
restricted to within the Bowmans membrane. Excimer laser photorefractive keratectomy for
treatment of keratoconus. J Refract Corneal Surg 1994;
ANISOMETROPIA DUE TO IATROGENICALLY 10:368-372. (2) (Mortensen J, Carlsson K, Öhrström
PRODUCED REFRACTIVE ERRORS
A. Excimer laser surgery for keratoconus. J Refract
Iatrogenic produced refractive errors are not Corneal Surg 1998; 24:893-989). As stated in those
uncommon but are decreasing in number due to the articles treating keratoconus is not contraindicated,
modern phacoemulsification technique, at least in the we find that keratoconus can safely be treated by
group submitted by the surgeons for cataract. This the excimer laser. The two “surface” methods can be
group consists of patients from surgery for amotio, used but never LASIK.
cataract, secondary IOL-implantation and PK I am not going to re-write the articles in this
(penetrating keratoplasty) without cylinder. The PK chapter, instead I will try to tell you more about how
group will be discussed more thoroughly further on, we evaluated our cases and how we treated them.
because the biggest problem in that group is often The keratoconus group has been evaluated after
astigmatism, not anisometropia. 5 treated eyes, then 24 eyes and now in this chapter
The group comprised 42 eyes, the largest number 40 eyes. The success rate of the first published group
coming from cataract surgery. The group’s mean was that 4 eyes out of 5 improved (80%), the second
refractive error before treatment: –6.05 D × –1.29 D, follow up study of 24 treated eyes showed that 14
(spherical equivalent: –6.69 D), after treatment: –0.8 eyes improved and now in the group of 40 eyes 22
D –1.01 D, (spherical equivalent: –1.31 D). The results eyes improved (55%).
are as good as the results you get when treating with The success rate is bound to reduce as time goes
PRK, as you surely would have expected. by due to the nature of the keratoconus disease. What
156 Mastering Advanced Surface Ablation Techniques
we postulated, and in my opinion succeeded in I shall now return to how we evaluated the
proving, was that it is not harmful to treat patients:
keratoconus as no acceleration of the disease was The patients should have a lengthy history of
seen, and that we succeeded in increasing the time keratoconus and not be able to wear a contact lens.
until PK might be needed. We know that some The refraction should be rather stable for the last
keratoconus patients will never need PK, we are not year. The corneal thickness at the apex of the cone
able to predict which patients will be in that group, was required to be more than half the peripheral
and we are not able to tell if we in the long run could thickness, evaluated by optical estimation with the
increase that group, but what we do know is that we slit lamp biomicroscopy, excessive scarring of the cone
surely can postpone the need of PK for several years involving the stroma was contraindicated. Further
for some of the patients. evaluation by the videokeratography (Topographic
In this early works the keratometry was done by Modeling System [TMS-1], computed Anatomy, Inc.).
the old TMS videokeratography,( Topographic The biggest obstacle to success is irregularity of the
Modeling System [TMS-1], computed Anatomy, Inc.) surface, not major ametropia. The surgery was done
When you evaluate the keratoconic eye with the by the old workhorse, the VISX 2020 B system with
modern Orbscan II videokeratography, which give spherical ablation, cylinder ablation or both. The
much more information, that will recommend you to spherical ablation was decentered to cover the
be much more careful what patient to treat. steepest part of the cone.
As a matter of fact I have seen acceleration of The videokeratographic charts of the keratoconus
keratoconus after 6 months after treating a can vastly differ in appearance: Most of the surface
keratoconic eye with PTK: 54 years old man, being normal with an inferior cone peripherally, the
keratoconus since at least 30 years became contact whole central surface can be engaged with the
lens intolerant, left eye treated in March 2003. topographic picture looking very much like an

Figure 18.2
 The Excimer Laser as Instrument in Phototherapeutic Laser Treatment 157

Figure 18.3

Figures 18.2 and 18.3: Pachymetry 393 um, in June he was happy good vision, but in September the keratectasia had accelerated and the
pachymetry reading was 264 um

astigmatic cornea, and the center can be irregular. preoperatively 0.5; postoperatively BSCVA 0.6 and
The type with the inferior cone can be viewed like 0.5 without SC. Was the patient satisfied? No. The
the picture that is seen after decentration and should result was quite good, but the expectation of the
be treated the same way: decenter the spherical patient exceeded the achieved result, so far.
ablation over the cone, look at the dioptric power Figure 18.5 shows the videokeratography of a
and treat approximately 2/3 of the value (9 diopters binocular keratoconus with heavy irregularity.
gives a treatment of 6 diopters). Measure the distance Preoperatively right eye BSCVA :0.13 (+2,0 sphere –
from the visual axis to the center of cone from the 6,0 cylinder ax 140°). Postoperatively right eye
videographic picture, and mark the measured BSCVA: 0,25 (-2.0 sphere). Treatment was done with
distance on the cornea before treating. diopters in a 5 mm zone decentered).
Now I shall give some examples of how we treated Left eye was treated -6 diopters in a 4-mm zone
(Figure 18.4). not decentered. Preoperatively BSCVA: 0.17 (-3,
Figure 18.3 shows a videokeratography of a sphere -6 cylinder ax 70°).
keratoconus eye with a typically inferior cone. Postoperatively BSCVA:0.17 (-1.0 sphere). The
Treatment was done transepithelially 52 my, followed patient was not satisfied and later had PK. This
by 5 D in a 4 mm zone that was decentered illustrates irregularity as the major obstacle to success;
approximately 2 mm inferiorly to cover the cone. 5 today, I would not have treated that patient.
diopters were chosen, as the cone was approximately Figure 18.6 shows the videokeratography of a
7 diopters over the center. Preoperative change of keratoconus type not uncommonly called globus type.
refraction: +4.0 sphere × -3 cylinder ax 110°. After 4 The patient was treated transepithelially 60 my (-2
months +2.75 sphere –0.5 cylinder ax 40°. BSCVA diopters sphere -6 cylinder ax 180°). Preoperatively
158 Mastering Advanced Surface Ablation Techniques

Figure 18.4: Videokeratography showing a keratoconus eye with a typically inferior cone

Figure 18.5: Videokeratography of a binocular keratoconus with heavy irregularity

 The Excimer Laser as Instrument in Phototherapeutic Laser Treatment 159

Figure 18.6: Videokeratography shows a keratoconus type not uncommonly called globus type
before PTK

Figure 18.7: Videokeratography shows a keratoconus type not uncommonly called globus type at
follow-up 11 months
160 Mastering Advanced Surface Ablation Techniques
BSCVA: 0.5 (-10 sphere -8 cylinder ax 180°). Follow- When you are treating an eye that has had PK
up 11 months, (Figure 18.7) BSCVA: 0.5 (0 sphere - you must always give corticosteroids in high dose
4.5 cylinder ax 90°) the patient was very satisfied. orally for at least a week, to avoid rejection of the
graft. In the treated groups we saw one rejection after
Conclusion PTK-treatment.
Keratoconus has been considered a contraindication For the last 2-3 years I have first performed
to excimer laser surgery because of the fear of relaxing cuts, if I have an eye with a astigmatism more
accelerating the disease and the fear that the than 4 diopters after PK. It is done under a LASIK
epithelium might not heal. You have to carefully flap; I penetrate the cornea in the steepest axis in
evaluate the eye before treating. We did not find two opposite points. The flap has to be sutured to
any changes in the cornea that should negatively secure that the cuts will not leak. If more than 2 to 3
influence the possibility to affecting a successful PK diopters of astigmatism remain, the flap is lifted after
if this should be needed in the future. Today we six months and an excimer laser treatment with the
believe that earlier surgery should not be done, new Technolas 217z laser is done. The astigmatism is split
videokeratography like the Orbscan II could change up in half the positive value and half the negative
the statements as more knowledge about the cornea value to get a more prolate cornea after treatment.
is provided. The patient described in the chapter was
Conclusion
treated exactly the same way with the scanning laser
as we did with the broad-beam laser on the surface Astigmatism can successfully be treated with the
of the cornea and acceleration of the keratectasia was excimer laser and the results are certainly better with
seen. Never promise the patient that you can arrest the LASIK procedure. With very high astigmatism
or heal his keratoconus. What you might do for him after PK, relaxing cuts under LASIK flap are first done.
is to extend the period till he might need PK. If more than 2 to 3 diopters of astigmatism remain,
excimer laser ablation is done after lift of the flap.
ASTIGMATISM
CORNEAL SCARS
Most astigmatism treated by us was iatrogenic. I have
chosen to deal with that problem in this session. This group is very heterogeneous consisting of eyes
The group consisted of 37 eyes, 25 eyes after PK with
and 12 eyes after cataract surgery or surgery for Corneal dystrophies (Reis-Bückler, lattice
corneal trauma. Most of the PK was due to dystrophy, Meesmann´s dystrophy, granular
keratoconus. dystrophy).
Treating astigmatism after penetrating
keratoplasty is a challenge. Did LASIK change that? Traumatic Scars
25 eyes were treated after PK by PRK. Preoperative: Scars after keratitis (Virogen, bacterial)
1,77 sphere –7,55 cylinder. Postoperative 0,39 sphere
– 3,33 cylinder. 5 eyes treated by LASIK. Preoperative: Before treating, you have to evaluate what you want
0,95 sphere –5,50 cylinder – Postoperative:-0,1 sphere to accomplish with the treatment: Reducing pain,
–1,63 cylinder. That could be an indication of a better increasing visual acuity, cosmetic reasons or help the
result with LASIK. eye to tolerate a contact lens.
12 eyes were treated in the other group seen after
Evaluation
cataract surgery or surgery for corneal trauma in this
group much better results were seen. Preoperative To understand the disease behind the scare is very
mean:-0. 35 sphere -4.60 cylinder. Postoperative important. The evaluation is done by
mean:+0.54 sphere -1.60 cylinder. This is acceptable videokeratography and slitlamp microscopy. If the
results. cause is a dystrophy, it is important to understand
 The Excimer Laser as Instrument in Phototherapeutic Laser Treatment 161

Figure 18.8

Figure 18.9
Figures 18.8 and 18.9: 52 years old man. PK 20 years ago due to keratoconus. Contact lens intolerant. relaxing
cuts under LASIK flap, from 13 d of astigmatism till 8 diopters. Treated after six months. VA 0.8 uncorrected,
Refraction: 0 sphere – 2.0 cylinder
162 Mastering Advanced Surface Ablation Techniques
the anatomy of the disease and even it’s nature, is it the future if so required without causing a major
slowly progressive, affecting the Bowman membrane, change in the refraction. Dystrophies from the
the stroma, the epithelium, does it cause recurrent Bowman membrane and in the epithelium are treated
erosion, irregularity of the surface or is it a dense as recurrent erosion. If the major optical problem
central macula that causes the bad visual acuity? comes from irregularity use a masking agent. Even if
I should even like to give a warning. I had two you have a combination of dense macula and surface
young men with a history of keratitis coming for a irregularity, try firstly to smooth the surface, then
polishing of the macula as it was suspected that the evaluate the result after that.
uneven surface of the cornea over the corneal macula Traumatic macula can be very deep and produces
caused their visual problems with reduced visual a major change in the refraction, again, be careful
acuity and monocular diplopia. Case one was a man first to smooth the surface and after that go for the
29 years old one-year before the actual visit had a change of refraction, and inform the patient that you
bacterial keratitis in the left eye in the center of the may need to do more sessions. Always try to
cornea. 6 months later he had VA 1.0 (-0,25 sphere – remember that what has been removed by the excimer
05 ax 60 degrees). laser, will not come back. If you treat a myopic patient
or a patient whom later will have a cataract operation,
you can of course treat more deeply without inflicting
harm to the patient. Irregularity of the surface is still
irregularity after the treating surface if you do not
use a masking agent. New agents are coming. Masking
is an art, using the epithelium, masking with paper,
contact lens and different floating agents (BSS,
methylcellulose, LaserVis).
If you are uncertain as to what caused the macula,
always suspect virus and then give systemic antiviral
medication to prevent a recurrent of the infection
that could be devastating for the result.
Do remember to carefully evaluate the sensibility
of the cornea; if you are treating a cornea with a
Figure 18.10: Macula after 1 year diminished sensibility you could have a big problem.
Orbscan II was done. Right eye normal, left eye The same applies if the lacrimation is in any way
(Figure 18.11) (Figure 18.11 Mattias OS) showed a adversely affected owing to reduced production or
keratectasia and thinning of the cornea to 320 μm. corrupted lubricating ability. Sjögrens syndrome and
Case two was a 28 years old man with a keratitis left post herpetic scars are relatively contraindicated in
eye 1999 in the inferotemporal part of the cornea. my opinion. Carefully evaluation of the blinking
November 2002 recidiv of the keratitis. A thinning ability and the state of the palpebrae is also of major
of the cornea and a thin macula was seen inferotem importance.
porally. VA left eye 0.9 uncorrected, but patient
Treatments
complained over monocular doubbelvision. Orbscan
II right eye normal. Left eye showed a keratectasia As you will understand from the above, there is no
and a thinning of the cornea to 292 μm (Figure 18.12). easy manual that gives all the answers, but again first
(Figure 18.12 Hanseriksson OS). Those patients of all try to treat as little as possible, at least at the
are not good candidates for PTK. first session, then you can come back if needed. We
Again, if you have a dystrophy try to treat as little did most treatments transepithelially with 50 to 70
as possible so that you can repeat the treatment in my followed by 20 my using a masking agent. When
The Excimer Laser as Instrument in Phototherapeutic Laser Treatment 163

Figure 18.11: Keratectasia seen one year after keratitis

Figure 18.12: Keratectasia after keratitis 3 years earlier

164 Mastering Advanced Surface Ablation Techniques
you are smoothing the surface, try also to use the irregularity. Visual acuity as best 0.2 in his right eye
biggest zone you can get from the laser beam. Try to and finger counting left eye (Figures 18.14 and 18.15).
avoid inducing irregularity. I waited for one year and then the right eye was
You can obtain really remarkable results when treated 50 my transepithelially and I tried to smooth
treating the dystrophies affecting the Bowman the surface. The result was 0.5 with contact lenses.
membrane and the epithelium; again, try first to The patient was very happy after that. The patient
smooth and do the treatment in more sessions, and The patient was seen at my clinic 6 months ago
be very careful. and had VA 1.0 both eyes, Orbscan II was done
Do not forget to be very conservative and do (Figures 18.16 and 18.17). A miraculous healing of
remember that the cornea heals very slowly. Do not the corneas had taken place. The nature is still the
haste; do tell the patient from the start that the healing greatest physician.
will be months and not weeks. I shall try to illustrate
that statement. The story goes back to 1995. Corneal Dystrophies
A 29-year-old man woke up after he had been The evaluation is very important to get to the right
wearing his contact lenses for at least 24 hours, he diagnosis. The dystrophies are often assessed
did not really remember as he had been celebrating. anatomically into pre-Bowman´s layer, Bowman´s
His problem was that he did not see anything so he layer, anterior stromal and stromal. The dystrophies
was led to our clinic. Evaluation showed finger are congenital and will recur, so the PTK treatment
counting both eyes, the spectacles he wore showed cannot be considered as a cure for the future problems
that he was -18 diopters in both eyes. Slitlamp caused by the dystrophies, that again points up the
microscopy showed contact lenses “glued” to the need to cause as little impact to the cornea as possible
epithelium, heavy oedema of both corneas to relieve the problem of the patient, so that the
(Figure 18.13) (Figure 18.13 670330dx9509). The procedure may be repeated in the future.
Generally, the problems most often seen with
dystrophies are recurrent erosion and irregularity
of the surface. The cloudiness of the stroma is more
seldom the cause that reduces the visual acuity.
The dystrophies treated were: lattice dystrophy,
map-dot-fingerprint, Meesmann´s dystrophy, Reis-
Bückler‘ s dystrophy, granular dystrophy (Groenouw
Type I), endothelial dystrophies and dystrophies of
uncertain diagnosis.
Our treatment strategy was to inflict as little
change to cornea as was needed. In this group we
find 33 eyes. 20 eyes had PTK treatment done
Figure 18.13: The corneas were cloudy and had severe oedema transepithelially followed by 20 micron in the stroma,
contact lenses were removed, resulting in almost often using a masking agent. 3 eyes had the diagnosis
totally removal of the epithelium. At firstly severe of lattice dystrophy which pathology is caused by
infection was suspected, but this could not be accumulation of amyloid material subepithelially in
confirmed. The corneas were cloudy and had severe the stroma, causing recurrent erosion and irregularity
oedema. The diagnosis of severe ischemia of the of the surface. Mean age 33 years. They were treated
corneas was proposed. The patient stayed for three transepithelially followed by 15 to 27 microns; Visual
weeks and he slowly regained some vision; the acuity increased in all eyes - please look at the
epithelium healed with severe scarring and Table 18.1.
 The Excimer Laser as Instrument in Phototherapeutic Laser Treatment 165

Figure 18.14

Figure 18.15
Figures 18.14 and 18.15: Videokeratography showing severe scarring and irregularity both eyes
166 Mastering Advanced Surface Ablation Techniques

Figure 18.16

Figure 18.17
Figures 18.16 and 18.17: Orbscan after 7 years showing regular corneal surface both eyes. But posterior
ectasia and corneal thinning, certainly not a good candidate for refractive surgery with the excimer laser
 The Excimer Laser as Instrument in Phototherapeutic Laser Treatment 167
Table 18.1: Lattice dystrophy, 3 eyes visual acuity pre-and
postoperatively and stromal ablation
Va Prop Sph Cyl Axis Stromal Va Postop Sph Cyl Axis
0,25 0.50 –1.00 80 25 0.80 1.75 –2.25 100
0,10 6.00 –3.00 0 20 0.50 6.00 –3.00 0
0,25 –3.00 –1.00 90 50 1.00 –1.50 –0.75 60

2 eyes had the diagnosis Groenouw Type I. the

lesions are sharply demarcated confined to the axial
portion of the cornea, usually beginning in the most
superficial portion of the stroma. The deposit is
believed to come from the epithelium. Recurrent and
irregularity often the biggest problem.
Those eyes were treated like recurrent erosion,
transepithelial followed by 10 microns in one eye and
Figure 18.18
the other eye was “polished” 20 micron using
methylcellulose as a masking agent. The results were
very good: both patients got rid of the erosions and
even gained in visual acuity (Figures 18.18 and 18.19).
One eye had the Meesmann dystrophy caused by
small cysts looking gray-white in the rima area. The
cysts are seen at the level of the Bowman membrane.
The complain is often a foreign body sensation and
recurrent erosion and may even be decreased visual
acuity. Our patient was treated transepithelially 50
microns, followed by 30 microns in a 6 mm zone
masked by methylcellulose. Visual acuity pre-
operatively 0.5 and post-operatively 1,0.
One eye with Map-Dot-Fingerprint Dystrophy
disorder involving the epithelium and the basement Figure 18.19
membrane had problems caused by recurrent erosion. Figures 18.18 and 18.19: Cornea with Groenow´s dystrophy pre-
and postoperative 20 years old man
The patient was treated transepithelially 50
microns followed by 11 microns. The patient had one ablation of the stroma. The result was very good,
relapse after 6 months but after that no problems. visual acuity went from 0.2 to 0.6 and was still stable
Reis-Bückler‘s dystrophy is symmetric, evident in after 14 months.
early childhood as recurrent erosive episodes. The rest of the group was classified as having
Patients develop decreased vision due to anterior corneal dystrophies with anterior involvement. As you
scarring and irregularity of the corneal surface. can see from the Table 18.2, the whole group had an
Two patients were found with the diagnosis and increase of visual acuity, but also a shift of refraction
one patient was treated transepithelially 50 microns to hyperopia in spite of the cautious treatments.
followed by 100 micron masked by Tetracain, the Today we always try to use the LASEK to inflect
patient did not improve and had PK. The patient was less pain and faster healing. The last 12 eye the group,
63 years old and had developed excessive scarring. which were eyes with Meesmann´s dystrophy, lattice
The other patient was 49 years old and was treated dystrophy and Groenow type I all healed and
50 microns transepithelially followed by 10 microns improved visual acuity.
168 Mastering Advanced Surface Ablation Techniques
Table 18.2: Corneal dystrophies with anterior involvement. The whole group had an increase of visual acuity, but also a shift of
refraction to hyperopia in spite of the cautious treatments
Visual Acuity Preoperative Ablation Ablation Visual Acuity Postoperative
Preoperative Sphere Cylinder Axis Micron Methode Postoperative Sphere Cylinder Axis
0.65 2.25 -0.75 85 20 transepithelial 50 micron 0.65 2.75 -0.75 85
0.25 0.50 -1.00 80 20 transepithelial 55 micron 0.90 1.75 -2.25 100
1.00 0.75 -0.75 0 5 transepithelial 55 micron 1.30 -0.50 -1.00 120
0.16 3.00 -2.00 125 46 transepithelial 55 micron + masking 0.65 1.75 -3.00 83
0.50 1.75 -2.50 90 40 transepithelial 50 micron + masking 0.80 2.50 -4.00 160
0.40 0.00 -5.00 160 33 transepit 70 my + 33 my + -4 cyl 0.80 2.50 -4.00 160

0.30 0.50 -2.00 165 26 transepithelial 50 micron + masking 1.00 3.00 -1.00 10

BAND KERATOPATHY

The group consisted of 16 eyes. Most eyes had

severely impaired function due to severe diseases.
Five treatments were carried out to improve visual
acuity, one treatment aesthetic the rest was to relieve
pain.
The treatments were transepithelially followed by
ablation from 18 to 200 microns to polish the surface,
often using a masking agent. With the ruff type of
band keratopathy you might need to remove the
A dense calcification manually before doing the
smoothing. You might even try EDTA before
continuing with the excimer laser.

Conclusion
Developing bandkeratopathy often indicates severe
disease of the eye. The treatment can often relieve
or diminish pain caused by recurrent erosion or
irregularity of the surface. Is it better than EDTA?
The outcome is not certain, but we have seen less
complication and pain for the patients, as the
epithelium will heal much faster and the treatment is
B often chosen by the patient as much the easier one to
Figures 18.20A and B: Immigrant from Ethiopia with unknown endure.
corneal dystrophy pre-and postoperative

Conclusion PTERYGIUM

PTK treatment of different corneal dystrophies often We meant to abolish or diminish the recurrens of the
gives very good results, especially if the problem is pterygium. The pterygium was surgically excised and
due to recurrent erosion or not too severe irregularity after that the denuded area was polished, often
of the surface of the cornea. Try to treat as little as under masking of methylcellulose, by the excimer
possible to obtain the desired result, as the dystrophy laser. Central macula or irregularities of the cornea
can often give similar problems in the future. were treated as earlier described. Did we see any
 The Excimer Laser as Instrument in Phototherapeutic Laser Treatment 169
Conclusion
We did not see that any beneficial effect uptained
from polishing the denuded area by the excimer laser
as compared to only surgical excision of the
pterygium.Treating macula of the central cornea was
successfully.

SUMMARY

PTK has matured from infancy to at least early teens

and has become an important therapeutic instrument
A in Ophthalmology of the 20th Century. We wait for
better custom ablation to come. Lamellar keratoplasty
could in combination with the PTK treatment improve
the quality of the outcome for the eyes that need a
PK.
Most PTK treatments were done with the broad
beam excimer lasers. Comparently much fewer
treatments were done by the flying spot excimer
laser, but I do think that it is clear that the
combination of LASIK and flying spot excimer laser
give an improved result in treating astigmatism and
the flying spot laser is the basis of the custom ablation.
The PTK stands the test of time, more than ten
B
years experience has been accumulated. We have to
Figures 18.21A and B: Band keratopathy in an eye operated with
silicon oil, pre- and postoperative
bring that knowledge out to our colleagues to let
our patients benefit from PTK treatment.
success in the group of 13 eyes? Yes- if visual acuity
was diminished due to central irregularity of the
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172 Mastering Advanced Surface Ablation Techniques

CHAPTER Myopic Photorefractive

19 Keratectomy using
Solid State Laser

Nikolaos S Tsiklis, George D Kymionis, George A

Kounis, Ioannis G Pallikaris (Greece)

INTRODUCTION an acronym: Light Amplification by Stimulated

Emission of Radiation. As a light source, a laser can
Myopic Photorefractive Keratectomy (PRK) using
have various properties (Figure 19.1), depending on
excimer laser systems of 193 nm wavelength have
the purpose for which it is designed and calibrated.7
proved to be a safe and reliable procedure.1, 2 Corneal
A typical laser emits light in a narrow, low-
photoablation using laser pulses in the far UV region
divergence beam and with a well-defined wavelength
(190-220 nm) offers precise tissue removal with
which corresponds to a particular colour if the laser
similar characteristics (ablation threshold, ablation
is operating in the visible spectrum. This is in contrast
rate and size of collateral damage zone).3 Two are
to a light source such as the incandescent light bulb,
the main sources of ultraviolet radiation used in
which emits into a large solid angle and over a wide
corneal photoablation; the ArF excimer laser (193 nm
spectrum of wavelength. These properties can be
wavelength) and the fifth harmonic of the Nd:YAG
summarized in the term coherence which is the most
laser which emits at the 213 nm wavelength.
important property of a laser light source.
The current trends towards advanced modern corneal
A laser consists of a gain medium inside an optical cavity,
ablations requires laser platforms with high pulse
with a mean to supply energy to the gain medium, and
frequencies, small laser spot size and eye tracking system
also of the gain medium pumping device. The gain medium
that can ensure accurate transfer of the energy on the
is a material (gas, liquid, solid or free electrons) with
cornea. Recently, solid state lasers are gaining popularity
appropriate optical properties. In its simplest form, a
in the refractive surgery community since they provide
cavity consists of two mirrors (input and output coupler
special technological features and many studies indicates
with 100% and 95% reflectiveness accordingly) arranged
that they can be used effectively as an alternative solution
such that light bounces back and forth, each time passing
to the traditional excimer laser systems.4-6 There are two
through the gain medium. Typically, one of the two
solid state laser platforms available in the market for
mirrors, the output coupler, is partially transparent. The
refractive surgery: Pulzar Z1 laser system (CustomVis)
output laser beam is emitted through this mirror. The
and LaserSoft (Katana Technologies GmbH).
pumping device activates the gain medium through
various means depending on the type of the medium
LASERS PRINCIPLES OF FUNCTION
material. More often electrical discharge is being used
Laser is a device that emits light through a specific for gas materials like excimer lasers or optical for solid
mechanism which is described by the term laser as materials like YAG lasers (Figure 19.2).
 Myopic Photorefractive Keratectomy using Solid State Laser 173

Figure 19.1: The unique laser properties—monochromaticity, directionality and coherence

Figure 19.2: A laser cavity—Basic components of a laser system

174 Mastering Advanced Surface Ablation Techniques
Excimer lasers are gas gain medium lasers and
are powered by a chemical reaction involving an
excited dimer, or excimer, which is a short-lived dimeric
molecule formed from two atoms, at least one of
which is in an excited electronic state. The most typical
excimer laser used in ophthalmology is the ArF at
193 nm wavelength.8-12
Solid state lasers are laser which are using a solid
material as gain medium which is optically pumped
using a flashlamp or diodes lasers. Solid state laser
gain materials are commonly made by doping a Figure 19.3: Non-linear optics principles
crystalline solid host with ions that provide the
required energy states. For example, the first working typically only observed at very high light intensities
laser was a ruby laser, made from ruby (chromium- such as those provided by pulsed lasers as the pulsed
doped sapphire). Neodymium is a common dopant in Nd:YAG.
various solid state laser crystals, including yttrium Nonlinear optics utilizes a number of optical
aluminium garnet (Nd:YAG). These lasers can produce phenomena in order to create higher harmonic from
high powers of 10W (for clinical use) in pulsed mode the principle one. The most common method is the
(10nsec pulse duration) in the infrared spectrum at frequency-mixing processes (Figure 19.4). After
1064 nm and is the most common used solid state laser creating second and third harmonic those frequencies
in ophthalmology. The spot size may be sized below are mixed together with the principle in order to
1mm and has true Gaussian shape.13,14 create higher harmonic like the fifth. Practically,
The Nd:YAG laser is used as a means of correcting frequency mixing is carried out by placing a special
posterior capsular opacification (after-cataract). crystal in a laser beam under a well-chosen angle.
Nd:YAG laser is used for peripheral iridotomy in These crystals have the necessary properties of being
patients with acute angle closure glaucoma, where it strongly birefringent, having specific crystal
has superseded surgical iridectomy.15,16 Frequency- symmetry and of course being transparent for and
doubled Nd:YAG laser (532 nm) is used in place of resistant against the high-intensity laser light.21-23
argon laser for pan-retinal photocoagulation in
patients with diabetic retinopathy.17-20 CustomVis Pulzar Z1 Solid State Laser
PULZARTM Z1 is a solid state refractive laser that is
Achieving the Fifth Harmonic
designed specifically for custom surgery, permitting
Nd:YAG solid state lasers have been introduced for an accurate approach to correcting both standard and
use in the refractive surgery during the last 5 years. non-standard vision disorders (Figure 19.5). Also it
In order to be used the proper ultraviolet wavelength is eliminating the need for toxic gases and storage
must be achieved. The principles of nonlinear optics and provides low maintenance costs and down-
(NLO) are being used for this purpose in order to time.(http://www.customvis.com/)
obtain the fifth harmonic frequency from the initial The wavelength is 213 nm and the pulse frequency
wavelength of 1064 nm (Figure 19.3). This harmonic is 300Hz. The system has a flying spot beam delivery
provides a wavelength in the far ultraviolet system with spot diameter 0.6 mm and Gaussian
(NLO) is the branch of optics that describes the profile producing thus a clean and smooth ablated
behaviour of light in nonlinear media, that is, media in surface. This small spot size allows excellent
which the polarization P responds nonlinearly to the customised ablation profiles as well as has more
electric field E of the light. This nonlinearity is efficient tissue ablation due to closer to absorption
 Myopic Photorefractive Keratectomy using Solid State Laser 175

Figure 19.4: Common laser wavelength and the photonic spectrum

of haze after surface treatments) raise queries

whether mitomycin C is absolutely necessarily after
high attempted corrections when using a solid state
laser.
For customised refractive surgery, a fundamental
requirement is the fast and accurate tracking
technique in order to position the laser spot precisely.
The Pulzar Z1 is using two tracking systems. The
ZTRAK (Figure 19.6) is the main tracking system and
is limbus based video eye tracking system. Most pupil
tracking systems do not compensate for pupil centre
movements due to the pupil diameter changes. The
ZTRAK system along with the secondary
Figure 19.5: The CustomVis Pulzar Z1 solid state laser system
GAZETRAK system provides the most efficient
positioning of each laser pulse over the cornea. The
peak of corneal collagen. 3 The solid state laser GAZETRAK system is able to monitor the angle of
technology enables better pulse to pulse stability patient’s gaze and then changes the fixation target
which minimizes errors depending on time stability. intra-operatively in order to deliver the energy of
It is free from hydration monitoring and the corneal each pulse accurately on the cornea. The Cyclorotation
hydration state is not any more a concern for the system finally is used to determine the patient’s
surgeon. Thus it is friendly with surface corneal fluid cyclorotation angle between the pre-operatively
and overcorrection or undercorrections are not upright position and the supine position. The
presented as often as they are with the use of excimer treatment is appropriately rotated to compensate any
lasers. The small size and the Gaussian profile of the cyclorotation (Figure 19.7).
laser spot also reduce thermal effect and collateral Finally the system uses the TRACEY wavefront
damage and thus improves patient comfort by system and custom software, called ZCAD, which
minimising corneal haze and scarring. The latter in provides the laser with the ability to operate in full
conjunction with the clinical observations (absence customise way. It uses information from pupillometry,
176 Mastering Advanced Surface Ablation Techniques

Figure 19.6: ZTRAK limbus eye tracking system principles

Figure 19.7: Cyclorotation correction for supine and upright patient position
 Myopic Photorefractive Keratectomy using Solid State Laser 177
refraction, topographic and wavefront data. The At the one year follow up examination all post
treatment plan is produced by inserting those data PRK eyes (100%) had uncorrected visual acuity
in the ZCAD software and in the laser 24 (Figure (UCVA) 20/25 or better while 95% saw 20/20 or
19.8). better. These results were far exceeds the FDA
standards requiring only 50% of eyes to achieve
CLINICAL RESULTS UCVA of 1.0 or better and 85% to be 0.5 or better
In our series, 115 consecutive patients (230 eyes) (Figure 19.9).
underwent primary bilateral myopic PRK with No eye lost more than one best spectacle corrected
CustomVis Solid State Laser and completed one year visual acuity (BSCVA) line, while 50% of eyes gained
follow-up. All procedures were performed in the one or more lines at the last follow-up after PRK.
Institute of Vision and Optics, University of Crete Changes in BSCVA during the follow-up examination
Greece. Mean patients age was 29.6 ± 7.13 years are summarized in Figure 19.10.
(range, 18 to 48 years) and the mean spherical Mean preoperative spherical equivalent refraction
equivalent error was –4.43 ± 1.81 D (range, –8.0 to (–4.43 ± 1.81 D) was reduced to –0.08 ± 0.20 D at one
–1.5 D of sphere and up to –4 D of cylinder). Table year postoperatively. All eyes were within ± 0.50 D of
summarizes patients’ demographic and refractive emmetropia. Refractive stability was obtained on the
data. All patients gave written informed consent in first postoperative month and remained stable during
accordance with the institutional guidelines and the the follow-up period with no significant changes
Declaration of Helsinki. between any interval (p>.05) (Figure 19.11). Only 5%

Figure 19.8: The ZCAD customised procedure software

178 Mastering Advanced Surface Ablation Techniques

Figure 19.9: Cumulative UCVA at 1, 3, 6 and 12 months after PRK

Figure 19.10: Change of BSCVA at 1, 3, 6 and 12 months after PRK

of eyes changed more than 0.50 D between 6 m and Experimental Corneal Histology
the one year post-operative examination. (Table 19.1) Forty pigmented rabbits (40 eyes) underwent myopic
No eye had intra-operative or early or late PRK using CustomVis Pulzar Z1 Laser System for the
postoperative complications. In all eyes epithelium correction of -6 D at 5 mm optical zone with 0.5 mm
healed in three to five days. Only three eyes had transitional zone. Rabbits were sacrificed
trace haze at 3 months post PRK and just one out of immediately after the ablation and up to 12 months
230 eyes at the last follow-up examination. postoperatively.
 Myopic Photorefractive Keratectomy using Solid State Laser 179
mutagenesis was seen, even though 213 nm
wavelength is closer to absorption peak of DNA.25
The clinical course and the histopathological findings
were similar after photorefractive keratectomy using
excimer laser system.26

Figure 19.11: Stability of intended correction during the follow-up

period after PRK

Table 19.1: Patients demographic and refractive data

No of Eyes / Patients 230/115

Sex (Male/ Female) 55/60
Age (yrs)
Mean ± SD 29.6 ± 7.13
Range 18-48
Preop Sphere (D)
Mean ± SD -4.13 ± 1.27
Range -1.5 to -8.0
Preop Cylinder (D)
Mean ± SD -1.26 ± 0.87
Range 0 to -4.0
One year Postop Sphere (D)
Mean ± SD -0.04 ± 0.15
Range 0.25 to -0.25
One year Postop Cylinder (D)
Mean ± SD -0.13 ± 0.18
Range 0 to -0.5

Light Microscopy (LM) and Transmission Electron B

Microscopy (TEM) Figures 19.12A and B: Rabbit corneal morphology
immediately after PRK. Light microscopy. Original magnification
These methods demonstrates smooth ablation x 160 (Figure 19.12a). Transmission electron microscopy,
surfaces in all samples with no edema, or distortion original magnification x 6600 (Figure 19.12b)
of the adjacent corneal stroma, indicating absence of
Confocal Microscopy Analysis
thermal damage (Figures 19.12A and B). The upper
stroma contained significant number of activated Confocal microscopy was performed pre- and
keratocytes with slight vacuolization while deeper postoperatively (up to one year follow up) at 20
stroma had normal structure of keratocytes and extra patients (40 eyes) after PRK using CustomVis Pulzar
cellular matrix in all postoperative examinations. Z1 Solid State Laser system with a modified confocal
Endothelial layer was intact and endothelial cells scanning laser ophthalmoscope (HRT II/ Rostock
appeared normal in all samples (Figure 19.13), a crucial Cornea Module, Heidelberg Engineering).
parameter for the safety of the procedure. During Corneal images of post PRK treated corneas
the entire 12 months of the study, no sign of corneal showed normal epithelial structure and regenerated
180 Mastering Advanced Surface Ablation Techniques

Figure 19.13: Normal Descemet’s membrane and endothelium 8 months

after PRK on rabbit corneas. Transmission electron microscopy, original
magnification x 6600

subepithelial nerve plexus one year after the surgery

(Figure 19.14A). Increased scattering was observed at
the ablation site (Figure 19.14B), while keratocyte
activation and abnormal scattering of the keratocyte’s
B
nuclei was observed at the stromal layers immediately
posterior to the ablation site (Figure 19.14C). On the
contrary, deeper stromal layers exhibit normal
keratocyte activation and scattering of keratocyte’s
nuclei with an oval shape and normal endothelium
cells in shape and size (Figure 19.14D). Repeated
measures analysis of cell density variance did not
indicate statistically significant differences in mean
endothelial cell density between preoperatively and
at any postoperative interval measurement.27 These
results are in accordance with previous confocal studies C
after PRK with excimer laser.28

CONCLUSION

Solid State Lasers seems to be the future in corneal

refractive surgery. CustomVis Pulzar Z1 Laser System
is a reliable, stable and robust laser platform with
low maintenance costs, providing special character-
istics essential for customized corrections. Whether
all the theoretical advantages of the solid state laser
D
platforms as compared to the excimer laser systems
have any practical impact on corneal healing and the Figure 19.14: Confocal microscopy in PRK patients. Regenerated
subepithelial nerve plexus 44 um (A). Surface ablation site 54 um (B).
final visual or refractive outcome, still need to be Stromal layer immediately posterior to ablation site 69 um (C). Deep
elucidated. stromal layer 405 um (D)
 Myopic Photorefractive Keratectomy using Solid State Laser 181
REFERENCES 16. Motschmann M, Utermann D. [Thermal photodisruptive
laser iridotomy. A retrospective long-term study]. Klin
1. O’Connor J, O’Keeffe M, Condon PI. Twelve-year follow- Monatsbl Augenheilkd 1995;207:22-8.
up of photorefractive keratectomy for low to moderate 17. Bandello F, Brancato R, Lattanzio R, Trabucchi G, Azzolini
myopia. J Refract Surg 2006;22:871-7. C, Malegori A. Double-frequency Nd:YAG laser vs. argon-
2. Trokel SL, Srinivasan R, Braren B. Excimer laser surgery green laser in the treatment of proliferative diabetic
of the cornea. Am J Ophthalmol 1983;96:710-5. retinopathy: randomized study with long-term follow-
3. Lembares A, Hu XH, Kalmus GW. Absorption spectra of up. Lasers Surg Med 1996;19:173-6.
corneas in the far ultraviolet region. Invest Ophthalmol 18. Bandello F, Polito A, Del Borrello M, Zemella N, Isola M.
Vis Sci 1997;38:1283-7. “Light” versus “classic” laser treatment for clinically
4. Anderson I, Sanders DR, van Saarloos P, Ardrey WJt. significant diabetic macular oedema. Br J Ophthalmol
Treatment of irregular astigmatism with a 213 nm solid- 2005;89:864-70.
state, diode-pumped neodymium:YAG ablative laser. J 19. Puthalath S, Chirayath A, Shermila MV, Sunil MS,
Cataract Refract Surg 2004;30:2145-51. Ramakrishnan R. Frequency-doubled Nd:YAG laser
5. Roszkowska AM, De Grazia L, Ferreri P, Ferreri G. One- treatment for premacular hemorrhage. Ophthalmic Surg
year clinical results of photorefractive keratectomy with Lasers Imaging 2003;34:284-90.
a solid-state laser for refractive surgery. J Refract Surg 20. Ren Q, Simon G, Legeais JM, et al. Ultraviolet solid-state
2006;22:611-3. laser (213-nm) photorefractive keratectomy. In vivo
6. Tsiklis NS, Kymionis GD, Kounis GA, et al. One-year study. Ophthalmology 1994;101:883-9.
results of photorefractive keratectomy and laser in situ 21. Yasukawa T, Yafai Y, Wang YS, et al. Preliminary results
of development of a single-mode Q-switched Nd: YAG
keratomileusis for myopia using a 213 nm wavelength
ring laser at 213 nm and its application for the microsurgical
solid-state laser. J Cataract Refract Surg 2007;33:971-7.
dissection of retinal tissue ex vivo. Lasers Med Sci
7. Drake G. Springer Handbook of Atomic, Molecular, and
2005;19:234-9.
Optical Physics: Springer New York 2006.
22. Wang L, Men Y. Comparison study of CsLiB6O10 and
8. Krasnov MM, Kurenkov VV, Polunin GS. [Photo-
beta-BaB2O4 as nonlinear media for optical parametric
refractive keratectomy by excimer laser for correcting
oscillators. Appl Opt 2003;42:2720-3.
myopia and myopic astigmatism]. Vestn Oftalmol
23. Dair GT, Pelouch WS, van Saarloos PP, Lloyd DJ, Linares
1998;114:16-8.
SM, Reinholz F. Investigation of corneal ablation
9. Pakhomova TA, Akopian VS, Shotter LL, Tamkivi RP.
efficiency using ultraviolet 213-nm solid state laser pulses.
[Eximer lasers in ophthalmologic surgery (review of the Invest Ophthalmol Vis Sci 1999;40:2752-6.
literature)]. Vestn Oftalmol 1990;106:69-74. 24. Van Saarloos PP, Rodger J. Histological changes and
10. Bloom LH, Brucker AJ. Lasers in ophthalmology. Surg unscheduled DNA synthesis in the rabbit cornea following
Clin North Am 1984;64:1013-24. 213-nm, 193-nm, and 266-nm irradiation. J Refract Surg
11. Krueger RR, Trokel SL. Quantitation of corneal ablation by 2007;23:477-81.
ultraviolet laser light. Arch Ophthalmol 1985;103:1741-2. 25. Marshall J, Trokel S, Rothery S, Krueger RR. A
12. Krueger RR, Trokel SL, Schubert HD. Interaction of comparative study of corneal incisions induced by
ultraviolet laser light with the cornea. Invest Ophthalmol diamond and steel knives and two ultraviolet radiations
Vis Sci 1985;26:1455-64. from an excimer laser. Br J Ophthalmol 1986;70:482-501.
13. Smiddy WE, Radulovic D, Yeo JH, Stark WJ, Maumenee 26. L’Esperance FA, Jr., Taylor DM, Del Pero RA, et al. Human
AE. Potential acuity meter for predicting visual acuity excimer laser corneal surgery: preliminary report. Trans
after Nd:YAG posterior capsulotomy. Ophthalmology Am Ophthalmol Soc 1988;86:208-75.
1986;93:397-400. 27. Tsiklis NS, Kymionis GD, Pallikaris AI, et al. Endothelial
14. Sohajda Z, Bekesi L, Berta A. In ophthalmology new cell desity after photorefractive keratectomy for moderate
possibilities for the use Nd:YAG laser. Acta Chir Hung myopia using 213 nm solid state laser system. J Cataract
1997;36:331-3. Refract Surg 2007;In press.
15. Spaeth GL, Idowu O, Seligsohn A, et al. The effects of 28. Moilanen JA, Vesaluoma MH, Muller LJ, Tervo TM. Long-
iridotomy size and position on symptoms following laser term corneal morphology after PRK by in vivo confocal
peripheral iridotomy. J Glaucoma 2005;14:364-7. microscopy. Invest Ophthalmol Vis Sci 2003;44:1064-9.
182 Mastering Advanced Surface Ablation Techniques

CHAPTER Wavefront Guided

Photorefractive Keratectomy—
20 Today and the Future

Weldon W Haw, Edward E Manche (USA)

INTRODUCTION adopted technology.1-2 Since then vision researchers

and refractive surgeons have become fluent in the
Over the years, refractive surgeons have been driven
language of wavefront optics.
to optimize results of keratorefractive surgery. Radial
The imperfections of an optical system can be broken
keratotomy and first generation excimer lasers treated
down into its components using Wavefront analysis. A
spherical myopia by simply inputting the amount of
plane wave of monochromatic light is distorted by
myopia to be treated in experienced based algorithms.
optical aberrations as it passes through an optical system
The evolution of more complex technology has resulted
in increasingly accurate and predictable results. (i.e. the eye). These distortions can be measured by
Improved quality of results has also been driven by evaluating this information in the form of a Zernike
the emergence of both diagnostic and therapeutic polynomial expansion.3 The cumulative wavefront error
wavefront technology. Wavefront technology allowed can be subdivided into its individual components by a
the customization of the refractive procedure, set of normalized Zernike polynomials that are best fit
minimized degradation of the quality of the vision to the measured wavefront error. The coefficient for
(i.e. contrast sensitivity) that occurs with corneal each Zernike term demonstrates the component’s
refractive surgery, and has been instrumental in relative contribution to the total root mean square (RMS)
allowing us to come closer to achieving the possibility error. In most normal ametropic eyes, lower order
of “supernormal” vision for many patients. aberration such as defocus (myopia or hyperopia) is
the dominant aberration, followed by astigmatism.
WHAT IS WAVEFRONT TECHNOLOGY? (Figure 20.1) Higher order aberrations (i.e. coma,
For many years, astronomers and mathematicians spherical aberration, trefoil, etc…) usually constitute a
realized the importance of using wavefront analysis small component (<10%) of the normal eye’s total
to optimize the capture of images by the telescopic aberrations. The amount of higher order aberrations
optical systems from immense distances. It was until can vary between individuals. In addition, pupil size is
only recently when vision researchers adopted this an important variable as higher order aberrations
technology for use in optimizing the human optical increase with increased pupil size. The benefits of
system. The Hartmann-Shack wavefront sensor, used correcting higher order aberrations are therefore
by astronomers to analyze atmospheric aberrations maximized in younger patients who typically have larger
above a telescope in real time was the first such pupils and under scotopic situations (i.e. night driving).
 Wavefront Guided Photorefractive Keratectomy—Today and the Future 183

Figure 20.1: Zernike Pyramid. Low order aberrations include the first two top rows. (1st order aberrations
include Tip and Tilt. 2nd order aberrations include Astigmatism and Defocus.) Higher order aberrations include any
rows below the 3rd row. (3rd order aberration include Trefoil and Coma. 4th order aberration include Tetrafoil,
Secondary astigmatism, and Spherical Aberration.) See text for detail

Although most available aberrometers measure to have suggestive that this process plays a significant
the sixth order, most refractive surgeons agree that role in the interpersonal variability and refractive
measuring to the fourth order is probably all that is stability of the procedure and can significantly impact
clinically relevant. At some point, higher order the results of custom ablation. 4-7 Unfortunately,
aberrations cease to be clinically significant as current algorithms do not accurately predict the
diffraction and the density and health of the retinal biomechanical response of the cornea for all
ganglion cells may limit an individual’s ability to individuals.
discriminate the quality of images cast upon the retina.
CLINICAL RESULTS
CUSTOM WAVEFRONT PRK
Several studies confirm the advantages of custom
Despite the ability to measure aberrations beyond wavefront guided PRK over conventional PRK (Table
the 6th order and the ability to precisely deliver 20.1). 8-14 Wigledowska-Proienska evaluated 126
excimer laser ablations based on these measurements, myopic or myopic astigmatic eyes of 112 patients that
the outcomes of custom wavefront PRK are underwent either wavefront guided PRK or
significantly limited by the 1) variable effects of the conventional PRK with the MEL 70 G-scan excimer
excimer laser on the cornea and the 2) differences in laser system with two-year follow-up.8 Total higher-
healing that occurs during the postoperative recovery order root-mean square increased by a factor of 1.18
period following PRK. Corneal biomechanical in the custom group versus 1.60 for the conventional
response to ablative surgery may significantly affect group. In addition there was a significant increase in
outcomes, and should be taken into account when coma and spherical aberration in the conventional
planning customized procedures.4-5 The unpredictable PRK group. The investigators concluded that custom
healing response is a dynamic process that can occur PRK demonstrated advantages over conventional
even years after the refractive procedure. Studies PRK including improved uncorrected visual acuity,
184 Mastering Advanced Surface Ablation Techniques
Table 20.1: Summary of custom wavefront guided PRK studies
Study - Authors Study Design Investigator’s Conclusions
Wigledowska-Promienska D, 126 eyes with myopia or myopic astigmatism Custom PRK reduced the number of higher
Zawojska I. (2007) undergoing custom PRK vs. conventional PRK order aberrations induced by the excimer laser
with the MEL 70 G Scan excimer laser. Two-year and improved uncorrected and spectacle
follow-up. corrected visual acuity when compared to
conventional PRK.
Mastropasqua L, Nubile M, 60 eyes of 60 patients randomized to wavefront Wavefront-guided PRK induced a smaller
Ciancaglini M, Toto L, Ballone E. guided PRK vs. conventional PRK with the increase of postoperative wavefront error
(2004) Asclepion Meditec flying spot Mel 70 excimer compared to conventional PRK, particularly
laser. 6 month follow-up. in patients with higher preoperative higher
order aberrations.
Nagy ZZ, Palagyi-Deak I, 150 eyes of 104 patients with spherical myopia Wavefront supported PRK was efficacious,
Kelemen E, Kovacs A. (2002) and myopic astigmatism treated with the safe, and predictable. Best corrected visual
Asclepion-Meditec MEL 70 G scan laser. 6 month acuity may be improved over results obtained
follow-up. with conventional PRK.
Mastropasqua L, Toto L, 56 eyes of 56 patients with myopia Wavefront guided PRK is safe, effective, and
Zuppardi E, Nubile M, randomized to receive wavefront guided PRK induces less third order coma aberration as
Carpineto P, Di Nicola M, with the Zywave Bausch & Lomb Technolas compared to standard PRK. The use of
Ballone E. (2006) 217z or conventional PRK. 6 month results. Zyoptix wavefront guided PRK is particularly
indicated in eyes with higher preoperative RMS
values.
Bahar I, Levinger S, Kremer I 40 eyes of 20 patients with suspected Wavefront supported PRK appears to be
(2006) keratoconus underwent wavefront supported effective for the treatment of myopia and
PRK with the Bausch & Lomb Technolas 217 z astigmatism in patients suspected
laser. All patients followed for a minimum of keratoconus. Longer follow-up is needed
40 months. to prove the safety of the procedure in this
patient population.
Dausch D, Dausch S, Schroder E. 30 eyes of 23 patients with myopic astigmatism Wavefront supported PRK with the Asclepion
underwent wavefront supported PRK with the MEL 70 laser was safe and effective. Daylight
Asclepion MEL 70 excimer laser. 12 months visual acuity and mesopic visual acuity
follow-up. outcomes remained stable over 1 year.

spectacle corrected visual acuity, and a reduction in corrected visual were not statistically significant
the number of higher order aberrations induced by between groups.
the excimer laser. Dausch, et al. treated 30 eyes of 23 patients with
Mastropasqua, et al. evaluated 60 eyes of 60 myopia less than -8.0 D (mean -3.76 D +/- 1.90 D)
patients with myopic astigmatism randomized to and cylinder less than -3.50 D (mean -0.81 +/-0.71 D)
receive custom PRK or conventional PRK with the with wavefront supported PRK using the Asclepion
MEL 70 excimer laser.9 Although wavefront error MEL 70 excimer laser. 13 Uncorrected visual acuity
increased in both groups, at six months, the custom was 20/16 or better in 47% (14 eyes) at 1 month, 67%
PRK treated group demonstrated a smaller increase (20 eyes) at 3 months, 77% (23 eyes) at 6 months,
in the root-mean-square compared to the 90% (27 eyes) at 9 months, and 83% (25 eyes) at 12
conventional PRK. (P<0.01) In the standard PRK months. No eyes lost more than 1 line of best
group, all higher order aberrations increased corrected visual acuity (BSCVA) at 3, 6, 9, or 12
compared to the wavefront guided PRK where there months. 13% (4 eyes) gained 2 or more lines of
was only a small increase in the trefoil and spherical BSCVA at 6, 9, and 12 months. BSCVA was 20/10 or
aberrations. The smaller increase of wavefront error better in 30% at 12 months. Visual acuity under low
in the wavefront-guided PRK group compared to the contrast was unchanged in 87% (26 eyes) at 12
conventional PRK group was more evident in eyes months.
with a preoperative RMS value > 0.4 microns. The Nagy, et al evaluated 150 eyes of 104 patients
postoperative accuracy, uncorrected and best treated with wavefront supported customized PRK
 Wavefront Guided Photorefractive Keratectomy—Today and the Future 185
for myopia and myopic astigmatism using the LIMITATIONS
Asclepion-Meditec MEL G-scan excimer laser.10 At 6
PRK has limitations regardless of whether
months, the mean postoperative visual acuity was
better than 20/20 and the mean best spectacle conventional or custom wavefront guided ablations
corrected visual acuity was 20/16. The average are performed. Postoperative pain, potential for
spherical equivalent on manifest refraction was -0.12 developing scarring and corneal haze, and slower
D. Predictability was excellent with 98.6% (148 of 150 visual rehabilitation are limitations inherent within
eyes) of eyes being within +/-0.50 D of intended the PRK procedure. Also, although higher-order
correction and 100% within +/- 1.0 D of intended aberrations increase in both LASIK and PRK, they
correction. 8.2% (11 of 150) of eyes demonstrated a are typically greater following LASIK possibly due
best spectacle corrected visual acuity (BSCVA) of 2 to the generation of a LASIK flap.12 Uncomplicated
or more lines better than their preoperative BSCVA lamellar flap creation is responsible for systematic
while no eyes lost 2 or more lines of BSCVA. The changes in the corneal topography and induction of
root mean square value for higher order aberrations higher order optical aberrations. Predictors of this
increased 1.4 times following PRK. response include stromal bed thickness, flap diameter,
Manche, et al presented preliminary results on and total corneal pachymetry.16 In addition, corneal
performing wavefront guided PRK in symptomatic surface healing following LASIK or PRK can result in
highly aberrated eyes following previous keratore- overall smoothing of the corneal surface as the
fractive surgery using the VISX S4 excimer laser and epithelium thickens over divots and thins over
the WaveScan Aberrometer.15 25 eyes of 21 patients bumps.17 This may partially negate the accuracy of
that had undergone previous keratorefractive surgery micron and sub-micron wavefront technology.7 In the
with LASIK (14 eyes), radial keratotomy (9 eyes), future, improved methods of pharmacologically or
and PRK (2 eyes) were treated using a customized biologically modulating the cornea’s response to the
nomogram and adjunctive intraoperative application excimer laser could help us realize the full potential
of 0.02% mitomycin C. At 6 months, sphere had been of wavefront technology.
reduced from -1.56 D +/-1.09 D to -0.15 D +/-0.42 D,
astigmatism was reduced +1.18 D+/0-0.83 D to 0.35 SUMMARY
D +/- 0.35 D, and the spherical equivalent was
reduced from -0.97D +/-1.04 D to +0.01D +/-0.37 D. Custom wavefront-guided PRK demonstrates
61% of eyes demonstrated an uncorrected visual promise in the correction ametropia. Avoiding the
acuity of 20/20 or better and all eyes had an mechanical variations due to the creation of the
uncorrected visual acuity of 20/30 or better. 83% of lamellar flap (i.e. LASIK) has potential benefits when
eyes were within +/- 0.5 D of intended correction dealing with the micron level of accuracy
and 100% of eyes were within +/- 1.0 D of intended demonstrated by wavefront diagnostic and
correction. 23% of eyes gained one or more lines of therapeutic modalities. In the future, we will have to
best corrected visual acuity. No eyes lost 2 or more reconcile with the biological variability resulting from
lines of best corrected visual acuity. There was a small interpersonal variations in corneal wound healing.
reduction of total higher order RMS values with a Unfortunately, advances in the clinically available
slight reduction in coma at the 6 month visit. No pharmacological and biological wound healing
change was noted in trefoil or spherical aberration modulation techniques have not kept pace with
at 6 months. Dr. Manche concluded that the advances in wavefront technology. Despite this
procedure improved uncorrected and best corrected shortcoming, custom wavefront guided PRK has
visual acuity, demonstrated good predictability and proven to be an important and valuable approach to
excellent safety. managing patients with ametropia.
186 Mastering Advanced Surface Ablation Techniques
REFERENCES 10. Nagy ZZ, Palagyi-Deak I, Kelemen E, Kovacs A.
Wavefront-guided photorefractive keratectomy for
1. Liang J, Grimm B, Goelz S, Bille JF. Objective measurement myopia and myopic astigmatism. J Refract Surg 2002;
of wave aberrations of the human eye with the use of 18(4):S615-9.
Hartmann-Shack wave-front sensor. J Opt Soc Am A 1994; 11. Mastropasqua L, Toto L, Zuppardi E, Nubile M, Carpineto
14(11); 2873-83. P, Di Nicola M, Ballone E. Zyoptix wavefront-guided
2. Howland HC. The history and methods of Ophthalmic versus standard photorefractive keratectomy (PRK) in
wavefront sensing. J Refract Surg 2000; 16(5):S552-3. low and moderate myopia: randomized controlled 6-
3. Thibos LN, Applegate RA, Schwiegerling JT, Webb R. month study. Eur J Ophthalmol 2006;16(2):219-28.
Standards for reporting the optical aberrations of eyes. J 12. Panagopoulou SI, Pallikaris IG. Wavefront customized
Refract Surg 2002; 18:S652-60. ablations with the WASCA Asclepion workstation. J
4. Roberts C. Biomechanics of the cornea and wavefront- Refract Surg 2001;17](5):S608-12.
guided laser refractive surgery. J Refract Surg 2002; 13. Dausch D, Dausch S, Schroder E. Wavefront supported
18(5):S589-92. photorefractive keratectomy: 12 month follow-up. J
5. Roberts C. The cornea is not a piece of plastic. J Refract Refract Surg 2003;19(4) 405-11.
Surg 2000; 16(4):407-13. Future challenges to aberration – 14. Bahar I, Levinger S, Kremer I. Wavefront-supported
free ablative procedures. J Refract Surg 2000; 16(5):S623-9. photorefractive keratectomy with the Bausch & Lomb
6. Wang M. The limits of wavefront-guided surgery. Zyoptix in patients with myopic astigmatism and
Refractive Eyecare for Ophthalmologists 2001; 5(19):31-4. suspected keratoconus. J Refract Surg 2006;22(6):533-8.
7. Netto MV, Wilson SE. Corneal wound healing relevance 15. Manche EE, Chien FY. Wavefront-guided PRK in the
to wavefront guided laser treatments. Ophthalmol Clin treatment of highly aberrated eyes following previous
North Am 2004;17(2):225-31, vii. keratorefractive surgery. Presented at the American
8. Wigledowska-Promienska D, Zawojska I. Changes in Academy of Ophthalmology, Las Vegas, NV, USA.
higher order aberrations after wavefront-guided PRK November 2006.
for correction of low to moderate myopia and myopic 16. Potgieter FJ, Roberts C, Co IG, Mahmoud AM, Herderick
astigmatism: Two-year follow-up. Eur J Ophthalmol 2007; EE, Roetz M, Steenkamp W. J Cataract Refract Surg 2005;
17(4):507-14. 31(1):106-14.
9. Mastropasqua L, Nubile M, Ciancaglini M, Toto L, Ballone 17. Wilson SE, Mohan R, Hong JW, Lee JS, Choi R. The wound
E. Prospective randomized comparison of wavefront- healing response after laser in situ keratomileusis and
guided and conventional photorefractive keratectomy photorefractive keratectomy: elusive control of biological
for myopia with the meditec MEL 70 laser. J Refract Surg variability and effect on custom laser vision correction.
2004;20(5):422-31. Arch Ophthalmol 2001;119:889-96.
 CHAPTER

21 Mitomycin C in Surface Ablation:

Benefits and Practical Use

Laura de Benito-Llopis, Miguel A Teus, Jorge L Alió (Spain)

INTRODUCTION Once activated by enzymes such as the cytochrome

p450 reductase 10-12, it acts as an alkylating agent and
Advanced surface ablation (ASA) has regained
produces cross-linking of DNA molecules, causing
popularity in refractive surgery practices because of
inhibition of DNA synthesis and, secondarily,
the absence of stromal flap-related complications
inhibition of cell mitosis. Its effect is more pronounced
associated with laser in situ keratomileusis (LASIK)
in those cells with a higher mitotic rate and it is widely
and because it allows treatment of thin corneas while
used systemically as a chemotherapeutic agent.13
achieving good outcomes in safety, efficacy and
Apart from that antiproliferative effect, the MMC
predictability in low1, moderate2 and high myopia.3,4
shows a cytotoxic effect that is not completely
Despite the disadvantages of ASA, i.e. slower visual
justified by its capacity of binding DNA.14 The
recovery and higher postoperative discomfort,
mechanisms for that cytotoxicity have not been
compared to LASIK, this procedure has become the
completely identified. Many studies have analyzed
technique of choice in patients with thin corneal
the cellular mechanisms that become activated by
pachymetry, those at risk for trauma, and those with
MMC and that could explain its cytotoxicity: it
corneal surface problems such as dry eye, recurrent
produces cycle cell arrest,15,16 upregulation of the
erosion syndrome or basement membrane disease.5,6
expression of cytokines such as IL-8 and monocyte
When the first surface ablation procedures
chemoattractant protein-1 (MCP-1) by the activation
(photorefractive keratectomy -PRK-) were used in
of protein kinases, 17 induction of Fas-mediated
refractive surgery, the most feared complication was
apoptosis 18,19 and also apoptosis through the
the loss of corneal transparency, namely corneal haze,
activation of caspase cascades with mitochondrial
that appeared most frequently associated with deep
dysfunction,18,20 T lymphocytes mediated cell lysis 21,
ablations.7,8 The use of mitomycin C (MMC) has
depletion of intracellular glutathione ,22 generation
reduced the risk of this complication and has
of reactive oxygen radicals 23 and secondary
undoubtedly played a deciding role in the revival of
amplification of the production of tumor necrosis
ASA techniques.
factor (TNF).24
On the other hand, it is not clear whether the cells
MITOMYCIN C: MECHANISMS OF ACTION
repair the DNA damage caused by the MMC25 or
Mitomycin C (MMC) is an antibiotic first isolated from whether the MMC effects are permanent. Some
cultures of Streptomyces caespitosus by Hata in 1956.9 studies with fibroblasts cultures suggest that these
188 Mastering Advanced Surface Ablation Techniques
cells do not suffer a permanent inhibition after a single
exposure to MMC26 and that the adjacent non-exposed
cells could replace them.27,28

INTERACTION OF MMC WITH THE CORNEAL

WOUND HEALING MECHANISMS AFTER SURFACE
ABLATION

Corneal Wound Healing after Surface Ablation

The mechanisms of corneal wound healing after ASA
induce the development of a fibrotic and
hypercellular scar at the site of the ablated area, in
the anterior stroma, characterized by an increased
keratocyte density, the differentiation of Figure 21.1: Subepithelial corneal haze 3 months after surface
myofibroblasts and the development of a dense ablation

extracellular matrix with abundant collagen type III.29 in order to diminish corneal wound healing and
Both the deepithelialization and the laser ablation decrease haze formation.38
cause apoptosis of the keratocytes,30 followed by When applied over the ablated stroma, the MMC
proliferation and migration of the surrounding produces: first, a higher rate of keratocyte apoptosis
keratocytes to repoblate the ablated area.31 Some of during the first hours after its application;39 then, a
these keratocytes differenciate into myofibroblasts,30 reduced keratocyte repopulation after 24 hours; four
which scatter more light than quiescent keratocytes, weeks afterwards, a diminished keratocyte and
not only from their nuclei but also from their cell myofibroblast density and less deposit of collagen
bodies and dendritic processes.29,32,33 At the same and extracellular matrix.20,40,41 These effects result in
time, they participate in remodelling the extracellular a demonstrated ability to reduce the loss of corneal
matrix, which leads to the formation of a newly transparency after ASA in animal models.42-44 In
synthesized extracellular matrix, denser and more human corneas in vitro, Rajan et al. 45 confirmed the
disorganized, which contributes to the loss of corneal lower keratocyte proliferation after MMC application,
transparency.29,32,33 This loss of corneal transparency although they did not observe an initially higher loss
is called corneal haze, and is one of the main problems of keratocytes when compared to the group that
of ASA (Figure 21.1). received surface ablation without MMC.
The most clearly related risk factor to develop The fact that the application of MMC triggers a
corneal haze is the ablation depth. 7,8 However, higher rate of keratocyte apoptosis is a sign of its
individual factors34 may determine a different corneal cytotoxic effect. The fact that it reduces the keratocyte
wound healing response between two patients repopulation is a sign of its antimitotic effect. MMC
receiving the same surgery, and also other extrinsic seems more effective as a prophylactic agent, to
factors, such as the exposure to ultraviolet prevent haze, than as a therapeutic agent, and some
radiation,35,36 can modulate that response. Therefore, mild haze frequently persists when it is used to
there is no evidence to establish the ablation depth eliminate a pre-existing dense haze (Figure 21.2).46,47
below which there is no risk for haze. The antimitotic capacity of the MMC to avoid
proliferation of the myofibroblasts seems more
MMC: Histopathologic effect on the Cornea
effective than its citotoxic capacity to eliminate the
The demonstrated efficacy of the MMC in controlling already differentiated myofibroblasts, as it was
cell proliferation28,37 led to its use in ASA procedures, demonstrated by Netto et al. with rabbit corneas.40
 Mitomycin C in Surface Ablation: Benefits and Practical Use 189
incidence of complications, 59 but it was not
completely free of adverse effects, and some authors
have reported corneo-scleral melting, when used in
pterygium surgery,60 and avascular blebs (Figure 21.3)
carrying risk of leaks and infection61 and corneal
decompensation,62 when used in glaucoma surgery.
In order to avoid those complications, the exposure
time to MMC has been reduced and it is advisable to
properly cover with conjunctiva the sclera exposed
to the MMC.59,63 Unfortunately, in pterygium and
glaucoma surgeries, there is no enough evidence as
to establish the optimal dose and exposure time to
maximize the effectiveness and safety of its use.9
Figure 21.2: Mild residual haze after treatment of previously dense
haze with surface scraping and MMC 0.02% for 2 minutes.

Sadeghi et al.48 had already demonstrated in vitro

that the concentration of MMC needed to achieve its
antiproliferative effect was lower than that needed
to cause cytotoxicity. Nevertheless, the mechanisms
of the MMC on the cornea are not clearly identified,
and while some studies consider that its antimitotic
activity is its most important mechanism of
action,40,47 others consider the cytotoxic effect causing
an increased keratocyte apoptosis as the main one.39,49

Use of Mitomycin C in Opthalmology Use of

Mitomycin C in Pterygium and Glaucoma
Surgeries
In Ophthalmology, the MMC was first used topically
after pterygium surgery to prevent its recurrence 50,51. Figure 21.3: Avascular bleb after exposure to mitomycin C during
glaucoma filtering surgery
The dose used was progressively diminished from
1.0 mg/ml to 0.2 mg/ml to improve its tolerance but
Use of Mitomycin C in Ocular Surface Neoplasias
maintaining the same effectiveness in avoiding
pterygium recurrence.52 Repeated topical application Due to its ability to inhibit cell proliferation especially
of MMC after pterygium surgery led to some in cells with a high mitotic rate, the MMC is used
complications, some of them severe, such as topically to treat ocular surface neoplasias, where it
glaucoma, corneal edema, corneal perforation, effectively decreases neoplasic proliferation.64-71 In
anterior uveitis and cataract. 53,54 One single these cases, the MMC is usually applied topically four
application of MMC intraoperatively in both times a day at a dose of 0.2 to 0.4 mg/ml during
pterygium surgery55,56 and in glaucoma filtering cycles of one or two weeks intercalated with intervals
surgery57,58 showed its effectiveness in inhibiting without treatment to improve its tolerance. Studies
fibroblastic proliferation, 28,37 and preventing with long-term follow-up have shown that the drug
recurrence of the pterygium and fibrosis of the is well-tolerated, the allergy and punctal stenosis
filtering bleb. The MMC applied just once being its main adverse-effects, with no serious
intraoperatively was associated to a very low complications.72
190 Mastering Advanced Surface Ablation Techniques

Use of Mitomycin C in Corneal Refractive Surgery (postoperative uncorrected visual acuity -UCVA- /
preoperative BSCVA) and less haze in the group that
First Uses in Corneal Refractive Surgery
received MMC. Gambato et al. 77 performed a
In 1991, Talamo et al.38 suggested the use of MMC as prospective study of 36 patients that underwent PRK
a modulator of the corneal wound healing response in one eye and PRK with intraoperative MMC 0.02%
to ASA. Their study in rabbits showed that those for 2 minutes in the contralateral eye to correct myopia
treated with topical MMC during 2 weeks after higher than -7.00 D. They found significantly less haze
surgery developed less subepithelial collagen deposit in the group that received MMC. Bedei et al. 79
than those not treated with MMC. Schipper et al.73 compared two groups (62 eyes in each one) treated
applied intraoperative MMC 0.04% during 5 minutes with PRK alone or with PRK with intraoperative
after PRK in rabbits and they observed lower MMC to correct myopia higher than –5.00 D. One
keratocyte density and less scar tissue after the year postoperatively, the group that received MMC
surgery. Majmudar et al.74 proposed its use to treat showed better BSCVA, better predictability and less
corneal scars secondary to refractive procedures. haze than the group not treated with MMC.
They reported a significant improvement in corneal
transparency with a single 2 minute intraoperative Adjustment of the excimer laser nomogram when using
application of MMC 0.02%. Later, this drug was used intraoperative mitomycin C: The use of MMC reduces
prophylactically to prevent haze formation after PRK. the corneal wound healing response to the laser
Carones et al.75 reported their results in 60 patients ablation and, therefore, causes overcorrection when
who underwent PRK to correct myopia from –6.00 the laser nomogram is not adjusted appropriately.80,81
to –10.00 D. They observed significantly less Usually, each surgeon develops its own nomogram
incidence of haze and better refractive (higher depending on his/her results, but it frequently
predictability) and visual results (less loss of best consists in an undercorrection of about 10% of the
spectacle-corrected visual acuity -BSCVA-) in the preoperative spherical refraction, depending on the
group that receive MMC 0.02% for 2 minutes over age and the refractive defect (Carones et al.: 10%;75
the ablated stroma, with no adverse side effects. Lacayo et al.: 8-15%; 81 Camellin: 20% in low
myopia)80. Usually, the programmed ablation for the
Current Use in Advanced Surface Ablation cylinder refraction is not modified 76,81.

Comparison of surface ablation outcomes with and without Surface ablation with mitomycin C for high myopia: ASA
intraoperative mitomycin C: Since those first reports,74,75 procedures without adjuvant MMC, once the learning
intraoperative MMC has shown to be very effective curve is overcome, 82 allow similar visual and
in preventing corneal haze after ASA76-79 and its use refractive results than LASIK in low1 and moderate
has broadened to include not only high but also myopia,2,83,84 avoiding stromal related complications.
moderately low ammetropia. Several comparative The introduction of MMC has allowed an
studies have shown less incidence of haze and better improvement of the outcomes of ASA when treating
refractive and visual results when MMC is used high myopia. The main risk in ASA techniques for
during ASA. Argento et al. 76 performed a high myopia without the use of MMC is the incidence
retrospective review of 30 eyes treated with laser- of clinically significant haze and regression, which
assisted subepithelial keratectomy (LASEK) with may lead to worse outcomes when compared to
intraoperative MMC 0.02% for 75 seconds compared LASIK.85 That is why LASIK has been long used as
with 28 eyes treated with LASEK without MMC to the excimer laser technique of choice in high
correct myopia of –5.75 D (mean spherical equivalent). ammetropia. However, as we have described, there
They reported significantly better efficacy index are several studies that suggest that ASA with
 Mitomycin C in Surface Ablation: Benefits and Practical Use 191

intraoperative MMC allows better refractive and Mitomycin C in surface ablation after other corneal refractive
visual results when compared to ASA without MMC procedures: The MMC has also allowed treatment of
in high myopia, with less incidence of haze.75-77 We complicated LASIK cases and retreatment after
performed a prospective, single-masked study of previous corneal refractive surgeries (such as radial
consecutive patients (228 eyes) that were scheduled keratotomy 87,88 or penetrating keratoplasty). In those
for refractive surgery, 114 eyes with LASEK and 114 cases, performing ASA has the advantage of treating
refractive-matched eyes with LASIK, to correct a the refractive defect while avoiding the risks of the
myopic defect of = –7.00 D (spherical equivalent) and stromal flap. However, when ASA was first used in
a cylinder = –3.50 D. We applied MMC 0.02% for eyes with previous surgical procedures, such as radial
60 seconds in all the LASEK procedures. keratotomy, it was associated with a higher incidence
The postoperative UCVA was significantly better of haze than that expected from the ablation depth. 89,90
after LASIK than after LASEK with MMC on days 1, Even if some series show low incidence of haze when
7 and 30 postoperatively, but the difference was not ASA is applied over complicated LASIK flaps,91-94
most of the surgeons use nowadays MMC to diminish
statistically significant 3 months postoperatively. Our
the risk of haze when using ASA over buttonholes
results showed no difference between both
or incomplete LASIK flaps 95-98 or penetrating
techniques regarding safety and efficacy and no
keratoplasty.99-100
difference in UCVA or BSCVA 3 months after
Residual refractive defects after LASIK, either due
surgery, although a trend toward overcorrection was
to undercorrection or to regression, would also
detected in the LASEK+MMC group, despite the
theoretically benefit from treatment with ASA when
planned undercorrection of 10% in this group.4
the estimated residual stromal bed does not allow
When LASIK is used to treat high degrees of
an in-the-bed enhancement. Carones et al.101 used
myopia, the complication that most ophthalmologists
PRK in 17 eyes to treat postLASIK regression. They
fear is post-LASIK ectasia. ASA theoretically
initially observed good visual and refractive results,
minimizes the risk of having this complication as it
but most of the eyes developed dense corneal haze
permits to leave a thicker residual stroma than (grades 3 and 4) several months after the surgery,
LASIK.6,86 The use of intraoperative MMC allows with myopic regression and loss of BSCVA. Even
similar refractive and visual results with both though ulterior series have not shown such a high
techniques. 4 The question whether the use of incidence of haze,92,102,103 this is still an important
MMC could lead to postsurface ablation ectasia has complication in these cases, even with ablation depths
not been answered yet, although no case has been only moderately deep (Cagil et al.103 reported haze
reported. with corrections of –2.00D or greater). The efficacy
The choice between LASIK and ASA for treating demonstrated by the MMC to diminish the incidence
high myopia when patients are candidates for both of haze after ASA, both primary 74-76 and after
procedures because of an adequate corneal thickness, previous refractive surgery procedures,88 leads to the
normal corneal epithelium, and the absence of a risk logic possibility that ASA with intraoperative MMC
of trauma may be based on the faster visual could be the safest and most effective way to treat
rehabilitation after LASIK or the lower risk of undercorrection or regression after LASIK when an
complications in ASA. For those patients who are not in-the-bed enhancement is not possible 102 .
candidates for LASIK because a residual stroma Nevertheless, no study has established the efficacy,
thinner than 250-300 μm is anticipated, ASA with safety and predictability of ASA with MMC in these
MMC offers a good alternative, with similar visual cases. The authors have noticed an important
results. tendency to overcorrection in these cases, and
192 Mastering Advanced Surface Ablation Techniques
recommend caution when using ASA with MMC to significant with the concentration used, the exposure
treat postLASIK residual refraction.104 time having less influence on the detected apoptosis.
Rajan et al.45 compared the effect of MMC 0.02%
Dose and Exposure Time applied for 1 or 2 minutes after laser ablation in
The first studies using intraoperative MMC during donated human corneas maintained in vitro,
ASA74 applied the MMC at a concentration of 0.02% comparing them with a control group. They described
during 2 minutes over the ablated stroma. Since then, an initial decrease in the number of keratocytes in
several studies have tried to establish a lower dose the anterior stromal similar in the three groups.
and a shorter exposure time that could still be However, in the control group, the keratocyte
effective.40,45,48,80 The effect of MMC is time and dose repopulation started sooner than in both MMC
dependent. Sadeghi et al. 48 studied the groups, and in the group exposed for 1 minute sooner
antiproliferative and cytotoxic effects of the MMC than in the group exposed for 2 minutes. Four weeks
on cultured human keratocytes. They observed that afterwards, the keratocyte density in the anterior
this drug achieved its antiproliferative effect with stroma was significantly lower in the groups that
much lower doses than those needed to produce received MMC, showing lower density with longer
cytotoxicity: after a 5 minute exposure, the lowest exposure time.
concentration that significantly (>50%) inhibited Camellin 80 reported his results using just a
keratocyte proliferation was 0.05 mg/ml. After that “brushstroke” of MMC 0.01% in 86 eyes that
exposure time, the median inhibitory dose was underwent LASEK compared to 100 eyes treated with
0.038 mg/ml and, in contrast, the median lethal dose LASEK alone. Although he reports a low incidence
was much higher than the greatest concentration of haze in both groups, he detects a statistically
tested in the study (0.5 mg/ml). significant difference favoring the MMC group.
Netto et al. 40 studied the effect of applying Despite this study by Camellin and those with
prophylactic MMC at two different concentrations animal models by Netto et al.40 and Song et al.39, the
(0.02% y 0.002%) and three different exposure times concentration of MMC most frequently used in the
(12 seconds, 1 minute, 2 minutes) in rabbits, clinical practice is still 0.02%.75-77,81 Regarding the
comparing them with a control group. They observed exposure time of the MMC when it is used
that MMC 0.002% for 12 seconds was as effective in prophylactically during ASA, based on the study by
preventing postoperative corneal haze as MMC 0.02% Netto et al.40 and due to the lack of other evidence
for 2 minutes, although this latter achieved a greater to establish the optimal exposure time, the tendency
reduction in the myofibroblast population is to reduce it. The MMC is usually applied for
postoperatively. In their study, that difference in the 12 seconds to 1 minute depending on the ablation
myofibroblast population did not seem to have clinical depth.76,78,81 This shortening in the exposure time tries
relevance, although possibly a greater number of cases to reduce the possible adverse side effects of the
could have detected significant differences in the MMC. However, the results of the studies by Song
incidence of haze between both groups. et al.39,49 suggest that reducing the concentration of
Song et al.39 studied the number of apoptotic MMC would be more effective that reducing the
keratocytes detected in deepithelialized rabbit exposure time, as the concentration of MMC detected
corneas after application of MMC 0.02% for 15, 30, both in the cornea and in the aqueous humor was
60 and 120 seconds and, on the other hand, MMC more correlated with the concentration used than with
0.005%, 0.01%, 0.02% and 0.04% for two minutes. the time exposed. Unfortunately, only the study by
They observed more apoptosis both with greater Camellin80 uses MMC with a lower concentration
concentrations and with longer exposure times, but (0.01%) in a group of patients, and although his results
the correlation was stronger and statistically suggest it is also effective, more studies with more
 Mitomycin C in Surface Ablation: Benefits and Practical Use 193
patients and wide ranges of ammetropia would be
necessary to establish its effectiveness before
reducing the concentration of MMC from the 0.02%
currently used in the clinical practice with safe and
effective results.
In our clinical practice, we apply MMC over the
ablated stroma at a dose of 0.02% and an exposure
time of 15 seconds per each 50 μm ablated. As no
study has demonstrated the exact ablation depth
below which there is no risk for haze, the cut off for
using prophylactic MMC was set at 50 μm of ablation
depth. Other authors suggest using it starting on a
certain number of dioptres ablated (such as –6.00D40)
or on a particular ablation depth (75 μm 81 or 100 Figure 21.4: Material to prepare mitomycin C dilution
μm105) or on an ablation depth/corneal thickness
ratio =0.18.8,105 7 to 9 mm of diameter, which is soaked in the MMC
When the MMC is used therapeutically along with solution and is placed carefully over the ablated
the scraping of the corneal surface to eliminate a pre- stroma. Jain et al. 108 have also proposed to use a ring
existing haze, frequently a longer exposure time is instead of a complete disk, in order to diminish the
used, usually two minutes as proposed initially by exposure of the central cornea to the MMC and
Majmudar et al. 74,106,107, since the cytotoxic effect of secondarily decrease the possible toxicity of the MMC.
the MMC to produce apoptosis of the pre-existing They report good results avoiding haze with their
myofibroblasts seems lower than its capacity to technique.47
prevent their appearance when applied
ADVERSE EFFECTS ON THE CORNEA
prophylactically, as we have discussed above. Netto
et al. 40, in their study with rabbit corneas, showed The complications associated with MMC in other type
that four weeks after the application of MMC 0.02% of surgeries, such as pterygium and glaucoma,54,60-62
for 2 minutes to treat pre-existing haze, have not been reported in refractive surgery. This
myofibroblastic population could still be detected. difference might be explained by the different
This population progressively disappeared during the mechanisms of MMC toxicity depending on the tissue
first six months after the surgery. exposed. The tissues in contact with MMC during
pterygium and glaucoma surgeries are richly
Preparation and Application
vascularized. The MMC can cause a vascular
The MMC dilution may be prepared as follows: 5 ml endothelial injury 109 and, secondarily, tissue
of balanced salt solution (BSS) or distilled water are necrosis.78 On the other hand, when applied on the
added to 2 mg of MMC, to obtain a 0.4 mg/ml dilution avascular corneal tissue, MMC directly affects the
of MMC. Using an insulin syringe, we take 0.5 ml of three main cellular types: epithelial (differentiated
this solution and we add 0.5 ml of BSS or distilled epithelium and limbal cells), stromal (keratocytes),
water, thus obtaining 1 ml with 0.2 mg of MMC, i.e. a and endothelial cells. Only the first two have
MMC concentration of 0.2 mg/ml (0.02%) (Figure 21.4). substantial mitotic activity. The effect of MMC is
There are several ways of applying the MMC over greater in those cells with a higher mitotic rate, and,
the ablated stroma. The easiest way to avoid leakage therefore, the epithelium and keratocytes would
of the MMC to the peripheral cornea or the limbus is theoretically be more altered by the MMC than the
to use a round cellulose sponge of approximately endothelium.110
194 Mastering Advanced Surface Ablation Techniques
Effect on the Corneal Epithelium 2 minutes. 112 As commented above, when used
prophylactically, the MMC is currently applied for a
Effect on the Development of Normal Corneal
Epithelium after Surface Ablation shorter time.76,78,81 Considering the results of Rajan
et al.45, those short exposure times could explain why
Regarding the effect of the MMC on the corneal corneal epithelial complications are rarely seen after
epithelium, studies using animal models show MMC use during ASA.
variable results. Chang 111 studied the effect of In our own experience, applying MMC 0.02%
different doses of MMC (0.01% y 0.02%) applied for during 30 seconds, we have not detected a significant
2 minutes in rabbit corneas and reported a dose- difference in the number of days further than
dependant delay in re-epithelialization, whereas postoperative day 5 (when all our ASA patients are
another study in rabbits 41 did not identify that delay reviewed to remove the bandage contact lens)
in re-epithelialization in eyes treated with MMC. necessary until a newly-grown, healthy-looking and
Rajan et al.45 studied the effect of MMC on human well-adhered epithelium covers the entire corneal
corneas in vitro. They analyzed the effect on re- surface when the eyes treated with MMC and those
epithelialization of no MMC compared to MMC 0.02% not treated with MMC are compared (unpublished
for 1 minute and for 2 minutes. They found a delay data) (Figure 21.5). During the postoperative follow-
in the latency until the re-epithelialization started that up, we do not find a higher incidence of punctate
was dependant on the time of application of the MMC, keratitis associated with the use of MMC, suggesting
but while they found no difference in the epithelial that after one application of MMC the epithelium is
migration rate (once the reepithelialization began) not only capable of healing the surgical corneal ulcer
between the group that received MMC 1 minute but also of normal turnover to maintain a healthy
compared to the control group, they observed a corneal epithelium. MMC does not seem to affect the
statistically significant delay until the corneal postoperative corneal epithelialization process in a
epithelialization was complete in the group that way that could be relevant to the clinical daily practice
received MMC for 2 minutes. when it is applied intraoperatively at the dose and
On the other hand, clinical studies on human exposure times currently used in ASA.
corneas in vivo suggest a lack of clinically relevant
epithelial toxicity.75,77,80,107 Lee et al. 78 followed 1011
eyes treated with PRK with intraoperative MMC
(0.02% for 30 seconds to 2 minutes) and reported a
delay in epithelialization only in 2 eyes. Argento et
al. 76 reported a retrospective review of 30 eyes
treated with LASEK with intraoperative MMC 0.02%
for 75 seconds comparing their results with those of
28 eyes who underwent LASEK without MMC. They
did not find a statistically significant difference in
the time needed for both groups to epithelialize.
In addition, studies of repeated topical application
of MMC to treat ocular surface neoplasias, where this
substance is in contact with the entire ocular surface Figure 21.5: Line of advancing new epithelium after surface
ablation
(limbus included), did not show relevant epithelial
changes, thus suggesting the absence of limbal Effect on the Development of Epithelial Hyperplasia
toxicity.72 There has been only one report of a case after Surface Ablation
of persistent punctate keratitis after PRK during There is another aspect of the possible toxicity of MMC
which MMC 0.02% was applied intraoperatively for over the epithelium that has not been thoroughly
 Mitomycin C in Surface Ablation: Benefits and Practical Use 195
studied: the effect of this drug on the development of already explained, it is in fact its effect on the corneal
epithelial hyperplasia. After ASA, epithelial hyperplasia stromal cellularity what causes its anti-haze
has been described,29,113,114 especially associated with effectiveness, since it increases the apoptosis of
small optical zones (≤ 5 mm) and deeper ablations, keratocytes and inhibits its activation, proliferation
where the change in dioptric power at the edge of the and differentiation into myofibroblasts.40-44,118 This
ablation zone is more abrupt.115,116 The epithelium antimitotic effect has led to fear the consequences of
reacts to stromal loss with hypertrophy of the cells of a possible long-term depletion of keratocyte
the basal layer and, if this hypertrophy is not enough population.30,40,119 However, before analyzing the
to get a smooth corneal surface, then an epithelial effect of the drug on keratocyte population, we have
hyperplasia develops to further smooth the to bear in mind the effect of the surgery itself on
surface. 29,117 A change in the pattern of epithelial those keratocytes. Different reports on this subject
hyperplasia associated with the use of MMC could be seem not to share an agreement.
a subtle sign of its epithelial toxicity.
The study by Rajan et al. previously described 45
using human corneas in vitro found that, one month
after the application of MMC, the epithelium was
similar in thickness and morphology in the control
group and in the group treated with MMC for
1 minute, but it was less differentiated and
significantly thinner in the group treated with MMC
for two minutes. Maybe a longer follow-up would
have permitted those differences to disappear.
We performed a prospective study of 64
consecutive patients (64 eyes) scheduled to undergo
LASEK to correct myopia (unpublished data). The
consecutive patients were separated into two age-
matched groups: those treated with MMC 0.02% for
30 seconds and those not treated with MMC. At the
1 month and 3 months postoperative examinations, a
masked observer measured the central corneal Figure 21.6: Confocal microscope image of keratocytes
thickness (CCT). We found a statistically significant
increase in CCT from 1 to 3 months after ASA in Long-term Effect of Surface Ablation on Keratocyte
both groups, regardless of the use of intraoperative Population
MMC. We found no significant difference in that CCT In a study by Rajan et al.31 in human corneas in vitro
increase between the group that received where they compared the effects of simple
intraoperative MMC and the group that did not deepithelialization, PRK and LASEK, they observed
receive MMC, suggesting that MMC 0.02% during an initial depletion of keratocytes in all the groups,
30 seconds does not seem to interfere with the followed by a progressive repopulation, so four
normal pattern of corneal regrowth, mainly due weeks after the surgery, the keratocyte density was
to epithelial hyperplasia, seen after laser surface similar to preoperatively, and, in some cases (with
ablation. deeper ablations) it was even higher than
preoperatively. However, other studies using
Effect on the Corneal Stroma
confocal microscopy in patients treated with ASA
The keratocytes constitute the second cell type found contradictory results. Herrman et al. 120
exposed to the MMC (Figure 21.6). As we have observed a reduced keratocyte density when
196 Mastering Advanced Surface Ablation Techniques
compared to preoperative values even 1 year after higher initial depletion of keratocytes after ASA, but
the surgery, despite the progressive repopulation caused a delay in repopulation that was exposure
detected. Similarly, Erie et al. found a decreased time-dependant, and, 4 weeks after surgery, the
keratocyte density when compared to preoperative keratocyte density in the anterior stroma was
density in a 3-year 121 and a 5-year follow-up 122. On significantly lower in the MMC-treated groups in an
the contrary, Frueh et al.123 described an increased exposure time-dependant manner. However, the
keratocyte density at examinations 1 month and short follow-up (1 month) cannot rule out the
4 months after ASA, and Moilanen et al.124 did not possibility of a progressive ulterior repopulation. The
find, either, a decreased cellularity 5 years after keratocytes of the posterior layers did not show
surgery. Moller-Pedersen et al. 32 described an alterations in any group.
increased keratocyte density in the anterior stroma The only study that refers to the keratocyte
1 and 6 months after the surgery, that returned to population after ASA with MMC in a series of patients
normal 1 year after surgery. The discrepancies is Gambato et al. 77. They used confocal microscopy
between those studies may be due to the different in 36 eyes treated with ASA and MMC 0.02% for
point of measurement using confocal microscopy.125 2 minutes. They observed an initial depletion of
Dawson et al. 29 performed a histological study of keratocytes, followed by a progressive repopulation
human corneas treated with different procedures and and keratocyte activation. Although they do not
found that ASA produced the formation of a provide numeric data, they report that, after 6 to 12
hypercellular fibrotic scar, with a higher density of months, keratocyte density and activation normalize.
keratocytes in the anterior stroma. They do not report a long-term depletion of
keratocytes in the ablated area. During all the follow-
Long-term Effect of Surface Ablation with Mitomycin up, the keratocytes of the most posterior stromal
C on Keratocyte Population layers appeared quiescent, with no change in their
In those few studies using intraoperative MMC, we density, similarly to the study by Rajan et al. 45, which
do not find agreement, either, on the long-term suggest that the MMC does not affect the deeper
effects of this drug on the keratocyte density. stromal layers.
Kim et al42, using rabbits, showed a decrease in Qazi et al.126 reported a case of late dense haze
the keratocyte population 3 months after ASA with that developed after uncomplicated ASA with
intraoperative MMC 0.02% for 2 minutes, when prophylactic MMC performed 17 months before. The
compared to a control group. Xu et al.44 also found, authors have also observed this late corneal scarring
in rabbits, a significant decrease in the keratocyte in a cornea previously treated with LASEK with
density in the group that received MMC for 5 minutes intraoperative MMC 0.02% for 1 minute one year
compared to the control group until 1 month after before. The corneal haze developed after epithelial
surgery, but examinations 12 and 26 months trauma (Figures 21.7A and B). These cases and the
afterwards did not find a significant difference. Netto observations made by Gambato et al. suggest that
et al40 studied the effect of MMC (0.02% and 0.002% stromal cellularity does not suffer from permanent
for 12 seconds to 2 minutes) on rabbit corneas and MMC effect.
observed a keratocyte depletion in the anterior Personal studies from our group have been
stroma in all the MMC-treated groups compared to investigating the evolution of confocal microscopy
the control group even 6 months after MMC of the corneas that have been treated with MMC at
application, but the group treated with MMC 0.002% concentrations of 0.002% for 30 seconds to 1 minute
for only 12 seconds showed less depletion than the and the evolution over time of these patients. In
other MMC-treated groups. figure 8 we display the appearance of one of these
In the study previously described by Rajan et al45 corneas after 6 months of the treatment with MMC.
with human corneas in vitro, the MMC caused no Deprivation of keratocytes is observed with almost
 Mitomycin C in Surface Ablation: Benefits and Practical Use 197
Effect on the Corneal Endothelium
The third corneal cell type that could be affected by
MMC application in corneal refractive surgery is the
endothelium. Among the three cell types in the
cornea, the endothelium is the one with the least
proliferation activity in normal conditions due to
contact inhibition and the presence in the aqueous
humor of different inhibitory factors.127-129 Torres et
al.130 and Song et al.39,49 detected the presence of
MMC in the aqueous humor after its application over
the deepithelialized cornea in animal models,
suggesting that the drug gets in contact with the
A posterior stromal layers and the endothelium, thus
raising the question of a possible toxicity of the MMC
in these corneal layers. It has been shown that the
direct exposure of the endothelium to the MMC at
the concentrations used over the ocular surface would
cause a rapid endothelial damage.131,132 Fortunately,
apart from an accidentally entrance of the MMC in
the anterior chamber during glaucoma filtering
surgery, that concentration does not get in contact
with the endothelium. The concentration of MMC
detected in the anterior chamber after its application
over the deepithelialized cornea is much
lower. 39,49,130 The studies by Rajan et al. 45 and
Gambato et al.77 showed that the keratocytes of the
B deep stromal layers are not altered by the MMC.
Gambato et al. also describes no morphological
Figure 21.7A and B: Corneal haze developed after epithelial trauma
in a cornea previously treated with laser-assisted subepithelial change in the endothelium after MMC application.
keratectomy (LASEK) and intraoperative mitomycin C 0.02% for 1 In a review of the literature on the effect of MMC
minute.
on the endothelium in refractive surgery, we found
complete lack of them at the mid superficial stroma. few and contradicting reports. Chang 111 studied the
There are minimal or no signs of active scarring and effect of different concentrations of MMC (0.01% and
corneal reflectivity is apparently normal. The 0.02% applied for 2 minutes) in a rabbit model and
keratocytes repopulate this deprived area of the found that MMC produced dose-dependent transient
cornea from the 12th to the 24th month following edema and a decrease in endothelial cell density. He
surgery. The rest of the confocal evolution of these reported this might be related to the fact that the
cases seems to be apparently equivalent to that which rabbit corneal endothelium has continuous mitotic
occurs in PRK treated corneas with no MMC except activity,133 unlike the human endothelium, and so
for lack of development of haze. Corneal reflectivity MMC may have a different effect on both types of
has been constantly superior in MMC treated corneas endothelium, with the rabbit endothelium being more
than in PRK corneas. sensitive to the antimitotic action of MMC.
198 Mastering Advanced Surface Ablation Techniques
McDermott et al.134 studied the effect of the direct treated with intraoperative MMC 0.02% for longer
application of BSS, MMC 20 μg/ml or MMC 200 μg/ml times (ranging from 30 seconds to 2 minutes
on the endothelium of donated human corneas. They depending on the ablation depth). Moreover, the
found no difference between the edema secondary investigators found a significant increase in the
to the application of BSS or MMC 20 μg/ml and no endothelial cell density 6 months after surgery.
ultraestructural changes attributable to direct We performed a prospective, observer-masked
exposure of MMC 20 μg/ml, whereas application of study that included 40 consecutive patients (80 eyes)
MMC 200 μg/ml rapidly induced edema with marked scheduled to have LASEK to correct myopia 138. We
ultraestructural changes. Torres et al.130 and Song et compared the endothelial cell count between those
al.39,49 detected MMC in the aqueous humor after treated with MMC (0.02% for 30 seconds) and those
application of MMC 0.02% for 2 minutes at a not treated with MMC. Similarly to the results of
concentration much lower than the 20 μg/ml that Lee et al.78, we found a statistically significant increase
McDermott et al. used in their study without causing in the endothelial cell density 3 months after surgery
endothelial damage, which suggests that the usual in both groups, regardless of the use of intraoperative
dose of MMC in refractive surgery does not reach MMC. We found no significant difference in the
toxic levels for the endothelium. In fact, there have endothelial cell count 3 months after surgery between
been no reports of corneal decompensation after the the group that received intraoperative MMC and the
use of intraoperative MMC in ASA at the dose (0.02%) group that did not receive MMC. Lee et al.78 suggest
and exposure time (12 seconds to 2 minutes) usually that this increase may have resulted from the
used in this type of surgery. The only case of corneal interruption in contact lens wear. Another explanation
edema after MMC use in refractive surgery occurred in may be the change in corneal magnification after laser
a patient after repeated topical application of MMC135, ablation. The decrease in the keratometric values due
so the patient received a final total dose of MMC to the myopic laser ablation profiles would produce
much higher than that usually applied during ASA. a decrease in the magnification of the image of the
Garweg et al. 136 observed that, while one single endothelial cells obtained by specular microscopy.139
application of MMC from 10 μg/ml to 100 μg/ml, The cells would consequently appear smaller than
applied in both cultured fibroblasts and cultured in the preoperative picture and would thus be
endothelial cells, did not cause any cytotoxic effect, counted erroneously as being more numerous
this effect appeared if the exposure was maintained (Figure 21.8A and B).
chronically for 7 days, even with lower concentrations. The lack of clinically evident endothelial toxicity
Morales et al.137 compared a control group (9 eyes) and the lack of an endothelial cell density decrease
that received no MMC and a study group (9 eyes) in our study and in the study by Lee et al.78 suggest
treated with intraoperative MMC 0.02% for that one application of MMC at the low concentration
30 seconds. Those authors found significant cell loss used in refractive surgery is insufficient to produce a
in the MMC group but not in the control group. cytotoxic effect in the endothelium.
However, the high standard deviation of endothelial
cell counts make results in studies with few patients CONCLUSION
unreliable, because the probability of having cases
with extreme counts (too low or too high) in a given In conclusion, MMC has shown to decrease the
group is high. There are two ways to increase the incidence of haze after ASA procedures, allowing
certainty: decrease the standard deviation (i.e. treatment with ASA not only of low and moderate
increase the reproducibility of the measurement) or myopia, but also of high myopia with similar visual
increase the number of cases studied. and refractive results than LASIK. There is a tendency
On the other hand, Lee et al. 78 reported no to reduce the dose and exposure time of MMC, as
decrease in the postoperative cell count in 1011 eyes several studies suggest that even low concentrations
 Mitomycin C in Surface Ablation: Benefits and Practical Use 199
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assisted photorefractive keratectomy in the treatment of I. Dry eye after photorefractive keratectomy with
buttonholed laser in situ keratomileusis flaps associated adjuvant mitomycin C. J Refract Surg 2006;22:511-3.
with epithelial ingrowth. J Cataract Refract Surg 113. Gipson IK. Corneal epithelial and stromal reactions to
2005;31:2026-30. excimer laser photorefractive keratectomy. I. Concerns
97. Lane HA, Swale JA, Majmudar PA. Prophylactic use of regarding the response of the corneal epithelium to
mitomycin-C in the management of a buttonholed LASIK excimer laser ablation. Arch Ophthalmol
flap. J Cataract Refract Surg 2003;29:390-2. 1990;108(11):1539-40.
98. Chalita MR, Roth AS, Krueger RR. Wavefront-guided 114. Lohmann CP, Reischl U, Marshall J. Regression and
surface ablation with prophylactic use of mitomycin C epithelial hyperplasia after myopic photorefractive
after a buttonhole laser in situ keratomileusis flap. J Refract keratectomy in a human cornea. J Cataract Refract Surg
Surg 2004;20:176-81. 1999;25:712-15.
 Mitomycin C in Surface Ablation: Benefits and Practical Use 203
115. Gauthier CA, Holden BA, Epstein D, Tengroth B, 127. Joyce NC. Proliferative capacity of the corneal
Fagerholm P, Hamberg-Nystrom H. Factors affecting endothelium. Prog Ret Eye Res 2003;22:359-89.
epithelial hyperplasia after photorefractive keratectomy. 128. Senoo T, Joyce NC. Cell cycle kinetics in corneal
J Cataract Refract Surg 1997;23(7):1042-50. endothelium from old and young donors. Invest
116. Hamberg-Nystrom H, Gauthier CA, Holden BA, Epstein Ophthalmol Vis Sci 2000;41:660-7.
D, Fagerholm P, Tengroth B. A comparative study of 129. Joyce NC. Cell cycle status in human corneal endothelium.
epithelial hyperplasia after PRK: Summit versus VISX in Exp Eye Res 2005;81:629-38.
the same patient. Acta Ophthalmol Scand 1996;74(3):228- 130. Torres RM, Merayo-Lloves J, Daya SM, Blanco-Mezquita
31. JT, Espinosa M, Nozal MJ, Bernal JL, Bernal J. Presence of
117. Dillon EC, Eagle RC Jr, Laibson PR. Compensatory mitomycin-C in the anterior chamber after
epithelial hyperplasia in human corneal disease. photorefractive keratectomy. J Cataract Refract Surg
Ophthalmic Surg 1992;23(11):729-32.
2006;32:67-71.
118. Chang SW. Corneal keratocyte apoptosis following
131. Nuyts RM, Pels E, Greve EL. The effects of 5-fluorouracil
topical intraoperative mitomycin C in rabbits. J Refract
and mitomycin C on the corneal endothelium. Curr Eye
Surg 2005;21:446-53.
Res 1992;11:565-70.
119. Netto MV, Mohan RR, Ambrosio R, Hutcheon AEK,
132. Hernández-Galilea E, Sanchez F, Guzman K, Moro MJ,
Zieske JD, Wilson SE. Wound healing in the cornea. A
review of refractive surgery complications and new Vazquez R, Barahona JM. Effect of mitomycin C on
prospects for therapy. Cornea 2005;24:509-22. corneal endothelium cells. In vitro study. Arch Soc Esp
120. Herrman WA, Muecke M, Koller M, Gabel VP, Lohmann Oftalmol 2000;75:515-21.
CP. Keratocyte density in the retroablation area after 133. Joyce NC, Navon SE, Roy S, Zieske JD. Expression of cell
LASEK for the correction of myopia. Graefe’s Arch Clin cycle-associated proteins in human and rabbit corneal
Exp Ophthalmol 2007;245:426-30. endothelium in situ. Invest Ophthalmol Vis Sci
121. Erie JC, Patel SV, McLaren JW, Hodge DO, Bourne WM. 1996;37:1566-75.
Keratocyte density in the human cornea after 134. McDermott ML, Wang J, Shin DH. Mitomycin and the
photorefractive keratectomy. Arch Ophthalmol human corneal endothelium. Arch Ophthalmol
2003;121:770-6. 1994;112:533-37.
122. Erie JC, Patel SV, McLaren JW, Hodge DO, Bourne WM. 135. Pfister RR. Permanent corneal edema resulting from the
Corneal keratocyte deficits after photorefractive treatment of PTK corneal haze with mitomycin: a case
keratectomy and laser in situ keratomileusis. Am J report. Cornea 2004;23:744-7.
Opththalmol 2006;141:799-809. 136. Garweg JG, Wegmann-Burns M, Goldblum D. Effects of
123. Frueh BE, Cadez R, Bohnke M. In vivo confocal daunorubicin, mitomycin C, azathioprine and
microscopy after photorefractive keratectomy in humans. cyclosporine A on human retinal pigmented epithelial,
A prospective, long-term study. Arch Ophthalmol corneal endothelial and conjunctival cell lines. Graefe’s
1998;116:1425-31. Arch Clin Exp Ophthalmol 2006;244:382-9.
124. Moilanen JA, Vesaluoma MH, Muller LJ, Tervo TM. Long- 137. Morales AJ, Zadok D, Mora-Retana R, Martínez-Gama E,
term corneal morphology after PRK by in vivo confocal Robledo NE, Chayet AS. Intraoperative mitomycin and
microscopy. Invest Ophthalmol Vis Sci 2003;44:1064-9.
corneal endothelium after photorefractive keratectomy.
125. Dawson DG, O’Brien TP, Edelhauser HF. Long-term
Am J Ophthalmol 2006;142:400-04.
corneal keratocyte deficits after PRK and LASIK: in vivo
138. de Benito-Llopis L, Teus MA, Ortega M. Effect of
evidence of stress-induced premature cellular senescence.
Mitomycin C on the Corneal Endothelium during Excimer
Am J Ophthalmol 2006;141:918-20.
126. Qazi MA, Johnson TW, Pepose JS. Development of late- Laser Surface Ablation. J Cataract Refract Surg
onset subepithelial corneal haze after laser-assisted 2007;33:1009-13.
subepithelial keratectomy with prophylactic 139. Isager P, Hjortdal JO, Ehlers N. Magnification changes in
intraoperative mitomycin-C. Case report and literature specular microscopy after corneal refractive surgery. Acta
review. J Cataract Refract Surg 2006;32:1573-8. Ophthalmol Scand 1999;77:391-3.
204 Mastering Advanced Surface Ablation Techniques

Cross-Linking Plus
CHAPTER
Topography-Guided PRK for
22 Post-LASIK Ectasia
Management

A John Kanellopoulos (Greece)

INTRODUCTION topography preoperatively suggesting forme fruste

keratoconus.2 It remains though quite a challenge to
LASIK surgery has become a medical phenomenon
explain why some “uneventful” procedures that had
throughout the world over the last 20 years.
perfect preoperative topography and well
It all started in the laboratories of the University
documented “enough” residual stromal bed thickness
of Krete in Greece and under the direction of Ioannis
may develop keratectasia.
Pallikaris, MD in 1988. It was the natural evolution
As a cornea surgeon I have had the opportunity
of the boom in automated lamellar surgery that was
to treat several patients with this dreaded
popularized in South America that same decade and
complication in the past. The initial treatment in the
the introduction of cornea shaping by the excimer
90’s was penetrating keratoplasty when the ectasia
laser. It has become one of the most common
could not be rehabilitated with RGP contact lenses.3
procedures humans undergo worldwide, and for
sure, the most common elective procedure that In the early 2000’s INTACS became a potential option.
medicine offers today. I have personally have not had a good clinical results
Throughout the years there have been several with INTACS in regard to their stability in ecstatic
lessons in LASIK that have been learned by refractive corneas.4 In 2002 I became involved with collagen
surgeons. One of those has been the limitation to the cross-linking with the use of UVA irradiation and
amount of laser ablation that the human cornea can topical riboflavin after I became familiar with the
withhold, before changing its biomechanical properties. work of Seiler Wollensak and Spoel in Dresden and
Post-LASIK ectasia has been recognized as a serious Zurich with this application.5-8 This is the case report
complication from the early years of LASIK of the first patient I encountered.9
development.1 Throughout this time several safety A 29-year-old patient that had underwent uniocular
“paradigms” have been arbitrarily communicated LASIK for the correction of myopic astigmatism 3 years
through meetings and publications establishing the ago. His initial UCVA was 20/80 and his BSCVA was
safety margin for residual stroma bed. 20/20 with a refraction of –2.00 –175 × 85. Three
Even today procedures performed years ago may months post-LASIK he began experiencing regression
complicate and develop ectasia. In most cases a very with myopia and astigmatism to the point of UCVA
small residual stromal bed is usually the isolated 20/200 and BSCVA 20/80 with –3.50 –2.00 × 120. Based
contributing factor along with irregular cornea on irregular topography and the loss in BSCVA, the
 Cross-Linking Plus Topography-Guided PRK for Post-LASIK Ectasia Management 205
treating physician soon recognized that a mechanism IMPROVEMENT IN VISUAL ACUITY
of ectasia had begun. Because this was not functionally
At 3 months, the patient’s UCVA improved from 20/
correctable with spectacles or contact lenses, the
400 to 20/70 and his BSCVA improved from 20/200
decision was made to implant intracorneal ring
to 20/40. The refraction changed from –4.50 –4.50 ×
segments for the management of this complication.
120 to –4.50 –4.00 × 115, and corneal topography
Unfortunately, the patient’s UCVA remained 20/200
changed as seen in Figure 1. The stability of these
and BSCVA 20/100. The treating surgeon
parameters and the corneal topography between
recommended cornea transplantation as the next step.
months 1 and 3 of this treatment, encouraged us to
My initial evaluation of the patient was made 11 months
proceed with topography-guided PRK. We sought
post-LASIK and 3 months after intracorneal ring
to reduce the irregular astigmatism and attempt to
implantation. Corneal thickness —by Orbscan (Bausch
provide the patient with visual acuity not requiring
& Lomb, Rochester, NY) and ultrasound pachymetry
spectacle or soft contact lens correction. Because the
—was 410 μm at the thinnest point, and the endothelial
patient’s corneal thickness was 410 μm, we were able
cell count was 2,750 cells per mm2 (Noncon Robo;
to treat his full spectacle correction using the
Konan Medical, Hyogo, Japan).
Allegretto® Wave excimer laser (Wavelight, Erlangen
Germany) topography-guided customized ablation
OPTIONS FOR TREATMENT
treatment (T-CAT) software. After placing 20%
We have had poor long-term outcomes with dilution of EtOH on the corneal surface for 30 seconds
intracorneal ring segments in post-LASIK ectasia4,a and subsequent epithelium removal, I performed laser
fact which we discussed with the patient. We treatment. A bandage contact lens was placed for 5
discussed the benefits and risks of corneal transplant, days and the patient was treated again with ofloxacin
as well as combined ultraviolet radiation and and prednisolone four times a day for 10 days. The
riboflavin treatment in order to achieve collagen bandage contact lens was removed at day 4,
cross-linking and biomechanical stabilization of the following complete re-epithelialization. One month
corneal ectasia. We then obtained patient consent to after topography-guided treatment, the patient’s
remove the failed intracorneal ring segments. I UCVA was 20/20- and BSCVA was 20/20 with a
treated his cornea with a single application of UV-A refraction of +0.50 –5.0 X 160. The corneal endothelium
radiation at 3 mW/cm2 for 30 minutes (KeraCure; count has remained stable at 2,700 cells per mm2. The
Priavision, Menlo Parl, Ca) combined with 0.1% patient complained of night vision symptoms of halos
riboflavin ophthalmic solution. This treatment was and ghosting. The patient is now at 34 months
performed after removing the corneal epithelium postoperative and enjoys UCVA of 20/20 with some
with 20% ETOH placed on the surface for 30 seconds. mild night vision problems and corneal topography
The riboflavin solution was applied for about 2 as shown in Figure 22.1. One can also appreciate the
minutes in order to soak the stromal bed and protect difference map between pre and post topography-
the iris, crystalline lens and retina from UV guided treatment in Figure 22.1, as well as the actual
irradiation. One drop every 2 minutes was applied ablation profile that was used for the treatment.
during the 30 minutes of irradiation. A bandage TREATMENT OF IATROGENIC KERATECTASIA
contact lens was placed on the cornea for 5 days, and
the patients was treated with topical ofloxacin 1% Different techniques have been suggested for the
(Ocuflox; Allergan, Irvine, Ca) and prednisolone treatment of iatrogenic keratectasia without
acetate 1% (Predforte, Allergan) four times a day for satisfactory outcomes either biomechanically or
10 days. The bandage contact lens was removed at visually, with the patient’s journey most frequently
day 4, following complete re-epithelialization. ending with pentrating conreal graft. Reports of the
206 Mastering Advanced Surface Ablation Techniques

Figure 22.1: This display of topographies depicts the following:

1. The cornea topography of this case when first seen by the authors with central cornea ectasia and mid-periphery flattening as an effect
of the INTACS that were present. At this point BSCVA was 20/200
2. The cornea topography here is 2 months following the removal of INTACS and 1 month following UVA collagen cross-linking.. The central
steepening is still present and the effect of the INTACS removal is appreciated compared to the previous image mostly at the mid-periphery,
that appears steeper now. At this point BSCVA was 20/200
3. The lower row image in the center is an estimated cornea topographic ablation pattern as a laser treatment plan of the topography-guided
procedure that took place in the case. It is notable that this ablation pattern is highly irregular with “deeper” ablation plan just inferiorly and
right to the center, that matches though the central cornea irregularity in the previous topographies.
4. The cornea topography here is 6 months following topography-guided PRK. The central cornea appears more regular and much flatter. At
this point BSCVA and UCVA is 20/20
5. The lower row image on the left is a comparison map. This map depicts the difference of subtracting the cornea topography 4 (final result)
from the cornea topography 1 (original state of this complication when encountered by us). The difference resembles impressively the
topography-guided ablation pattern (next image to the right) demonstrating effectively the specificity of this treatment in reducing the
pathogenic cornea irregularity, which we theorize that contributed in the drastic improvement of BSCVA
 Cross-Linking Plus Topography-Guided PRK for Post-LASIK Ectasia Management 207
use of riboflavin/UVA corneal cross-linking have been A 28-year-old male physician underwent LASIK
shown to slow down keratoconus and progressive in November 2002. for –5.50 –1.50 X015 (20/20) OD
iatrogenic ectasia. During the past 3 years, we have and –4.25 –1.25 X0168 (20/20) OS. Four months
had extensive experience with customized following surgery, the uncorrected vision was 20/25
topography-guided excimer ablations which we have in both eyes. The manifest refraction was +0.25
presented and reported. 10,11 This customized –1.25 X090 (20/20) OD and was +0.25 –0.25 X110
approach can, in our opinion, address the extreme (20/15) OS but the topography suggested the early
cornea irregularity that these cases may have and development of ectasia . At this time, the keratometry
enhance visual rehabilitation. This was the first report readings were 38.75/39.25X22 (OD) and 38.50/39.00
of post-LASIK ectasia treatment using a combination × 162 (OS) and the pachymetry readings were 375
of UVA collagen cross-linking to stabilize the corneal microns (OD) and 407 microns (OS).
biomechanics, followed by surface excimer laser The patient returned on February 21, 2005, with
ablation for visual rehabilitation. Remarkable corneal an uncorrected vision of 20/40 in the right eye and
stabilization, together with full visual rehabilitation, 20/20 in the left eye. A manifest refraction in the
leads us to believe that this approach may have a affected right eye of –0.75 –3.50 × 091 (20/30), and
wider application in the near future. Considering the +0.75 –0.50 × 0128 (20/20) OS. The topography at this
tremendous burden on the patient in everyday life, point suggested the presence of ectasia only in the
as well as the medical-legal issues involved in such a right eye 22.2A and Orbscan 22.2C.
complication of elective excimer laser refractive
surgery as iatrogenic keratectasia, we feel that the MINIMAL CORNEAL THICKNESS
combined procedure discussed here is now a valuable Special emphasis must be taken to ensure minimal
alternative to therapeutic cornea transplantation and corneal thickness preoperatively because of potential
should be considered in any case that enables the cytotoxic effects of UVA on corneal endothelial cells.
application of this treatment. Previous experimental studies in rabbit corneas have
It is though in my opinion necessary for the investigated dose-dependent cytotoxicity to the
clinician to take special consideration in treating these corneal endothelium. Surface irradiance according to
cases. By no means can the excimer laser be the protocol described herein, may not be used in
considered an instrument for emmetropia in these corneas thinner than 350 μm. This mimimal thickness
patients in a fashion similar to routine LASIK and/ should also be respected in human corneas. The laser
or PRK refractive cases. The treatment should be treatment must be applied with caution because more
directed towards “ normalizing” the cornea surface rigid corneas may have a different ablation depth-
and allowing for improvement of BSCVA. There is per-pulse than the untreated one. Indeed, it appears
an obvious danger in thinning these corneas to much to result in over-corrections when these corneas are
by giving in to the “temptation” to correct the treated with excimer laser versus a normal PRK or
refractive error. This was the initial desire of these LASIK procedure. For this reason, our recom-
patients anyway. Having no previous work to relay mendation is to use 75 to 80% of the measured sphere
on, I arbitrarily took a conservative approach to the and cylinder as a correction parameter when planning
matter and limited the refractive laser treatment to the ablation with T-CAT software. Larger
the minimum and never to allow removal of over 50 comparative studies and longer follow-up is necessary
microns the thinnest cornea. in order to validate the long-term efficacy of this
Several cases followed this success story over the combined treatment with UV/riboflavin followed by
last 5 years. We have presented a case series at the topography-guided excimer laser treatment.10 The
AAO annual meetings in 2005 and 2006. refractive and topographic stability of more than 3
A similar example (Figures 22.2A to E). years, however, appears to validate this minimally
208 Mastering Advanced Surface Ablation Techniques

B
Cross-Linking Plus Topography-Guided PRK for Post-LASIK Ectasia Management 209

D
210 Mastering Advanced Surface Ablation Techniques

Figures 22.2A to E: A 28-year-old male physician underwent LASIK in November 2002. for –5.50 –1.50 X015 (20/20) OD and -
4.25 –1.25 X0168 (20/20) OS. Four months following surgery, the uncorrected vision was 20/25 in both eyes. The manifest
refraction was +0.25 –1.25 X090 (20/20) OD and was +0.25 –0.25 X110 (20/15) OS but the topography suggested the early
development of ectasia. At this time, the keratometry readings were 38.75/39.25X22 (OD) and 38.50/39.00x162 (OS) and the
pachymetry readings were 375 microns (OD) and 407 microns (OS)
The patient returned on February 21, 2005, with an uncorrected vision of 20/40 in the right eye and 20/20 in the left eye. A
manifest refraction in the affected right eye of –0.75 –3.50 X091 (20/30), and +0.75 –0.50 X0128 (20/20) OS. The topography at
this point suggested the presence of ectasia only in the right eye 2a and Orbscan 2c
Two years following UVA collagen crosslinking with refractive error of –2.00 –3.00 X0170 (20/30). the uncorrected vision in
the affected right eye was 20/30, with a manifest refraction of –1.50 –1.75 X073 (20/20). The Orbscan at this point is 2d and the
comparison 2b and 2e of pre and post UVACCL appearance of the posterior cornea elevation is self explanatory

invasive treatment of iatrogenic keratectasia and leads Can LASIK “ regressions” be a form of ectasia?
us to believe that it may have an even wider I would like to present another case to you:
application in the near future. We have utilized this Six years ago, a 34-year-old female underwent
modality in idiopathic keratoconus cases as well with LASIK for –11.00 D of myopia (Figures 22.3A to C).
similar results.11 As a cornea surgeon I do feel that During the procedure a Moria M2 (Moria; Antony,
UVA CCL maybe the single most important France) microkeratome was used to create a 125– μm
introduction in cornea surgery and keratoconus and flap (calculated with subtraction pachymetry) and an
cornea ectasias in general over the last 25 years. Allegretto ® 200 Hz laser (Wavelight; Erlangen,
If our initial clinical experience holds true I the Germany), with a planned 6 mm optical zone, was
future follow up it may be able to significantly used to conserve tissue. Total treatment centrally was
minimize the necessity for cornea transplantation in planned to 130 μm. The residual cornea bed
ectatic cornea disorders. measured 320 μm. For 5 years after the surgery, the
 Cross-Linking Plus Topography-Guided PRK for Post-LASIK Ectasia Management 211
patient was satisfied, and plano, with 20/20 visual proceed with collagen cross-linking with the
acuity. The patient now presents 20/40 UCVA and PriaVision device (PriaVision, Menlo Park, California)
20/20 BSCVA, with eyes measuring –1.50 D and for 30 minutes in conjunction with 1% riboflavin
–0.75 D. No ectasia is evident on the topography and solution applied every 2 minutes to the surface of
Oculus Pentacam (Oculus Optikgerate GmbH, the deepithelialized cornea. Initially the patient was
Wetzlar, Germany). unsatisfied and experienced pain and discomfort for
The patient’s preoperative measurements: Central the first 10 days while the epithelium healed. That
cornea thickness is approximately 460 μm. changed at 1 month follow-up, however, when we
I have relatively extensive experience in cases like discovered her UCVA was back to 20/20 and her
this, as I have seen many patients treated for high refractive error was –0.25 D. In the end, our patient
myopia in the past. None of my cases have developed achieved a VA of 20/15. I would therefore use this
any corneal I have seen this type of LASIK regression case to confirm previous reports on the biomechanical
many times in the past and have addressed the changes of the cornea following LASIK, and establish
problem several different ways. In some cases, I have a significant biomechanical effect of the UVA cornea
re-lifted the flap to do an additional enhancement, cross-linking to the operated cornea—with a change
after measuring the flap thickness intraoperatively in the posterior cornea contour centrally and
in order to avoid significantly reducing the paracentrally Figure 22.3C. This is a comparison map
postenhancement residual stromal bed (Since 2000, I of the posterior cornea surface by the Wavelight
have tried to adhere to the guideline of 270 μm for Oculyzer (Pentacam). The first map on the left is the
residual stroma following LASIK). Another potential pre-UVA CCL posterior cornea surface devoid of any
method of treatment for this patient would be to signs of ectasia. The middle map is the same posterior
perform a customized retreatment with asphericity surface one month following UVA CCL. It is evident
adjustment as an additive (Wavelight 400 Hz that there has been been a flattening change, more
Allegretto Wave Eye-Q laser; Wavelight Laser evident in the difference map on the right, The mid-
Technologie AG, Erlangen, Germany). I would periphery of the posterior cornea shows a “flattening”
include a treatmentgoal of –0.50 D for the Q value effect confirming the biomechanical change in this
(asphericity), in ordertoreduce spherical aberrations cornea following the collagen cross-limking. This
that are typically induced during the correction of effect appears to have corrected the late regression
high myopes. The hope is that the post-enhancement of –1 Diopter.
Q value would be less positive. Through past I believe this case shows that any surprise
experience, we have learned that correction of –10.00 regressions noted—even years—after LASIK could
D shifts the 30° asphericity of the cornea from an be biomechanical changes of the cornea, and could
average –0.30 D to ±2, therefore inducing significant be treated by this minimally invasive alternative.
spherical aberrations. In the case of this patient, I Figure 22.4 decribe a similar case: These are
chose not to use either of the previously mentioned Pentacam comparison maps of a 27 y/o female that
options. Considering that the cornea was stable, I underwent LASIK for –10 OU 5 years ago.
pulled from my experience with UVA collagen cross- She had an enhancement fro –1.00 OU 3 years ago
linking as a means to rehabilitate ectatic corneas after and deteriorated again to –1.5D.
LASIK. I proposed that the patient was experiencing Instead of enhancement she underwent UVA CCL
a late biomechanical shift of the thinned cornea. The and the refraction regression reversed to plano. The
patient and I discussed the option of cross-linking pentacam comparison of pre and post UVA CCL for
the cornea and then enhancement, if necessary. I the sagittal curvature front (Figure 22.4A) and
determined that performing an enhancement first posterior cornea elevation (Figure 22.4B) shows the
may not be successful if the refraction continued to biomechanical change of cross linking that produced
regress in the future. We therefore decided to the regression reversal.
212 Mastering Advanced Surface Ablation Techniques

B
 Cross-Linking Plus Topography-Guided PRK for Post-LASIK Ectasia Management 213

C
Figures 22.3A to C: Picture 3A is the 2000 preoperative Orbscan of the right eye Figure 3B is the 2006 postoperative
pentacam of the same treated eye 3c: 1 month post-UVA CCL pentacam images of the same cornea that establish a
significant biomechanical effect of the UVA CCL to the operated cornea with a change in the posterior cornea contour
centrally and paracentrally

Figure 22.4: These are Pentacam

comparison maps of a 27 y/o female that
underwent LASIK for –10 OU 5 years
ago
214 Mastering Advanced Surface Ablation Techniques
REFERENCES 7. Spoerl E, Huhle M and Seiler T. Induction of cross-links in
corneal tissue. Exp Eye Res 1998;66:97-103.
1. Binder PS. Ectasia after laser in situ keratomileusis. J 8. Hafezi F, Mrochen M, Jankov M, Hopeler T, Wiltfang R,
Cataract Refract Surg 2003,29:2419-29. Kanellopoulos A and Seiler T. Corneal collagen cross
2. Randleman JB, Russell B, Ward MA, Thompson KP, linking with riboflavin/UVA for the treatment of induced
Stulting RD. Risk factors and prognosis for corneal ectasia kerectasia after laser in situ keratomileusis 2007.
after LASIK.Ophthalmology 2003;110(2):267-75. 9. Kanellopoulos A. Management of post-LASIK ectasia
with UVA collagen-cross linking followed by customized
3. Klein SR, Epstein RJ, Randleman JB, Stulting RD. Corneal
topography-guided PRK - an efficient approach to avoid
ectasia after laser in situ keratomileusis in patients without
corneal transplantation. Letter-to-the-editor in press
apparent preoperative risk factors. Cornea 2006; Ophthalmology 2007.
25(4):388-403. 10. Kanellopoulos AJ. Topography-guided Custom re-
4. Kanellopoulos A, Pe L, Perry H, and Donnenfeld E. treatments in 27 symptomatic eyes. J Refract Surg. Sept/
Modified Intracorneal Ring Segment Implantations Oct 2005;21:S513-8.
(Intacs) for the Management of Moderate to Advanced 11. Kanellopoulos AJ and Pe L. Wavefront-guided
Keratoconus: Efficacy and Complications. Cornea Enhancements using the Wavelight Excimer Laser in
2006;25:29-33. Symptomatic Eyes Previously Treated with LASIK. J
5. Wollensak G, Spoerl E and Seiler T. Riboflavin/ultraviolet Refract Surg 2006,22:345-9.
-a-induced collagen cross linking for the treatment of 12. Kanellopoulos AJ , Binder PS. Collagen cross-linking
keratoconus. Am J Ophthalmol 2003,135:620-7. (CCL) with Sequential topography-guided PRK. A
6. Seiler T, Hafezi F. Corneal cross-linking-induced stromal temporizing alternative to penetrating keratoplasty. J of
demarcation line. Cornea 2006,25:1057-9. Cornea (in press).
 CHAPTER Wavefront Optimization and

23 Astigmatism Correction with

the Allegretto® Excimer Laser

Jerome Bovet, Auguste Chiou (Switzerland)

INTRODUCTION One of the most innovative features of the laser

excimer Allegretto ® is the way it incorpo-
The term, “wavefront-optimized”(Figure 23.1),
rates wavefront optimization in rendering proper
describes the unique ablation profile and proprietary
treatment. It is the only vision-correcting laser
algorithms incorporated into the Allegretto® excimer
system that takes into account the starting curvature
laser (Figure 23.2).
radius of the cornea being treated. The laser excimer
Allegretto® is specifically designs to preserve the most
normal curvature characteristics (and thereby
optimize visual quality) as a consequence of
treatment.
In earlier laser systems (treating nearsightedness),
the optical zone (Figure 23.3), or area of correction,
was centered on the front of the cornea; the result
was a flattened circular area that ended with an abrupt
edge, causing unwanted side effects like poor night
vision, glare, and halos (Figure 23.4).
Laser treatment patterns (called algorithms) then
Figure 23.1: Allegretto Wave Excimer System Overview evolved to apply peripheral treatment in a blend zone
around the optical zone.1
There is a problem that arises, however, in treating
the peripheral cornea with older laser systems. All
prior laser systems are designed to be calibrated on
flat plastic test surfaces. However, the cornea is
curved, and when treating on the downslope of the
domed surface (everywhere but the top dead center
of the dome), some laser energy is scattered rather
than being absorbed by the target tissue. This
problem becomes more pronounced the more
Figure 23.2: Allegretto laser beam distribution peripheral the laser aims from “straight down”.
216 Mastering Advanced Surface Ablation Techniques

Figure 23.3: Gaussian profile Figure 23.5: Ablation frequency

Figure 23.4: Ablation profile Figure 23.6: The eye tracker

In order to fully understand the significance of in one position, striking parallel through the axis and
wavefront-optimization, it is first necessary to consider perpendicular to the central cornea.
the ideal pre- and postoperative shape of the cornea. When laser pulses hit the center of the cornea,
they are fully absorbed. But in the corneal periphery,
NORMAL CORNEAL SHAPE AND ASPHERICITY
the laser beam meets the cornea at an incline due to
The natural shape of the human cornea is aspheric the cornea’s curved shape (Figure 23.7).
with a prolate shape or higher in the center (Figures Changing the angle of incidence will alter the
23.5 and 23.6) (where the optical power is less in the round spot into a larger, elliptical shape, thereby
corneal periphery) Figure 21. In a normal pre- distributing laser energy over a larger surface. The
operative eye, corneal steepness decreases from the photoablative effect,4 therefore, decreases, causing a
central cornea to the periphery with progressive reduction in effective peripheral ablation at an optical
peripheral flattening.2,3 zone of 8 mm, the effective energy (energy over a
All refractive laser systems utilize a light beam surface) used for corneal tissue ablation at the
(whether broadbeam or scanning spot) that is fixed periphery is reduced by as much as 20% compared
 Wavefront Optimization and Astigmatism Correction with the Allegretto® Excimer Laser 217

Figure 23.7: The eye tracker

with the ablation at the central cornea.5 Most laser

systems flatten centrally to create an oblate cornea.
This oblate shape causes spherical aberration, which
degrades the quality of vision, and increase the
spherical aberration.6

SPHERICAL ABERRATION (Figure 23.8)

Figure 23.8: The eye tracker
A type of optical aberration resulting from failure of
a lens (or optical system) to form a perfect image of a
designed to preserve the naturally aspheric shape of
monochromatic, on-axis point source object. Spherical
the cornea to a degree that older lasers simply could
aberration is a form of ‘higher-order’ aberration.7 A
not achieve. This compensation produces a smooth,
lens can be perfectly spherical in curvature, but that
cleanly sculpted optical surface.
does not mean that parallel light rays entering near
In earlier laser correction systems, the “optical
the center of the lens will intersect the lens axis at
zone,” or area of correction, was centered on the front
the same point behind the lens as rays entering from
of the cornea; the result was a flattened circular area
more peripheral points. The differences in where
that ended with an abrupt edge, causing unwanted
these rays intersect determines the amount of
side effects like poor night vision, glare, and halos.
spherical aberration. When rays from a point on the
Understanding that the cornea is a sphere, the
axis passing through the outer lens zones are focused
laser excimer uses a proprietary treatment that is
closer to the lens than rays passing the central zones,
adjusted to the patient’s individual corneal curvature.
the lens is said to have negative spherical aberration;
To overcome the induction of spherical aberrations
if the outer zones have a longer focal length than the
resulting from reflection and reduced photoablative
inner zones, the lens is said to have positive spherical
effect beyond the central cornea, the laser applies
aberration. Spherical aberration can be corrected by
additional pulses in the periphery of the cornea to
lenses with aspheric design.12
pre-compensate for these energy losses (Figure 23.9).
In this manner, the spherical shape of the cornea
WAVEFRONT OPTIMIZED TECHNOLOGY9
is preserved.
The Allegretto ® system, by design, applies extra This compensation, combined with the incredibly
pulses to the peripheral cornea in order to compensate small, 1 mm size of the laser, produces a smooth,
for the angle of the laser beam. In this manner, the effective optical zone that produces what can only
laser anticipates and corrects for any cosine offset be described as high performance vision (Figure
issues. In addition, the laser treatment is specifically 23.10).
218 Mastering Advanced Surface Ablation Techniques

Figure 23.9: Ablation

Figure 23.10: Myopique ablation profile

 Wavefront Optimization and Astigmatism Correction with the Allegretto® Excimer Laser 219
The wavefront-optimized algorithm takes into and reduces the cornea’s ability to focus light.
consideration each patient’s preoperative keratometry Astigmatism is a refractive error of the eye in which
value (or corneal steepness). The desired there is a difference in degree of refraction in different
postoperative aspheric contour is maintained, even meridians (i.e., the eye has different focal points in
in the outer areas of the cornea, resulting in a large, different planes.) For example, the image may be
true optical zone (Figure 23.3). Due to the additional clearly focused on the retina in the horizontal
peripheral ablation, the actual blend zone is (sagittal) plane, but not in front of the retina in the
minimized. vertical (tangential) plane.

CLINICAL IMPLICATIONS Types of Astigmatism

Clinical studies have shown that conventional laser Based on Axis of the Principal Meridians
surgery results in a significant induction of higher
Regular astigmatism—principal meridians are
order aberrations.9 The most significant increase in
perpendicular.
the type of higher order aberration following
With-the-rule astigmatism—axis lies between 0
refractive surgery occurred for spherical aberrations.
and 30 or 150 and 180 degrees.
Aberrations describe a distortion of light through
Against-the-rule astigmatism—axis lies between
an optical system; spherical aberrations are like
60 and 120 degrees.
concentric rings of power. If the normal corneal
Oblique astigmatism—axis lies between 30 and 60
asphericity is changed, it will result in induced
or 120 and 150 degrees.
spherical aberrations.
Clinical results from the FDA when it was Irregular astigmatism—principal meridians are not
approved in 2003 shown the following statistics: perpendicular.
At one year after treatment, more than 93% of Axis is always recorded as an angle in degrees,
patients said they saw at least as well or better than between 0 and 180 degrees in a counter-clockwise
they had with glasses or contacts before treatment. direction. 0 and 180 lie on a horizontal line at the
More than 98% of patients achieved 20/40 vision level of the center of the pupil, and as seen by an
one year after treatment. observer 0 lies on the right of both eyes. Although it
Nearly 60% of near-sighted patients achieved 20/ is unproven, there remain proponents of the theory
16 vision after one year of treatment. that astigmatism allows a greater pallet of colors to
Both near- and far-sighted patients reported an reach the brain.
improvement in their reaction to bright lights and
night driving glare after treatments. In addition, near- Based on Focus of the Principal Meridians
sighted patients reported an improvement in Simple astigmatism
sensitivity to light. Simple hyperopic astigmatism—retina coincides with
Predictable results are the norm for the treatment. first focal line.
More than 90% of patients achieve refraction within Simple myopic astigmatism—retina coincides with
1 diopter of their target correction. second focal line.
The procedure has a total re-treatment rate of less Compound astigmatism
than 5% of patients. Compound hyperopic astigmatism—both focal lines
are in front of the retina.
ASTIGMATISM
Compound myopic astigmatism—both focal lines
Is an affliction of the eye, where vision is blurred by are behind the retina.
an irregularly shaped cornea. The cornea, instead of Mixed astigmatism—focal lines are on both sides
being shaped like a sphere, is ellipsoidal (like an egg) of the retina (straddling the retina).
220 Mastering Advanced Surface Ablation Techniques
PHOTOREFRACTIVE EXCIMER LASER ASTIGMATIC
CORRECTION

The excimer laser corrects simple myopia by applying

a greater amount of laser energy to the central cornea
than to the peripheral cornea. This technique can be
accomplished by opening and closing a circular
aperture through which the laser light passes or by
using a scanning laser to direct pulses primarily to
the central cornea. This results in the central stromal
tissue receiving more ablation than the peripheral
cornea, thereby creating a convex surface. 13 Figure 23.11: Myopic and Astigmatism ablation
Hyperopic corrections can be achieved by a process
in which tissue in the peripheral area receives more
laser energy than that in the central area. Myopic
astigmatic corrections are achieved by applying the
laser energy in an elliptical pattern along the central
part of the flat meridian, thereby flattening the steep
axis Figures 23.11 and 23.12. Alternatively, hyperopic
astigmatic14 correction is achieved by applying the
laser energy preferentially in the periphery,
steepening the flat axis Figures 23.13 and 23.14.
“Mixed astigmatism is particularly challenging for
doctors to treat because it requires that both a myopic
and hyperopic treatment be applied to the cornea, Figure 23.12: Myopic and Astigmatism ablation
often in two consecutive treatments. The new
approval for the ALLEGRETTO® WAVE will enable
ophthalmologists to provide one treatment while
conserving more corneal tissue in comparison to other
available approaches.”
Mixed astigmatism or irregular astigmatism
describes the unequal curvature of the cornea in which
one principal meridian is myopic and the other is
hyperopic. Mixed astigmatism causes distorted vision
at both near and far distances because of the way in
which distortions occur on different portions of the
eye’s surface Figure 23.15.
Figure 23.13: Hyperopic and Astigmatism ablation
WAVEFRONT-GUIDED LASER VISION CORRECTION

Recent advances in techniques used to gather atmospheric distortions when viewing distant objects
refractive data allow for correction of not only in space through high-powered telescopes.
myopia, hyperopia, and astigmatism but also higher By applying wavescan analysis, coma, trefoil,
order aberrations. This wavescan digital technology quadrafoil, higher order spherical aberration, and
was originally developed for astrophysics to reduce astigmatism can be corrected. These higher order
 Wavefront Optimization and Astigmatism Correction with the Allegretto® Excimer Laser 221

Figure 23.14: Hyperopic and Astigmatism ablation Figure 23.15: Mixed Astigmatism ablation

aberrations are visually significant for many patients. conditions, along with increased visual acuity in low-
The LASIK or PRK or LASEK procedure does not contrast conditions.
change but rather the method of mapping the visual Clinical results of wavefront-guided LASIK to
imperfections (optical aberrations) is different. correct myopic astigmatism by Mrochen et al 11
Zernike polynomials are used to provide a convenient showed that, in a group of 35 eyes tested, 93.5% of
mathematical expression of the aberration content in eyes were at an uncorrected visual acuity level of
the optical wavefront, resulting in more precise 20/20 or better at 3 months. This technology has also
measurements than with standard methods. been helpful in the treatment of mixed astigmatism,
The wavefront aberrations are then transferred as reported by Maloney.
into an ablation profile that is applied using variable
CONCLUSION (Figure 23.16)
beam or scanning spot technology. Variable spot sizes
are used to remove corneal tissue with an excimer Allegretto ® excimer laser also features a unique
laser. This translates to decreased subjective approach to corneal sculpting. The normal curvature
perception of halos and glare, especially in mesopic of a healthy cornea is prolate.

Figure 23.16: Myopique ablation profile

222 Mastering Advanced Surface Ablation Techniques
The laser not only treats the cornea centrally, but 5. Mrochen, MC, Kaemmerer M, Riedel P, Seiler T. Why do
we have to consider the corneal curvature for the
also peripherally. The laser uses proprietary
calculation of customized ablation profiles? Investigative
nomograms to adjust the asphericity of the cornea to Ophthalmology & Visual Science 2000;41:S689.
perform a prolate ablation based on the anterior 6. Seiler T, Kaemmerer M, Mierdel P, Krinke H-E. Ocular
curvature readings. This prolate curvature, in part, optical aberrations after photorefractive keratectomy for
myopia and myopic astigmatism. Arch Ophthalmol
accounts for the excellent quality of vision during
2000;118:17-21.
the day and night. 7. Marcos S. Aberrations and visual performance following
The wavefront optimize offers a treatment that standard laser vision correction. Journal of Refractive
incorporates wavefront principles to patients with Surgery 2001;17:S596-601.
8. Mrochen M, Donitzky C, Wullner C, Loffler J. Wavefront-
nearsightedness, farsightedness and astigmatism.10
optimized ablation profiles: theoretical background. J
Every procedure is tailored to the patients’ corneal Cataract Refract Surg 2004; 30: 775-85.
curvature and refraction with the intention to preserve 9. Cummings, A. Visual outcomes with the ALLEGRETTO
the natural aspheric cornea shape and to maintain or WAVE‘ Excimer Laser: Results of a European trial. Ocular
Surgery News 2003:32-4.
improve quality of vision and visual acuity.
10. MacRae S, Krueger R, Applegate R. Customized Corneal
Ablation: The Quest for SuperVision. New Jersey:
REFERENCES SLACK, 2001, p146.
11. Mrochen M, Kaemmerer M, Seiler T. Clinical results of
1. Garg Ashok, Alio J, Pajic B, Metha C K (Eds). Mastering
wavefront-guided laser in situ keratomileusis 3 months
the techniques of lasik, Epilasik and lasek techniques and
after surgery. J Cataract Refract Surg 2001;27(2):201-7.
technology, Jaypee Brothers medical Publishers new Dehli
12. Seiler T, Kaemmerer M, Mierdel P, Krinke HE: Ocular
2007.
optical aberrations after photorefractive keratectomy for
2. Applegate RA, Howland HC. Refractive surgery, optical
aberrations, and visual performance. J Refract Surg 1997; myopia and myopic astigmatism. Arch Ophthalmol 2000;
13:295-9. 118(1):17-21.
3. Holladay JT, Dudeja DR, Chang J. Functional vision and 13. Febbraro JL, Aron-Rosa D, Gross M, et al. One year clinical
corneal changes after laser in situ keratomileusis results of photoastigmatic refractive keratectomy for
determined by contrast sensitivity, glare testing, and compound myopic astigmatism. J Cataract Refract Surg
corneal topography. J Cataract Refract Surg 1999;25:663-9. 1999;25(7):911-20.
4. Mrochen M, Seiler T. Influence of corneal curvature on 14. Vinciguerra P, Epstein D, Azzolini M, et al. Algorithm to
calculation of ablation patterns used in photorefractive laser correct hyperopic astigmatism with the Nidek EC-5000
surgery. Journal of Refractive Surgery 2001;17:S584-7. excimer laser. J Refract Surg 1999;15(2 Suppl): S186-7.
 CHAPTER

24 Optical Quality Analysis after

Surface Excimer Laser Ablation

Yan Wang, Wei Wang, Jichang He, Kanxing Zhao, Yongji Liu
(China)

INTRODUCTION the slit lamp. Additional light scattering may be from

corneal stromal haze or scars after such as refractive
Recently, interests in surface excimer laser ablation,
surgery.
such as photorefractive keratectomy (PRK), laser
epithelial keratomileusis with a manual (LASEK), or Diffraction
mechanical epithelial lift (Epi-LASIK), have grown
and are accepted by more and more refractive Diffraction is defined as “…any deviation of light
surgeons in procedures. In terms of safety, these rays from a rectilinear path which cannot be
procedures avoid the risks caused primarily by interpreted as reflection or refraction.”. Huygens’
microkeratome cuts in lamellar ablation (LASIK). This Principle is employed to explain diffraction. It states
chapter presents the evaluation of optical quality and that every point on a wavefront acts as a source of
visual performance after surface excimer laser tiny wavelets that move forward with the same speed
ablation. as a wave; the wavefront at a later instant is the
surface that is tangent to the wavelets.
ASSESSMENT OF OPTICAL QUALITY For the optical system, which is free from
aberrations, the image quality is determined only by
Image Blur of the Human Eye
diffraction. For the eye, when the pupil size is smaller
Generally, there are three sources of image blur in than 3 mm, it is considered that the eye is only
the human eye:1 affected by diffraction, which means diffraction is
the dominant factor to determine the quality of the
Light Scatter retinal image and such an eye is said to be
Light scattering occurs when incident light passes “diffraction-limited”. If a point source is imaged by
through the cornea and lens and is a feature not only the aberration-free optical system, due to the
of the diseased cornea. In reality, a clear cornea is diffraction, instead of a perfect point image, a blurred
about 90% transparent and scatters about 10% of image called an Airy disk is obtained on the image
incident light.2 If the cornea were 100% transparent, plane. The effect of the diffraction is determined by
its gray-blue optical section would not be visible in the size of the aperture.
224 Mastering Advanced Surface Ablation Techniques
Optical Aberration to the wave theory, and the lights with the same
phases form wavefront. In the case of ideal image-
Optical aberration can be described as wavefront
formation, a divergent spherical wavefront from a
error. It is one of the fundamental descriptions of
the optical quality of an optical system,3 is one of the single point of an object is focused on the retina with
key components defining retinal image quality, and a convergent spherical wavefront. But, with
becomes increasingly troublesome as the surface aberrations in the real eye, the real wavefront is
power and aperture increases. More details of this distorted and deviated from the ideal convergent
aberration will be described later. spherical wavefront, thus, resulting in wavefront
aberrations.
Assessment of Optical Quality Ray aberration is linked to wavefront aberration
by the fact that the wavefront is the orthogonal
The quality of an optical system may be specified in
trajectories of the pencils of light rays. Functionally
three different but related ways. 4 The first is to
both ray and wavefront aberrations describe the
describe the detailed shape of the image for a simple
optical defects in the eye, but the wavefront
geometrical objection such as a point spread function
aberration provides more precise and complete
(PSF), which describes the response of an imaging
information.
system to a point source. The second method is to
Optically, the wavefront aberration is the
describe the loss of contrast suffered when an image
departure of the wavefront from the ideal wavefront,
of a sinusoidal grating is cast, such as the modulation
which is usually a spherical wavefront. The wave
transfer function (MTF). The third method is to
aberration function, W(x,y), is defined as the distance
describe the deviation of light rays from perfect
in optical path length (product of the refractive index
reference rays (ray aberrations) or in terms of the
and path length), from the reference sphere to the
deviation of the optical wavefront from the ideal
wavefront in the exit pupil measured along the ray
reference wavefront (wavefront aberrations), which
as a function of the transverse coordinates (x,y) of
is more fundamental and from which all of the
the ray intersection with a reference sphere centered
secondary measures of optical quality (PSF, MTF and
on the ideal image point. The reference sphere is a
others) can be derived.
sphere that passes through the axial exit pupil point;
WAVEFRONT ABERRATION its radius is approximately equal to the distance
between exit pupil and image plane. The word
Wavefront Aberration and Ocular Aberration approximately is used to indicate that the radius of
Optical aberrations can be explained with two the reference sphere can be varied to provide a better
different theories: the geometrical optical theory and fit to the wavefront; this corresponds to choosing an
the wave optical theory. An optical system such as image plane that is different from (and perhaps better
the eye can be used as an example to explain the two than) the paraxial image plane. It is not the wavefront
theories. itself but it is the departure of the wavefront from
With the geometrical optical theory, light is treated the reference spherical wavefront as indicated in
as a ray, and all of the rays from a single point should Figure 24.1.5
converge to a single retinal point if the eye is optically The aberrations can be divided into two main
ideal. In a real eye, however, optical defects in the types: chromatic aberrations and monochromatic
optical system make the rays deviate from its ideal aberrations. Chromatic aberration occurs because all
pathway and result in spread light spots, instead of optical materials have slightly different refractive
a single point. In this situation, the rays are said to indexes for each wavelength. Thus the different
be aberrated, and the eye has aberrations. wavelengths in object light are refracted by different
Alternatively, we treat the light as wave, according amounts, and images in different colors may be
 Optical Quality Analysis after Surface Excimer Laser Ablation 225

Figure 24.1: Wave aberration function for a distant point object

axially blurred or laterally displaced. Most optical spherical aberration was greater than that of coma-
systems are designed to minimize these aberrations. like aberration when the pupil enlarged, which was
The monochromatic optical aberrations of optical consistent with the asymmetrical nature of the eye
systems increase as the incident ray heights and the (Figure 24.2).
field of view increase. Although the spherical-like aberration increased
The normal emmetropic eye could be considered to a greater extent than the coma-like aberration with
“free of aberration”, when the pupil diameter is less the larger pupil size (6 mm), coma-like aberration
than 3 mm. With the pupil diameter increasing, the was still dominant (approximately 56% of higher
quality of the retinal image decreases due to the order aberration). This is consistent with the normal
increase in optical aberrations.6, 7 Therefore, for an eye, aberrations are relatively low and ruled by coma-
eye, the effects of the aberration are very pupil-size like aberration.10
dependent. The optical aberrations generally increase
Description of Wavefront Aberration
with increasing pupil size.8, 9 Consequently, the optical
quality of the retinal image can vary significantly with One way to show wavefront aberration is the
pupil size. wavefront aberration map, in which wavefront error
There were some interesting findings from our is plotted on 2-dimensional pupil plane. The
previous study, [9] in which we demonstrated a advantage of the wavefront map is that it directly
difference in magnitude of the high-order aberrations shows how the wavefront aberration varies across
with different sized pupils in myopic eyes. The results the pupil, and thus is easy to localize the wavefront
showed not all aberrations were weighted equally error. The wavefront aberrations, however, are very
by pupil size. From detailed analysis, the change in complicated in distribution and usually have a highly
226 Mastering Advanced Surface Ablation Techniques

Figure 24.2: Zernike aberration in 3rd to 6th order in 4 mm, 5 mm and 6 mm pupil size. Error bars indicate the standard error of the mean

irregular shape. In order to communicate the of the radial polynomial R |mn| and the index m
wavefront aberration easily, the irregular wavefront describes the azimuthal frequency of the sinusoidal
aberrations are decomposed into a series of regular component; Nm n
is the normalization factor.
functions, such as Zernike polynomials, Seidel series Because these polynomials are mutually
or Fourier expansions. Due to the fact that the exit orthogonal, the polynomials and radial polynomials
pupil of the eye is a circle, Zernike polynomials serve satisfy the following equations:
as a set of the basis functions that are orthogonal π
over a circle of unit radius. They are particularly useful ∫ρ 2
≤|
Znm ( ρ ,θ ) Znmʹ ʹ ( ρ ,θ ) ρ dρ dθ =
n+1
δ mmʹδ nnʹ
and have been widely applied in the field of visual
1 1
optics, and clinicians are accustomed to seeing this ∫0
Rnm ( ρ ) Rnmʹ ( ρ ) ρ d ρ =
2 ( n + 1)
δ nnʹ
information displayed as a Zernike polynomial
expansion.11 In polar coordinates (P, θ), the Zernike As shown above, the index m and n are needed
polynomials are defined as following: to describe an individual polynomial. However in

{ Nnm Rnm ( ρ ) cos mθ , m > 0

the field of visual optics, a single indexing scheme is
Znm ( ρ ,θ ) = − Nnm Rnm ( ρ ) sin mθ , m < 0
useful for describing Zernike expansion coefficients
which should always be used. Now, the description
of Zernike aberrations with a single index is
= = { 1, m = 0
0, m ≠ 0 standardized by OSA.12
In this way, wavefront aberrations are
( n− m ) / 2
( −1)s ( n − s ) ! characterized by coefficients of the Zernike functions,
R (ρ) =
m
∑ s! ⎡⎣0.5 ( n + m − s ) ⎤⎦ ! ⎡⎣0.5 ( n − m − s ) ⎤⎦ !
ρ n−2 s
n s=0 in one-dimensional plot. In additional to the
simplicity, the Zernike aberration description has
Where is the radial coordinate ranging from 0 to another advantage, which is that the classical
1 and θ is the azimuthal component ranging from 0 geometrical aberration terms can be easily found in
to 2π; The index n describes the highest power (order) the Zernike aberration terms.
 Optical Quality Analysis after Surface Excimer Laser Ablation 227
In order to package the wavefront error into Measurement of Wavefront Aberration
individual building blocks, a set of normalized Since Smirnov measured wavefront aberration first
Zernike polynomials are best fit to the measured in the human eye using a subjective technique in
wavefront error. In the normal ametropic eye, defocus 1961,13 a variety of aberrometric techniques have
(i.e. myopia or hyperopia) is by far the largest been developed, especially during the last 10 years.
aberration, followed by astigmatism. These are low All of the techniques have employed the same
order terms. When we disuse the importance of each principle of ray-tracing, but differed from each other
Zernike polynomial, the Zernike pyramid is useful. in the way to trace the ray aberrations. Basically, the
As we go down the rows from the top, we go from first step to measure wavefront aberrations is to
low order to high order. The first three Zernike measure ray aberrations, usually the transverse
polynomials are not shown in the Figure 24.3 because aberrations, for an array of sample points across the
they correspond to piston, tilt and tip, which may pupil area. Because the light rays are orthogonal
not be the aberrations of the eye. The first row (i.e. trajectories of the wavefronts, the transverse
sphere and cylinder, which is the lower order aberrations are the measures of the derivations (or
aberrations) is what we would normally measure and slopes) of the wavefront aberrations. From the
prescribe in spectacles. The second row is called the measures of the slopes, wavefront aberrations are
third order aberrations. Anything beyond lower mathematically derived using a fitting procedure.
order is lumped under the term higher order There is no significant difference in the fitting
aberrations. In the normal ametropic eye, higher procedure, but the technique used to measure the
order aberrations are a relatively small component, ray aberrations differ from one aberrometer to
comprising about 10% of the eye’s total aberrations. another.

Figure 24.3: Wavefront error for Zernike modes though the fifth radial order
228 Mastering Advanced Surface Ablation Techniques
Most available techniques can be categorized method, the ray aberration is detected by the subject’s
either by the way to sample the ray aberrations or eye and registered by an operating mouse of the
by the way to register the ray aberrations. According computer, thus it depends on the subject’s response.
to the differences in aberration sampling, the Whereas the objective method measures the spots of
aberrometers can be divided as either successive light rays imaged in CCD camera, and the ray
sampling or simultaneous sampling. With successive aberrations are analyzed by image processing. The
sampling methods, the aberrations are measured measurement with the objective method, thus,
from one point to another across the pupil. Instead, depends on the sensitivity and the resolution of the
the simultaneous sampling method is used to measure CCD camera, as well as the accuracy of the image
the aberrations for the whole pupil area processing.
simultaneously. An advantage of the simultaneous Wavefront aberrations can be measured by
method over the successive methods is its speed. But, wavefront sensors, and are shown in maps of Figure
in principle it has the cross-talking problem, which 24.4 and Figure 24.5. Wavefront sensors only measure
makes the measurement range limited. the distortion of a light wave as it is altered by passing
According to the methods to register ray through the optics of the eye. It does not measure
aberrations, the techniques can be divided as light scatter, chromatic aberration, or diffraction
subjective or objective methods. With a subjective phenomena.

Figure 24.4: Two-dimensional maps of the wavefront aberrations and each Zernike coefficients. (A) with subjective
method (B) with objective method from different patients
 Optical Quality Analysis after Surface Excimer Laser Ablation 229

Figure 24.5: Three-dimensional map of the wavefront aberrations and each Zernike coefficients

Wavefront aberration and surface laser ablation and LASIK respectively16, 17, 18. But little research has
(PRK, LASEK, Epi-LASIK Surgery) been done to study these higher order aberrations
after PRK and how PRK compares with LASIK in
Ocular higher-order aberrations features analysis
these aspects. We have a prospective study to
after surface laser ablation surgery
investigate the effects of photorefractive keratectomy
Following corneal refractive surgery, the most (PRK) and laser in situ keratomileusis (LASIK) on
notable change is the increase in spherical-like higher order wavefront aberrations and analyze their
aberration.14, 15 the results revealed that the spherical- characteristics.[15]
like aberration increased significantly with increasing This prospective study involved thirty-two eyes
pupil size with an unaltered cornea. Such effects with similar refractive powers (between –5.0 to –6.0D
should be taken into account to explain the post- preoperatively) because previous reports showed the
operative outcome of the aberration, as well as for increase of optical aberration was more pronounced
the evaluation of night vision problems, can be in patients with a higher magnitude of refractive
overcome by the best strategy in wave-guided correction.19 LASIK and PRK were performed with
ablation algorithm. the same parameters of a 6 mm diameter optical zone
Many studies have shown that higher-order and a 7 mm diameter transition zone ablation
aberrations (third-order and higher), mainly spherical respectively. The results showed overall higher order
aberration and coma, significantly increase after RK, aberrations were increased from 0.55±0.26 μm
230 Mastering Advanced Surface Ablation Techniques
preoperatively to 0.93 μm±0.37 μm(PRK) and 0.79 μm secondary coma, which appeared higher in the PRK
± 0.38 (LASIK)postoperatively. This was a 1.69 fold group. Whether they were associated with slight
increase in the PRK group(t = 3.95, p < 0.001) and a irregularity of corneal surface needs further
1.43 fold in the LASIK group(t = 2.60, p < 0.05). At researches although histological finding showed
three months,the mean RMS value for higher-order more wound healing activity and marked keratocyte
(3rd to 6th)were significantly increased compared to responses to laser stromal ablation in cornea treated
the corresponding preoperative values, p < 0.05. The with PRK than in those treated with LASIK.21
fourth order aberrations (spherical like aberration) Our study also showed PRK induced more optical
were increased by a 2.64 fold in PRK and a 2.31 fold aberration prominently in higher order aberrations
in LASIK (Figure 24.6). compared to LASIK. These higher order aberrations
in PRK may have been induced by wound healing.
LASEK was devised in 199822 and has shown some
clinical advantages such as: Absence of stromal flap
problems (epithelial ingrowth, corneal flap-related
complications and corneal ectasia);23, 24 possibility for
larger optical zone; ability to treat thinner corneas;25
correcting higher amounts of myopia26 and less pain
and less sub-epithelium haze than with standard
PRK.27
We had an investigation that compared the wave-
front aberrations status post LASEK and LASIK. This
randomized study included 96 eyes of 58 myopic
patients. Forty-seven (47) eyes of the 28 patients had
LASEK and 49 eyes of the 30 patients had LASIK.
Figure 24.6: Comparison of 3rd and higher order aberration 3 With a 3 mm pupil, there were no significant
moths post PRK and LASIK differences in BCVA, refractive errors and wavefront
The creation of a lamellar flap during LASIK might aberrations postoperatively (P > 0.05, independent-
affect contor and higher order aberrations. When we sample t test). With the 6 mm pupil, however, LASIK-
compared LASIK with the PRK group, the difference treated eyes exhibited significant higher aberrations
of RMS was not statistically significant. However, than LASEK-treated eyes for 4th order (P = 0.042)
we found a more significant increase in terms of and 5th order (P = 0.021) aberrations. For each Zernike
Zernike coefficients 6, 7 and 8 in the LASIK group coefficient, there were significant difference in
than in the PRK group, and a more significant increase horizontal trefoil (C33 , P = 0.025), oblique quatrefoil
in coefficient 18,19 and 20 in the PRK group than in (C – 44 , P = 0.018) and spherical-like aberrations
the LASIK group. In the standardized double- (C04 , P = 0.032) (Figure 24.7).
indexing scheme these coefficients are terms C3–3, Our results suggested that after myopic corneal
C3–1, C31, C5+1 C5+3 and C5+5 respectively.20 The reason refractive surgery, the 3rd-order aberrations were
for C3–3, C3–1, C31 being higher in the LASIK group dominant on postoperative eyes, which was in
may be related with the edge or the root of the flap agreement with Moreno-Barriuso E et al,28 despite
with LASIK. Or eccentricity caused by instability of the fact that the patients in our study presented lower
observance since the fixed light could be blurred after preoperative myopia (-4.97D, –6.5 D in Esther’s).
the flap is left open during the procedure. We When examined more closely, the amount of coma
postulated that this was caused by the placement of aberrations (C-13 and C13 ) for a 6 mm pupil did not
the hinge. The C 5+1 C 5+3 and C 5+5 correspond to differ between LASEK and LASIK. These results
 Optical Quality Analysis after Surface Excimer Laser Ablation 231

Figure 24.7: (a) Average higher order Zernike coefficients for 3 mm pupils after LASEK and LASIK.
Numbering and sign convention is that of the OSA VSIA task force. On the lower x-axis the monomial
system for Zernike polynomial numbering is used. In the double-indexing system, the subscript is
indicated in each frame (i.e., third order, fourth order, fifth order) and the superscript is indicated on the
upper x-axis. Error bar are intersubject standard deviations. (b) Average of the higher order Zernike
coefficients for 6 mm pupils. P ≤ 0.05 differences are of statistical significance.

might indicate that there was no intergroup difference Some histological findings also showed more
in terms of decentration, tilt, and asymmetry of the wound healing activity and marked keratocyte
corneal surface, which were among the sources of responses to laser stromal ablation in corneas treated
coma aberration. The use of an eye tracker could have with PRK than those treated with LASIK.[21] The types
decreased the prevalence or incidence of the coma of would healing mechanisms affecting the patterns
aberrations. of the wavefront aberrations needs further research.
However, horizontal trefoil (C 33), oblique Another interesting finding in this study was that
quatrefoil (C-44) and spherical-like aberrations (C04) for 6 mm pupils, both (C04) and S4 (RMS for the 4th
have shown significant differences between these two order) in LASIK eyes showed higher values than
groups. For (C33) and (C-44), the LASEK group was those in LASEK eyes] (C04) (t = –2.201, P = 0.032), S4
significantly higher than that in LASIK [(C33)(t = 2.31, (t = –2.074, P = 0.042)]. This might indicate that the
P = 0.025), (C-44) (t = –2.434, P = 0.018)], this result spherical-like aberrations in LASIK were really
was in agreement with our previous study comparing greater than those in the LASEK group. The reason
PRK and LASIK. for the increase of spherical aberrations was perhaps
232 Mastering Advanced Surface Ablation Techniques
correlated with the conversion of biodynamic and to identify the underlying optical components and
the healing of the corneal flap cut.29, 30 Since the modes the way in which they may cause adverse effects on
near the center of each radial order had a greater visual performance.
impact on the visual performance (more letters lost) Assessments of corneal haze and visual function
than modes near the edge of the pyramid,31 compared have been made largely, but few on the quality of
with the influence of (C–34), the role of (C33) and (C–44) optical system.41, 42
could be neglected. In addition, RMS corresponding We had a report on corneal haze and higher order
to S5 in the LASIK group was also higher than those distribution of wavefront aberration after surface
in the LASEK group, which correspond to secondary excimer laser ablation.43 The investigation showed
coma. Thus LASIK procedures might degrade the RMS of the higher order aberration with corneal haze
visual performance. We postulated that this was was slightly higher than ones of the post-PRK.
caused by the placement of the hinge. The creation However, no statistically significant directional
of a lamellar flap after LASIK might affect contor changes were found in our data. P< 0.05. It indicated
and higher order aberrations.
less of an affect on the optical aberration in mild and
This was agreed with previous studies. Several
moderate corneal haze than expected.
studies have reported an increase in optical wave-
The result, however, is in agreement with several
front aberrations after different laser surgeries.
previous reports on measurements of other optical
Oshika et al.32 reported an increase in higher-order
function outcomes. Some studies show that visual
corneal aberrations after refractive surgery, and they
performance is inversely related to the amount of
also observed a greater induction of spherical-like
haze. And haze did not appear to be an important
aberrations after LASIK compared to PRK. Although
contributing factor to explain the presence of
the procedures they studied were different from
persistent visual disturbances. 44 Monochromatic
ours, both PRK and LASEK are associated to the
surface excimer laser ablation, and are fundamentally wavefront aberrations are mainly caused by surface
similar surgeries. There was research on Epi-LASIK irregularity of the cornea and the lens, miss-alignment
that showed higher order aberration increased of optical axis between the cornea and the lens, and
significantly postoperatively after EPI-LASIK with an imbalance of aberrations between the cornea and
only mild symptoms and mild haze.33 the lens. Laser ablation on the corneal surface may
break aberration balance between the cornea and the
Ocular Higher-order Aberrations and Complication lens for the preoperative eye, and perhaps also
after Surgery induces more irregularity in the anterior corneal
Corneal haze is one of major complication of surface surface. The amount of wavefront aberrations
excimer laser corneal ablation. Over the past years, induced by laser surgery could depend on
it has been extensively investigated at chemical and multiple factors. These may include the level of
histological levels, and was attributed to epithelial the patient’s preoperational aberration, the depth
hyperplasia, newly synthesized collagens and of photoablation, the system for performing
proteoglycans during the wound healing.34,35,36 While surgery, the experience of surgeon and the corneal
the haze was believed to mainly influence corneal haze.
transparency, it was found to highly correlate with We found that coma-like aberration showed
regression of refractive power.37,38 And thought to slightly higher mean aberrations in the haze group
be mainly responsible for visual preference such as than the control group among the high order
the impaired contrast sensitivity after PRK. 39,40 aberrations, though there is no significant meaning.
Subepithelial haze may be one of the possible Zernike coefficients analysis showed C3–1 and C3+1
causes of surgical-induced aberrations. It is necessary showed higher than the control eyes, which might
 Optical Quality Analysis after Surface Excimer Laser Ablation 233
be caused by the slight corneal wrinkle. Coma consists MODULATION TRANSFER FUNCTION
of a bulge above the plane, adjacent to each other
but on opposite sides. Most corneal haze appeared As mentioned previously, the optical quality for an
to have a fairly uniform distribution within the optical system can also be evaluated in an objective
ablationzone, but a more heterogeneous distribution manner using the modulation transfer function
with a longer follow-up time44. In the eyes with more (MTF).46
severe corneal haze (the example in our previous According to Fourier Transform, an object can be
study)43, different regions of the pupil had a wrinkled presented as the superposition of various sinusoidal
region that showed a difference in direction and gratings with different spatial frequencies,
magnitude for aberration. This is consistent with the orientations and phases. Each sinusoidal grating has
irregular reflection observed in topography with an a contrast defined as
Orbscan measurement. (Imax-Imin)/(Imax+Imin).
Based on the results of this study, optical Representing objects in this way makes it easy to
aberrations with corneal haze give a various effects understand the effects of the optical system in terms
on the amount and character of the higher-order of contrast for different spatial frequencies. When
aberration (Figure 24.8). the object is imaged by a certain optical system such

Figure 24.8: Wavefront aberration maps and the Zernike coefficients for the eye with corneal haze after 3 months of
the Epi-LASIK surgery. (A) all order aberrations (B) higher order aberrations (C) Zernike coefficients
234 Mastering Advanced Surface Ablation Techniques
as the eye, a degraded image is usually formed due The advantage of MTF is that it provides a
to the aberrations and diffraction of the optical continuum of unique rankings by which to evaluate
system. In the same way, the image of the object can the fundamental spatial resolution performance of
also be presented as the superposition of the an imaging system.
sinusoidal gratings with different contrasts, which Many methods have been developed to calculate
are usually different from the contrasts of the object MTF. Campbell and Gubish 48 and Howland and
Howland49 determined the MTF of the eye using
at the corresponding spatial frequencies. The
subjective methods. The time, cost and observer’s
degradation of the contrast for a certain frequency is
efforts of these methods became the main challenge
called modulation which can be described as
in the application of these techniques for
(output contrast) / (input contrast) = Mo/Mi.
compensating lenses. 50 Recently some objective
In other words, how much contrast is lost – techniques have been introduced to obtain the MTF.
modulation simply being another word for variance. Liang51 and Walsh52 calculated the MTF based on the
As we can see from the definition of the modulation, wavefront aberrations. The eye’s MTF was taken as
its maximal value is 1, which means the contrast of the autocorrelation of the eye’s pupil function. This
the sinusoidal grating is transformed by the optical objective method allowed us to quickly obtain the
system without degradation. The larger the MTF with great reliability.
modulation is, the less the loss is. Therefore, for an
optical system such as the human eye, if the MTF and Surface Laser Ablation
modulations for all the available frequencies are large,
We had measured the wavefront aberrations with
the image being formed by the eye is better, which LASEK, and made a comparative study with LASIK,
means the eye can acquire more details of the object. and then calculated the modulation transfer function
Before we move on to modulation transfer (MTF) for both 3- and 6 mm pupil sizes to determine
function, a few minutes should be given to understand whether these two procedures induced different
the spatial frequency. The number of spacings per optical changes and different visual performance after
unit interval in a specimen is referred to as the spatial the refractive surgery(Figure 24.9).
frequency, which is usually expressed in quantitative The average heights of MTFs across the eyes of
terms of the periodic spacings (spatial period) found subject for different pupil sizes were shown in Figure
in the specimen.47 Sine-wave frequencies, usually in 24.9, together with the corresponding diffraction-
units of cycles/mm, are used as the metric for limited MTF (for both 3 mm and 6 mm pupils and
specifying detail in an MTF plot. These frequencies 580 nm wavelength). The MTF curves show that, after
are always plotted as the independent variable on correction of sphere and cylinder, average optical
the X-axis. quality in these eyes were dependent on pupil size.
Over a large range of spatial frequencies, the average
As the object is composed of sinusoidal gratings
MTF in the 3 mm pupils were almost identical
with different spatial frequencies, the modulation of
between LASEK and LASIK eyes, and both of them
contrast should be measured at different spatial
were close to the diffraction-limited curve [Figure
frequencies. When the modulation of contrast for
24.9(a)]. While for 6 mm pupil diameter, the MTF
each available frequency is obtained and plotted along was much lower than those for the 3 mm pupils across
the y-axis, the resulting curve is the modulation all spatial frequencies and the diffraction-limited
transfer function (MTF). As we can see from the curve. We also can see that the LASEK curve was
above, two items are required for defining the MTF: higher than that of the LASIK at spatial frequencies
spatial frequency, a measure of spatial detail, and less than 60 c/deg. (55c/deg: t = –1.96, P = 0.05).
modulation of contrast, a fundamental measure for From the MTF curve [Figure 24.9(b)], it can be
determining how well that detail is preserved. seen that with a 6 mm pupil, LASEK was higher than
 Optical Quality Analysis after Surface Excimer Laser Ablation 235

Figure 24.9: (a) Average MTF for the postoperative eyes computed from the wavefront aberrations obtained with the 3 mm pupils for LASEK
(square) and LASIK (circle) eyes; the diffraction-limited MTF was included for comparison purpose. (b) Represent the MTF for a
6 mm pupil

that for LASIK at spatial frequencies less than 60c/ laser surgery, surface excimer laser ablation (LASEK)
deg. Generally speaking, the spatial frequency and llamellar ablation (LASIK). The results showed
equaling 60 c/deg corresponds to a visual acuity (VA) a dependence of optical quality on the surgical
equaling 2.0, which is the maximum resolving power procedure. There was no difference between the two
of human eye. At this frequency the image modulation groups for a 3 mm pupil size; but for a larger pupil
produced by the eye’s optics is equal to the size, the MTF for LASEK was higher than that for
modulation required by the retina. Thus, from the LASIK at spatial frequencies less than 60 c/deg, which
MTF curves it can also be seen that the visual quality was the maximum frequency resolved by human eye.
of LASEK is better than that of LASIK. Therefore the relative research of LASEK and LASIK
In summary, our study described the statistical awaits further investigation. Figure 24.10 showed
results of the MTF made on the postoperative eyes the pre- and post-LASEK MTFs for the eye with -
for two pupil sizes with two different type of excimer 8.50 D.

Figure 24.10: The radial averaged MTFs computed for all aberrations for the eye with LASEK (OPD scan and OPD
station, Nidek, Japan). (A) Preoperative measurement (B) One week postoperatively
236 Mastering Advanced Surface Ablation Techniques
ASSESSMENT OF VISUAL PERFORMANCE in which contrast sensitivity changes as a function of
the spatial frequency of the target is called the contrast
Visual performance is multidimensional, including
sensitivity function).
visual acuity, color vision, peripheral acuity, contrast
An advantage to measuring contrast sensitivity
sensitivity, and many others.53 Visual acuity is the
at high spatial frequencies and other spatial
traditional measure of the visual performance. Since
frequencies is that it can provide a more sensitive
MTF cannot be directly measured, one can measure
measure of blur than acuity.55, 56 Contrast sensitivity
the ability of the observer to detect sinusoidal
is more strongly related to certain visual tasks, such
gratings at threshold contrast as a function of spatial
as face recognition than is visual acuity.53
frequency. The resulting function is called the contrast
For normal eyes with increasing spatial frequency,
sensitivity function (CSF).
contrast sensitivity increases to a peak and then
decreases, the highest spatial frequency detected
Contrast Sensitivity Function (CSF)
without aliasing will be neural limited.
An object in space does not generally reflect the same The decrease in contrast sensitivity after the peak
brightness from all point. The variation in brightness at moderate spatial frequencies is principally due to
of an object can be characterized by a quantity called ocular optic. The decrease in contrast sensitivity at
contrast. The contrast of an object is defined as: low spatial frequencies is attributable to natural
Imax- Imin processing.53
Imax- Imin The reductions in contrast sensitivity is caused
where Imax is the maximum brightness and Imin is by a combination of increased optical aberrations and
the minimum brightness.54 increased forward light scatter.
Snellen acuity is commonly tested with targets,
Contrast sensitivity & Refractive Surgery
either illuminated or projected charts that approximate
100% contrast. Therefore, when we measure Snellen The population of patients undergoing refractive
visual acuity, we are measuring the smallest optotype surgery differs greatly from other patients. They
at approximately 100% contrast that can be resolved often have good corrected visual acuity pre-
by the visual system. It evaluates only the ability to operation; their functional expectations for post-
resolve fine detail under a condition of maximum surgical visual performance are very high.57 They may
contrast. be quite sensitive to subtle changes in visual changes
In fact, an optical system with an excellent of visual perception. Also, the refractive surgeons
resolution of 100% contrast targets may have poor have been aware that the visual performance of the
performance when tested with targets of lower refractive patient may not be represented accurately
contrast. by visual acuity measurement in the refracting lane.
The Contrast Sensitivity Test is a clinical test of The usefulness of contrast sensitivity evaluation
spatial vision, which can help a surgeon understand in patients who have undergone refractive surgery
how the visual system responds to contrast as a procedures is widely recognized. Contrast sensitivity
function of spatial frequency. assesses the combined visual impact of light scattering,
In clinic, we present a patient with targets of optical aberration or defocus that may occur following
various spatial frequencies and peak contrasts. A plot refractive surgery.58, 59 (Figure 24.11)
is then made of the minimum resolvable contrast Contrast sensitivity can explain symptoms of
target that can be seen for each spatial frequency. reduced vision in patients with good visual acuity
The minimum resolvable contrast is the contrast since it can provide important information about
threshold. The reciprocal of the contrast threshold is world vision. Such patient can also be counseled that
defined as the contrast sensitivity, and the manner his or her vision is likely to be worse in low contrast
 Optical Quality Analysis after Surface Excimer Laser Ablation 237
contrast sensitivity at all spatial frequencies did not
differ from that obtained preoperatively.
Lee et al60 have a comparative study for mescopic
contrast sensitivity between PRK and LASIK. The
results showed LASIK significantly decreased more
mescopic contrast sensitivity than PRK in myopia with
a refractive error of less than –6.0D, especially at the
middle and high spatial frequencies of 6, 9 and 12
c/deg. Although visual acuity is 20/20 or better under
photopic conditions (85 cd/m2), PRK and LASIK can
induce significant reductions in contrast sensitivity
(CS) under mescopic condition (5 cd/m2).
One study on contrast sensitivity after PRK 61
indicated that corneal irregular astigmatism,
including asymmetry and higher order wave quality
Figure 24.11: Contrast sensitivity chart from vector vision components, was significantly related to the
(Courtesy of Vector Inc.) deterioration of contrast sensitivity.
situations, such as at dawn and at dark, etc. It is Tanake and colleagues reported that the
possible for high contrast acuity to remain normal or deterioration of low contrast visual acuity after PRK
near normal, while contrast sensitivity in the is mainly attributable to the increases in wavefront
midspatial frequencies is decreased. Such a midspatial aberration, instead of light scatter (or corneal
frequencies loss results in objects having a “washed haze).62
out” appearance. The literature concerning contrast sensitivity
Montes –Mico and Charman’s study58 have shown evaluation after refractive surgery has shown there
contrast sensitivity measurements at 6 and 12 c/deg was an initial contrast sensitivity loss after surgery
appear to be most useful in the assessment of patients for each spatial frequency evaluated. However,
who have undergone laser refractive surgery because contrast sensitivity gradually increased over time
defocus and optical aberrations primarily affect the after surgery, becoming essentially stable 6 and 12
higher spatial frequencies. They conducted a study months postoperatively.63, 64 Dai’s study33 has shown
and measured contrast sensitivity at different spatial that contrast sensitivity decreased 1 month after
frequencies (at 1.5, 3, 6, 12, and 18 c/deg) as an index Epi-LASIK surgery, then recovered gradually. The
of visual recovery after photorefractive keratectomy value restored to the preoperative level in low and
(PRK) and laser in situ keratomileusis (LASIK). The moderate myopia. However ,the contrast sensitivity
results showed that although a statistically significant was not restored to preoperative level until 1 year in
reduction in contrast sensitivity at all spatial patients with spherical equivalent refraction =
frequencies in PRK patients during the first and third –10.0 D. This was suggestive that surface ablation is
month, contrast sensitivity recovered to preoperative not a good indication for high myopia.
values by 6 months after surgery. In LASIK patients, A reduction in contrast sensitivity has also been
decreased contrast sensitivity values 1 month after found after the LASEK operation. However, Scerrati
surgery were also obtained at all spatial frequencies. compared LASIK and LASEK after a 6 months
After 3 months, contrast sensitivity at 1.5 and 3 c/ postoperatively and found slightly better contrast
deg had recovered and did not differ significantly sensitivity in the LASEK–treated group.47
from preoperative values, although at other It is also possible for contrast sensitivity to be
frequencies it remained reduced. At 6 and 12 months, improved by wavefront guided custom ablation,
238 Mastering Advanced Surface Ablation Techniques
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240 Mastering Advanced Surface Ablation Techniques

CHAPTER Treatment of Epithelial

25 Irregular Astigmatism

Waldir Neira Zalentein, Juha M Holopainen,

Timo MT Tervo, (Finland)

INTRODUCTION LASER VS. MECHANICAL CORRECTIONS

Since its introduction by Trokel (1983)1 excimer lasers Compared to conventional lamellar surgeries,11-13 PTK
have been employed for refractive surgery.2 Argon reaches an accuracy that is well beyond any manual
fluoride excimer lasers emit photons at 193 nm surgical technique.14 Incisions made with laser are
wavelength. Due to the high energy release excimer more regular, tend to show better tissue
laser are able to break intramolecular bonds without reorganization, and shorter time of healing than
any significant collateral thermal damage to the nonlaser techniques. Corneas treated by PTK show
adjacent tissue. On average, 0.25 μm of corneal tissue formation of new extracellular matrix and basement
is ablated per pulse. 3 In 1995, 4 FDA approved membrane which presumably allows the regrowing
phototherapeutic keratectomy (PTK) as a therapeutic epithelium to adhere on the basement membrane and
modality to treat anterior corneal pathologies such anterior stromal surface.
as stromal opacities, inflammations, dystrophies, Lateral interactions as adjacent tissue distortion,
degenerations, and surface irregularities. 3, 5 The distant disorganization or DNA damage secondary
objective of PTK in the treatment of anterior corneal to ultraviolet (193 nm) radiation have been shown to
pathologies is to improve epithelial adhesion by be minimal and within the requirements of safety
smoothing the basal membrane or to remove enough for the human eye.14
tissue to eliminate a stromal opacification. The
indication of PTK for eyes with surface irregularities EPITHELIAL HEALING AFTER PTK
is to create a smooth and uniformly thick corneal
surface. Secondary changes in corneal power are quite After PTK, the cornea is resurfaced by a cascade of
common after PTK.6 They may either show a shift events. 15-17 This process begins with a cellular
towards myopia or hyperopia. Hyperopic changes reorganization and protein synthesis followed by
seem to occur more frequently6-9 and have been found epithelial migration,18 which involves expression of
to be related to the ablation depth. Different certain growth factors16 and proteolytic enzymes
antihyperopia treatments have been proposed8,9 but systems and ends with the maturation of adhesion
the refractive results remain somewhat complexes 19,20 and innervation. 21,22 Corneal
unpredictable.10 resurfacing is completed within 1 week.23,24 One to
 Treatment of Epithelial Irregular Astigmatism 241
3 months later, anchoring fibrils adhering to the If the corneal epithelial surface appears regular
corneal stroma can be found. 2,25 The number of and the aim is to treat an irregular anterior stroma a
hemidesmosomes that play a key role in the adhesion transepithelial PTK is first performed. This allows a
between the epithelium and the stroma has been smooth and regular ablation surface and removes any
reported to increase as late as 39 months following alterations at the level of Bowman’s membrane or at
PTK.20 the anterior stroma. If an irregular epithelial surface
with an smooth anterior stroma is suspected, this
INDICATIONS approach would result in creation of an irregular
stromal contor. In these cases a surface modulator
The primary goal of PTK is to treat corneal pathologies
(polymerizing liquids, erosion mask or molds) can
located in the anterior 20% of the cornea. 3 This
be used to facilitate the ablation of the irregularities
includes, e.g. corneal degenerations and dystrophies,
until that a smooth surface is reached.31,34
superficial corneal opacities and scars. PTK has also
More sophisticated techniques use information
been employed to improve corneal surface
from VK and WF to correct refractive irregularities.
smoothness and to decrease irregular astigmatism.26
Those techniques include vector planning, 35,36
Although PTK is an effective and safe procedure,
topographically-guided correction, 37,38 and
complications such as loss of lines of visual acuity,
wavefront based photoablation.39,40
recurrences of pathology, secondary changes in
refraction, delayed corneal wound healing, corneal EPITHELIAL IRREGULAR ASTIGMATISM
infection and scarring may occur.5
Irregular astigmatism can be defined as any lack of
PREOPERATIVE EVALUATION symmetry or geometric plane in the refracted ray of
lights that reach the retinal plane.41 The cornea gives
Patients undergoing PTK must be asked for systemic
2/3 of the optical power of the eye.42 The tear film
diseases and ocular history. Normal corneal
and the anterior surface are the most important parts
sensitivity should be verified. Previous medical
of this system. Accordingly, any disorder at this level
conditions and ocular surgeries need to be known.
will be probably expressed as irregular astigmatism.
Preoperative evaluation for PTK candidates usually
The corneal epithelium is in a state of continuous turn-
includes videokeratography (VK) and /or wavefront
over with exfoliating apical cells being replaced by
analysis. VK based on a placido disc system can
underlying wing cells. 43 Consequently, any
estimate the corneal curvature and elevation profile
irregularity that depends on the epithelium may be
with an accuracy of 0.25 D or 2 - 3 μm27,28 and within
unstable or susceptible to a change.
these limits allow measurement of corneal irregular
Map-dot-fingerprint dystrophy (MDF) belongs to
astigmatism. Wavefront technology (WF) based on,
the anterior basement membrane dystrophies and is
e.g. Hartmann - Shack analysis is a system which
commonly associated with recurrent corneal erosion
is almost 25 times more accurate than VK. 29,30
syndrome (RCES).44,45 MDF may be present in as
WF can measure the complete refractive status,
much as 15% of the population46,47 although it may
including irregular astigmatism with an accuracy of
not be associated with biomicroscopically observable
0.05 μm.
changes at the time of examination.48 Yet, exclusively
DIFFERENT TECHNIQUES TO TREAT SURFACE epithelial irregularities can create irregular
IRREGULARITIES astigmatism in patients with MDF26 (Figure 25.1,
a. VK preoperative, b. VK post). In vivo Confocal
Depending upon the corneal disorder to be treated microscopy46,47 and optical coherence tomography
and the postoperative goals, different PTK strategies (OCT)48 have shown variations in epithelial thickness
are available. in eyes with recurrent erosion syndrome despite the
242 Mastering Advanced Surface Ablation Techniques
fact that the superficial epithelium appears normal The standard preoperative examinations
under a biomicroscope. Furthermore, confocal performed before laser refractive procedures (VK,
microscopic findings in patients with map dot WF) cannot show the anatomical location of the tissue
fingerprints often show linear structures of 50 – 100 in the eye’s optical system that generate the optical
μm height arranged in parallel below the epithelium, irregularity. VK and WF measurements are routinely
cysts with a diameter between 50 and 400 μm and a performed with an intact epithelium and the
basement membrane showing long (at least 300 μm), photoablative procedures (PTK, PRK, LASEK, LASIK,
highly reflective, linear structures.46 Optical coherence Epi-LASEK) are planned and performed based on
tomography analysis shows that central epithelial the results obtained from VK and WF devices.51
thickness varies from 70 ± 13 μm (range 49 to 88 μm). The use of surface modulators, vector planning,
The pathophysiology of RCES has yet to be fully custom corneal ablations or WF to correct irregular
elucidated but it seems to be related to a defect in astigmatism are based on images taken from the
the adhesion of the basal epithelial cells to the cornea with an intact epithelium. VK evidence regular
Bowman layer. 44,49 This, in addition to variable or irregular astigmatism. In the case of WF, the RMS
epithelial thickness might contribute or generate a (root-mean-square) error is an objective term that
morphologically irregular anterior corneal surface gives the magnitude of the error in the optical system
and it may be translate into irregular corneal of the eye. 29 However, it can not revel whether the
astigmatism.50 irregularity is in the stroma or in the epithelium.

Figure 25.1: A. Left panel: Preoperative videokeratography of MDF with irregular astigmatism; B. Right panel: Postoperative videokeratography
after PTK showing a regular astigmatism. (Reprinted with permission from SLACK Incorporated: Zalentein, W. N., Holopainen, J. M., & Tervo, T.
M. (2007). Phototherapeutic keratectomy for epithelial irregular astigmatism: an emphasis on map-dot-fingerprint degeneration. Journal of
Refractive Surgery, 23(1), 50-57.)
 Treatment of Epithelial Irregular Astigmatism 243
If we assume that the astigmatism is due to epithelial Accordingly, irregular astigmatism was proven to
irregularity and a WF PRK is performed after depend exclusively upon the corneal epithelium.
epithelial removal, irregular astigmatism may be Importantly, the standard preoperative examinations
produced rather than treated by WF. Since up to 15% performed before laser refractive procedures, cannot
of the population may be affected by MDF /RCES detect the anatomical location of the tissue in the eye’s
49,50
and since the number of excimer laser procedures optical system that generates the optical irregularity.
are rapidly increasing this may be a major factor Eyes with a history of MDF/RCES or topo-
impairing the results of WF corrections. graphical changes compatibles with irregular
astigmatism should be subjected to correction (vector
SURGICAL TECHNIQUE planning, topographically-guided correction or
wavefront—based photoablation WF – based
Patients under suspicion of irregular astigmatism
photoablation) with extreme caution. We recommend
secondary to epithelial irregularity should receive a
that in suspected cases epithelial abrasion and PTK
laser ablation using PTK after a manual epithelial
should be performed first and the WF data rechecked
removal. In our technique we scrape the whole corneal
after this procedure prior to stromal refractive
epithelium except 0.5 to 1.0 mm from the limbus,
correction.
subsequently the PTK procedure is performed with
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246 Mastering Advanced Surface Ablation Techniques

CHAPTER Excimer Laser PRK and

26 Corneal Scars: Refractive
Surgery to the Rescue

Arun C Gulani (USA)

INTRODUCTION will require penetrating keratoplasty. Even then we

can surely come back with the excimer PRK for
Corneal scars of practically any etiology (previous
dealing successfully with the postop astigmatism).
refractive surgery, infective keratitis including ulcers
For scars which are anterior (most of them are)
and even herpetic corneas, chemical burns, post-
we need to determine depth (plan for corneal build
traumatic, dystrophies and degenerations) can all be
up as needed if thin/thick/irregular, etc).
addressed using the Excimer Laser PRK in a refractive
Supra-Bowman scars can be peeled off under the
mode towards unaided emmetropia.
excimer laser and PRK continued to full refractive
As explained in my previous publications, we need
correction.
to apply the 5S system to first achieve a clear and
If the scar looks like it is not a sheet of tissue but
stable cornea, then all we need to do is derive the
optimum shape (as long as there is no progressive or actually become part of the corneal stroma (i.e.
irreversible intraocular pathology) for unaided herpetic scars which are usually gelatinous on
emmetropia. touching) then use that scar as a masking agent to
This ability to prepare any cornea for Laser Vision perform the refractive PRK without lifting or
Surgery and to repair any cornea from Laser Vision removing it. These techniques are published in a video
Surgery is what I have introduced as a specialty - journal format for viewing.
Corneoplastique™ which includes a spectrum of Remember on removing the epithelium a lot is
brief, topical, aesthetically pleasing and visually revealed. Many a keratoconus scar is actually staring
promising surgeries in single or multiple stages if at you, waiting to be removed.
needed. I usually use mitomycin C on determining safety
Complete and thorough evaluation of the optical intraoperatively in conjunction with laser surgery.
system of the eye from the cornea to the retina is Patients are educated that the present day options
necessary. This complete information is important like penetrating keratoplasties can always be a back
because concept of Corneoplastique™ uses the up and can be done even if all the corneoplastique
complete anterior segment and finally the cornea as surgeries fail; while if the corneoplastique -laser
a platform for visual rehabilitation. approach works (you would obviously have a good
Corneal scars in particular can be easily salvaged idea before surgery otherwise you would not
unless they are full thickness into the cornea (which proceed—very much like refractive surgery) then
 Excimer Laser PRK and Corneal Scars: Refractive Surgery to the Rescue 247
they are looking forward to enjoying good unaided
vision (As ophthalmologists we should still aim for
20/20) without extensive surgeries and rehabilitation
times inclusive of just topical anesthesia, brief
procedures, aesthetically appealing and visually
promising techniques (so literally they have a
dual benefit—Scar management and refractive
correction).
As eye surgeons we must always strive for 20/20
no matter what caused their pathology. I exercise
the same caution in patient selection and technique
selection as in all my lasik/refractive surgery
cases. We have an obligation to do the best we can
with the patient’s safety and outcome as our primary Figure 26.1: Preop. corneal scar
goal.
Educating patients about these options and also
outlining the complete plan to 20/20 makes them a
team player with you as you cautiously procceed
building success on success. In my practice I use the
Pentacam (oculus) as an adjunct to my thought process
and the ReSeevit High Definition Imaging system
(veatch ophthalmics) to document my outcomes and
also translate my thought process for the patients
and their families. This also provides the confidence
that they gain from you since they know you have
thought through the whole process before embarking
on the stages rather than performing surgery and
then making plans as you go.
They also understand that their 20/20 will not be Figure 26.2: Postop. after scar peel and simultaneous excimer
laser refractive surgery to 20/20 vision and total clarity
as good as a virgin refractive case (This applies to us
too. We are all striving for vision better than 20/20
in all our lasik patients) but given where they are
coming from and given what minimal trauma they
will be going through this option is a Win - Win for
the team (patient and doctor).
Also, if the patient is already very happy at any
intermediary stage (If you were planning combined
stages), stop! The patient and their satisfaction is what
we are addressing – not a topography chart (Figures
26.1 to 26.4).
In summary, practically any ocular situation
provided it has visual potential and no ongoing
or uncontrolled visually debilitating pathology can
be addressed to achieve its best unaided visual
capacity. Figure 26.3: Preop. corneal scar (post fungal ulcer)
248 Mastering Advanced Surface Ablation Techniques
BIBLIOGRAPHY
1. Gulani AC. “A New Concept for Refractive Surgery:
Corneoplastique”. Ophthalmology Management 2006;
57-63
2. Gulani AC. “ Corneoplastique: Art of Vision Surgery”
Video Journal of Cataract and Refractive Surgery. Vol
XXII. Issue 2006;3.
3. Gulani AC. Corneoplastique. Techniques in Ophthalmology
2007;5(1):11-20.
4. Gulani AC. «Como manejar logicamente a los pacientes
postlasik” Review of ophthalmology en Espanol., 2007;
Edicion #19, 14-17.

Figure 26.4: Post-excimer Laser refractive surgery using the scar as

a masking agent. Even though you see the residual scar postop , this
patient sees 20/15 uncorrected
 CHAPTER

27 Corneal Wound Healing after

Excimer Laser Ablation

Jes Mortensen (Sweden)

INTRODUCTION ANATOMY OF CORNEA

Why can an imprint made 10 years ago in the cornea Before we proceed we shall look at the anatomy of
stay unchanged? That was the question I put to myself the major player in this story: The cornea.
when I retreated an eye that had undergone PRK ten The cornea is anatomically described as consisting
years earlier for myopia (Figure: retreatment after of three tissue layers. From the anterior to the
ten years). The eye had regressed one diopter. When posterior:
the epithelium was removed the stepwise imprint The corneal epithelium is a multi cellular, stratified
made by the VISX 20/20 iris-diaphram delivery layer of fast growing and easily regenerated cells. The
system was revealed as though it had just been cells are increasingly flattened approaching the surface
ablated. It was as if the ablation had been made in and are similar to the cells of the skin, desquamated
piece of plastic; but “the cornea is not a piece of from the surface, but that is a very slow process.
Between the first and the second tissue layer is
plastic” as pointed out by Cynthia Roberts, PhD.1
Bowman’s layer, often referred to as a membrane;
To get an answer to my question, I had to review
this is as it consist of a condensed layer of collagen
the scientific literature about wound healing in the
fibres densely interwoven to form a felt-like sheet.
cornea. Including M. Elizabeth Fini, PhD: “Keratocyte
The corneal stroma has a unique three dimensional
and Fibroblast phenotypes in the repairing cornea”.9
network consisting of thin uniform fibrils with a
William J Dupps, Jr and Steven E Wilson: “Biomechanics
diameter about 25 nm aligned in parallel lamellae;
and wound healing in the cornea”.17 Per Fagerholm each fibril has a coating of proteoglycans with special
MD, PhD: “Wound healing after photorefractive water-holding properties.3 The lamellae are arranged
keratectomy”.6 parallel to the corneal surface, but communicate with
The usual reaction to tissue damage is a fibrotic adjacent layers by their fibrils. That communication
response leading to healing by formation of scar is especially seen in the periphery of the cornea,
tissue; a reparative process. The corneal tissue often building a stronger corneal tensile strength in the
heals by a regenerative process restoring the function periphery than in the centre of the cornea.
of the cornea without scar tissue. Such a reaction is The keratocytes form a three-dimensional
also seen in fetal wound healing during the first network, building a continuous syncytium with the
trimester. To understand this we shall look at the other keratocytes; we shall later learn the importance
steps taking place in wound healing of the cornea of this for the rapid dissemination of the apoptic
directly after trauma. response in the cornea to a trauma.
250 Mastering Advanced Surface Ablation Techniques
The organization of the stromal extra-cellular The first reaction tacking place in the cornea as a
matrix (ECM) is very precise. This exact structure is reaction to a trauma (e.g. scraping of the epithelium,
believed to be crucial for the transparency of the cut with a scalpel, PRK, Lasik and even a viral
cornea. Two theories try to account for the infection in the epithelium) is a cell death of the
transparency of cornea:1 the lattice model; that the anterior keratocytes by apoptosis thinning the stroma
light scatter by individual fibrils is cancelled by according to the magnitude of the injury.8 This was
destructive interference from the scatter of light from first described by Dohlman et al 1968 7 the
other individual fibrils.2 If the wavelength of light is understanding of apoptosis had of course not
long compared with the fibril spacing, as it is in the developed at that time. The apoptosis starts after one
cornea, the material should be transparent, and if the hour with a peak after approximately 4 hours. An
vacuum wavelength is of the same order as the fibril interesting hypothesis on the selective advantaged
spacing, as in the sclera, it should be opaque.5 The apoptosis of the keratocytes is that it can be a way to
spacing of the neighboring collagen fibrils must be obstruct a virus infection in the epithelium to
less than 200 nm to allow transparency according to spreading to the stroma.8
this theory. Descemet’s membrane is a thin layer Within a few hours after the trauma, polymorph
serving as the basement membrane for the nuclear leucocytes invade the wound followed later
endothelium. by mononuclear cells. These cells help to remove dead
The endothelium consists of a monolayer of cells cells and stromal remnants and fight bacterial
essential for the solute transport between the anterior intruders.9 The process of repair starts with activation
chamber and the corneal stroma. The endothelium is of the keratocytes around the acellullar zone that arise
the pump that preserves the exact hydration of the after the cell death of the keratocytes. The keratocytes
stroma, which assures the exact structure essential develop to the fibroblasts. The fibroblasts excrete
for the corneal transparency. fibronectin in the wound area which may allow the
There are no blood vessels in the cornea; fibroblasts to migrate on the fibronectin. 10 The
the nourishment is by the aqueous humor in the altered composition of the EMC probably explains
anterior chamber and from the limbal blood vessels. the opacity of the repair tissue. The fibroblast also
up regulates the synthesis of enzymes capable of
The cornea is innervated by 70 to 80 long and short
degrading the new ECM; among these are matrix
ciliary ending in unmyelinated nerve ends making
metalloproteinase and other proteinases. A gradual
the cornea one of the most sensitive tissues in the
interleaving between the stromal collagen lamellae
body.6
and the collagen lamellae at the wound edge
CORNEAL WOUND HEALING emerges.11 The remodelling of the stroma to a more
mature state contributes to restoration of the
The model of wound healing in the body almost transparency of the cornea.
always follows the same pattern: 1) Inflammation, A new cell type appears at the contraction phase
early polymorph nuclear leukocyte invasion, late, one to two weeks after the trauma to cornea: the
monocyte invasion; 2) granular tissue formation and myofibroblasts, which are characterized by the
re-epithelialization; 3) new matrix formation and intracellular appearance of α-smooth muscle actin.10
remodelling of the matrix; 4) wound contraction; 5) The myofibroblasts are believed to differentiate from
collagen accumulation and normalization of the the fibroblasts; (same studies have questioned that
number of cells in the scar. These steps are all seen in hypothesis showing that they are derived from the
the corneal wound healing but are modulated and bone-marrow).15
down regulated giving a regeneration of the corneal Restoration of the epithelial basement membrane
tissue the end product rather than scar tissue that is crucial for the delicate balance between stromal
would severely injure the function of the eye as a regeneration and developing fibrotic scar tissue.18
visual organ. Myofibroblasts often disappear after the following
 Corneal Wound Healing after Excimer Laser Ablation 251
weeks12, but if a defective basement membrane arises keratocytes after 10 to 12 days, similar regenerative
the wound healing would be reparative rather than response is seen after epithelial debridement.14 It is
regenerative with a fibrotic response due to the possible for the keratocytes to proliferate and migrate
myofibroblasts (causing haze in photorefractive as a response to a corneal wound healing without
keratectomy?) Can Bowman’s layer reform after conversion to activated fibroblasts. In this way a
removal? A study of corneas undergoing radial regenerative response takes place fully restoring the
keratomy 5 to 10 years earlier showed that a layer cornea to normal. All these different processes in
similar to Bowman’s layer develops around the wound healing of the cornea are controlled by
ectopic epithelium in the cuts. 13 A homeostatic different cytokines and interleukins, but I have on
interaction between the epithelial cells and the purpose tried not to stray into the labyrinth of all
keratocytes in the stroma is suggested to maintain these chemical transmitters, —instead I refer to the
the normal structure of the cornea 14 .These references after the chapter (Figures 27.1 to 27.6).
observations suggest that the epithelium actively
participates in the formation and maintenance of
Bowman’s layer. Re-epithelization after a defect as
PRK is typically takes 48 to 72 hours. Epithelial healing
is complete after six weeks when permanent
anchoring is restored to the basal membrane. The
epithelial restoration is crucial to restore a barrier
against bacteria but also in the modulation leading
to a regenerative response instead of a fibrotic repair
with scar tissue. The cornea undergoes a homeostatic
remodelling like the skin and other tissue with
collagen matrix but with a much slower turn over.
The answer to the question why the corneal often
express a regenerative wound healing is that the Figure 27.1
cornea as the whole eye is an immune-privileged
site16, meaning that it is relatively protected against
immune response to foreign or self-antigens. The
historical definition of an immune privileged site is
an anatomical site where a transplanted allograft
survives for an extended period of time in an immune
competent host. Today the immune privilege is
considered a dynamic rather than passive process.
In a grafted cornea the anatomic features works
together with immune-regulation to prevent rejection;
this process will never stop - rejection can take place
in spite of decades of silence.
The cornea is remarkably tolerant to injury be
freezing, the cornea can regenerate after a full
Figure 27.2
thickness injury of the cornea without forming
fibrotic scar tissue, almost as a fetal wound healing Figures 27.1 and 27.2: Severe ischemia of the cornea after contact
lens wear. The cornea was cloudy and had severe edema. The
regeneration.2 Cells start to regenerate and invade epithelium healed with severe scarring and irregularity but after three
from the undamaged area of stroma within 24 hours. weeks increasing transparency of the cornea. Visual acuity increased
from CF to 20/100. After one year 20/40 with contact lens. The patient
By 5 to 7 days the damaged area has been invaded was seen after 7 years. The cornea had totally regenerated and
by the new cells which gradually transform to normal visual acuity: 20/20
252 Mastering Advanced Surface Ablation Techniques

Figure 27.3 Figure 27.4

Figure 27.5
Figures 27.3 to 27.5: On the 28th of August 2001 severe keratitis of the right eye was seen after contact lens wearing. Visual acuity: Hand
movement. Culture was positive: Pseudomonas aeruginosa, Klebsiella, Staphylococcus aureus. Topical and intravenous antibiotics were
given. On the 11th of September 2001 amniotic membrane patching was performed. At the visit on the 4th of October 2001 the amniotic
membrane covered the large tear; the nasal part of the cornea begins to clear. Last visit March 2003 an incredible wound healing has taken
place; visual acuity: 20/50. Stromal thinning was seen, but the cornea was completely transparent

CONCLUSION

In the beginning of this chapter I asked: Why can an

imprint made 10 years ago in the cornea by PRK stay
unchanged? The answer is that the cornea is an
immune-privileged site.16 The fibroblasts in cornea
can respond to injury during wound healing by
proliferating without activation and in this way the
repair can be regenerative. The imprint will stay
unchanged in spite of the dramatic apoptic response
from the keratocytes to excimer laser ablation. “A
sealing of the cornea” has taken place.

Figure 27.6: (Retreatment after 10 years): Imprint seen ten years

after Excimer laser ablation
 Corneal Wound Healing after Excimer Laser Ablation 253
REFERENCES corneal wound healing. Invest. Ophthalmol. Vis. Sci
1995;36:809-19.
1. Cynthia Roberts. The Cornea is Not a Piece of Plastic, 11. Davison PF, Galbavy EJ. Connective tissue remodelling
Journal of Refractive Surgery Vol 16, 2000. in corneal and scleral wounds. Invest. Ophthalmol. Vis.
2. Maumenee AE, Kornblueth W. Regeneration of corneal Sci. 27, p. 1478.
stromal cells I: Technique for destruction of corneal 12. MC Helena, F Baerveldt, WJ Kim, SE Wilson, et al.,
corpuscles by application of solidified (frozen) carbon Keratocyte apoptosis after corneal surgery, Invest.
dioxide. Am J. Ophth 1948;31:459.
Ophthalmol. Vis. Sci (1998);39:276-83.
3. Hedbys BO. The role of polysaccharides in corneal
13. Melles GR, Binder PS, Moore MN, Andersson JA.
swelling. Exp. Eye Res 1961;1:81-91.
4. David B, Ameen, Marilyn F. Bishop, Tom McMullen. A Epithelial-stromal interactions in human keratotomy
Lattice Model for Computing the Transmissivity of the wound healing. Arch Ophthalmol 1995;113:1124-30.
Cornea and Sclera, Biophys J 1998;75(5):2520-31. 14. Wilson SE, Kim, W-J. Keratocyte Apoptosis: Implications
5. Benedek GB. Theory of transparency of the eye. Appl. on the Corneal Wound Healing, Tissue Organization, and
Optics 1971;3:459-73. Disease. Invest, Ophthalmol. Vis. Sci 1998;39:220-26.
6. Per Fagerholm. Wound healing after photorefractive 15. J Bhawan, G Majno. The myofibroblasts. Possible
keratectomy, Journal of Cataract and Refractive Surgery derivation from macrophages in xanthogranuloma, Am.
2000;26(3):432-47. J Dermatopathol. 11 (1989=, 255-8.
7. Dohlman CH, Gasset AR, Rose J. The effect of the absence 16. Steilein JW. Molecular basis of ACAID. Ocular
of corneal epithelium or endothelium on stromal Immunology and Inflammation 1997;5:217-8.
keratocytes. Invest Opthalmol Vis sci 1968;7:520-34. 17. William J Dupps, Jr. and Steven E Wilson,. Biomechanics
8. Wilson SE, Kim W-J. Keratocyte Apoptosis: Implications
and wound healing in the cornea. Experimental Eye
on Corneal Wound Healing, Tissue Organization, and
Research 2006;83(4):709-20.
disease. Investigative Ophthal & Vis Sci 1998;39(2):220-6.
9. Fini M. Keratocyte and fibroblast phenotypes in the repairing 18. Stramer, Brian M, Zieske, James D, Jung, Jae-Chang,
in the cornea, Progress in Retinal and Eye Research Austin, Jeffrey S, Fini M Elizabeth. Molecular mechanisms
1999;18:529-51. controlling the fibrotic repair phenotype in cornea:
10. Jester JV, Petroll WM, Barry PA, Cavanagh HD. implications for surgical outcomes. Invest, Ophthalmol.
Expression of α-smooth muscle (α-SM) actin during Vis. Sci 2003;44:4237-46.
254 Mastering Advanced Surface Ablation Techniques

CHAPTER

28 The Effect of Moxifloxacin

and Gatifloxacin on
Short-term and Long-term
Outcomes following PRK
Jenna M Burka (USA)

INTRODUCTION antibacterial properties also has an inhibitory effect

on corneal epithelial wound healing and can delay
Antibiotics drops are routinely used as prophylaxis
the healing process. Consequently, this leads to an
following ocular surgery. The epithelial defect increased risk of infection, haze and scarring that can
created in photorefractive keratectomy (PRK) leaves result in negative visual outcomes.5
patients especially susceptible to bacterial keratitis The commercial preparations of moxifloxacin and
making the choice of antibiotic prophylaxis crucial. gatifloxacin differ in several ways that may contribute
Fluoroquinolones have excellent broad spectrum to the effect on corneal wound healing. Gatifloxacin
coverage, good ocular tolerance and are commonly is formulated as a 0.3% solution with a pH of 6.0.
used following refractive surgery. Moxifloxacin is prepared as a 0.5% solution with a
The two newer fourth-generation fluoro- pH of 6.8. Normal tear pH is approximately 7.5 but
quinolones, gatifloxacin (Zymar, Allergan, Irvine, can increase in the setting of an infection with
California) and moxifloxacin (Vigamox, Alcon phagocytosis. As the difference between the pH of
Laboratories, Forth Worth, Texas) have distinct the antibiotics and the pH of the tears increases the
advantages over their predecessors. Resistance of solubility of the antibiotics decrease and precipitates
some organisms to ciprofloxacin, levofloxacin and can form on the corneal surface. This precipitation
ofloxacin have been reported, however, this has yet may then block epithelial migration into the wound
to be a significant problem with moxifloxacin and or prevent epithelial regeneration thereby inhibiting
gatifloxacin. 1,2,3 The second and third-generation wound healing.5,6
fluoroquinolones have also been shown to be less A second important difference between the two
effective against several important pathogens, formulations is the use of preservatives. Moxifloxacin
Streptococcus viridans, Streptococcus pneumonia and is preservative free while gatifloxacin is preserved
Staphylococcus aureus, as well as atypical mycobacteria with 0.005% benzalkonium chloride (BAK). Several
compared to the newer generation of fluoro- studies have reported an adverse effect of BAK on
quinolones. corneal epithelium,7,8,9 however, other studies have
Fluoroquinolones work by inhibiting topoisomerase found that BAK has no effect on corneal healing.10
II (DNA gyrase) and topoisomerase IV, thereby Corneal wound healing is a complex process that
hindering the ability of bacteria to replicate.4 This begins immediately following surgery. The release
mechanism of action which gives fluoroquinolones of cytokines results in keratocyte activation and
 The Effect of Moxifloxacin and Gatifloxacin on Short-term and Long-term Outcomes 255
myofibroblast differentiation. A delay in wound safety (measured as best spectacle corrected visual
healing leads to an increase in activated keratocytes acuity within one line of preoperative levels at three
and myofibroblasts. The number of these cells present months or longer postop), and complications or
is directly related to the development of haze and adverse events were reported.
therefore refractive outcomes. Thus a delay in wound In the first-half of the study we found that overall
closure may lead to poor visual outcomes. A study eyes treated with moxifloxacin healed faster and had
comparing epithelial healing and visual outcomes smaller epithelial defects than eyes treated with
following PRK among patients with varying degrees gatifloxacin. Both eyes healed on the same day in 18
of myopia and astigmatism demonstrated a of 35 subjects (51.4%). In the majority of the remaining
correlation between epithelial healing and visual 17 subjects, however, the moxifloxacin-treated eye
performance, noting that faster epithelial healing healed first. Moreover, all six of the eyes that took
resulted in a spherical equivalent closer to emmetropia two days longer than their fellow eye to heal were
by 12 months postop.11 Another study evaluating gatifloxacin-treated. Although median healing time
the use of amniotic membranes to promote epithelial for both groups was 4 days (moxifloxacin range: 3 to
healing found that not only did those eyes with the 7 days, gatifloxacin range: 3 to 9 days, P = 0.01), only
amniotic membrane heal faster but they had a 69% of gatifloxacin-treated eyes had healed by day 4
statistically significant difference in visual outcomes compared with 80% of the moxifloxacin-treated eyes.
6 months after treatment. The amniotic membrane Overall, on each post-operative day, defect sizes were
greater for the gatifloxacin-treated eyes. This
group had less refractive error and a decreased
difference was statistically significant on day 4 (P =
incidence of corneal haze.12 In contrast, a study
0.027), and a similar trend was seen on day 5 (P =
comparing three techniques of epithelial removal prior
0.055).
to refractive surgery found no correlation between
Despite a difference in epithelial healing between
epithelial healing and long-term outcomes. Although
moxifloxacin and gatifloxacin treated eyes, in the
they did find a statistical difference in healing rates
second part of the study we found equivalent long-
they found little difference in long-term results,
term outcomes. Measurements of visual outcomes
including UCVA, BSCVA, and refractive error.13
(BSCVA, UCVA), refractive outcomes (MSE) and
In order to further investigate these differences
complications (haze rate) demonstrated no significant
between moxifloxacin and gatifloxacin we conducted
difference between groups. Although faster healing
a two-part prospective, randomized, double-blinded
times did not have an effect on long-term results,
study at the Center for Refractive Surgery, Walter
the more favorable epithelial healing profile with
Reed Army Medical Center, Washington, DC to
moxifloxacin may provide another factor to consider
determine how the two preparations may alter
in selecting antibiotic prophylaxis for corneal
corneal wound healing and visual outcomes following
refractive surgery.
PRK. 14,15 Thirty five subjects were enrolled and
randomized to one of two groups. Patients in group REFERENCES
A used moxifloxacin in the right eye and gatifloxacin
1. Goldstein MH, Kowalski RP, Gordon YJ. Emerging
in the left eye while those in group B used the reverse fluoroquinolone resistance in bacterial keratitis.
after undergoing PRK in both eyes. In the first-half Ophthalmology 1999;106:1313-8.
of the study subjects were examined daily to 2. Hwang DG. Fluoroquinolone resistance in
ophthalmology and the potential role for newer
determine the rate of epithelial healing. The primary
ophthalmic fluoroquinolones. Surv Ophthalmol 2004;49(2
outcome measure was time to epithelial healing. The suppl):S79-S83.
size of epithelial defects was also examined. In the 3. Kowalski RP, Dhaliwal DK, Karenchak LM, et al.
second-half of the study long-term secondary Gatifloxacin and moxifloxacin: an in vitro susceptibility
comparison to levofloxacin, ciprofloxacin, and ofloxacin
outcomes such as visual outcome (as measured by using bacterial keratitis isolates. Am J Ophthalmology
uncorrected visual acuity and manifest refraction), 2003;136:500-5.
256 Mastering Advanced Surface Ablation Techniques
4. Mandell GL. Quinolones. Principles and practice of 10. Collin HB, Grabsch BE. The effect of ophthalmic
infectious diseases, 5th edn. Orlando: Churchill preservatives on the healing rate of the rabbit corneal
Livingstone 2000;406-7. epithelium after keratectomy. Am J Optom Physiol Opt
5. Patel GM, Chuang AZ, Kiang E, Ramesh N, Mitra S, Yee 1982;59:215-22.
RW Epithelial healing rates with topical ciprofloxacin, 11. Serrao S, Lombardo M. Corneal epithelial healing after
photorefractive keratectomy: analytical study. J Cataract
ofloxacin, and ofloxacin with artificial tears after
Refract Surg 2005;31(5):930-7.
photorefractive keratectomy. J Cataract Refract Surg
12. Lee HK, Kim JK, Kim SS, Kim EK, Kim KO, Lee IS, Seong
2000;26:690-4. GJ. Effect of amniotic membrane after laser-assisted
6. Wilhelmus KR, Abshire RL. Corneal ciprofloxacin subepithelial keratectomy on epithelial healing: clinical
precipitation during bacterial keratitis. Am J Ophthalmol and refractive outcomes. J Cataract Refract Surg
2003;136:1032-7. 2004;30(2):334-40.
7. Dutot M, Pouzaud F, Larosche I,et al. Fluoroquinolone 13. Lee HK, Lee KS, Kim JK, Kim HC, Seo KR, Kim EK.
eye drop-induced cytotoxicity: role of preservative in Epithelial healing and clinical outcomes in excimer laser
P2X7 cell death receptor activation and apoptosis. Invest photorefractive surgery following three epithelial
Ophthalmol Vis Sci 2006;47(7):2812-9. removal techniques: mechanical, alcohol, and excimer
8. Kossendrup D, Wiederholt M, Hoffmann F. Influence of laser. Am J Ophthalmol 2005;139(1):56-63.
14. Burka JM, Bower KS, VanRoekel RC, Stutzman RD,
cyclosporin A, dexamethasone, and benzalkonium
Kuzmowych CP, Howard RS. The effect of fourth-
chloride (BAK) on corneal epithelial wound healing
generation fluoroquinolones gatifloxacin and moxifloxacin
in the rabbit and guinea pig eye. Cornea 1985;86;4:177-
on epithelial healing following photorefractive
81. keratectomy. Am J Ophthalmol 2005;140(1):83-7.
9. Lazarus HM, Imperia PS, Botti RE, Mack RJ, Lass JH. An 15. Burka JM, Bower KS, VanRoekel RC, Stutzman RD,
in vitro method which assesses corneal epithelial toxicity Kuzmowych CP. The effect of moxifloxacin and gatifloxacin
due to antineoplastic, preservative and antimicrobial on long-term visual outcomes following photorefractive
agents. Lens Eye Toxic Res 1989;6:59-85. keratectomy. J Refract Surg 2007;23:414-7.
 Prophylactic Mitomycin C to
CHAPTER Inhibit Haze Formation after

29 Photorefractive Keratectomy for

Residual Myopia following
Radial Keratotomy
Belquiz A Nassaralla, Stephen D McLeod,
João J Nassaralla Jr (Brazil)

INTRODUCTION lenses, and reoperations, including redeepening

procedure, extending existing RK incisions, placing
Radial keratotomy (RK) was at one time the most
additional RK incisions, or excimer laser treatment.4
common surgical procedure used to correct myopia
The effectiveness and safety of the use of the 193-
after its modernization by Fyodorov, in the 1970s,
nm excimer laser to perform photorefractive
but the popularity of this technique has markedly
keratotomy (PRK) for correcting physiologic myopia
decreased since the advent of other technologies.1 In
has been well documented. 5-7 PRK ablates tissue
this procedure, radial incisions allow the peripheral
directly from the central cornea.6,7 Thus, performing
cornea to flex, leading to a compensatory flattening
PRK after RK has the theoretical advantage of
of central cornea. The amount of central flattening
changing the corneal curvature with minimal adverse
that can be achieved with RK, however, is limited.2
effect on corneal biomechanical stability. However,
Although various algorithms were used, RK was
PRK is accompanied by the risk of haze formation,
found to be limited in its precision. Overcorrections
and there is evidence that this risk is elevated after
and undercorrections are among the most frequent
RK.
sequelae of this procedure. Moreover, RK appears to
be inherently unstable, and in a 1994 report of the HAZE
multicenter prospective Evaluation of Radial
keratotomy (PERK) study, 43% of patients had a Corneal transparency depends on precise distribution
hyperopic shift of 1.00 diopter (D) or more by 10 and regular spacing of collagen fibers with remarkably
years after treatment.2 As a safeguard against the uniform diameter, and on the regularity of their
development of hyperopia, several investigators packing, which together lead to reduced scattering
advocated “conservative RK,” leaving the patient with of light. 8 In addition, proteoglycans and glyco-
intentional undercorrection. saminoglycans are important macromolecules present
Residual myopia after RK, whether intentional or in the extracellular matrix that also contribute to
unexpected, may result because of excessively high corneal clarity.9 Keratan sulfate proteoglycans are
preoperative myopia, a large optical zone, few involved in the regulation of collagen fibril diameter,
incisions, shallow incisions, or unresponsiveness of and dermatan sulfate proteoglycan modulates
the eye to RK. 3 Therapeutic strategies to correct interfibrillar spacing and the lamellar adhesion
residual myopia after RK include spectacles, contact properties of corneal collagens.8,9
258 Mastering Advanced Surface Ablation Techniques
In the event of corneal surgery or trauma, the concerns was reported by Maloney et al.3 In this
natural conformation of the extracellular matrix is study, a total of 107 eyes underwent PRK for residual
altered, along with changes in cellular density and myopia: 90 eyes after RK, 7 eyes after astigmatic
phenotype, associated with the production of keratotomy (AK), 7 eyes after RK and AK, 1 eye after
disorganized extracellular matrix components.10 This hexagonal keratotomy, and 2 eyes after cataract
abnormal wound healing response also includes surgery. All cases were followed for 1 year. Only 79
epithelial hyperplasia, disruption of Bowman’s layer, (74%) eyes had visual acuity =20/40, and 67 (63%)
presence of newly formed type III disorganized eyes were within 1.00 D of the intended correction.
collagen, vacuolization of keratocytes, and abnormal Thirty-one (29%) eyes lost =2 lines of BSCVA, and 12
activation of fibrocytes. 11,12 The final result is a (11%) eyes lost ≥ 4 lines. Moderate to severe central
decrease in tissue transparency referred to as corneal corneal haze developed in nine (8%) eyes, and
haze or opacity.12 irregular astigmatism was suggested to be responsible
There are likely many factors related to haze for visual loss.
formation after PRK. These may include the amount
of correction, the depth of ablation, and the time
required for the closure of the epithelial defect.13
Also, individual factors (especially related to
decreased tear film production), ambient conditions
(exposure to UV radiation can induce haze), laser
characteristics (broad-beam laser with irregular
ablation areas are more commonly associated with
haze formation than flying spot lasers with more
homogeneous ablations) have been suggested to play
a role in the mechanisms that leads to corneal haze.14
It has been postulated that apoptosis occurs in
keratocytes immediately after PRK, when the Figure 29.1: Slitlamp photograph of an eye with central corneal haze
following PRK for the treatment of residual myopia after previous
activated migrating keratocytes from the remaining radial keraotomy
stroma produce increased amounts of disorganized
collagen and cellular matrix, severely reducing Azar et al4 advised against using PRK to correct
corneal transparency.15 residual myopia after RK in patients with high myopia
before and after RK due to increased risk of haze
development. Probst and Macht30 present evidence
PRK AFTER RK
that patients at greatest risk for haze formation
Several investigators have reported the use of PRK include those with more than 8 RK incisions, an optical
for the treatment of residual myopia after previous zone ≤ 3.0 mm, preoperative corneal haze from the
RK.16-30 Although numerous early reports suggested RK procedure, or increased splay of the RK incisions.
that surface excimer laser ablations could be safely Although recent technologies such as flying spot
applied to corneas with previous RK,16-26 a series of lasers that provide large and smooth ablations have
subsequent studies indicated increased risk of haze reduced the stromal reaction that causes haze
formation, irregular astigmatism, and loss of best formation, haze continues to be the major
spectacle-corrected visual acuity (BSCVA) associated complication after PRK.31
with PRK after RK.3,4,27-30 Figure 29.1 shows a slitlamp To improve the results of PRK, attention has been
photograph of an eye with central corneal haze focused on modulating the process of postprocedural
following PRK for the treatment of residual myopia wound healing. Topical corticosteroids have been
after previous RK. One of the first studies to raise used to inhibit haze formation after PRK.32,33 The
 Prophylactic Mitomycin C to Inhibit Haze Formation 259
main mechanism through which corticosteroids may with myopia following RK41. This report was based
prevent haze is inhibition of collagen synthesis.32,33 on the study of a series of PRK procedures
However, long-term corticosteroid treatment may performed at the Goiania Eye Institute, Goiania, GO,
cause relevant side effects: ocular hypertension, Brazil, between 2001 and 2003 by a single surgeon
glaucoma, and cataract. 34 Moreover, controlled (B.A.N.) on eyes that had undergone RK between
clinical trials have not demonstrated any significant 1988 and 1993 in different eye care centers.
role of topical corticosteroids in haze prevention.32 All eyes had low residual myopia (spherical
equivalent refraction ≤ 4 diopters (D), no central
MITOMYCIN C corneal opacity, and corneal pachymetry >500 μm,
and only patients with 8 cut RK patterns were
Among topical drugs evaluated to prevent or treat
included. Immediately after laser treatment, all
corneal haze, Mitomycin C (MMC) has recently
patients received a single topical application of MMC
generated significant interest.35-41 MMC inhibits DNA
0.02 % by placing a soaked 8.0 mm diameter Merocel
synthesis, preferentially affecting rapidly dividing
(Medtronic Xomed Surgical Products Inc, Jacksonville,
cells, is fast-acting, and induces long-lasting
Fla) sponge over the ablated stroma for 2 minutes.
suppression of keratocyte activity after a single dose.
The sponge was then removed and discarded, and
MMC application after PRK has been shown to
the corneal surface, conjunctiva, and fornices were
suppress corneal haze and to markedly reduce
vigorously irrigated with balanced salt solution (20
keratocyte numbers in the anterior stroma,36 and
cc) to dilute and remove residual MMC.
prophylactic intraoperative application of a single
Before PRK with MMC, mean spherical equivalent
dose of MMC solution after PRK has been observed
refraction was
to lead to lower haze rates and more accurate
–2.72±0.76 D (range: –1.50 to –4.00D). Mean spherical
refractive outcomes.37 Majmudar et al reported a
equivalent refraction was +0.08±0.38 D (range: –0.75
successful series of 30 eyes treated using a 0.02%
to +0.75) 1 month, –0.12±0.40 D (range: –0.75 to +0.50)
MMC solution to prevent recurrent haze after PRK
3 months, and –0.18±0.35 D (range: –0.75 to +0.50) 12
and radial keratotomy.35 Although this study was
months postoperatively. At last follow-up, 19 eyes
performed in a limited series, it assessed short-term
were within 0.50 D of intended correction, and all
safety of the use of 0.02% MMC. Carones et al
eyes were within 0.75 D. No eye required retreatment
reported the results of the prophylactic use of MMC
for refractive correction. Figure 29.2 shows mean
to inhibit haze formation after PRK for medium and
spherical equivalent refraction over time.
high myopia in eyes that were unsuitable for LASIK.37
Slight regression in myopic correction based on
This study showed that the use of a single
spherical equivalent refraction was noted 3 months
intraoperative application of MMC 0.02% after PRK
after surgery, but stability was achieved thereafter.
led to positive refractive and visual results over a
One month postoperatively, UCVA improved by
6-month period. The same authors also documented
≥ 11 Snellen lines in all eyes. Uncorrected visual acuity
the absence of relevant corneal complication with this
in 21 (95.5%) eyes was ≥ 20/40, 11 (50%) eyes ≥ 20/
modality.37 The successful control of haze formation
25, and 2 (9%) eyes ≥ 20/20. After 12 months, UCVA
in these circumstances prompted us to examine the
in 17 (77.3%) eyes was ≥ 20/40, 9 (41%) eyes ≥ 20/25,
efficacy and safety of the prophylactic use of MMC
and 2 (9%) eyes ≥ 20/20. Due to a slight regression in
0.02% to inhibit haze formation after PRK for residual
effect, 7 (31.8%) eyes lost 1 line of UCVA compared
myopia following RK with 1-year follow-up.
to results found at 1 month after PRK with MMC.
OUR PERSONAL EXPERIENCE Figure 29.3 shows results of UCVA over time.
Twelve months after surgery, BSCVA was ≥ 20/40
We have reported our experience with the use of in 21 (95.5%) eyes and ≥ 20/25 in 12 (54.5%) eyes.
MMC to prevent haze after PRK treatment in eyes Only 1 (4.5%) eye lost 2 lines of BSCVA. This loss
260 Mastering Advanced Surface Ablation Techniques

Figure 29.2: Box plots show spherical equivalent refraction before Figure 29.4: Box plots show best spectacle corrected visual acuity
and after photorefractive keratectomy with a single, intraoperative before and after photorefractive keratectomy and a single intraoperative
topical application of mitomycin C 0.02% in eyes that previously topical application of mitomycin C 0.02 % in eyes that previously
underwent radial keratotomy. Median (solid line), interquartile range underwent radial keratotomy. Median (solid line), interquartile range
(box), and outliers (circle) are also shown. Error bars represent (box), outliers (circle), and extreme (asterisk) values are also shown.
standard deviation Error bars represent standard deviation

count was 2150±180 cells/mm2 (range: 1800 to 2650

cells). At 3 months after PRK with MMC, mean
endothelium cell count was 2100 ± 205 cells/mm2
(range: 1680 to 2540 cells), and at 12 months was 2200
± 210 cells/mm 2 (range: 1680 to 2500 cells). No
statistically significant difference was found in
endothelial cell count during follow-up.
With regards to corneal haze, At 1 month,
3 (13.6%) eyes showed grade 1 haze and 1 (4.5%) eye
grade 0.5 haze. After 3 months, all 3 eyes continued
to show grade 1 haze, and 2 (9%) eyes developed
grade 0.5 haze. Twelve months after PRK with MMC,
no spontaneous attenuation in corneal haze was
noted. Three eyes showed grade 1 haze and 2 eyes
grade 0.5 haze at 1 year. Haze was considered related
to irregular astigmatism in 1 (4.5%) eye.
Figure 29.3: Box plots show uncorrected visual acuity before and
after photorefractive keratectomy and a single intraoperative topical In this study, we found that uncorrected visual
application of mitomycin C 0.02% in eyes that previously underwent acuity and residual refractive error improved in all
radial keratotomy. Median (solid line), interquartile range (box), and
extreme (asterisk) values are also shown. Error bars represent eyes with minimal haze formation and loss of BSCVA
standard deviation 12 months following PRK with MMC, which was
performed after RK. This is in contrast with other
was attributed to haze grade 0.5 and irregular reports that describe significant risk of lost BSCVA
astigmatism. Figure 29.4 shows BSCVA over time. and haze formation without use of MMC.3,4,27-30
In this study, we included an evaluation of We used a conservative approach in our study,
endothelial cell change associated with MMC use and and treated 80% of residual myopia. We noted a slight
PRK treatment. Preoperative mean endothelial cell regression between 1 and 3 months postoperatively
 Prophylactic Mitomycin C to Inhibit Haze Formation 261
that stabilized, similar to the healing pattern of 3. Maloney RK, Chan WK, Steinert R, Hersh P, O’Connell
M A multicenter trial of photorefractive keratectomy for
postoperative PRK for primary myopia. In a study of
residual myopia after previous ocular surgery. Summit
PRK (without MMC) for residual myopia following Therapeutic Refractive Group. Ophthalmology 1995;102:
RK, Probst and Macht30 used a conservative approach, 1042-53.
treating only 60% to 70% residual myopia, based on 4. Azar DT, Benson RA, Hardten DR. Photorefractive
keratectomy for residual myopia after radial keratotomy.
the variation of approximately 20% response they had PRK after RK Study Group. J Cataract Refract Surg
previously observed. Probst and Macht30 recommend 1998;24:303-11.
that the target refraction of residual myopia for PRK 5. Salz JJ, Maguen E, Nesburn AB, Warren C, Macy JI,
Hoffbauer JD, Papaioannou T, Berlin M. A two-year
after RK be –0.50 D to allow for an anticipated experience with excimer laser photorefractive keratectomy
progressive hyperopic shift after RK. In our study, for myopia. Ophthalmology 1993;100:873-82.
treating 80% of residual myopia and applying MMC, 6. Talley AR, Sher NA, Kim MS, Doughman DJ, Carpel E,
Ostrov C, Lane SS, Parker P, Lindstron RL. Use of the 193
12 months after surgery, mean spherical equivalent
nm excimer laser for photorefractive keratectomy in low
was –0.18 D. to moderate myopia. J Cataract Refract Surg 1994;20:
The potential effect on corneal endothelium 239-42.
following PRK with MMC after RK is of some concern. 7. Amano S, Shimizu K. Excimer laser photorefractive
keratectomy for myopia: two-year follow-up. J Refract
It is well documented that RK incisions never Surg 1995:11:S253-60.
completely heal, and the permeability of MMC 8. Conrad GW, Funderburgh JL. Eye development and the
through these corneal incisions compared to the appearance and maintenance of corneal transparency.
Trans Kans Acad Sci 1992;95:34-8.
normal stroma is unclear. Although PRK with MMC 9. Maurice DM. The transparency of the corneal stroma.
has been studied without report of endothelium Vision Res 1970;10:107-8.
decompensation, 35-38 we elected to include an 10. Hanna KD, Pouliquen YM, Waring GO III, Savoldelli M,
Fantes F, Thompson KP. Corneal wound healing in
evaluation of endothelial cell count in our study. We
monkeys after repeated excimer laser photorefractive
found no statistically significant difference in keratectomy. Arch Ophthalmol 1992;110:1286-91.
endothelial cell count during follow-up. 11. Krueger RR, Binder PS, McDonnell PJ. The effects of
The efficacy and side effects of PRK with MMC excimer laser photoablation on the cornea. In:Salz JJ,
McDonnell PJ, McDonald MB, (Eds). Corneal Laser
after RK will be established with continued follow- Surgery St Louis, Mo:Mosby-Year Book Inc; 1995;11-44.
up. We recognize that significant corneal haze and 12. Jester JV, Petroll WM, Cavanagh HD. Corneal stromal
scarring may occur many months after refractive wound healing in refractive surgery: the role of
myofibroblasts. Prog Retin Eye Res 1999;18:311-36.
surgery, and we will continue to follow the patients
13. Moller-Pedersen T, Cavanagh HD, Petroll WM, Jester JV.
enrolled in this study for emergence of haze and Corneal haze development after PRK is regulated by
scarring. However, this experience seems to indicate volume of stromal tissue removal. Cornea 1998;17:627-
that a single, intraoperative application of MMC 0.02% 39.
14. Lipshitz I, Lowenstein A, Varssano D, Lazar M. Late onset
for 2 minutes appears to be effective in preventing corneal haze after photorefractive keratectomy for moderate
haze following PRK for residual refractive error after and high myopia. Ophthalmology 1997;104:369-74.
RK, is not associated with significant ocular morbidity, 15. Wilson SE, He YG, Weng J, Li Q, McDowall AW, Vital M,
Chwang EL. Epithelial injury induces keratocyte
and provides a method for the management of apoptosis: hypothesized role for the interleukin-1 system
residual myopia following RK. in the modulation of corneal tissue organization and
wound healing. Exp Eye Res 1996;62:325-7.
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photorefractive keratectomy after undercorrected radial
1. Pallikaris IG, Papadaski TG. From keratomileusis to LASIK keratotomy. Refract Corneal Surg 1991;7:146-50.
– Evaluation of lamellar corneal procedures. Refractive 17. Seiler T, Jean R. Photorefractive keratectomy as a second
Surgery. Jaypee, 210-5. attempt to correct myopia after radial keratotomy. Refract
2. Waring GO III, Lynn MJ, McDonnell PJ. PERK Study Corneal Surg 1992;8:211-4.
Groups. Results of the prospective evaluation of radial 18. Hahn TW, Kim JH, Lee YC. Excimer laser photorefractive
keratotomy (PERK) study 10 years after surgery. Arch keratectomy to correct residual myopia after radial
Ophthalmol 1994;112:1298-308. keratectomy. Refract Corneal Surg 1993;9:S25-9.
262 Mastering Advanced Surface Ablation Techniques
19. Durrie DS, Schumer DJ, Cavanaugh TB. Photorefractive R, Piovella M, Mehta CK, Eds. Mastering the Techniques
keratectomy for residual myopia after previous refractive of Corneal Refractive Surgery. New Delhi, Jaypee Brothers
keratotomy. J Refract Corneal Surg 1994;10:S235-8. Medical Publishers 2006:20-36.
20. Meza J, Perez-Santonja JJ, Moreno E, Zato MA. 32. Gartry DS, Kerr Muir MG, Lohmann CP, Marshall J. The
Photorefractive keratectomy after radial keratotomy. J effect of topical corticosteroids on refractive outcome and
Cataract Refract Surg 1994;20:485-9. corneal haze after photorefractive keratectomy: a
21. Nagy ZZ, Suveges I, Nemeth J, Fust A. The role of excimer prospective, randomized, double-blind study. Arch
laser photorefractive keratectomy in treatment of Ophthalmol 1992;110:944-52.
residual myopia followed by radial keratotomy. Acta Chir 33. Carones F, Brancato R, Venturi E, et al. Efficacy of
Hung 1995-1996;35:13-9. corticosteroids in reversing regression after myopic
22. Lee YC, Park CK, Sah WJ, Hahn TW, Kim MS, Kim JH. photorefractive keratectomy. Refract Corneal Surg
Photorefractive keratectomy for undercorrected myopia 1993;9(suppl):S52-6.
after radial keratectomy: two year follow up. J Refract 34. Becker B, Mills DW. Corticosteroids and intraocular
Surg 1995;11:S274-9. pressure. Arch Ophthalmol 1963;70:500-7.
23. Kwitko ML, Gow JA, Bellavance F, Woo G. Excimer 35. Majmudar PA, Forstot SL, Dennis RF, Nirankari VS,
photorefractive keratectomy after uncorrected radial Damiano RE, Brenart R, Epstein RJ. Topical mitomycin-C
keratotomy. J Refract Surg 1995;11:S280-3. for subepithelial fibrosis after refractive corneal surgery.
24. Nordan LT, Binder PS, Kassar BS, Heitzmann J. Ophthalmology 2000;107:89-94.
Photorefractive keratectomy to treat myopia and 36. Xu H, Liu S, Xia X, et al. Mitomycin C reduces haze
astigmatism after radial keratotomy and penetrating formation in rabbits after excimer laser photorefractive
keratoplasty. J Cataract Refract Surg 1995;21:268-73. keratectomy. J Refract Surg 2001;17:342-9.
25. Al-Rajhi AA, Risco JM, Badr IA, Teichmann KD. 37. Carones F, Vigo L, Scandola E, Vacchini L. Evaluation of
Photorefractive keratectomy after radial keratotomy. J
the prophylactic use of mitomycin-C to inhibit haze
Refract Surg 1996;12:801-5.
formation after photorefractive keratectomy. J Cataract
26. John ME, Martines E, Cvintal T. Photorefractive
Refract Surg 2002;28:2088-95.
keratectomy for residual myopia after radial keratotomy.
38. Gambato C, Ghirlando A, Moretto E, Busato F, Midena E.
J Cataract Refract Surg 1996;22:901-5.
Mitomycin C modulator of corneal wound healing after
27. Ribeiro JC, McDonald MB, Lemos MM, Salz JJ, Dello Russo
photorefractive keratectomy in highly myopic eyes.
JV, Aquavella JV, Swinger CA. Excimer laser
photorefractive keratectomy after radial keratotomy. J Ophthalmology 2005;112:208-18.
Refract Surg 1995;11:165-9. 39. Netto MV, Mohan RR, Ambrosio Jr R, Hutcheon AEK,
28. Burnstein Y, Hersh PS. Photorefractive keratectomy Zieske JD, Wilson SE. Wound healing in the Cornea. A
following radial keratotomy. J Refract Surg 1996;12:163- review of refractive surgery complications and new
70. prospects for therapy. Cornea 2005; 24:509-22.
29. Gimbel HV, Sun R, Chin PK, van Westenbrugge J. Excimer 40. Netto MV, Mohan RR, Sinha S, Sharma A, Gupta PC,
laser photorefractive keratectomy for residual myopia Wilson SE. Effect of prophylactic and therapeutic
after radial keratotomy. Can J Ophthalmol 1997;32:25- mitomycin C on corneal apoptosis, proliferation, haze
30. and long term keratocyte density. J Refract Surg 2006;
30. Probst LE, Macht JJ. Conservative photorefractive 22:562-74.
keratectomy for residual myopia following radial 41. Nassaralla BA, McLeod SD, Nassaralla Jr. JJ. Prophylactic
keratotomy. Can J Ophthalmol 1998;33:20-7. Mitomycin C to inhibit corneal haze after photorefractive
31. Lin JT. Scanning laser technology for refractive surgery. keratectomy for residual myopia following radial
In:Garg A, Pallikaris IG, Hoyos JE, Avalos-Urzua G Pinelli keratotomy. J Refract Surg 2007;23:226-32.
 CHAPTER

30 Recent Advances in
Photorefractive Keratectomy

C Banu Cosar (Turkey)

INTRODUCTION apoptosis occurs in keratocytes immediately after

PRK, when the activated migrating keratocytes from
Photorefractive keratectomy (PRK) was first
the remaining stroma produce increased amounts of
successfully applied in a normally sighted eye by Mc
disorganized collagen and cellular matrix, severely
Donald in 1988.1 The use of PRK as a mainstream
reducing corneal transparency. 3 It has been
refractive modality declined during the late 1990s
suggested, but not conclusively confirmed, that the
and early 21st century due to the dramatic increase in
development of postoperative corneal haze after PRK
laser in situ keratomileusis (LASIK). However, there
is associated with the removal of the epithelial
has been a resurgence of interest in the PRK
basement membrane. There are likely many factors
procedure, especially because of the increased
related to haze formation. These may include the
number of post-LASIK ectasia cases.2
depth of ablation, the smoothness of the stromal
In this chapter, recent advances in PRK such as
surface, and the time required for the closure of the
mitomycin C (MMC) and ascorbic acid use,
epithelial defect. The current generation of excimer
customized PRK (wavefront-guided, topography-
lasers are characterized by smoother ablation profiles
guided, and Q factor customized), PRK with solid
and reduced treatment times, which may be
state lasers and presbyopia treatment with PRK are
associated with reduced risk of haze formation3,4.
discussed.
Clinically insignificant corneal haze is present in most
PRK WITH MMC eyes that have PRK and may last for 1 to 2 years after
surgery. Clinically significant haze only occurs in a small
Haze after PRK percentage of eyes, usually less than 0.5 to 3%,
Haze is characterized by subepithelial fibrosis caused depending on the level of correction and other factors.4
by an abnormal wound healing response, confirmed Two types of haze are observed after PRK. The
by histologic studies that show epithelial hyperplasia, more common type of haze is the typical transitory
disruption of Bowman’s layer, presence of newly haze that is noted between 1 and 3 months after
formed type III disorganised collagen, vacuolization surgery. This type of haze is rarely associated with
of keratocytes and abnormal activation of fibrocytes. clinical symptoms and usually disappears within the
Although common, the definite etiology of corneal first year after the surgery. The other type of haze
haze remains obscure. It has been postulated that (late haze) is much less common and is usually noted
264 Mastering Advanced Surface Ablation Techniques
between 2 and 5 months after the procedure in an MMC 0.02% by placing a soaked 8.0 mm diameter
eye that has otherwise had a normal outcome after Merocell sponge over the ablated stroma for 2 minutes
surgery. Late haze may severely compromise vision is performed. The sponge is then removed and the
due to a marked decrease in transparency and corneal surface, conjunctiva, and fornices are
regression of the refractive correction. Late haze, vigorously irrigated with balanced salt solution (20
along with the refractive regression associated with cc) to dilute and remove residual MMC.
it, also resolves over time. Late haze usually persists
longer than the more common type of early haze and Mitomycin C Side Effects
in some cases may take more than 3 years to resolve. MMC use with surgical interventions other than PRK
Disappearance of haze is associated with resulted in some serious complications. Following
disappearance of myofibroblasts and remodeling of administration of MMC in pterygium surgery, vision-
disorganized stromal collagen.4 threatening complications such as secondary
glaucoma, corneal edema, corneal perforation, iritis,
Mitomycin C use as Prophylaxis and Treatment
photophobia, and, pain were reported.18 This is why,
for Haze
some surgeons have expressed concern that
Mitomycin C, a potent antiproliferative agent with mitomycin C added to the common decrease in flap
alkylating properties, inhibit the proliferation of keratocyte density could, in some cases, result in late
fibroblasts and keratocytes. Mitomycin C inhibits corneal melting or keratectasia.4
DNA synthesis, preferentially affecting rapidly In many studies of MMC use with PRK, no toxic
dividing cells, is fast-acting, and induces long-lasting or side effects were reported.5-16 However, Kymionis,
suppression of keratocyte activity after a single dose.3 et al reported a patient with dry eye after bilateral
Mitomycin C is used prophylactically with PRK PRK with mitomycin C treatment in one eye. Fifteen
to prevent haze. MMC is also effective for the months after surgery no improvement was noted in
treatment of haze after a previous PRK. In this that patient. 19 In another study with 1011 eyes
situation, the epithelium is debrided and MMC is undergoing PRK with MMC, delayed epithelial
applied without laser ablation.5,6 healing was noted in 2 eyes.20
For the prophylaxis of haze; MMC is used with: The effect of MMC with PRK on corneal
• Primary PRK endothelium was also investigated by various authors
• PRK enhancements after RK, PRK, and LASIK and no significant difference between the
• PRK after LASIK flap complications such as button
preoperative and postoperative endothelial cell
hole and irregular flaps
density by specular microscopy was found. 3,20,21
• PRK after corneal surgery such as penetrating
However, in one study of 18 eyes, the endothelial
keratoplasty.
cell loss was statistically significant at one month and
MMC with PRK could also be combined with
at three months after PRK with MMC.22
phototherapeutic keratectomy (PTK) after LASIK flap
complications such as buttonhole and epithelial in
ASCORBATE PROPHYLAXIS AFTER PRK
growth. In all instances, MMC use was reported to
lower haze rates.5-16 Azar and Jain suggested that After PRK, the ascorbic acid levels of the tear fluid
mitomycin C be applied with rings instead of disks, decreases significantly. Because ascorbic acid is the
considering the higher recurrence of haze in the major scavenger of superoxide radicals in tears, topical
periphery of the cornea.17 ascorbic acid therapy was hypothesized to help
eliminate the harmful effect of free radicals from
Surgical Technique of PRK with MMC
excimer laser surgery.23
The PRK procedure is performed as usual. Immediately Stojanovic, et al evaluated whether prophylactic
after laser treatment, a single topical application of systemic ascorbic acid influences the average level of
 Recent Advances in Photorefractive Keratectomy 265
haze and the incidence of late onset corneal haze after studies concluded that wavefront-supported PRK
photorefractive keratectomy (PRK). One week, 1, 3, appears to be safe and effective for the treatment of
6, and 12 months after surgery, the group myopia and astigmatism.13, 26-31
supplemented with oral ascorbate (201 eyes) showed
less haze than the group without ascorbate Comparison between Standard PRK and
supplementation (314 eyes).24 Wavefront-guided PRK
However, routine prophylactic use of ascorbate Wavefront guided PRK was compared to the standard
can be recommended only after a randomized, PRK by various authors. In one study, 28 eyes were
prospective clinical trial substantiates its efficacy. treated with wavefront-guided PRK and 28 eyes with
standard PRK using the same laser (Bausch & Lomb
WAVEFRONT-GUIDED PRK Technolas 217z). 32 In another study, wavefront-
guided PRK and conventional PRK on 30 eyes each
Wavefront sensors are instruments designed to
were performed with Asclepion Meditec flying spot
provide a quantitive analysis of the whole wavefront
MEL 70 excimer laser.33 Both of these studies found
reflected (or projected) light entering the eye and
that wavefront-guided PRK induced a smaller
reaching the retina. The clinical investigation of these
increase of postoperative wavefront-error compared
devices allowed a better understanding of the impact
to conventional PRK and concluded that wavefront-
that high order abrrations can have on visual
guided PRK is particularly indicated in eyes with
performance. Normal, virgin eyes usually have low,
higher preoperative RMS values.32,33
visually insignificant levels of high order aberrations.
Wavefront-guided PRK was also used to treat
Eyes after corneal surgery (refractive or therapeutic)
hyperopia. Nagy et al reported better results with
usually reveal an increase in high order aberrations7.
wavefront-guided PRK (WASCA) than those
Wang et al performed LASIK and PRK in 32 eyes
achieved with traditional PRK.34
with similar refractive powers. They found a 1.69
Comparison of wavefront-guided PRK with
fold increase in the PRK group and a 1.43 fold increase
wavefront-guided LASIK.
in the LASIK group in overall higher order
Panagopoulou and Pallikaris performed
aberrations. At 3 months, the mean RMS value for
wavefront-guided LASIK and wavefront-guided PRK
higher-order (3rd to 6th) were significantly increased
using Meditec MEL-70 G-scan excimer laser. They
compared with the corresponding preoperative
stated that WASCA PRK revealed better outcomes
values for both LASIK and PRK. The fourth order
than WASCA LASIK.35
aberrations, spherical like aberration, were dominant
by a 2.64 fold in PRK and a 2.31 fold in LASIK. TOPOGRAPHY-GUIDED PRK
Different influences of the PRK group and LASIK
group were shown in the various zernike components. Irregular corneal astigmatism has posed a challenge
Thus, PRK and LASIK both have their own features. to refractive surgeons for a long time. Ultimately,
The difference between the two types of surgery may technological advances have led to two promising
be correlated with the change of the corneal shape, customized approaches: wavefront measurements
the conversion of biodynamics, the healing of the and corneal topography.36
corneal cut, and re-structured corneal epithelium Topography-guided treatment has several
and/or the stroma.25 advantages over wavefront-guided treatment. First,
Several authors have performed wavefront- as it is based on the corneal surface, it is theoretically
guided PRK treatments in limited case series. possible to restore the natural aspheric shape of the
Wavefront guided PRK is used for primary treatments cornea. Second, by disregarding the aberrations that
as well as enhancements after previous refractive originate from the intraocular structures that change
surgery including RK, PRK, and LASIK. All these with age or accommodation, it concentrates on
266 Mastering Advanced Surface Ablation Techniques
correcting the non-physiological irregularities. Third,
it can be used in patients with corneal scars, where
media opacities are present, as its measurement is
based solely on the surface reflection. Fourth, it can
also be used in highly irregular corneas, which are
beyond the limits of wavefront measuring devices,
as the cornea contributes two thirds to the total
dioptric power of a normal eye. And finally,
topography maps are relatively easy and intuitive to
interpret, and most refractive surgeons are more
familiar with these maps than with wavefront maps.36
The major disadvantage of topography-guided
ablation comes from the same fact that it ignores the
rest of the intraocular structures, thus decreasing the
predictability of the refractive outcomes. The
topography alone can serve for calculating the best-
fit ideal anterior corneal contour to reduce the corneal
irregularities, but the newly achieved curvature may Figure 30.1: A conic section is the intersection of a plane with a cone.
By changing the angle and location of intersection, a circle, ellipse,
not be adequate for the particular eye, when the parabola, or hyperbola can be produced
remainder of the intraocular structures exert their
effect on refraction.36 fits the portion of cornea to be described. If we accept
In the literature, topography guided PRK was this approximation, the profile of a meridian can be
reported to provide successful results especially after defined with two values only:
previous refractive surgery (for enhancement, small • The apical radius (which is on the vertex of the
hyperopic and myopic excimer laser optical zones, conic), which can be expressed in terms of a circle
decentration), for corneal scars (injury, with the same degree of curvature,
postinfectious), and after keratoplasty.37-44 • A shape factor, which represents the variation in
curvature from the apex towards the periphery, which
Q FACTOR CUSTOMIZED PRK defines the degree of asphericity. This last parameter
The expression “aspheric surface” simply means a can be defined in a number of different ways. Four
surface that is not spherical. However, this expression different coefficients are used to express the shape
is commonly used to indicate the surfaces that can be factor of a conic, each one of which is used in a
described by the equation of a conic. In geometry, different way to quantify the same thing: the conic
the conic curves have been given this name because parameter p, the shape factor E, the eccentricity e,
they are generated by the section of a cone with a and the coefficient of asphericity Q. If one of these
plane more or less tilted with respect to the base, indices is known, the others can be calculated using
and these include the circle, ellipse, parabola, and the conversion formulas in Table 30.1.45
hyperbola (Figure 30.1). Each of these curves, if Table 30.1: Formulas of conversion between various shape
rotated on its axis of symmetry, creates a sphere, an factors of a conic section

ellipsoid, a paraboloid, and a hyperboloid, p Q e e2

respectively. These solid figures are called conicoids.45 p= – 1-Q 1– e2 1–e2
The typical corneal section is a prolate ellipse, Q= p-1 – – e2 –e2
consisting of a more curved central part, the apex, e= Ö1–p Ö–Q – Ö e2
with a progressive flattening towards the periphery. e2 = 1–p –Q e2 –
The asphericity of the cornea usually is defined by p = conic parameter, Q = asphericity, e = eccentricity, e2 = index
determining the asphericity of the conicoid that best of asphericity
 Recent Advances in Photorefractive Keratectomy 267
Table 30.2 summarizes the various types of conic higher attempted corrections. A higher percentage
sections with the corresponding values of the different of patients with better low-contrast uncorrected
shape factors.45 visual acuity and best corrected visual acuity was
Table 30.2: Different types of conical section with the observed in the aspheric PRK group than in the
coresponding values of the various coefficients of asphericity conventional PRK group.
p Q e e2 They concluded that aspheric profile PRK might
Hyperbola <0 <-1 >1 >1 induce a smaller increment of total wavefront error,
Parabola 0 -1 1 1 related to a smaller increase in spherical aberration,
Prolate ellipse 0<p<1 -1<Q<0 0<e<1 0< e2 <1
Circle 1 0 0 0 and better maintain the physiology of the corneal
Oblate ellipse >1 >0 <0 <0 surface than conventional treatment.47
Average normal cornea 0.78 -0.22 0.45 0.22
p = conic parameter, Q = asphericity, e = eccentricity, e2 = index PRK IN THE TREATMENT OF PRESBYOPIA
of asphericity
Presbyopia is loss of accommodation by age. There
Myopic PRK changes asphericity, increasing Q to are various treatment options for presbyopia
an oblate value. 46 The effect of reduction in the including spectacles, contact lenses (monovision or
spherical aberration due to flattening is generally not bifocal lenses) and refractive surgery. Surgical options
sufficient to compensate for the increase in spherical for the treatment of presbyopia are still questionable
aberration due to the substantial variation in shape in terms of safety and/or efficacy. Refractive surgery
obtained with the majority of the current ablation procedures for the treatment of presbyopia steepen
profiles.The opposite occurs with hyperopic cornea by means of excimer laser, the holmium:YAG
treatments, as the current ablation profiles produce laser, or radiofrequency energy. Procedures that
a hyperprolate cornea. This variation in shape expand or relax the sclera, intracorneal implants,
produces a negative spherical aberration,which multifocal and accommodative intraocular lenses are
usually is not compensated by the increase in positive also used.48-51
from the increased curvature.45 PRK has been used in the treatment of presbyopia
Mastropaque et al performed a 6-month by inducing monovision. Wright et al treated 21
controlled trial to to analyze ocular wavefront error myopic presbyopic patients with PRK. They induced
and corneal asphericity (Q) in patients treated with monovision by undercorrecting the nondominant eye
aspheric profile photorefractive keratectomy (PRK) by 1.25 diopters for near vision and correcting the
compared with patients having conventional PRK to dominant eye with emmetropia for distance vision.
correct myopia and myopic astigmatism. In this study, Sixteen emmetropic patients who had PRK served as
50 eyes were treated with aspheric profile PRK using a control group. Monovision PRK patients had better
the MEL 80 flying-spot excimer laser, and 24 eyes near vision than control PRK patients, with minimal
were treated with standard PRK using the MEL 70 compromise in stereo acuity and overall high patient
flying-spot excimer laser. Postoperative wavefront satisfaction.52
error increased in both groups. Six months after Apart from conventional monovision (dominant
surgery, there was a smaller increase in root mean eye corrected for distance), crossed monovision
square (RMS) of total higher-order aberrations and (dominant eye corrected for near) was also evaluated
spherical aberration (59% and 106%, respectively) in by Azar et al, and reported to result in satisfactory
visual outcomes.53
the aspheric profile PRK group than in the
conventional PRK group (94% and 136%,
PRK WITH SOLID STATE LASERS
respectively). The aspheric profile PRK group showed
more prolate corneal asphericities than the During the past 10 years, solid state lasers have
conventional group with increasing oblateness for improved to become a reliable source for treating
268 Mastering Advanced Surface Ablation Techniques
organic and inorganic tissue materials. The advantage 8. Bedei A, Marabotti A, Giannecchini I, Ferretti C,
Montagnani M, Martinucci C, Barabesi L. Photorefractive
of solid-state lasers over excimer lasers is a
keratectomy in high myopic defects with or without
considerable reduction of problems associated with intraoperative mtomycin C: 1-year results. Eur J
excimer lasers, permitting a high pulse to stability, Ophthalmol 2006;16(2):229-34.
smaller spot size, and higher repetition rate. Due to 9. Gambato C, Ghirlando A, Moretto E, Busato F, Midena E.
Mitomycin C modulation of corneal wound healing after
absence of gas, solid-state laser maintenance costs photorefractive keratectomy in highly myopic eyes.
are lower and noise level during operation is Ophthalmology 2005;112(2):208-18.
significantly less.54 10. Solomon R, Donnenfeld ED, Thimons J, Stein J, Perry
HD. Hyperopic photorefractive keratectomy with
Recently, Tsiklis et al and Roszkowska et al
adjunctive topical mitomycin C for refractive error after
reported one year results of PRK for myopia using a penetrating keratoplasty for keratoconus. Eye Contact
213 nm wavelength solid-state laser (CustomVis and Lens 2004;30(3):156-8.
LaserSoft, respectively). They both concluded that 11. Hashemi H, Taheri SM, Fotouhi A, Kheiltash A. Evaluation
of the prophylactic use of mitomycin C to inhibit haze
PRK with solid state lasers is safe and effective.54, 55 formation after photorefractive keratectomy in high
Also, Anderson et al reported solid-state, myopia: a prospective clinical study. BMC Ophthalmol
neodymium:YAG laser PRK in 3 patients with 2004;14:4-12.
12. Solomon R, Donnenfeld ED, Perry HD. Photorefractive
irregular astigmatism (CustomVis). The laser’s
keratectomy with mitomycin C for the management of a
combination of a small spot, a fast pulse rate, and LASIK flap complication following a penetrating
ultrafast tracking/scanning resulted in good results keratoplasty. Cornea 2004;23(4):403-5.
in those 3 patients with irregular astigmatism.56 13. Chalita MR, Roth AS, Krueger RR. Wavefront-guided
surface ablation with prophylactic use of mitomycin after
Yet, long term results with larger samples are a buttonhole laser in situ keratomileusis flap. J Refract
necessary to establish the safety and efficacy of PRK Surg 2004;20(2):176-81.
with solid state lasers. 14. Weisenthal RW, Salz J, Sugar A, Mandelberg A, Furlong
M, Bagan S, Kandleman S. Photorefractive keratectomy
for treatment of flap complications in laser in situ
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 CHAPTER Clinical Comparisons Regarding

31 Surface Ablation between H EYE

TECH B and L and MEL 80 Zeiss
Excimer Laser

Bojan Pajic, Hermann Anhalm, Jörg Müller (Switzerland)

AIM

The Aim of the study is to compare two different

excimer laser, it is said of H.EYE.TECH B and L and
MEL 80 Zeiss, regarding clinical outcome performing
surface ablation.

PATIENTS AND METHODS

Exclusion criteria were age below 23 years, collagenosis,

dry eye, herpes keratitis, corneal dystrophies as
keratoconus, preceding surgery, glaucoma, amotio
retinae, macula degenerations, diabetes mellitus. During
6 months of follow-up, prospective 111 eyes were treated Figure 31.1: H EYE TECH B and L
with H EYE TECH B and L excimerlaser (group 1)
(Figure 31.1) and 105 with the MEL 80 (group 2) (Figure
31.2) at treatment zones of up to 7 mm according to the
patient’s mesopic pupil size. The mean patient age was
36 years (range 23-62 years) in group 1 and 32 years
(range 23- 59 years) in group 2. Enrolled patients fulfilled
the general criteria for undergoing laser vision
correction: stable refraction, no ocular disease, and no
previous refractive surgery or systemic disease likely
to affect the epithelial healing. Furthermore, enrolled
patients had either anatomic limitations to undergoing
LASIK surgery or expressed a preference to undergo a
surface ablation procedure for the correction of their
refractive error. All enrolled patients confirmed that
they would be available for follow-up for at least 6
months after the surgery. Figure 31.2: MEL 80 Zeiss
272 Mastering Advanced Surface Ablation Techniques
The preoperative examination included manifest (SD) with an astigmatism of –0.74D ± 0.77(SD) in
and cycloplegic refraction, corneal video- group 1 and –3.48 D ± 2.08 (SD) with an astigmatism
keratography, biomicroscopy, scotopic pupil size of –0.66 D ± 0.63 (SD) in group 2.
measurement, applanation tonometry, and dilated
funduscopy. Uncorrected visual acuity (UCVA) and SURGERY PROCEDURE LASEK
best spectacle-corrected visual acuity (BSCVA) were
measured. All the operations were performed by one After topical anesthesia and lid speculum application,
surgeon at the Department of Refractive and Cornea a semi sharp circular well is used to administrate 20%
surgery, Vedis, Klinik Pallas, Switzerland. In the alcohol is used for 25 to 35 seconds on corneal surface.
current series, Focus Night and Day bandage contact Prior to alcohol exposure, positioning marks were
lenses (CIBA Vision Ophthalmics, Embrach, used to mark the corneal surface. The margins of the
Switzerland) were used. Postoperative medication delineated area were freed using a hockey knife and
included Ketorolac-Trometamol 4 times daily (Acular, leaving up to three clock-hours of intact margins for
Allergan Ophthalmics) for 7 days and combined eye hinge. The loosened epithelium was then peeled back
drops of tobramycin-dexamethasone 4 times daily using a Merocel sponge. After standard laser ablation,
(Tobradex, Alcon Laboratories Inc., Fort Worth, TX) the epithelial sheet was gently repositioned using
until the completion of corneal surface re- intermittent irrigation. The epithelium was carefully
epithelization. Prescribed artificial tears (Vislube, realigned using the preplaced positioning marks and
Chemedica SA) were prescribed to be used at the allowed to dry for three to five minutes. A combined
patient’s discretion. The patients were informed about eye drops of tobramycin-dexamethasone (Tobradex,
the investigative character of the procedure and the Alcon Laboratories Inc., Fort Worth, TX) was applied,
alternative surgical methods for the correction of followed by placing a bandage contact lens to reduce
their refractive error and signed a consent form. the mechanical friction by the eyelid and to reduce
Patients were followed up daily until the epithelial postoperative pain.
healing was complete and the therapeutic lens was
removed. Examination during the early postoperative DATA ANALYSIS
period included recording of UCVA and Statistical analysis was performed using SPSS 14.0
biomicroscopy. After the removal of the bandage software. Paired-samples t tests, independent samples
contact lens, patients were followed up at 1-, 3-, and t tests, and Chi-squares were applied. A P-value of
6-month postoperative intervals. Examination less than 0.05 was considered statistically significant.
included manifest refraction, biomicroscopy,
applanation tonometry videokeratography, and
RESULTS
contrast sensitivity testing. Subepithelial haze was
graded according to a predetermined as follows: 0, After 6 months the spherical equivalent (SE) were in
clear cornea; 1, trace haze; 2, mild haze; 3, moderate myopic eyes –0.05D ± 0.27 (SD) with an astigmatism
haze; and 4, marked haze. Data were collected on of –0.02D ± 0.12(SD) in group 1 and –0.13D ± 0.35 (SD)
standardized case report forms and then entered into with an astigmatism of –0.20D ± 0.27 (SD) in group 2.
a central database for analysis. The uncorrected visual acuity (UCVA) were
The effectivity of both lasers were investigated postoperative in group 1 after 1 months for 85%, after
measuring pre- and postoperative refraction, best 3 months for 94% and after 6 months for 100% better
corrected visual acuity pre (preBSCVA) and or equal 0.8 (Figure 31.3), for 96% better or equal
uncorrected visual acuity postoperative after 1.0. The uncorrected visual acuity (UCVA) were
refractive surgery (postUCVA), complication and postoperative in group 2 after 1 months for 81%, after
clinical outcome. The mean preoperative spherical 3 months for 93% and after 6 months for 87% better
equivalent (SE) were in myopic eyes –2.23D ± 1.10 or equal 0.8, for 87% better or equal 1.0. (Figure 31.4).
 Clinical Comparisons Regarding Surface Ablation between H EYE TECH B and L 273

Figure 31.3: H EYE TECH B and L: UCVA – percentage efficacy

Figure 31.4: MEL 80 Zeiss: UCVA – percentage efficacy

In group 1, 94% after 1 months, 97% after 3 months After 6 months in group 1, 33% gained one line of
and 100% after 6 months of refractive outcome were visual acuity and 67% were unchanged (Figure 31.7).
within +/- 0.50D from the target refraction After 6 months in group 2, 100% were unchanged
(Figure 31.5). In group 2, 80% after 1 months, 60% regarding visual acuity (Figure 31.8).
In group 1 haze was seen in 6 eyes, 4 eyes with
after 3 months and 100% after 6 months of refractive
stage 1 and 2 eyes with stage 2, and 4 eyes in group
outcome were within +/- 0.50 D attempted from the 2, 2 eyes with stage 1 and 2 eyes with stage 2, what is
target refraction (Figure 31.6). not significant with p > 0.05.
274 Mastering Advanced Surface Ablation Techniques

Figure 31.5: H EYE TECH B and L: Refractive outcome within percentage attempted

Figure 31.6: MEL 80 Zeiss: Refractive outcome within percentage attempted

 Clinical Comparisons Regarding Surface Ablation between H EYE TECH B and L 275

Figure 31.7: H EYE TECH B and L: Change in BSCVA and percentage Safety

Figure 31.8: MEL 80 Zeiss: Change in BSCVA and percentage Safety

The mean (±SD) time of epithelial healing was 4.1 Regarding the normograms following regression
±0.76 days (range, 3-6 days) in group 1 and 4.14 ±0.79 formulas could be calculateted:
days (range, 3-6 days) in group 2. The epithelial healing For H.EYE.TECH B and L:
was complete after 6 days for all cases postoperatively. spherical correction attempted – laser setting:
Bandage contact lenses were removed on the third day. y = 0.79x + 0.34 R2 = 0.47
276 Mastering Advanced Surface Ablation Techniques
astigmatism correction attempted – laser setting: and less than 0.6 dpt of undercorrection for the MEL
y = 1.08x + 0.06 R2 = 0.84 80 Zeiss. For attempted correction up to –4 D the
For MEL 80 Zeiss: undercorrection increases up to 0.63 D for
spherical correction attempted – laser setting: H.EYE.TECH B and L whereas the undercorrection
y = 0.78x + 0.79 R2 = 0.85 decreases up to 0.12 D for MEL 80 Zeiss. The
astigmatism correction attempted – laser setting: normograms should have to be evaluated for each
y = 0.91x + 0.10 R2 = 0.69 surgery room and for each surgeon for ever for the
(Tables 31.1 and 31.2) MEL 80 Zeiss excimer because of a non-linear-
normogram.
Table 31.1: Normogram for spherical correction attempted – laser
setting
DISCUSSION
H EYE TECH B and L MEL 80 Zeiss
spherical correction spherical correction Both used excimer lasers have a Scanning-Spot and
Attempted Laser Setting Laser Setting active eye-tracker systems. B and L’s H EYE TECH
dpt dpt dpt
have further more a dynamic rotational eye-tracker
–1.5 –1.47 –0.91 system. The spot diameter is in the H EYE TECH B
–1.75 –1.78 –1.23
–2 –2.1 –1.55 and L 1 respectively 2 mm applicated with a
–2.25 –2.42 –1.87 “truncated” Gaussian beam profile, in the MEL 80
–2.5 –2.73 –2.19 Zeiss excimer laser 0.7 mm with a overlapping spot
–2.75 –3.05 –2.51
–3 –3.37 –2.83
Gaussian beam profile. Seiler et al. postulated that
–3.25 –3.68 –3.15 an ideal customization can best be created with a
–3.5 –4 –3.47 Gaussian beam with optimized spot overlap and a
–3.75 –4.32 –3.79
scanning laser with a spot size smaller than 1mm
–4 –4.63 –4.12
–4.25 –4.95 –4.44 diameter. Also eye tracking becomes more critical
–4.5 –5.27 –4.76 for the smaller laser spots, also in order to adequately
–4.75 –5.58 –5.08 follow and track saccadic eye movement inclusive
–5 –5.9 –5.4
cyclorotation during laser vision correction, a very
fast sampling rate tracker (>200Hz) is required 1.
Table 31.2: Normogram for astigmatism correction attempted – laser
setting Philippe Dumarey has seen with the Mel 80 a frequent
H EYE TECH B and L MEL 80 Zeiss decentrations and overcorrections cause by small
astigmatism correction astigmatism correction spot, higher speed and by not sufficient eyetracker
Attempted Laser Setting Laser Setting system. Reduction of spot diameter was shown to
dpt dpt dpt make the correction more susceptible to eye
–0.25 –0.29 –0.16 movement induced error. A smaller spot size is only
–0.5 –0.52 –0.44
–0.75 –0.75 –0.71 beneficial when eye movement is neutralized with a
–1 –0.98 –0.99 tracking system with a latency <5 ms.2 Regarding B
–1.25 –1.21 –1.26 and L’s H EYE TECH excimer laser there will be an
–1.5 –1.44 –1.54
optimization of the ablation depth for the Zyoptix
–1.75 –1.68 –1.81
–2 –1.91 –2.09 TissueSaving algorithm in the future and is mainly a
–2.25 –2.14 –2.36 result of use of the 2 mm und 1 mm truncated
–2.5 –2.37 –2.64 Gaussian laser beam profile. A tissue save of 20%
–2.75 –2.6 –2.91
–3 –2.83 –3.19 compared with the PlanoScan algorithm is seen.
Zyoptix TissueSaving is a reliable algorithm for LASIK
Up to –2.5 D of correction there are less than 0.25 D with only 14 μm measured ablation depth per diopter
of undercorrection for the H EYE TECH B and L by full corrected optical zone of 6.5 mm3.
 Clinical Comparisons Regarding Surface Ablation between H EYE TECH B and L 277
There is not a significant difference regarding H EYE TECH excimer laser and MEL 80 excimer
clinical outcome between groups for surface laser are both safe excimer lasers for surface ablations.
treatment. With Zyoptix TissueSaving algorithm of H EYE
For the H EYE TECH excimer laser the TECH excimer laser we will have in the future
normograms are perfect up to –2.5 D of LASEK possibilities to save more corneal tissue for having a
treatment. For higher correction a linear good higher stability. The MEL 80 excimer laser is very
calculated undercorrection can be seen. For the MEL fast and easy to use.
80 excimer laser it is especially that undercorrection
are seen for treatment below –2.5 D over –4 D. The ACKNOWLEDGMENTS
normogram in between is perfect. Thus it is very
I thank for distinct support of Dr Gerhard Youssefi,
difficult to create a clinical use treatment normogram,
Anton Hilger (Technolas) for personal and technical
because it is not linear. Also Dr Dan Rheinstein has
advice.
developed a complex, non-linear-normogram for the
MEL 80. REFERENCES
Several reports have investigated the safety,
efficacy, predictability, and stability of LASEK. Azar 1. Seiler T, Dastjerdi MH. Customize corneal ablation. Curr
Opin Ophthalmol 2002;13:256-60.
and associates found that all patients had an UCVA 2. Bueeler M, Mrochen M. Simulation of Eye-tracker Latency,
of 0.5 or better at one week, where 64% had 0.8 or Spot Size, and Ablation Pulse Depth on the Correction of
better. At one months, 92% of eyes examined had Higher Order Wavefront Aberrations With Scanning Spot
UCVA of 0.8 or better4. Taneri et al. reported that Laser System. J Refract Surg. 2005;21:28-36.
3. Neuhann Th, Bauer M, Lege B, Hassel J, Hilger A.
approximately 95% of the eyes were ±1.0 D of Comparison of the Bausch and Lomb LASIK Treatment
emmetropia after four weeks. At one year not loss Algorithms Zyoptix TissueSaving vs. PlanoScan in terms
of BSCV was present.5 Partal et al. Found that 66% of calculated and measured ablation depth. Presented at
ESCRS, London 2006.
and 98% of the eyes had postoperative UCVA of 1.0
4. Azar DT, Ang RT, Lee BJ, et al. Laser subepithelial
or better and 0.5 or better, respectively.6 Claringbold keratomileusis : electron microscopy and visual outcomes
found that the UCVA was 0.5 or better in 83.8% of of flap photorefractive keratectomy. Curr Opin
eyes at day 4. At two weeks, all eyes were completely Ophthalmol 2001;12:323-8.
5. Taneri S, Feit R, Azar DT. Safety, efficacy and stability
epithelialized, and the UCVA was 0.5 or better in indices of LASEK correction in moderate myopia and
91.8% of the eyes.7 In a large series, Anderson et al. astigmatism. J Cataract Refract Surg 2004;30:2130-7.
found that patients with a preoperative SE between 6. Partal AE Rojas MC, Manche EE. Analysis of the efficacy,
0 and 6.0D had better UCVA at three months than predictability,and safety of LASEK for myopia and
myopic astigmatism using the Technolase 217 excimer
those with a preoperative SE between 6.1 and 12.0 D. laser. J Cataract Refract Surg 2004;30:2138-44.
Clinically significant haze was observed in 1.6% of 7. Claringbold TV II. Laser-assisted subepithelial
eyes.8 keratectomy for the correction of myopia. J Cataract
Refract Surg 2002;28:18-22.
In our study in both groups, the clinical outcome
8. Anderson NJ, Beran RF, Schneider TL. Epi-LASIK for the
is similar to those with the literature using a LASEK correction of myopia and myopic astigmatism. J Cataract
surface surgery technique. Refract Surg 2002;28:1343-7.
278 Mastering Advanced Surface Ablation Techniques

CHAPTER

32 PRK—Past,
Present and Future

Srinivas K Rao (India), Dennis SC Lam (China)

ADVANCED SURFACE ABLATION reshaping. Working with submicroscopic precision, the

193 nm laser photons break the intermolecular bonds
Advanced surface ablation is a term used to describe
in corneal tissue, liberating fragments of the molecules
alternative surgical approaches for photorefractive which speed from the corneal surface at supersonic
procedures that do not preserve the Bowman’s layer, velocities. The athermal nature of this process, termed
but may have a beneficial effect on corneal wound “photoablative decomposition” allows precise
healing compared with conventional photorefractive contoring of the corneal shape, and the use of
keratectomy (PRK). The evolution of these Munnerlyn’s formula is the basis for the current
procedures in corneal refractive surgery, key algorithms for myopic excimer refractive ablations.
principles, surgical technique, an outcomes, are The corneal recontoring that is achieved prompted
outlined in this chapter. great enthusiasm about the ability of this ‘magical’
Although radial keratotomy was effective in process to correct all degrees of myopia – from the
treating myopic refractive errors of the eye, the need low to the extreme and performing the procedure of
to make multiple, long, nearly full-thickness incisions photorefractive keratectomy (PRK) for 20 or more
in the cornea, subsequent weakening, possibility of diopters of myopia was the accepted norm in the initial
surgical complications and the need for technical skill, days of excimer surgery.
slowed the further development of the procedure. The initial use of the excimer laser for refractive
The destabilization of the cornea with a continued surgery required the removal of the corneal
hyperopic shift in refraction, and the need for epithelium using a variety of techniques, thereby
multiple, complicated incisions to correct hyperopia exposing the Bowman’s layer. This layer and the
or co-existing astigmatism — with further underlying stroma were then ablated using the laser
destabilization of the corneal structure resulted in a to achieve the desired refractive correction. Despite
waning enthusiasm for the procedure. With the previous experience that indicated that damage to
advent of the ultraviolet excimer laser, radial the Bowman’s layer by other conditions resulted in
keratotomy is no longer a popular procedure for the corneal healing by scarring, this was not a common
treatment of refractive errors. occurrence after photorefractive keratectomy (PRK),
Introduced to corneal use by Trokel and Srinivasan1 especially when performed for low to moderate
in 1983, the excimer laser has rapidly gained myopia (<6D). Classifications were evolved also to
precedence as the procedure of choice for corneal indicate that patients were ‘slow’, ‘normal’, or
 PRK — Past, Present and Future 279
‘aggressive’ healers2 to account for the variable haze (grade 3 and 4). Similar experiences were noted
occurrence of this complication. The effects of ablation by other surgeons as well.
zone size and depth, postoperative use of steroids This led to a search for a better procedure, which
and cold irrigating solutions were explored as a means culminated when the precision of excimer laser
of reducing the incidence of this complication. ablation was married with the mechanical keratomes
An event that received much attention in the post- that were first manual, then semi-automated, and then
PRK healing process was the formation of a peculiar fully automated. This procedure termed laser in situ
electron-dense membrane on the ablated stromal keratomileusis (LASIK) was met with even greater
surface that serves as a basement membrane for the enthusiasm than PRK – from both patients and
regenerating epithelium. Once the epithelium has surgeons. It allowed nearly painless, incredibly rapid
migrated to cover the defect in the ablation bed, the restoration of vision, since the epithelium was
basal layer is then able to reconstitute the basement undisturbed and did not have to regenerate and
membrane and adhesion complexes and there is no recover, as in PRK. Since there was segregation of
recurrent corneal erosion syndrome that is sometimes the interface from the epithelium, a very gentle healing
seen when accidental trauma causes a corneal process was noted. This meant that two of the great
epithelial defect. Hence, the PRK procedure seemed disadvantages of PRK were overcome – regression
to be the answer to the surgical treatment of and haze formation. Thus, LASIK continued to gain
refractive errors. popularity and soon replaced PRK in many treatment
However, with increasing experience, surgeons centers, much as phacoemulsification overcame
quickly realized that PRK for the treatment of higher conventional extracapsular cataract extraction.
degrees of refractive errors often resulted in corneal These differences in corneal wound healing with
haze formation with poor visual function and quality. PRK and LASIK quickly translated into important
Our clinical experience with PRK clearly demonstrated differences in clinical outcomes. In a study comparing
this loss of efficacy of the procedure in eyes which the efficacy of the two procedures in low myopia (–2
received higher amounts of myopic correction.3 We to –5.5 diopters),4 fifty-two eyes of 26 myopic patients
noted this with the broad beam Summit Omnimed received PRK on one eye (PRK eye) and LASIK on
200 excimer laser, in a study performed between the other (LASIK eye) in a randomized manner. At 1
November 1993 and August 1994. PRK was performed year, 24 patients (92.3%) were examined, when the
in 139 eyes of 127 patients (mean age 26.9 ± 6.21 years, mean spherical equivalent refraction was -0.08 ± 0.38
range, 19 to 52 years) followed for a mean period of diopter in the PRK eyes and -0.14 ± 0.31 diopter in
11.7 ± 3.63 months (range, 6 to 22 months), in whom the LASIK eyes, and the uncorrected visual acuity
the mean preoperative myopia was –8.23 ± 3.32 was 20/20 or better in 15 PRK eyes (62.5%) and 19
diopters (D) (–2.63 to –19.50 D). Of these eyes, 101 LASIK eyes (79.2%); no eye lost 2 or more Snellen
(72.7%) had a preoperative myopia greater than lines of spectacle-corrected visual acuity. Both
–6.00 D; and 32 (23.0%) had a preoperative myopia procedures were stable throughout the first year. One
greater than –10.00 D. At last follow-up, 73 (52.5%) PRK eye developed dense subepithelial corneal haze.
eyes were within ±1.00 D of emmetropia, 92 (66.2%) Nineteen patients (79.2%) preferred the LASIK
eyes had an uncorrected visual acuity of ≥ 6/12, and procedure because of the fast, painless recovery. In
12 (8.6%) eyes lost 2 or more lines of spectacle this study, PRK and LASIK were found to be similarly
corrected visual acuity. Severe corneal haze (grade 3 effective, predictable, stable, and reasonably safe for
to 4) was seen in 20 (14.4%) eyes at last follow-up. the correction of myopia between –2.00 and –5.50 D.
Statistical analysis revealed that the only risk factor However, patients preferred LASIK because of the
independently associated with regression ≥ 2.00 D advantages of earlier visual recovery and the reduced
following PRK was the occurrence of severe corneal pain after the procedure.
280 Mastering Advanced Surface Ablation Techniques
A similar study was performed in patients with refraction, the authors concluded that LASIK is a
moderate myopia.5 The authors performed LASIK better method for correction of high myopia, based
and PRK in fellow eyes of thirty-three patients with on analysis of postoperative complications and loss
a manifest refraction of –2.50 to –8.00 D, in a of the preoperative best-spectacle corrected acuity.
randomized manner. Follow-up was 90% at 1 and 2 Since LASIK gained in popularity soon after its
years. At baseline, mean (+/–standard deviation) introduction, the majority of surgeons and patients
spherical equivalent manifest refraction was –4.80 ± preferred LASIK resulting in the replacement of PRK
1.60 D in LASIK-treated eyes and –4.70 ± 1.50 D in as the procedure of choice. Given this overwhelming
PRK-treated eyes. At 1 day after surgery, 81% of predominance of LASIK in the past 17 years since its
patients (21 eyes) reported no pain in the LASIK- inception, comparative studies of PRK and LASIK in
treated eye, whereas no patient (0%) reported being the recent past have not been performed. Hence,
pain-free in the PRK-treated eye. At 3 to 4 days after many of the studies in literature with this data are
surgery, 18 (80%) LASIK-treated eyes either from investigators using the earlier generation broad-
improved or remained within 1 line of baseline beam lasers. Although data from studies using
spectacle-corrected visual acuity; only 10 (45%) PRK- current generation lasers, comparing the outcomes
treated eyes achieved this result. At 2 years after of PRK and LASIK is lacking, the differential healing
surgery, 18 (61%) LASIK and 10 (36%) PRK-treated patterns in the two procedures make it very likely
eyes achieved an uncorrected visual acuity of 20/20 that the improved outcomes noted after LASIK in
or better, with no statistically significant difference higher refractive errors are likely to persist.
in refractive outcome between the two techniques. Currently, consensus among surgeons indicates that
Quantitative videokeratography showed more PRK is likely to result in excellent outcomes when
regularity after LASIK. Complications were similar myopia less than 4 D is treated and is likely to result
in the two groups. Patients preferred LASIK by a in good outcomes when errors between 4 and 6 D
margin of 2 to 1 at 1 year but showed no preference are treated. In higher errors, the risks of regression
at 2 years. Using a 6 mm diameter single-pass, large and corneal haze increase, resulting in an increase in
area ablation and an automated microkeratome to the risk-benefit ratio.
treat myopia of –2.50 to –8.00 D with 1.00 D or less As with many surgical procedures however, these
astigmatism in 1994, the authors used LASIK to advantages come at a cost. Ironically, the corneal flap
produce a higher percentage of eyes with an which provided most of the advantages was also the
uncorrected visual acuity of 20/20 or better, more weak link of the procedure. The act of slicing the
regular postoperative corneal topography, less cornea results in a significant destabilization of the
postoperative pain, and more rapid recovery of structural integrity,7 resulting in the occurrence of a
baseline spectacle-corrected visual acuity than PRK. new problem – iatrogenic corneal ectasia, with the
Both LASIK and PRK achieved successful correction corneal shape changing over time to resemble that of
of low-to-moderate myopia at 1 and 2 years after an eye with keratoconus. However, the worrying
surgery. Thus, in this group of myopes, a difference element with this complication is that seemingly
in outcomes was seen as the amount of treated normal eyes have also developed this problem after
myopia increased. LASIK – in these eyes, an arbitrary limit of safety
In another study, the authors compared patients has been proposed – retaining 250 microns of corneal
receiving PRK (15 eyes) and LASIK (33 eyes) for the tissue in the stromal bed. Using these ‘rules’ however
treatment of extreme myopia (over -9.25 D).6 One limits the extent of myopic correction that can be
year after surgery, a refractive outcome within ± 1.0 safely performed, since the importance of having an
D was noted in 47% of the PRK group and 54% of the ablation zone that matches the mesopic pupil size is
LASIK group. Despite the similar outcomes in also now considered important, and most surgeons
 PRK — Past, Present and Future 281
consider the use of a 6 mm ablation zone the minimum regenerative process by the production of cytokines.
acceptable. This cross talk between the regenerating epithelium
We recently reported a patient who had refractive and the stromal keratocytes is believed to be
surgery using LASIK in one eye and PRK in the fellow responsible for keratocye apoptosis, myofibroblast
eye, for equivalent myopia, and developed ectasia in transformation, and an increase in the keratocytes
the LASIK, but not PRK eye.8 Apart from these populations in the anterior stroma. By retaining a
structural concerns, with the recent advances in the flap of epithelium in LASEK, it is believed that this
surgical approach to LASIK, increasing attention is wound healing process can be modulated to result in
focused on the correct of wavefront aberrations of better clinical outcomes.
the eye to try and ensure that the aberrations are Alcohol application is performed using a well to
either corrected or at least minimized. Since these hold the alcohol on the central corneal surface and
alterations of the corneal surface are in the order of prevent it from running over the rest of the ocular
microns, concerns have been expressed that ‘draping’ surface. While some surgeons apply the well directly,
a thick corneal flap over the ablated surface may other use a semi-sharp trephine to first incise the
minimize the effectiveness of these fine changes. epithelium along four-fifths of its circumference, which
Given these important concerns, there is now a trend allows the uncut portion to serve as a hinge. If this
towards performing a procedure that permits the step is performed, then it is best done before the alcohol
advantages of LASIK – decreased corneal healing application. The well for alcohol application is placed
response with better refractive predictability and firmly on the corneal surface to control the eye and
reduced scarring, but which retains the integrity of also to ensure that the fluid does not trickle onto the
the corneal architecture better – as in PRK, allowing rest of the ocular surface. It is usually centered on the
subtle changes etched on the corneal surface to pupil and is of a size that is about 1 to 2 mm larger
produce the desired effect. than the intended ablation zone diameter.
A procedure that attempts to fulfill the above The alcohol is then applied into the well – freshly
requirements – retaining the best of both PRK and prepared solutions of 96 to 99% pure alcohol diluted
LASIK, has been termed laser subepithelial to 18 to 20% are used. Exposure times longer than 40
keratomileusis (LASEK) and was introduced in 1996 to 45 seconds have been shown to result in loss of
by Azar, 9 although it was later popularized by viability of the majority of the epithelial cells in the
Camellin,10 who also coined the descriptive term flap. Restricting the exposure time to 40 seconds
mentioned earlier. Briefly, the procedure involves would preserve at least 50% of the cells, with shorter
the use of diluted alcohol to loosen the epithelial times resulting in greater preservation. After the time
attachments to the underlying corneal stroma, is counted down, the alcohol is quickly removed from
enabling its removal as a hinged sheet. The laser the well either by absorbing it with weck cell sponges,
ablation is performed on the exposed stroma and the or by using suction through the hollow handle used
epithelial sheet is then replaced, as in the case of a to hold the well in place. In the event of difficulty in
LASIK flap. Studies have indicated that the stromal raising the epithelial flap after the first application of
epithelial interactions responsible for haze following alcohol, surgeons usually try a second application of
PRK are influenced by both temporal and spatial alcohol for 10 to 15 seconds to facilitate the
relationships between regenerating epithelium and procedure.
keratocytes.11 In eyes undergoing PRK, the initial Subsequent to alcohol exposure and removal, the
healing response after surgery is epithelial well is removed from the eye and the surface is
regeneration, and the advancing epithelial fronts first thoroughly irrigated with balanced salt solution to
cover the bare stromal surface to re-establish the ensure complete removal of any residual alcohol from
barrier. Once this is achieved, the epithelium the ocular surface. If the epithelium had not been
undergoes hyperplasia and also influences the stromal previously cut with a trephine then the marked edge
282 Mastering Advanced Surface Ablation Techniques
must be incised. This can be performed with the edge lesser correction, keratocytes apoptosis and
of a sharp forceps such as the jeweller’s forceps or a inflammatory cell infiltration in both groups was
modified Vannas’ scissors as in Azor’s technique. If similar. However, with higher corrections, a
the epithelium had been first incised with a trephine, significant increase in keratocytes apoptosis was
then it needs to be lifted off the underlying corneal noted in the PRK group, with an increased
surface, and this is performed with a variety of transformation to myofibroblasts and synthesis of
personalized instruments that come in different chondroitin sulphate in the ablated stromal areas. In
combinations. Usually a semi-sharp curved knife in another study, the investigators compared the tear
the shape of a hockey stick is used. Once the plane of levels of transforming growth factor – beta1 (TGF-
elevation of the epithelium is defined, it is beta1) in the tears of 15 patients who underwent PRK
subsequently elevated along the entire extent of the and LASEK in fellow eyes for the treatment of
flap, working towards the hinge. Azar has described myopia.13 They noted significantly higher TGF-beta
the use of Weck cell sponges for this maneuver. 1 levels in the tears from eyes that had PRK compared
Once the epithelium has been dealt with, the stromal to those that had LASEK at day 1 and day 2 after
surface is cleaned to remove any debris and the excimer surgery. Although this difference persisted at day
ablation is performed in the standard fashion. Some 7 after surgery, it was no longer statistically
surgeons prefer to customize their nomogram for LASEK significant. A statistically significant higher corneal
and reduce the amount of ablation compared to that haze score was noted in PRK eyes at 1 month,
for PRK by varying amounts. Subsequently, the although these differences were no longer significant
epithelial flap which has been kept moist, it floated back at month 3 and 6 examinations. They postulated that
into position, taking care to avoid damaging the delicate the increased TGF-beta1 in the tears in the early
structure. As mentioned earlier, while some surgeons postoperative period after PRK may be responsible
align the edges of the epithelial flap meticulously, others for the increased healing and corneal haze noted in
pay less attention to this facet of the surgery. After the first postoperative month in PRK eyes. In a
waiting for 2 to 5 minutes for the flap to adhere, a prospective study, 27 patients with myopia between
bandage contact lens is placed and antibiotic and 3 and 6.5D were treated with PRK and LASEK in a
steroids drops are applied. No pad is used. The common fellow eye design.14 After a follow-up of 3 months,
postoperative regimen will include antibiotics, steroids, there were no significant between-eye differences in
and tear substitutes applied topically although the epithelial healing time, UCVA, or refractive error.
combinations and dosages and durations used are highly However, LASEK-treated eyes had lower
variable. Less often, topical cycloplegics at the conclusion postoperative pain scores (P =.047) and corneal haze
of surgery and postoperative topical non-steroidal scores (1 month; P =.02) than PRK-treated eyes.
agents may be used. Since most patients will experience Seventeen patients (63%) preferred the LASEK
discomfort, oral analgesics will be required in the procedure. Similar results were reported in another
postoperative period. study in patients treated for a similar range of myopic
Thus, it appears that LASEK is safe and effective refractive error.15 A study from China evaluated the
in the treatment of mild and moderate myopia two procedures in patients undergoing treatment for
although it is technically more difficult to perform a slightly higher range of myopia (up to 8D).16 They
than PRK. Since it has been suggested as a procedure reported faster epithelial healing times and higher
that has the advantages of PRK and LASIK, a review pain scores after PRK. Although unaided visual acuity
of studies that have compared these procedures is and manifest refractions were similar in the two
important. In a rabbit study using a paired eye design, groups after surgery they noted less corneal haze
the effects of low (3D) and high (7D) myopic after LASEK. Thus, it appears that in eyes treated
corrections performed using PRK and LASEK were for low to moderate myopia, LASEK may have lesser
studied at 7 days after surgery.12 In eyes with the pain in the postoperative period, and refractive
 PRK — Past, Present and Future 283
outcomes similar to or better than that of PRK, with surgeons preferring the use of alcohol. This has raised
less corneal haze. These benefits are probably also concerns about the viability of the epithelial cells in
present when higher degrees of myopia are treated, the flap, especially with high alcohol concentrations
although the upper limit of myopia for safe treatment and prolonged exposure times. Efforts to limit the
is not clear. exposure time however appear to be associated with
A similar comparison of LASEK and LASIK for a lesser percentage of success in raising a good epithelial
the treatment of myopia up to 6 D in fellow eyes of flap. At present, concentrations of alcohol higher than
patients has been reported. 17 At 6 months after 20% and exposure times longer than 40 seconds are
surgery, there was no statistically significant considered unacceptable. The procedure can also be
difference in UCVA, BSCVA, spherical and cylindrical of a much longer duration that PRK and LASIK since
refractive error, Schirmer’s test, or tear break-up time raising the epithelial flap takes careful effort. In an
between groups. Contrast sensitivity values in the attempt to retain the benefits of the epithelial flap, but
LASIK eyes were lower in comparison to preoperative also speed up the process, retain a greater viability of
values, but there was no change in the LASEK group. the epithelial cells, and perform the procedure in a
The authors concluded that LASEK for low myopia more reproducible manner, a technique has evolved
was safe and effective with predictable results, to include the use of a mechanical device to raise the
offered early refractive stability, and may be epithelial flap.
considered an alternative for LASIK. A study of
wavefront aberrations after LASIK and LASEK in
two groups of patients found that total corneal
aberrations increased similarly after LASEK and
LASIK with the 7.0 mm pupil, but did not change
with the 3.0 mm pupil.18 Although data are limited,
it does appear that the visual outcomes in eyes with
low to moderate myopia may be similar after LASEK
and LASIK, making the former procedure a useful
alternative in eyes with thin corneas that may be
unsuitable for LASIK.
Despite these good results, there are some A
limitations with LASEK. Corneal wound healing
problem such as haze formation can still occur
especially in high myopia cases. Corneal haze can be
prevented or treated with intraoperative application
of mitomycin C (0.02% for 15-60 seconds). (Figures
32.1A and B) Moreover, LASEK is technically a
challenging procedure, and since there appears to be
some variability in the ease with which an epithelial
flap can be created in different patients, the
repeatability of the procedure may be lesser when
compared to PRK and LASIK. Surgeon skill and
experience seem to be important in being able to
reproducibly produce a good epithelial flap. While B
some procedures have been described that eschew the
Figures 32.1A and B: (A) Shows corneal haze in a post-LASEK eye;
use of alcohol to raise the corneal epithelial flap, these (B) Shows a clear cornea after removal of the haze and treating the
are still performed in a limited fashion, with most stromal bed with intraoperative mitomycin C (0.02% for 1 minute)
284 Mastering Advanced Surface Ablation Techniques
Two aspects of the flap created in LASEK have The procedure is automated and hence is likely
come under scrutiny recently. The use of alcohol and to be faster and more reproducible than LASEK.
its effects on the health of the epithelial cells in the After preparing the eye as for LASEK, a mechanical
flap has been alluded to earlier. While the range of device similar to a microkeratome is used. A vacuum
alcohol dilutions and exposure times have been ring holds the eyes in place and makes it more turgid.
titrated, the role of viable cells in the modulation of The head of the keratome is then fitted on to the
the healing process is still not very clear. It is obvious ring as in LASIK, and makes a translational pass
from the preceding sections that in LASEK, the across the cornea. The head contains a proprietary
epithelial flap acts as a natural contact lens that blade that is unlike the sharp blade used in LASIK
decreases postoperative pain and haze formation. and this enables it to find the plane of resistance
Thus, if the barrier effect is what is important, then offered by the Bowman’s layer, and subsequent
the viability of the epithelial cells may not be critical. separation of the epithelium occurs at this plane. The
However, the extent of cytokine release by the dying head does not amputate the flap, but creates a hinge.
cells and their putative effect on stromal healing is This facilitates easy lifting of the epithelial flap, and
still unclear. Until further studies are able to elucidate after completing the excimer ablation, it can be
the importance of this factor, it may be prudent to reposition and the concluding steps are as for LASEK.
preserve the viability of as many of the epithelial cells Although the use of the microkeratome does make
as possible in the epithelial flap, which then means the procedure technically less challenging, problems
the use of minimal alcohol for this process, or do occur. As with LASIK, there are instances when
preferably – no alcohol. Another aspect of flap the epithelial flap has problems – amputation, partial
creation is the plane of cleavage of the epithelial sheet. or irregular flap, holes in the flap, and no cut.
From past experience with recurrent corneal erosions However, unlike in LASIK, these often do not have
following trauma, and in eyes with anterior basement the same connotations and the procedure can often
membrane dystrophy, the importance of a healthy be salvaged, or converted to PRK. The cost of buying
basement membrane in maintaining a normal the keratome for epi-LASIK and the recurring cost
epithelial layer has been established. of the blades also have to be considered. While initial
Hence, a procedure that may be able to overcome results with epi-LASIK are encouraging, there is as
the two potential concerns with LASEK may be of yet limited information on the comparative
interest to ophthalmologists. Pallikaris described such performance of this technique as compared to PRK,
a procedure and termed it epipolis laser in situ LASEK and LASIK. Hence more data is needed to
keratomileusis (Epi-LASIK). In this approach, a assess if the theoretical advantages that have been
mechanical device is used to separate the epithelial described with epi-LASIK flap creation translate into
flap from the cornea and the rest of the procedure superior clinical results.
proceeds as in LASEK. Analysis of the separated flaps As with other excimer procedures, these
in eyes that have had Epi-LASIK reveals that the modifications are also subject to the modulating
plane of separation of the epithelium with this influences of ultraviolet light that have been noted
approach is not within but under the basement in eyes that undergo PRK. Hence, patients should be
membrane of the epithelium.19 A smoother basement encouraged to use ultraviolet light protection eye
membrane with minimal cellular fragmentation was wear in the first year after surgery, at least in
noted. Thus, with this procedure there is a flap which environments where exposure to high ambient levels
has not been subjected to the toxicity of alcohol, and of ultraviolet light is common.20 Similarly, the risk of
has a smoother plane of separation from the reactivation of Herpes simplex keratitis exists and
underlying cornea, which results in better appropriate precautions must be observed. The use
preservation of the epithelial morphology. of cold saline may help obviate some of the thermal
 PRK — Past, Present and Future 285
effects that have been recently described in eyes group has reported on the use of a novel AM ointment
undergoing PRK, especially when higher corrections in rabbits undergoing PRK and showed that this may
are attempted.21 have some beneficial effects.28 Anecdotally, other
Initially considered an option for the treatment of modalities that have been described in conjunction
eyes that had responded to previous surface ablations with advanced surface ablation procedures to
with significant corneal scarring, mitomycin C (MMC) improve outcomes, include autoserum tears, vitamin
use has now been described for primary procedures C and non-steroidal anti-inflammatory agents.29
as well.22 In eyes undergoing LASEK, 0.01% MMC Advanced surface ablation thus represents the
was used as a brushstroke and the results were exciting new frontier in the saga of excimer corneal
compared with another group of eyes that had LASEK refractive surgery that started in 1987. It represents
without MMC. The patient group comprised those an attempt to bridge the structural advantages of PRK
with low and high myopia, and the results indicated with the refractive advantages of LASIK. While both
that although the use of MMC was associated with LASEK and epi-LASIK attempt to provide the same
less corneal haze, especially in the high myopic groups, benefits, they do so in different ways that have their
it also resulted in greater refractive unpredictability pros and cons. Whether one is definitively better will
and increased higher order aberrations. They become clearer as more studies are reported. The
concluded that the role of MMC in these procedures use of the newer options such as wavefront
required further study. As with MMC use in other correction, topography guided ablations, and
situations, the ideal dose and duration of exposure attempts to modulate corneal asphericity may be
are not clear as also the potential for long-term better served by surface ablation techniques, although
complications. A recent article has reported a possible this is yet to be conclusively determined. While the
decrease in keratocyte density in the anterior stroma use of adjuncts such as MMC offer significant
after PRK and in the flap and retroablated area after advantages in the management of complex cases, their
LASIK at 5 years of follow-up.23 Although the number potential for complications indicates that care must
of eyes followed-up is small and some methodologic be exercised in their use, and their role in routine
issues exist, this is a matter for concern. Since MMC is surgery remains limited. Finally, while the putative
known to be toxic to corneal stromal keratocytes when role of these advantages with surface ablations can
used as an adjunct in PRK, its use must be tempered be argued, until the enigma of post-LASIK ectasia is
with caution.24 solved, there will continue to be interest in and
Another adjunct that has been used in the co- evolution of these procedures.
management of eyes undergoing surface corneal
ablation using the excimer laser is amniotic membrane REFERENCES
(AM).25 Initial studies in rabbits showed that the use 1. Trokel SL, Srinivasan R, Braren B. Excimer laser surgery
of AM after transepithelial PRK in rabbits precludes of the cornea. Am J Ophthalmol 1983;96:710–5.
polymorphonuclear cell infiltration, and decreases 2. Durrie DS, Lesher MP, Cavanaugh TB. Classification of
variable clinical response after photorefractive
lipid peroxidation and keratocytes death. In a
keratectomy for myopia. J Refract Surg 1995;11:341-7.
subsequent study, the authors also reported that the 3. Rao SK, Mukesh BN, Bakshi H, Sitalakshmi G,
use of AM after PRK in rabbits was effective in Padmanabhan P. Photorefractive keratectomy: the
reducing corneal scarring.26 Similar benefits were Sankara Nethralaya experience. Ophthalmic Surg Lasers
1996;27:S444-53.
reported in a clinical study of patients undergoing 4. El-Danasoury MA, el Maghraby A, Klyce SD, Mehrez K.
LASEK for the treatment of myopia. By placing a comparison of photorefractive keratectomy with excimer
strip of AM in the lower limbus of one group, the laser in situ keratomileusis in correcting low myopia (from
–2.00 to –5.50 diopters). A randomized study.
authors reported better visual and refractive Ophthalmology 1999;106:411-20.
outcomes and lower corneal haze scores in cases 5. El-Maghraby A, Salah T, Waring GO 3rd, Klyce S, Ibrahim
compared to controls.27 Based on these results another O. Randomized bilateral comparison of excimer laser in
286 Mastering Advanced Surface Ablation Techniques
situ keratomileusis and photorefractive keratectomy for the anterior corneal surface after laser-assisted subepithelial
2.50 to 8.00 diopters of myopia. Ophthalmology keratectomy and laser in situ keratomileusis: preliminary
1999;106:447-57. study. J Cataract Refract Surg 2004;30:1929-33.
6. Juhas T, Kozak I, Klisenbauer D. The excimer laser and 18. Pallikaris IG, Naoumidi II, Kalyvianaki MI, Katsanevaki
severe myopia—comparison of LASIK and PRK. Cesk VJ. Epi-LASIK: comparative histological evaluation of
Slov Oftalmol 2000;56:161-5. mechanical and alcohol-assisted epithelial separation. J
7. Lam DS, Leung AT, Wu JT, Cheng AC, Fan DS, Rao SK, Cataract Refract Surg 2003;29:1496-501.
Talamo JH, Barraquer C. Management of severe flap 19. Stojanovic A, Nitter TA. Correlation between ultraviolet
wrinkling or dislodgment after laser in situ keratomileusis. radiation level and the incidence of late-onsetcorneal haze
J Cataract Refract Surg 1999;25:1441-7. after photorefractive keratectomy. J Cataract Refract Surg
8. Rao SK, Srinivasan B, Sitalakshmi G, Padmanabhan P. 2001;27:404-10.
Photorefractive keratectomy versus laser in situ 20. Maldonado-Codina C, Morgan PB, Efron N. Thermal
keratomileusis to prevent keratectasia after corneal consequences of photorefractive keratectomy. Cornea
ablation. J Cataract Refract Surg 2004;30:2623-8. 2001;20:509-15.
9. Taneri S, Zieske JD, Azar DT. Evolution, Techniques, Clinical 21. Camellin M. Laser epithelial keratomileusis with
Outcomes, and Pathophysiology of LASEK: Review of the mitomycin C: indications and limits. J Refract Surg
Literature. Surv Ophthalmol 2004;49:576–602. 2004;20:S693-8.
10. Condon P, Camellin M: LASEK may offer the advantages 22. Erie JC, Patel SV, McLaren JW, Hodge DO, Bourne WM.
of both LASIK and PRK. Ocular Surgery News Corneal Keratocyte Deficits After Photorefractive
International Edition, 1999. Keratectomy and Laser In Situ Keratomileusis. Am J
11. Esquenazi S, He J, Bazan NG, Bazan HE. Comparison of Ophthalmol. 2006,15; [Epub ahead of print]
corneal wound-healing response in photorefractive 23. Kim TI, Pak JH, Lee SY, Tchah H. Mitomycin C-induced
keratectomy and laser-assisted subepithelial keratectomy.
reduction of keratocytes and fibroblasts after
J Cataract Refract Surg 2005;31:1632-9.
photorefractive keratectomy. Invest Ophthalmol Vis Sci
12. Lee JB, Choe CM, Kim HS, Seo KY, Seong GJ, Kim EK.
2004;45:2978-84.
Comparison of TGF-beta1 in tears following laser
24. Park WC, Tseng SC. Modulation of acute inflammation
subepithelial keratomileusis and photorefractive
and keratocyte death by suturing, blood, andamniotic
keratectomy. J Refract Surg 200;18:130-4.
membrane in PRK. Invest Ophthalmol Vis Sci
13. Lee JB, Seong GJ, Lee JH, Seo KY, Lee YG, Kim EK.
2000;41:2906-14.
comparison of laser epithelial keratomileusis and
25. Wang MX, Gray TB, Park WC, Prabhasawat P, Culbertson
photorefractive keratectomy for low to moderate
myopia. J Cataract Refract Surg 2001;27:565-70. W, Forster R, Hanna K, Tseng SC. Reduction in corneal
14. Hashemi H, Fotouhi A, Foudazi H, Sadeghi N, Payvar S. haze and apoptosis by amniotic membrane matrix in
Prospective, randomized, paired comparison of laser excimer laser photoablation in rabbits. J Cataract Refract
epithelial keratomileusis and photorefractive keratectomy Surg 2001;27:310-9.
for myopia less than -6.50 diopters. J Refract Surg 26. Lee HK, Kim JK, Kim SS, Kim EK, Kim KO, Lee IS, Seong
2004;20:217-22. GJ. Effect of amniotic membrane after laser-assisted
15. He TG, Wang LJ, Sun ZY, Shi XR. Comparison of laser subepithelial keratectomy on epithelial healing: clinical
subepithelial keratomileusis and photorefractive and refractive outcomes. J Cataract Refract Surg
Keratectomy for the correction of myopia. Zhonghua 2004;30:334-40.
Yan Ke Za Zhi 2004;40:579-82. 27. Kim TH, Lee DY, Rho JH, Rho SH, Yoo KW, Ahn HB,
16. Kaya V, Oncel B, Sivrikaya H, Yilmaz OF. Prospective, Yoo YH, Park WC. Application of newly developed
paired comparison of laser in situ keratomileusis and laser amniotic membrane ointment for photorefractive
epithelial keratomileusis for myopia less than –6.00 keratectomy in rabbits. Ophthalmic Res 2006;38:58-61.
diopters. J Refract Surg 2004;20:223-8. 28. Yee RW, Yee SB. Update on laser subepithelial
17. Buzzonetti L, Iarossi G, Valente P, Volpi M, Petrocelli G, keratectomy (LASEK). Curr Opin Ophthalmol
Scullica L. Comparison of wavefront aberration changes in 2004;15:333-41.
Section
3

Advanced
Surface Ablation
Technique II:
Epi-LASIK
 CHAPTER

33 Epi-LASIK Personal
Experience
with the Amadeus II

Frank Goes (Belgium)

EPI-LASIK PRINCIPLE—INDICATIONS mechanically without requiring the preparation of the

cornea with alcohol or another chemical agent.
As compared with LASIK, Surface Ablation
Mechanical separation not only prevents any potential
procedures are less invasive (in terms of corneal
toxic effect of alcohol on the separated epithelial sheet,
biomechanics), prevent any microkeratome related-
but also provides a rather automated surgical
complications, and provide the only alternative for
procedure with a short learning curve for an
laser vision correction for eyes with either thin or
experienced refractive surgeon.8-11
neovascularized corneas or deep-set eyes. The idea
The principle of mechanical epithelium separation
of Camellin and Cimberle1, Camellin2, and others3,4
is based on the specific mechanical properties of
to maintain an epithelial flap that can be replaced on
Bowman’s layer so that the epikeratome’s separator
the cornea after photoablation has renewed the
moves forward following the pathway of least local
interest of refractive surgeons toward surface
resistance.
treatments.
The procedure involves the mechanical separation
Lee et al5 provided the first clinical evidence that
of the epithelium from the stroma with a specially
patients treated with laser epithelial keratomileusis
designed device. It therefore involves no toxic
- LASEK - for low and moderate myopia had lower
substances. Moreover, research has shown that
postoperative pain and haze scores than patients
around 85 per cent of the epithelial cells in the
treated with photorefractive keratectomy (PRK).
separated flap remain viable.7
Although the beneficial effect of the retained epithelial
sheet has been questioned by other investigators, an
What is Epi-LASIK?
increasing number of authors suggest that the
replacement of epithelium onto the ablated cornea Epi-LASIK, or advanced surface ablation, was
may provide advantages over conventional PRK for initiated to avoid the common problems associated
the correction of myopia. with PRK and LASEK, such as postoperative pain,
Epi-LASIK was first described by Pallikaris et delayed visual rehabilitation and the risk of haze.
al6,7 as an alternative to LASEK for the correction of Furthermore, complications normally associated with
myopia and myopic astigmatism. Epi-LASIK’s LASIK such as dry eye, diffuse lamellar keratitis,
fundamental difference from LASEK is that the irregular stromal flap cuts (i.e. partial flaps, thin flaps,
separation of the epithelial sheet is obtained button holed flaps, decentered flaps and free flaps),
290 Mastering Advanced Surface Ablation Techniques
induced higher order aberrations, epithelial specimens proved that the manual technique was less
ingrowth, flap striae, interface debris, corneal ectasia, invasive to epithelial integrity than LASEK using
glare, halos, and night vision problems are avoided. either alcohol concentration.
Ioannis Pallikaris6-7-12 conceived the idea of epi- In 2003 Pallikaris IG et al.7 also described advances
LASIK. He recognized that a dull-edged plastic in subepithelial Excimer refractive surgery techniques:
separator, which moves across the path of least Epi-LASIK.
resistance, has the potential to separate the epithelium Epipolis laser in situ keratomileusis was an
successfully below the basement membrane and just alternative modality of epithelial separation with the
above Bowman’s layer. Several published studies use of a device that features a blunt oscillating blade.
have demonstrated the safety and efficacy of the This surgical approach did not require the use of
technique for the correction of low myopia. alcohol for epithelial loosening.
The main advantage of epi-LASIK is the avoidance In 2005, Pallikaris IG et al.12 evaluated Epi-LASIK:
of flap related problems (e.g. induced higher order preliminary clinical results of an alternative surface
aberrations) because biomechanics of the cornea are ablation procedure. Forty-four eyes of 31 patients
not compromised. Creation of a LASIK flap leads to had Epi-LASIK for the correction of low myopia.
disruption of the structural stability and Mean preoperative spherical equivalent was –3.71
biomechanical function of the cornea. The severing diopters (D) +/– 1.2 (SD) (range –1.75 to –7.00 D) and
of the lamellae results in a loss of tension, allowing the mean baseline LogMAR best spectacle-corrected
the peripheral lamellar tissue to absorb water, thereby visual acuity was –0.01 +/– 0.06 (range 0.10 to –0.10).
flattening the cornea at the center, and as the Their preliminary clinical results in 2005 suggested
periphery is untouched, a relative steepening at the that epi-LASIK is a safe and efficient method for the
periphery may result. If not counteracted by the Q correction of low myopia.
value measures, higher order aberrations or an oblate
a cornea may ensue. EPI-LASIK TECHNIQUE COMPARED TO OTHER
Several studies have demonstrated a significant SURFACE OR STROMAL TECHNIQUES
change in the induced postoperative higher order
Netto et al.13 studied wound healing in the cornea in a
aberrations from flap creation alone. By not creating
review of refractive surgery complications and new prospects
a flap, the problems of buttonholes, micro –or
for therapy.
macrostriae, diffuse lamellar keratitis, epithelial
Since we know that the corneal wound healing
ingrowth, free flaps, slipped flaps or dislocated flaps
response is of particular relevance for refractive
are eliminated. The procedure allows corrections for
surgical procedures since it is a major determinant of
thinner corneas that could not be done with LASIK
efficacy and safety, the purpose of their review was
because the chance for ectasia is less.
to provide an overview of the healing response in
refractive surgery procedures.
Pallikaris and Epi-LASIK
They concluded that a better understanding of
Pallikaris was the first to introduce Epi Lasik in 2003 the complete cascade of events involved in the corneal
In 2003 he6,7 compared the effect of mechanical and wound healing process and anomalies that lead to
alcohol-assisted (15-20%) excision on the histological complications is critical to improve the efficacy and
ultrastructure of epithelial disks from human corneas safety of refractive surgical procedures. Recent
in the Vardinoyiannion Eye Institute of Crete, advances in understanding the biologic and molecular
University of Crete, Medical School, Crete, Greece. processes that contribute to the healing response
The mechanical separation did not affect the bring hope that safe and effective pharmacologic
normal cell morphology of the excised epithelial modulators of the corneal wound healing response
disks. Transmission electron microscopy of the may soon be developed.
 Epi-LASIK Personal Experience with the Amadeus II 291
Several studies compared comfort, pain and Dai et al.16 evaluated the one-year outcomes of
predictability between epi-LASIK and LASEK–PRK. epi-LASIK for myopia. Their study comprised 302
eyes of 162 patients. Epi-LASIK was performed with
O’Doherty et al.14 compared mechanical epithelial
an automatically rotational epikeratome (KM-5000D).
separation using the epi-LASIK technique with alcohol
Epithelial separation was achieved mechanically
assisted separation (LASEK) in a contralateral study;
without the use of alcohol. At 1 year postoperatively,
epi-LASIK in one eye and LASEK in the other eye.
83.3% of eyes were within +/– 1D of attempted
Epi-LASIK offered comparable visual and
refraction. Grade 0.5 haze was found in 2 eyes: all
refractive results to other surface ablation techniques
other eyes had no haze. No eye lost any lines of
with lower levels of postoperative pain only for the
BSCVA, whereas 16.7% eyes gained 1 or 2 lines of
first 2 hours. However, they found a high rate of
BSCVA.
flap failure and conversion to PRK. Epi-LASIK
They concluded that epi-LASIK was a safe and
patients had the best day 1 visual acuity, (33%).
efficient method to correct myopia with the
Torres et al. 15 compared postoperative pain
advantage that it has only mild symptoms and mild
associated with epi-LASIK versus photorefractive
haze.
keratectomy in a prospective observer-masked
Katsanevaki et al.17 in 2007 evaluated the clinical
randomized study including 40 eyes of 20 patients
results of epi-LASIK for the treatment of low to
with myopia and astigmatism who received epi-
moderate myopia and myopic astigmatism. (–3.74 +/
LASIK (Moria epi-K) in one eye and PRK in the
– 1.46) in 234 eyes using the Centurion SES
contralateral eye.
epikeratome and the Allegretto Wavelight laser.
In their study epi-LASIK and PRK had similar pain
The mean epithelial healing time was 4.70+/-0.87
on postoperative day 1, but epi-LASIK demonstrated
days (range, 3-7 days), with mean LogMAR UCVA
statistically more pain than PRK on days 3 and 6.
on the day of re-epithelization of 0.26+/–0.14 (range,
0.7-0.0). One year after the treatment, the spherical
Different Studies Evaluated the Clinical Results
of Epi-LASIK equivalent of the treated eyes (n = 222) ranged from
–1.25 to +0.625 D (mean+/–SD, –0.18+/–0.6 D), with
Anderson et al.3 in 2002 analyzed results after laser- 80.33% of the eyes within 0.5 D (96.72% within 1 D)
assisted subepithelial keratectomy (Epi-LASIK) for of the attempted correction. At the same interval,
myopia and myopic astigmatism. Three hundred forty- 86% of the eyes had clear corneas and 14% clinically
three eyes of 188 patients with myopia or myopic insignificant (trace) haze, whereas 60% of the eyes
astigmatism were prospectively evaluated after having had a line gain of 1 or more lines of BSCVA. Mean
epi-LASIK by a single surgeon using the VISX Star S2 LogMAR contrast sensitivity of the treated eyes at 4
Excimer laser: the follow-up was 6 months. different spatial frequencies was improved or
At 6 months the mean UCVA was 20/40 or better remained unchanged throughout the follow-up
in 98% of patients. At 3 months 78% of patients were period.
within +/– 0.5D of indented correction: at 6 months Their one-year visual and refractive results after
this improved to 85%. The mean time to epithelial epi-LASIK suggested that epi-LASIK was a safe and
healing was 4.76 days (range 3-9 days). efficient method for the correction of low to moderate
According to them epi-LASIK was a safe and myopia and myopic astigmatism.
effective treatment for the correction of myopia and Robert Mitchell18 analysed his first 1000 epi-LASIK
myopic astigmatism. Most patients achieved cases done with the Moria (Antony France) separator.
postoperative visual acuities comparable to those with His practice is now 100% flap free epi-LASIK.
laser in situ keratomileusis and photorefractive Using EpiK, discarding the flap, his 20/20 rates
keratectomy. There was a low incidence of for epi-LASIK were five times better than PRK at
postoperative haze and pain. one week postoperative. Postoperatively all his eyes
292 Mastering Advanced Surface Ablation Techniques
were within 0.5 D of emmetropia. His enhancement Differences in Corneal Sensitivity Rehabilitation
rate dropped to 6% and no eye lost more than one were noted by Kalyvianaki
line. As a regime he used an Acuvue Oasis (Vistakon) Kalyvianaki et al.22 compared the effect of Epi-LASIK or
bandage contact lens and most of his patients had good Laser in situ Keratomileusis (LASIK) on corneal sensitivity
visual recovery at day 3, those who did not use artificial and tear function in a prospective, non-randomized
tears frequently needed 5 days to heal fully. comparative clinical trial. Seventy-nine eyes (Group A)
Dr Fishman19 compared epi-LASIK and PRK in a underwent epi-LASIK and 61 eyes underwent LASIK
contralateral study of 20 patients and epi-LASIK (Group B) for the treatment of myopia.
against mechanical debridement (Epi-LASIK with flap There was a significant difference in corneal
removal) in fellow eyes of a second group of 20 sensitivity between the two groups at all post-
patients. The results showed that epi-LASIK had a operative intervals. The epi-LASIK-treated eyes had
benefit for minimizing discomfort immediately after faster rehabilitation of corneal sensitivity and tear
surgery and that visual rehabilitation was fastest in function than the LASIK-treated eyes.
the lamellar epithelial debridement group.
The Effect on Haze Formation was Studied by
Histological Studies were Performed by Several Long et al
Authors
Long Q et al.23 compared the incidence and degree
20 of corneal haze formation following laser sub-
Chen et al. compared change in stromal cells after
Epipolis laser in situ keratomileusis (epi-LASIK) and epithelial keratomileusis - LASEK and epithelial laser
laser-assisted subepithelial keratectomy (LASEK) on in situ keratomileusis - epi-LASIK, and examined its
the corneal stromal cells, and evaluated their effects correlation with tear film transforming growth factor-
on corneal haze histopathologically. Forty-eight New beta1 (TGF-beta1) levels. Their prospective,
Zealand white rabbits (96 eyes) were randomly interventional, clinical trial included 20 eyes (20
treated with epi-LASIK in one eye and LASEK in the patients) randomly assigned to undergo LASEK or
other, and 2 rabbits (4 eyes) without any treatment epi-LASIK. The level of TGF-beta1 in tear fluid was
were used as control. Cornea stromal cell apoptosis measured preoperatively and 1, 3, and 5 days
was evaluated by terminal deoxyribonucleotidyl postoperatively. Corneal haze was graded at 1 and 3
transferase-mediated deoxynuridine triphosphate months after surgery, and the relationship with TGF-
nick end labelling (TUNEL) assay. beta1 levels was determined.
There was less stromal cell apoptosis, proliferation They concluded that less corneal haze was noted
and myofibroblast generation in epi-LASIK than that after epi-LASIK than LASEK. According to them a
in LASEK. Therefore they concluded that comparing positive correlation between corneal haze and tear fluid
with LASEK, epi-LASIK induced less corneal haze TGF-beta1 levels on the first postoperative day suggest
response in correcting myopia. a possible mechanism for the observed difference.
Katsanevaki VJ et al. 21 studied the epi-LASIK Taneri 24 reported on epi-LASIK in irregular
histological findings of separated epithelial sheets 24 hours cornea’s, he completed epi-LASIK with no
after treatment. intraoperative complication in the presence of an
They reported the histological findings of four irregular stromal surface after amputation of a LASIK
flap. This procedure may extend our options in the
eyes of three patients who underwent epi-LASIK
management of LASIK flap-related complications.
treatment for the correction of low myopia.
Histological examination of specimens in these
AMADEUS II – PRODUCT DESCRIPTION
four eyes showed that 24 hours after mechanical
separation the epithelial cell’s morphology was close The Amadeus II Microkeratome is a system with an
to normal. all-in-one handpiece designed to perform both LASIK
 Epi-LASIK Personal Experience with the Amadeus II 293
and epi-LASIK with full control over lamellar and • It ensures predictable, uniform LASIK and
epithelial flap parameters. Featuring computer- epithelial flaps or epithelial separation
controlled, intelligent design, Amadeus II • The ease of use and error free assembly is remarkable
Microkeratome provides surgeons with the safety • The keratome maximizes suction performance in
and confidence of voice-confirmation of instrument all environments
readiness, and maintains precise tissue parameters • The instrument virtually eliminates the occurrence
throughout the procedure (Figure 33.1). of pits and crevices in the device for potentially less
bacterial adherence and friction than stainless steel.

A Predictable Result Starts with Superior

Materials
Amadeus II Microkeratome builds on the Amadeus
legacy of virtually fail-proof assembly and
unsurpassed material integrity. From design to
implementation of this latest technology, Amadeus II
Microkeratome brings the level of precision required
for predictable results. The ergonomically enhanced,
titanium micro-handpiece and control cable are
lightweight to minimize pressure on the eye during
the procedure. It also reduces surgeon fatigue and
Figure 33.1: Amadeus II Apparatus operating field clutter allowing full visualization of
the flap and epithelial tissue during LASIK and surface
The Amadeus II ablation procedures.
• Performs LASIK and Surface Ablation with one
Amadeus II Microkeratome: Technical Data
device
• Allows full customization of flap and epithelial • Physical dimensions: Control unit 9.7”x9.0”x14.2”
tissue parameters (245x200x360 cm); 17.5 lbs (8 kg); Handpiece 5 oz
• Utilizes computer-controlled cutting and/or gentle (135 g)
separation • Microkeratome handpiece motor: Maximum Blade
• Assembles one way, off the eye with only four oscillations (no load) 20,000 rpm. Blade
simple pieces advancement rate 1.5-4.0 mm/sec.
• Uses an audible voice confirmation of system
readiness Indications for Use
• Allows for altitude adjustment for suction pressure The Amadeus II Epikeratome is intended for use in
• Is ergonomically enhanced, solid block titanium the separation of epithelium from the cornea in
construction preparation for subsequent surgical procedures on
• Uses exclusive SurePass LASIK Blade and Surface the denuded cornea.
Separator.
Device Description
Benefits of Amadeus II
The Amadeus II Epikeratome is a modification of the
The benefits of Amadeus II are as follows: ACCM/Amadeus Microkeratome, which is firmly
• The instrument is cost effective, convenient and established in the market for several years. In the
space-efficient course of a product update, the designs of blade and
• It has a flexibility to perform various types of laser blade holder have been modified to provide
vision correction procedures surgeons with the option to perform epi-LASIK.
294 Mastering Advanced Surface Ablation Techniques
The surgical principles of the Amadeus II
epikeratome and its predicate device are essentially
identical. To perform a lamellar corneal resection,
the cornea is held in position by means of a suction
ring, and vacuum is applied to increase intraocular
pressure to a level allowing the epikeratome blade
to move across the cornea in a mode similar to that
of a carpenter’s plane. The corneal flap is made by
the same operating principle as in the predicate device,
i.e. a blade is advancing and simultaneously
oscillating horizontally and perpendicular to the
advancement direction. A control unit provides Figure 33.2: Suction ring

power and a controlled vacuum for fixing the eye.

The corneal flap created by the epikeratome consists
of the entire epithelium; this flap structure is obtained
by modifications of the blade and the blade holder.
The Amadeus II epikeratome comprises three
major groups of components: (Figures 33.2 to 33.5)
a. A handpiece, incorporating the suction unit, the
blade holder, the epikeratome epi-LASIK blade
and the motor Unit. The handpiece offers several
safety features designed to prevent product
malfunction or incorrect use, and allows the
surgeon to handle the Epikeratome with only one
hand.
b. A control unit with touch-screen interface,
managing the epikeratome’s cutting action and the
automatic documentation of the chosen cutting Figure 33.3: Easy assembling of instrument
parameters and user interface dialogs.
c. Two footswitches that serve to actuate and
discontinue the epikeratome cutting procedure.
The standard actuation footswitch serves to
initiate suction and the epikeratome cutting action.
Disposable components of the Amadeus II
epikeratome system are 1) a sterile plastic
epikeratome blade and 2) a sterile vacuum tubing
kit. Additionally, an autoclavable instrument tray is
provided for sterilization.
Upgrades to the Amadeus II microkeratome
(Advanced Medical Optics) enable doctors to perform
conventional LASIK, epi-LASIK, and lamellar
epithelial debridement with the same tool.
Improvements also allow surgeons to have more
flexibility and control over surgical parameters.
The ability to adjust surgical parameters such as Figure 33.4: Instrument ready; assembled before
oscillation speed, translation speed, and suction and placement on the eye
 Epi-LASIK Personal Experience with the Amadeus II 295

Figure 33.5: Front screen of the Amadeus II

create different flap thicknesses and diameters gives

surgeons extensive control over the procedure, he
explained. The ability to have more surgeon control
over flap parameters is one of the major advantages
of the Amadeus II (Figures 33.6 to 33.9).

Designed with Flexibility in Mind

The system allows choosing the procedure – LASIK
or epi-LASIK – that is the best for you and your
patient. To meet the evolving surgical needs with
surface ablation techniques, the Amadeus II
microkeratome also provides the option of
maintaining an epi-flap or going epi-free – completely
removing the epithelial tissue with computer-
controlled accuracy; complete flexibility in an all-in-
one device. Figure 33.6: Separators for Lasik and Epi-LASIK

AMADEUS II FOR LASIK Donnenfeld ED et al.25 investigated the effect of hinge

position on corneal sensation and dry eye syndrome after
Several papers reviewed different microkeratomes laser in situ keratomileusis (LASIK) in a prospective,
for lasik applications as far as quality of cut, randomized, self-controlled trial of fifty-two patients
reproducibility, thickness of flap and complication >/= 18 years of age undergoing bilateral LASIK.
rate were concerned. In all these studies the Amadeus Patients underwent bilateral LASIK with the superior-
had excellent results, proving the excellent quality of hinge Hansatome microkeratome in one eye and the
the Amadeus instrument. nasal-hinge Amadeus microkeratome in the other eye.
296 Mastering Advanced Surface Ablation Techniques

Figure 33.7: Nomogram for Lasik

 Epi-LASIK Personal Experience with the Amadeus II 297

Figure 33.8: Nomogram for epi-LASIK

Overall, dry eye signs and symptoms were Corneal sensation and dry eye signs and
greatest during the immediate postoperative period symptoms decreased immediately after LASIK and
and improved at all subsequent time intervals. Dry improved at all time periods between 1 week and 6
eye signs and symptoms were generally greatest in months in eyes with both a nasal-hinge flap and a
the eyes with a superior-hinge flap and milder in eyes superior-hinge flap. However, the loss of corneal
with a nasal-hinge flap. sensation and presence of dry eye syndrome were
298 Mastering Advanced Surface Ablation Techniques

Figure 33.9: Settings Dr Lackerbauer

 Epi-LASIK Personal Experience with the Amadeus II 299
greater in eyes with a superior-hinge flap than in eyes heads for the Amadeus microkeratome (AMO, Irvine,
with a nasal-hinge flap. CA).
Hoffmann S et al.26 compared flap quality and Mean flap thicknesses were 153 +/– 18 (range 97-
thickness in an experimental setting using the 187 micro m) OD and 134 +/– 25 micro m (range 79-
Amadeus and Carriazo/Barraquer microkeratomes. 174 micro m) OS for the 140-micro m head; 182 +/–
One hundred and sixty-three fresh porcine 26 micro m (range 105-220 micro m) OD and 163 +/–
cadaver eyes were used to cut corneal flaps. One 29 micro m (range 105-216 micro m) OS for the 160-
hundred and thirty-five eyes were cut using the micro m head; and 235 +/– 24 micro m (range 198-
Amadeus microkeratome with various settings of 258 micro m) for the 180-micro m head. Flap thickness
head advance and oscillation rate, 28 eyes using the was significantly thicker for the first eyes cut (right
Carriazo/Barraquer microkeratome (Supratome). eyes) and was positively correlated with increasing
The variation of oscillation rate and head advance corneal thickness in both eyes. For the first eyes cut,
led to significant differences in flap thickness. Optimal flap thickness was also significantly thicker than the
cut quality was achieved with 1 mm/s head advance labelled thickness specified by the manufacturer. They
and 8,000 rpm in the Amadeus microkeratome. With concluded with the Amadeus microkeratome, LASIK
this setting the smallest target deviations in flap flap thickness correlated with central corneal
thickness were obtained among the results with thickness for the 140-micro m head. Reuse of the
lowest range (median 170 micro m, interquartile microkeratome blades produced significantly thinner
range 18 micro m, target 160 micro m). The Amadeus LASIK flaps on second eyes cut.
microkeratome demonstrated a statistically significant Thompson RW et al.29 used noncontact optical
lower deviation from the target thickness ( P<0.001) coherence tomography (Zeiss OCT) for the
and also a lower range than the Supratome (median measurement of corneal flap and residual stromal bed
127 micro m, interquartile range 30 micro m, target thickness after laser in situ keratomileusis.
140 micro m; P<0.001). The corneal flap thicknesses of 26 eyes of 15
The Amadeus microkeratome achieved a patients were measured following LASIK in which
statistically significant lower deviation in flap the flap was created using the Amadeus
thickness than the Carriazo/Barraquer micro- microkeratome: 160-micro m head, 9.5-mm ring, 4.0-
keratome. mm/s translation speed, 8000 oscillations/m, and full
Jabbur NS and O’Brien Tp 27 compared the vacuum. Zeiss Humphrey OCT-2 line scans were
incidence of intraoperative corneal abrasions using performed on postoperative days 1 and 7.
the Hansatome (Bausch and Lomb Surgical) and In bilateral cases a single blade was used for both
Amadeus (Advanced Medical Optics) micro- eyes. The mean flap thickness of 15 first eyes was
keratomes. significantly greater than that of the 10 second eyes:
The incidence of intraoperative corneal abrasions 181 +/– 31 micro m vs. 143 +/– 41 micro m (P < 0.01).
was significantly higher with the Hansatome A positive correlation was found between the
microkeratome than with the Amadeus preoperative pachymetry and corneal flap thickness.
microkeratome (P = 0.014). There was a significant Tehrani M et al.30 evaluated the cut quality using
correlation between increasing patient age and the the Amadeus microkeratome with different settings;
incidence of corneal abrasions with both micro- the quality of keratectomy specimens created with
keratomes (P<0.05). the Amadeus microkeratome (AMO) using scanning
Jackson DW, Wang L and Koch DD28 evaluated electron microscopy (SEM).
the accuracy and precision of corneal flap thickness Corneal cuts were performed in freshly
following laser in situ keratomileusis (LASIK) enucleated pig eyes using the Amadeus micro-
performed using the 140-, 160-, and 180-micro m keratome with 9 combinations of oscillation rate and
300 Mastering Advanced Surface Ablation Techniques
head-advance speed. For the cutting trials, oscillation In a prospective consecutive nonrandomized
rates of 8000, 13,000, and 18,000 rpm and head- comparative study, patients were divided into 2
advance speeds of 1.0, 2.5, and 4.0 mm/s were groups. In Group 1 (75 eyes), 3 microkeratomes were
chosen. used: Moria LSX One, Moria M2, and Amadeus
Solomon KD et al.31 in the Flap Thickness Study (AMO); 25 eyes per microkeratome.
Group determined the flap thickness accuracy of 6 With the Amadeus microkeratome, the mean flap
microkeratome models and determine factors that thickness was 140.0 micron centrally, 152.5 superiorly,
might affect flap thickness. 128.5 micron inferiorly, 145.0 micron temporally, and
This multicenter prospective study involved 18 147.0 micron nasally. Statistically significant
surgeons. Six microkeratomes were evaluated: AMO differences (P>0.05) were found in the 4 sectors of
Amadeus, Bausch and Lomb Hansatome, Moria the flap. With vectorial analysis, there was no
Carriazo-Barraquer, Moria M2, Nidek MK2000, and statistically significant difference between
Alcon Summit Krumeich-Barraquer. Eyes of 1061 superonasal and superotemporal hinge placement in
consecutive patients who had laser in situ the cardinal and oblique components but there was a
keratomileusis were included. statistically significant difference in the axis change
The results demonstrated variability between the with both placements (P>0.05).
6 microkeratome models. Device labelling did not Hammer T et al.34 evaluated four microkeratome
necessarily represent the mean flap thickness models: quality and reproducibility of cut edge and cut
obtained, nor was it uniform or consistent. Thinner surface as determined by scanning electron microscopy.
corneas were associated with thinner flaps and They compared the quality and reproducibility
thicker corneas with thicker flaps. In addition, first of cuts produced by four automatic microkeratomes:
Amadeus, Hansatome, Summit-Krumeich-Barraquer
cuts were generally associated with thicker flaps when
(SKBM), and Supratome. For the adjustable models
compared to second cuts in bilateral procedures.
(Amadeus and SKBM), the effects of oscillation
Chan CC et al.32 in 2005 assessed the safety and
frequency and blade feed rate were determined. As
efficacy of the Amadeus microkeratome after
a method: Eight cuts (flap thickness 160 to 180
experience with the first 2000 cases in a retrospective
micro m) were made with each microkeratome at each
review of the flap-related complications of 2000 laser
parameter setting and examined using a scanning
in situ keratomileusis (LASIK) procedures performed
electron microscope.
by one surgeon using the Amadeus microkeratome.
As a result the four microkeratomes performed
There were 35 cases of minor epithelial defects
similarly on overall quality of the cut surface (range:
(1.8%) and four eyes with major epithelial defects
78 to 88% of theoretical maximum). Performance
(0.2%). There were no cases of suction loss,
differences were clearer for cut edge quality. The
buttonholes, or incomplete or damaged flaps. There Amadeus produced cuts of the highest quality in
were four free caps (0.2%). Twenty-five cases had 62.5% of cases (at both settings), compared with only
minor wrinkles and two cases had significant folds 12.5% of cases with the Hansatome.
requiring relifts. Thinner corneas resulted in thinner Overall, high frequency with low blade feed rate
flaps (P < 0.0001). Reuse of the blade resulted in was desirable for reproducible sharp edges and cut
thinner flaps (P = 0.0001). area quality. However, at very high frequencies (e.g.
They concluded the Amadeus to be a safe and 14,000 rpm with the SKBM) tissue is displaced,
reliable microkeratome. Corneal thickness and reuse producing an uneven cut area.
of the blade affected flap thickness.
Güell JL et al. 33 determined the corneal flap MITOMYCINE C
thickness profile produced by 3 microkeratomes and
the topographic changes induced by flap creation in Do we need MMC (Mitomycine C) in order to avoid
laser in situ keratomileusis (LASIK). haze after epi-Lasik?
 Epi-LASIK Personal Experience with the Amadeus II 301
Mitomycin C is an antimetabolite that has seen MMC group it was 0.1, and in the control group, 0.27
increased use in ophthalmology over the past several (all differences P<0.05).
decades. From glaucoma surgery to the management He also experienced that the use of mitomycine C
of various corneal disorders, mitomycin C seems to 0.01% with LASEK significantly decreased
be a viable tool in the management of scar and haze subepithelial haze. However, refractive outcome was
formation. less predictable. High order aberrations increased
With the constant evolution of refractive surgery, after LASEK with MMC.
mitomycin C has come to the forefront as a modulator Lacayo GO and Majmudar PA.37 in 2005 described
of corneal wound healing after excimer laser surface how and when to use mitomycin-C in refractive
ablation. surgery.
The use, advantage and necessity of applying Bedei A et al.38 in 2006 studied the results of the
mitomycine C was discussed in several papers. prophylactic use of mitomycin C (MMC) to reduce
Carones F et al35 in 2002 evaluated the results of haze formation and refractive regression after excimer
the prophylactic use of mitomycin C to inhibit haze laser photorefractive keratectomy (PRK) for high
formation after excimer laser photorefractive myopic defects (>5 diopters). A total of 124 eyes of
keratectomy (PRK) for medium and high myopia, 62 patients were divided into two groups of 31
–6 to –10.0 D, in eyes that were not good candidates patients. One group received a MMC 0.02% and the
for laser in situ keratomileusis (LASIK). results were compared after one year. There were
After PRK, the study group eyes were treated with differences concerning the predictability: group A
a single intraoperative dose of mitomycin C (0.2 mg/ 69.3% within +/– 0.5D, group B 50% (phakic = 0.06%)
mL), applied topically with a soaked microsponge and 3 eyes loss of a decimal fraction concerning the
placed over the ablated area and maintained for 2 safety. Group A no eye > decimal loss, group B one
minutes. The control eyes did not receive this eye loss of more than one line and 13 eyes loss of a
treatment. decimal fraction.
No toxic or side-effects were encountered There was a smaller incidence of corneal haze in
postoperatively. At six months 87% of study group the group for which MMC was used (p value = 0.005).
and 47% of controls were within +0.5D of attempted In this study, the application of MMC 0.02%
correction (P = 05). No study group eye had a haze solution immediately after PRK produced lower haze
higher than 1, but 63% of controls did (P = 01). rates and had better predictability and improved
The prophylactic use of a diluted mitomycin C efficacy 1 year after treatment.
0.02% solution applied intraoperatively in a single Netto MV et al39 in 2006 analyzed the effect of
dose after PRK produced lower haze rates, and prophylactic and therapeutic mitomycin C on corneal
produced better UCVA and BCVA results, and more apoptosis, cellular proliferation, haze, and long-term
accurate refractive outcomes than those achieved in keratocyte density in rabbits.
the control group. They determined the mechanism through which
Camellin M.36 in 2004 assessed the advantages and topical mitomycin C prevents and treats corneal haze
safety of using mitomycin C (MMC) with laser after photorefractive keratectomy (PRK) and they
epithelial keratomileusis (LASEK) by measuring high examined the effects of dosage and duration of
order aberrations of the cornea. exposure.
100 LASEK eyes that got a brushstroke of MMC TUNEL-positive apoptotic cells marginally
0.05% were compared to 100 LASEK eyes without increased in all mitomycin C groups whereas Ki67-
MMC. positive mitotic cells decreased significantly following
Mean haze in the low myopia MMC group was mitomycin C application. A greater decrease in
0.06 and in the control group, 0.11; in the high myopia myofibroblasts was noted with prophylactic
302 Mastering Advanced Surface Ablation Techniques
mitomycin C treatment than therapeutic mitomycin C an epikeratome to lift the sheet and then reposits it
treatment. They concluded that mitomycin C after the ablation, the pro-inflammatory cytokines
treatment induces apoptosis of keratocytes and will leak out four to five days later, but it won’t
myofibroblasts, but the predominate effect in inhibiting matter, as the stroma will have passed its moment of
or treating haze appears to be at the level of blocked vulnerability.
replication of keratocytes or other progenitor cells of Eric Donnendfeld,41 took part in a controlled, 20-
myofibroblasts. Treatment with 0.002% mitomycin C patient (40 eyes) study comparing traditional epi-
for 12 seconds to 1 minute appears to be just as effective LASIK to both PRK and epi-LASIK with removal of
as higher concentrations for longer duration in the the sheet (called lamellar epithelial debridement in
rabbit model. However, a persistent decrease in the study).
keratocyte density in the anterior stroma could be a The results of the study were that removing the
warning sign for future complications and treatment flap gave the fastest visual rehabilitation, faster than
should be reserved for patients with significant risk either Epi-LASIK or PRK. He hypothesized that this
of developing haze after PRK. is because the regular borders of the epithelial flap
create a more rapid and smooth re-epithelialization,
Personal Comment which we don’t get that healing suture line through
the visual axis that we see so commonly with PRK.
So all clinical and histological studies highlighted the
So, if someone wants to see as quickly as possible
benefits of MMC in preventing haze after surface
with surface ablation removing the flap is the fastest
ablation. However, since haze is becoming much less
way. As far as the most comfortable way of doing
frequent with the use of modern lasers, the use of
surface ablation, epi-LASIK was more comfortable
MMC has to be reserved for ablations of 80 micron or
in the study than either PRK or lamellar epithelia-
more or for specific. Additional studies with longer
debridement. Lamellar epithelial debridement was
follow-up are necessary to evaluate long-term effects,
more comfortable than PRK.
and ideal MMC concentration and exposure time.
Specifically, at day one, the average pain score
ADVANTAGES OF EPI-LASIK – SEPARATE REVIEW- was a three for epi-LASIK on an increasing pain scale
LATEST UPDATES from 1 to 10. It was 4.5 for lamellar epithelial
debridement and about a 6.5 for PRK. On day three,
According to Marguerite McDonald40 there are many epi-LASIK and lamellar epithelial debridement had
strong scientific underpinnings as to why epi-LASIK the same level of pain. The return of visual acuity
might be better than any other surface procedure. was about two days faster with lamellar epithelial
The main one is that, by leaving the living, though debridement than with the other surgeries, and the
fatally injured, sheet of cells over the ablated area, epithelial defect healed about 18 hours faster with
by the time the cells actually die about five days later LED than with PRK.
the underlying stroma will have long since passed In this small group, he noticed better vision in the
its stage of vulnerability to all those pro-inflammatory very early stages in conventional epi-LASIK eyes, as
cytokines. During normal PRK, though, the cell well as less pain.
membranes rupture because the surgeon has used As for why there might be a difference between
the Amoils brush or a spatula to remove the the modalities, Dr. Soloway42 agrees with the theory
epithelium, and there is an immediate release of these of Raymond Stein 43, who says that the epithelial
pro-inflammatory cytokines from the billions of cells separator gives a very sharp, atraumatic delineation
that are crushed. This release can lead to, in some at the edge of the bed.
cases, haze and regression. Current theory, supported Dr Tetz44 also thinks there’s a difference outcome
by indirect evidence, holds that if the surgeon uses from how the epithelium is removed in surface
 Epi-LASIK Personal Experience with the Amadeus II 303
ablation cases. “The degree of hydration on the 500 patients with this technique, and no one has
corneal bed makes a difference, too, “he says. “When developed haze.
you debride epithelium with a hockey-stick shaped Drs Swanson and Rashid 46also started by putting
blade, you have some drier areas and some wetter the flap back on the eye, but have since decided to
areas, causing the epithelium to come off a bit sticky remove it. “We thought it formed an extra barrier
in areas where it’s really dry or to be thicker in areas against infection, and that it would make the patient
that are wetter.” more comfortable. We now believe patients are more
So, questions still swirl around the practice of comfortable without the flap, and we haven’t seen
removing the sheet, as well as the more basic practice any infections.’’
of epi-LASIK itself and whether it’s truly better than Dr Rashid46 also prefers epi-LASIK to LASEK. “Epi-
PRK. Maybe some larger scale studies will eventually LASIK eliminates toxic alcohol symptoms, makes a
yield the answers. better flap, provides a smooth Bowman’s surface to
Dr Soloway 42 concluded a contralateral study ablate, reduces pain and saves time,” he says.
with epi-LASIK patients in which we left the flap on It removes the fear factor. The only thing we
one eye and discarded the flap from the other eye. needed to do was reduce the postoperative pain.
The differences were not huge, but patients reported Epi-LASIK doesn’t denervate the cornea. This
slightly less pain in the eye with the flap and he found means patients have a much lower risk of post-
a slightly smaller chance of developing haze when surgical dry eye, compared to LASIK.
the flap is retained. Recovery only takes two to three days. Dr Milne45
notes that one argument in favor of LASIK is the
Take or Leave the Flap The Jury’s Still Out speed of recovery, but he says recovery from epi-
According to Dr. Milne45 , replacing the flap can also LASIK is quite rapid. “I did a study of 100 eyes, and
cause problems that have a major impact on visual in all but three cases the patients were able to return
recovery. “With my first 100 epi-LASIK patients, I to work by day three,”he says. “I do epi-LASIK on
laid the flap back down,’ he says. “For 5 or 6 percent Thursday, and Monday morning the patient is back
of those patients, visual recovery was delayed several at work.
months because they grew epithelial cells either on “Studies of the Amadeus II that have evaluated
top of or underneath the flap. They ended up with epithelial healing following epi-LASIK and lamellar
multiple basement membranes, which affected their epithelial debridement also have shown that these
vision until the epithelium sorted it all out. “In patients have the fastest visual rehabilitation of any
contrast, when you remove the flap, visual recovery form of surface ablation. They have return of good
is very quick,” he continues. “The skin cells right next visual function a day or two faster than you see with
to where you’ve lifted the flap are completely healthy conventional PRK,” Dr Donnenfeld 41said.
– they haven’t been traumatized in any way. So they The new epi-LASIK head is the primary factor
heal back across much more quickly than when enabling more rapid epithelialization and a shorter
they’re removed with alcohol debridement or with period of visual rehabilitation. Also, because of the
a brush. And the cells that get pushed to the center reduced metalloproteinases associated with epi-
are vital, so there’s no central area of dead cells – LASIK, there is a reduced incidence of postoperative
one of the problems with PRK.” haze and a lower risk of pain and photophobia.
Dr. Milne adds that the main argument he’s The ability to perform the three procedures with
favoring for putting the flap back is to reduce the the same microkeratome gives the doctors another
incidence of haze. If he’s doing a laser treatment that subset of patients they can treat those who are
will go below 75 μm in depth, he uses mitomycin C reluctant to undergo surgery with a blade and are
0.05 mg/cc for 20 to 30 seconds. He has treated almost concerned about flap thickness, Appler said.
304 Mastering Advanced Surface Ablation Techniques
“This is the thinnest flap you can get, and it really Under the Microscope
doesn’t involve a blade either, so it can help the
In another study, microscopic examination, Aris
doctors treat some patients that would otherwise not
Kollias48 showed that epi-LASIK flaps created with
want to have LASIK.”
the Amadeus II microkeratome have good structural
The versatility of the Amadeus II in epithelial integrity and that the stromal surface below was
removal also may make surgery possible for patients smooth and free of irregularity.
who otherwise might not have been suitable The study involved the examination of cross
candidates, such as those who have thin corneas or sections of corneal tissue obtained from two human
dry eyes, she added. donor eyes that had undergone epithelial separation
with the epikeratome. Light microscopy of the
UCVA and BCVA Improving During follow-up:
specimens showed that the epithelial sheets were
Reports XXIV Congress of ESCRS
thoroughly separated with no evident anatomical
Dr Mathur reported as follows: abnormalities. It also showed that stratification of
“The mean uncorrected visual acuity on the day the separated epithelium layer and cell shape were
when the epithelium was completely healed and the well conserved and that the cleavage plane was
bandage contact lens was removed was around 20/40. located at Bowman’s membrane.
However, the proportion with UCVA 20/25 or better In addition, scanning electron microscopy showed
rose from 55.5 percent at one month to 89.1 percent a very consistent transition from adherent epithelium
at six months, and over 90 percent of eyes saw 20/40 to the denuded area. The Bowman’s layer in the
or better throughout the follow-up period. specimens have a very smooth surface without any
Best-corrected visual acuity also improved during remains of basal lamina or basal cells.
follow-up, she noted. At one month’s follow-up, 26.5 Moreover, examination of Bowman’s layer with
percent lost one line of BCVA and 18.4 percent lost transmission electron microscopy showed only minor
two lines, and only 8.2 percent gained a line. But at superficial irregularities at high magnification (x4500).
six months’ follow-up, no eyes lost two lines of BCVA He demonstrated that using the epi-LASIK
separator of the microkeratome Amadeus II, our in
and nearly 30 percent had gained one line, 5.9 percent
vitro study demonstrates a high cut quality. The
gained two, and only 10.9 percent lost one line.
resulting cleavage plane at Bowman’s membrane is
The proportion with clear corneas or only trace
well suited for following excimer laser ablation.
amounts of haze increased from 67.6 percent, at one
In a presentation at the XXIV Congress of the
month, to 89.4 percent, at three months, and 95.1
ESCRS Dr Gamaly49 presented results of a study in
percent, at six months. The remaining eyes had only
which 25 Middle Eastern patients underwent PRK in
mild amounts of haze.
one eye and epi-LASIK with the Moria epi-K
Their conclusions: Although it is not a totally pain-
(epikeratome) in the other. It showed that while both
free procedure and does not have the rapid visual groups of eyes had similar results in terms of visual
recovery of LASIK, epi-LASIK provides reasonable outcomes and pain there was less haze in the eyes
visual performance in the early postoperative period undergoing epi-LASIK.
with a majority of patients having very good vision Dr Gamaly noted that the most important
minimal irritation and negligible haze. difference between the two groups was in the
The Amadeus II guided epi-LASIK group presents occurrence of subepithelial haze. In the epi-LASIK
a slightly better refractive outcome concerning eyes there was a trace of haze in 29 percent and the
efficiency, precision, stability and safety. This could remaining eyes remained totally clear at six moths.
be due to a faster wound healing process because of By comparison, in the PRK-treated eyes 29 percent
the smooth separation of the epithelium layer and had a trace of haze, 21 percent had level one haze,
the lack of ethanol vapor with its influence on the seven percent had level two haze and seven percent
energy absorption according to Dr Lackerbauer.47 had level three haze.
 Epi-LASIK Personal Experience with the Amadeus II 305
INDICATIONS We try to keep the epithelial sheet and only
discard it when it is damaged. Although the jury is
Surface versus Intrastromal in Belgium
still out (see discussion earlier on - take it or leave it)
In Belgium Surface ablation - PRK, LASIK, and epi- most surgeons agree that there is less discomfort when
LASIK- has become more popular since 2005; what we leave the flap in place.
used to account for 20% of treatments now accounts In Belgium, the standard of care for surface
for 30 to 40% of treatments. LASIK never became ablation includes the use of iced water for rinsing
popular in the southern part of Belgium, as 95 to 100% immediately after treatment. For ablations of more
of treatments have always been PRK or LASEK. than 80 μm we apply during 20 seconds a sponge
Overall, however, the majority of Excimer laser soaked with mitomycin C - 0.02% - following the laser
surgeons in Belgium are performing LASIK, since the treatment immediately before the application of iced
recuperation time of BCVA is dramatically different water. According to the literature this way of doing
and faster compared to surface ablation. prevents haze formation.
Although we are more aware of the minimal risk
of iatrogenic keratectasia, recent surveys demonst- WHY THE AMADEUS II?
rate that the risk is less than feared and that reported
Because at the time of purchase in February 2006 this
cases are probably incipient keratoconus cases that
was the only instrument allowing LASIK and epi-
were not previously diagnosed.
LASIK and because the Amadeus had an excellent
Personal Indications for Surface-Epi-LASIK track record for lasik surgery. We have not been
disappointed in this 16 months period since we could
For us the indication for Surface Ablation is preferred not register one single breakdown or failure in using
in the equipment in over 900 eyes.
1. The presence of corneal irregularities that could Besides that the Amadeus is extremely versatile
point towards incipient keratoconus, allowing placement of the hinge in all directions,
2. Cases with a thin cornea (i.e. less than 500 μm for
nasally as well as temporally. We also experienced
–3.00 D and up),
that the pressure applied during the suction for
3. Patients practicing violent sports such as karate
Surface (560 mmHg) was extremely well tolerated
boxing etc;
by the patient. Not one of our patients experienced
4. After previous ocular surgery such as retinal
pain or real discomfort during the procedure.
detachment -glaucoma.
5. Patients with an extreme form if dry eye condition.
Complications
When the decision for Surface is made, our choice
is epi-LASIK, using a separation device such as the In the 16 month period we had not one technical
Amadeus II (Advanced Medical Optics, Inc., Santa difficulty using the instrument. It worked always
Ana, California) - Performing the epithelial separation smoothly and the application was always possible
using a mechanical device is more elegant (i.e. think even in eyes with small palpebral fissure. In around
on PR-produces a nicer flap) is less toxic (i.e. no 4 % of cases we had to use the instrument without a
alcohol), and results in less pain and discomfort in speculum because of narrow palpebral fissure or
the healing period according to the reports mentioned deepset eyes and this worked out without any
earlier in this chapter. problem.
We always send the patients home with a video We never experienced incursion of the blade into
registration of their own surgery and looking at the the corneal stroma. Over the whole period not one
procedure effectuated by a mechanical device is much case of infection was registered.
more - state of the art - than looking at the manual Also enhancements after previous epi-LASIK or
debridement with a blunt rude instrument. Lasik and PRK as well as Primary epi-LASIK after
306 Mastering Advanced Surface Ablation Techniques
previous Radial Keratotomy were feasible without At day five the epithelium is healed in more than
any difficulty. 95% of eyes and the bandage contact lens is removed.

Technique Excimer Laser Treatment

Preparation: three days before treatment patients The laser treatment is done using the Carl Zeiss
have to apply a cleaning rinsing product on the Meditec laser with eye tracker (Figure 33.10); this is
eyelashes twice a day in order to get rid of eventual a flying spot laser with the following characteristics:
contamination.
All our patients get a preparation with Clozan® in
the waiting area as an anxiolyticum and three times a
drop of Ciloxan® at ten minutes interval before
treatment. Patients treated are mixed with the patients
waiting for surgery so that they can openly exchange
experiences; besides that video camera’s are
transmitting the images of the surgery room to the
waiting area where friends of family members can
watch. This is extremely reassuring for the patients.
Patients get their first drops of anesthetic
(Unicain®; oxybuprocaïne) on the surgery table. We
guide the patients through the procedure so that
nothing unexpected will appear and they appreciate Figure 33.10: Zeiss Mel 80 Laser

that very well.

• Gaussian beam
The pressure of the Amadeus is set at 560 mm Hg – 0.7 mm effective ablation spot size
with the Amadeus II for epi-LASIK. The hinge width • Optimized lower treatment time
is set at 1.1 to 1.2 mm according to the corneal diameter, – Shot frequency 250 Hz
the speed is set at 1.5 mm per second in contrast to – Increased beam fluence/ablation rate
LASIK where the speed is 2.5 to 3.0 mm per second. – Proprietary shot-distribution pattern
The tables advice on the width of the ring, usually - Minimizing surface heating effects
9 mm will be ok. The ring should be smaller for small • IR video tracking:
corneas and steep eyes and larger for the opposite. – Ultrafast video tracking (real 250 Hz) - pulsed IR
At the end of the procedure after eventual – Auto-pupil centration
application of MMC (if more than 80 Micron ablation) The laser is FDA approved in the USA for myopia
and pouring iced water (see earlier) one drop of and myopic astigmatism and is CE marked in Europe
Aculare Rand of Ciloxan® is applied followed by the for myopia hyperopia astigmatism and topolink.
The predictability, accuracy and safety range of this
bandage contact lens.
laser is remarkable. Recently Oculign Iris Registration
The day of surgery and the four days to follow
was added; this compensates for an eventual X Y
all patients get a regimen of conservative-free artificial offset and cyclo- torsion during the treatment.
tears (Oculotect Unidose) each hour during the day,
Tobradex® (tobramycine-dexamethasone) and RESULTS OF EPI-LASIK USING AMADEUS II
Aculare® 4x day.
At day 4 after surgery the bandage contact lens is Methods
removed and the regimen is changed to artificial tears For this study we retrospectively reviewed 226 eyes
4 to 8 times a day according to the necessity during treated for myopia and myopic astigmatism using
at least 6 weeks and FML® fluorometholone 3xday the Amadeus II with epi-LASIK technique. We
during 4 weeks and 2xday for another 2 weeks. analyzed the data at 1, 3 and 12 months.
 Epi-LASIK Personal Experience with the Amadeus II 307
As usually happens, happy and satisfied patients • Mean UCVA: 0.98+/–0.22
don’t come back for follow- up visits unless they are • Mean Sf.Eq.: 0.12+/–0.36 D
extremely motivated (means when they are paid for At that time not one had lost 2 lines or more and
it), so the number of patients tested at 12 months is 20 eyes had gained 2 lines or more.
small. At one year all eyes were within 0.5 of intended
correction.
Preoperative Data The surgery went without any complications in
The preoperative myopia ranged between –0.25 and all eyes; we never experienced incursion of the
–8.75 D: the mean value being –3.72 SD +/–2.08 D. keratome into the stroma and in more than 95% of
The cylinder value ranged between 0 and –4.5D: eyes the procedure provoked only a slight
the mean value being –0.98 +/–1.03 D. disturbance without any pain. In the other 5%
The mean preoperative BSCVA (best spectacle additional comfort (tetracaïne® 0.1%) drops were
corrected visual acuity) was 0.96+/– 0.14: only eyes applied x4 day.
with a BCVA of at least 0.7 were included.
Comment
At one month results were as follows:
Reviewing our data and comparing them to our
• Mean BSCVA: 0.92+/–0.17
LASIK data50 we found that
• Mean UCVA (uncorrected visual acuity): 0.77+/–
1. It took longer time for the epi-LASIK eye to
0.26
achieve the Optimal UCVA. The first four days
• Mean Sf.Eq. (spherical equivalent): –0.037+/–0.52
after surgery the majority of them was incapable
D
of performing at 100% activity. Also at one month
• At that time 46 eyes had lost 2 lines or more and
the mean UCVA was 0.77 compared to 0.94 at three
30 eyes had gained 2 lines or more of BSCVA.
months: this is caused by the epithelial remodeling
At three months results were as follows and by the slight haze present in these eyes during
• Mean BSCVA: 1.04+/–0.13 healing. (Figure 33.11)
• Mean UCVA: 0.94+/–0.22 2. Once the healing period is finished the outcomes
• Mean Sf.Eq.: –0.014+/–0.26 D for UCVA and BCVA are excellent; at three
• At that time not one had lost 2 lines or more and months the mean UCVA was 0.94 and this even
60 eyes had gained 2 lines or more. improved to 0.98 at one year.
• At three months 208/226 = 92 % eyes were within 3. The safety record of this procedure is also
+/–0, 5 D; of intended correction, and 224/226 remarkable; although 46/226 eyes lost two lines
= 99% of eyes were within +/–1.0 D; only 2 eyes of BCVA at one month (due to healing);at three
(with a preop astigmatism of more than 3 D.) had months not one eye lost two lines or more and 60/
an refractive outcome of –1.25 D of intended 226 eyes gained two lines or more of BCVA. With
correction. LASIK we obtained similar results; at one year 13%
All our treatments were done with the Mel 80 of eyes gained two lines of BCVA (Figure 33.12).
Zeiss laser using the appropriate ablation profiles. 4. The predictability using the combination of epi-
At three months not one eye had a haze of more LASIK with the Amadeus II and the Zeiss Mel 80
than 0.5; haze was zero in the huge majority of eyes laser was excellent; at three months 92% of eyes
(over 90%). and at one year 100% of eyes were within +/–0.5
At that time a redo - enhancement - was done or D of intended correction. With LASIK using the
planned in 18/226 eyes = 7%. Mel 80 laser at one year 96% of eyes were within
At one year follow-up only 40% of patients were +/–0.5 D (Figure 33.13).
available and results were as follows: 5. The efficacy index (UCVA post compared to BCVA
• Mean BSCVA: 0.99+/–0.14 pre) was extremely good; at one year 0.98/0.96 =1.02.
308 Mastering Advanced Surface Ablation Techniques

Figure 33.11: UCVA and BCVA at 1 (green) 3(red) and 12 (yellow) months after EpiLasik with Amadeus II.
1.0 equals 20/20;0,5 equals 20/40

Figure 33.12: Safety at one and three months

6. The stability was excellent; mean Sf.Eq. at three CONCLUSION

months was –0.014 compared to 0.12 at one year
Literature reviews demonstrate that
(Figure 33.14).
1. Epi-LASIK is a safe and accurate technique.
 Epi-LASIK Personal Experience with the Amadeus II 309

Figure 33.13: Predictability at 3 (green) and 12 months (red)

Figure 33.14: Stability of refraction up to one year after epi-LASIK

2. The haze discomfort and pain after epi-LASIK using 2. The outcomes, once the healing period is finished,
appropriate techniques are less than after LASEK. are as good as best outcomes with LASIK; 92%
3. The Amadeus II is an excellent and safe instrument of eyes +/–0.5 D at three months and 100% at one
to perform epi-LASIK. year.
Our personal results demonstrate that: 3. The treatment is extremely safe; not one eye losing
1. The healing takes longer with epi-LASIK than after BCVA at three months or later on and 17 % gaining
LASIK. two lines at one year (Figure 33.15).
310 Mastering Advanced Surface Ablation Techniques
13. Netto et al. Wound healing in the cornea: a review of
refractive surgery complications and new prospects for
therapy. Cornea. 2005;24:509-22.
14. O’Doherty et al. Postoperative pain following epi-LASIK,
LASEK, and PRK for myopia. J Refract Surg. 2007;23:133-
8.
15. Torres et al. Early postoperative pain following Epi-LASIK
and photorefractive keratectomy: a prospective,
comparative, bilateral study. J Refract Surg 2007;23:126-
32.
16. Dai et al. One-year outcomes of epi-LASIK for myopia. J
Refract Surg 2006;22:589-95.
17. Katsanevaki et al. One-year clinical results after epi-LASIK
for myopia. Ophthalmology 2007,22.
18. Mitchell R. My first 1.000 Epi-Lasik cases. Ophthalmology
Management March 2007.
19. Fishman Ophthalmology Times 2006.
20. Chen et al. Stromal cells change after epipolis laser in situ
Figure 33.15: Summary
keratomileusis and laser-assisted subepithelial
keratectomy in rabbits. Zhonghua Yan Ke Za Zhi
REFERENCES 2006;42:796-801.
21. Katsanevaki et al. Epi-LASIK: histological findings of
1. Camellin M et al. LASEK technique promising after 1 separated epithelial sheets 24 hours after treatment. J
year of experience. Ocular Surg News 2000;18:14-17. Refract Surg 2006;22:151-4.
2. Camellin M. Laser epithelial keratomileusis for myopia. J 22. Kalyvianaki et al. Comparison of corneal sensitivity and
Refract Surg 2003;19:666-70. tear function following Epi-LASIK or laser in situ
3. Anderson et al. Epi-LASEK for the correction of myopia keratomileusis for myopia. Am J Ophthalmol.
and myopic astigmatism. J Cataract Refract Surg. 2006;142:669-71.
2002;25:1343-7. 23. Long et al. Correlation between TGF-beta1 in tears and
4. Azar et al. Laser subepithelial keratomileusis: electron corneal haze following LASEK and epi-LASIK. J Refract
microscopy and viusal outcomes of photorefractive Surg 2006;22:708-12.
keratectomy. Curr Opin Ophthalmol 2001;12:323-8. 24. Taneri S. Epi-LASIK after amputation of a LASIK flap. J
5. Lee et al. Comparison of laser epithelial keratomileusis Refract Surg 2006;22:613-6.
and photorefractive keratectomy for low to moderate 25. Donnenfeld et al. The effect of hinge position on corneal
myopia. J Cataract Refract Surg 2001;27:565-70. sensation and dry eye after LASIK. Ophthalmology.
6. Pallikaris et al. Advances in subepithelial excimer 2003;110:1023-9.
refractive surgery techniques: Epi-LASIK. Curr Opin 26. Hoffmann et al. Impact of head advance and oscillation
Ophthalmol 2003;14:207-12. rate on the flap parameter: a comparison of two
7. Pallikaris et al. Epi-LASIK: Comparative histological microkeratomes. Graefes Arch Clin Exp Ophthalmol
evaluation of mechanical and alcohol-assisted epithelial 2003;241:149-53. Epub 2003 Jan 28.
separation. J Cataract Refract Surg 2003;29:1496-1501. 27. Jabbur et al. Incidence of intraoperative corneal abrasions
8. Gabler et al. Vitality of epithelial cells after alcohol and correlation with age using the Hansatome and
exposure during laser-assisted subepithelial keratectomy Amadeus microkeratomes during laser in situ
flap preparation. J Cataract Refract Surg 2002;28:1841-6. keratomileusis. J Cataract Refract Surg 2003;29:1174-8.
9. Kim et al. Twenty percent alcohol toxicity on rabbit corneal 28. Jackson et al. Accuracy and precision of the Amadeus
epithelial cells: electron microscopic study. Cornea microkeratome in producing LASIK flaps. Cornea.
2002;21:388-92. 2003;22:504-7.
10. Chen et al. Human corneal epithelial cell viability and 29. Thompson et al. Noncontact optical coherence
morphology after dilute alcohol exposure. Invest tomography for measurement of corneal flap and
Ophthalmol Vis Sci 2002;43:2593-2602. residual stromal bed thickness after laser in situ
11. Stramer et al. Molecular mechanisms controlling the keratomileusis. J Refract Surg 2003;19:507-15.
fibrotic repair phenotype in cornea: implications for 30. Tehrani et al. Evaluation of cut quality using the Amadeus
surgical outcomes. Invest Ophthalmol Vis Sci microkeratome with different settings. J Cataract Refract
2002;44:4237-46. Surg 2004;30:2415-9.
12. Pallikaris et al. Epi-LASIK: preliminary clinical results of 31. Solomon et al. Flap thickness accuracy: comparison of 6
an alternative surface ablation procedure. J Cataract microkeratome models. J Cataract Refract Surg
Refract Surg. 2005;31:879-85. 2004;30:964-77.
 Epi-LASIK Personal Experience with the Amadeus II 311
32. Chan et al. Amadeus microkeratome: experience with 38. Bedei et al. Photorefractive keratectomy in high myopic
the first 2000 cases and lessons learned. Clin Experiment defects with or without intraoperative mitomycin C: 1-
Ophthalmol 2005;33:356-9. year results. Eur J Ophthalmol 2006;16:229-34.
33. Güell et al: Corneal flap thickness and topography changes 39. Netto et al. Effect of prophylactic and therapeutic
induced by flap creation during laser in situ keratomileusis. mitomycin C on corneal apoptosis, cellular proliferation,
J Cataract Refract Surg 2005;31:115-9. haze, and long-term keratocyte density in rabbits. J Refract
34. Hammer et al. Evaluation of four microkeratome models: Surg 2006;22:562-74.
quality and reproducibility of cut edge and cut surface as 40. McDonald Marguerite: Why I … my microkeratome.
determined by scanning electron microscopy. J Refract Review Ophthalmol 2005;80-1.
Surg 2005;21:454-62. 41. Donnenfeld Eric Review Ophthalmology 2005;80-1.
35. Carones et al. Evaluation of the prophylactic use of 42. Soloway B. Review Ophthalmology 2005.
mitomycin C to inhibit haze formation after 43. Stein R. Review Refractive Surgery 2005.
photorefractive keratectomy. J Cataract Refract Surg 44. Tetz M. Review Ophthalmology 2006;37-43.
2002;28:2088-95. 45. Milne. Review Ophthalmology 2006;37-43.
36. Camellin M. Laser epithelial keratomileusis with 46. Rashid. Review Ophthalmology 2006.
mitomycin C: indications and limits. J Refract Surg 47. Lackerbauer C. XXIV Congress of ESCRS 2006.
2004;20:693-6. 48. Kollias A. XXIV Congress of ESCRS 2006.
37. Lacayo GO, Majmudar PA. How and when to use 49. Gamaly T. XXIV Congress of ESCRS 2006.
mitomycin-C in refractive surgery. Curr Opin Ophthalmol 50. Goes. Lasik for myopia with the Zeiss Meditec Mel 80.
2005;16:256-9. J Refract Surg 2005;21:691-7.
312 Mastering Advanced Surface Ablation Techniques

CHAPTER

34 Presby-Epi-LASIK in
Pseudophakic Eyes with the
Wavelight Allegretto

Frederic Hehn (France)

INTRODUCTION lens). That’s the reason why we are thinking that

presbylasik technique does not increase the natural
Presby-LASIK has got now a worldwide acceptance
existent coma. Then to avoid to increase coma presby-
among ophthalmologists community.
LASIK must be centered. Inspired of multifocal or
In some cases LASIK is not possible, then we
bifocal soft lens for presbyopia, that’s give good
practice epi-LASIK. Presby-LASIK in pseudophakic
results in many cases, the therapeutic choice will be
eye make sense to proof the truthfulness of the optical
to place distant vision in center or not. Some authors
basement of this technique; and consequently the
have got good results with a small optical zone for
durability of the results in phakic patients. In this
near vision in the the very center cornea.
article we analyze the relationship between Q value
asphericity and the amount of spherical aberrations.
We observe what’s happen during accommodation;
propose 3 shapes of corneal presbyopia compensa-
tion, and finally give some examples with topolink
treatments.
Natural eye is a bioptic optical system with a variable
axial myopic additional power due to the crystalline
lens. Because evidently along visual axis (object to
macula) the vision will be the more discriminate with
Figure 34.1: Coma
the best contrast sensitivity and MTF (modulation of
transfer function ) for the both near and far vision. This RELATIONSHIP BETWEEN Q VALUE ASPHERICITY
bioptic system produces the best near and distant visual AND AMOUNT OF SPHERICAL ABERRATIONS
acuity, in using crystalline lens accommodation which
can be achieve. Because Presby-LASIK can not restore The difficulty is to understand that, the Q value
accommodation, it just can be a good compromise asphericity and the spherical aberrations (SA) make
between near and distant vision. change together, but they haven’t got the same 0
Natural eye present some coma HOA due to the reference. Q value is due to the difference of
difference between visual axis (object to macula) and keratometry between the center cornea and the
optical axis (apex of cornea to the center of crystalline medium cornea ( 6.5 mm OZ). If keratometry increase
 Presby-Epi-LASIK in Pseudophakic Eyes with the Wavelight Allegretto 313

Figure 34.2: Q value and SA relationship

from the central to the peripheral cornea Q value is pseudokeratoconic corneal ectasia. But there are many
positive, and the cornea profile is called oblate. At publications about ectasia even in case of previous
the contrary Q value is negative and the cornea profile hyperopic eye, or sufficient residual stromal bed more
is called hyperprolate. In normal cornea mean Q < 0 than 250μ. The last years it appears that biomechanical
(– 0.25) and SA >0 (0.25μ). If the keratometry is properties of the cornea have to be considered.
constant the cornea profile is spherical Q = 0, and Especially the corneal hysterisis CH, which measures
SA >> 0 (1μ or more). If Q value = –0.55 then SA = 0. the combined elasticity and viscosity of the cornea,
These basements are checked up in the with the ora machine. ORA ocular response analyzer
(Figure 34.2). is now a routine exam in our office before presby-
Q value is measured by the topograph, for instance LASIK. In considerations with others parameters:
the TOPOLYZER of wavelight, it can give also the corneal thickness, topography, If CH < 9 we practice
amount of SA due to the cornea. At the contrary the an epi-LASIK instead of a LASIK.
aberrometer like ANALYZER of wavelight , measure We have choice the epilasik GEBAUER, because
the total SA of the both corneal and crystalline lens. the procedure is very fast only 20 seconds. The
Generally negative SA occurred in the crystalline , and epilasik head present an applanation plate and a
positive SA in the cornea, therefore the total amount special shape of one single use blade. In fact the blade
of SA in young people is often null. edge is not symmetrical. The angle of posterior face
of the blade is minor than the anterior angle. That
WHY EPI-LASIK IS NECESSARY IN SOME CASES
the reason why stromal intrusion is impossible, and
It’s well know that a thin cornea < 500 μ, has not to multiple enhancements with epi-LASIK after a
be treated by LASIK, according with the risk of previous epi-LASIK on the same eye are possible.
314 Mastering Advanced Surface Ablation Techniques

Figure 34.3: Ocular response analyzer

Figure 34.4: EpiLift: asymmetrical blade avoid stromal injuries

Epi-LASIK creates a very thin epithelial flap, cornea. This haze can give regression and halos.
which needs a contact lens wearing, during 3 days to That’s the reason why we definitively treat hyperopic
ensure his stability and healing. We must be careful by LASIK or Femtosecond.
with the management of the contact lenses, especially
INTEREST OF USING A SPHERICAL ABERRATION
no water must entry inside eyes to avoid
FREE IOL TO CORRECT PRESBYOPIA IN PSEUDO-
acanthameoba infection. The second problem with
PHAKIC EYE
epi-LASIK is the risk of haze. About more than
personal 500 cases we’ve got no haze grade 3 or 4 in If we are using the B and L akreos adapt IOL, Q value
myopic eyes, if enough steroid drops have been of this IOL is –0.55 then it creates no SA. Therefore, the
instilled (four times a day, during 8 weeks). At the crystalline implantation does not modify the corneal
contrary it remains a haze grade 3 or 4, in hyperopic rebuilt shaping for presbyopia compensation. A
treatment, as the shape of a concentric ring in medium pseudophakic eye with this kind of IOL, give us a pure
 Presby-Epi-LASIK in Pseudophakic Eyes with the Wavelight Allegretto 315

Figures 34.5 and 34.6: Corneal multifocality can give intermediate and near vision in pseudophakic eyes

human corneal model, to well understand what exactly aberration. We have verified this fact in using our
presby-LASIK does. Secondly Presby-LASIK in tcherning wavelight aberrometer system and obtain
pseudophakic eye make sense to proof the truthfulness exactly the same results: We place our 16 years old son
of the optical basement of this technique; and behind aberrometer and present to him myopic lens to
consequently the durability of the results in phakic turn he to hyperopia and force he to accommodate; we
patients. And we are thinking that: When our patients relate these results as shown in Figure 34.7 and 34.8.
would have been cataract surgery, they would keep Then presby-LASIK must mime natural accommoda-
the results of their previous presby-LASIK. Monofocal tion with Q value negative, ideally Q = – 1.00 and
IOL give a good distant vision (DV). But the patient, increasing negative spherical aberration. The
due to the natural multifocality of the cornea, can have variation between preop and postop SA has to be
also an intermediate vision (iv): that’s called the depth Δ SA = – 0.130 μ for 3 diopters of accommodation.
of focus. By a modification of the SA of the cornea it Then we have to pass from a prolate cornea to a
will be possible to increase the depth of focus until hyperprolate cornea; hyperprolate cornea
patient will be able to read without glasses. = pseudoaccommodative cornea.

WHAT HAPPENS WITH Q VALUE AND SA DURING Three Profiles of Centred Presby-LASIK which
ACCOMMODATION can Give Q = – 1.00
Distant Vision in Central Cornea
The augmentation of anterior curvature of the crystalline
lens give a myopic shift with an increasing of Z2,0 The centered presby-lasik technique with distant
zernike polynoma : Without myopia no near vision vision in the center give a very good distant vision
possible. But in concern of HOA only spherical and a useful optional near and intermediate vision.
aberration C12 or Z4,0 have significant modification The difficulties remain the necessity to get high
according to a study (2). These authors demonstrate luminance for reading a book. The goal of presby-
that during accommodation the variation of spherical lasik is not to completely erase spectacles but to
aberration are always negative, and most interesting decrease the patient’s glasses dependency. Figures
point is that variation is precisely and linearly correlated 34.10 and 34.11 shows ideal presby-LASIK profile.
to the amount of accommodation in using a hartmann- This way give excellent distant vision and an
shak aberrometer system. Variation of SA = –0.0435 μm optional useful near and intermediate vision. We
/diopter. Therefore, 3 diopters of accommodation practice at first a hyperopic treatment of
correspond to a variation of – 0.130 μ m in SA. Presby- + 3.00 diopters on a large 6.5 or 7.0 mm OZ to get a
LASIK technique must simulate accommodation in good near vision. Secondly we performed a myopic
creating a myopic zone and also negative spherical treatment of – 3.00 on a small OZ depending on pupil
316 Mastering Advanced Surface Ablation Techniques

Figures 34.7 and 34.8: During crystalline accommodation SA decrease of –0.130 µ for 3 diopters

Figure 34.9: Hyperprolate corneal shape looks like lens accommodation

Figures 34.10 and 34.11: Distant vision in central cornea is a natural shape
 Presby-Epi-LASIK in Pseudophakic Eyes with the Wavelight Allegretto 317
size to get a very good vision in central cornea as treatment. That’s the best of because, that’s give large
naturally it is. We measure also our results in using OZ. It’s a good compromise for emmetropic and
the TOPOLYZER topograph of wavelight. We are hyperopic eyes. the resulting shape is a continuous
using the very precise allegretto wavelight, argon hyperprolate shape.
fluor excimer laser , with a little flying spot of 0.8 mm Near vision will be excellent, but distant vision
diameter and a high speed delivery system of 400 Hz, could be poorer. This technique is perfect for large
and eye tracker so. This first presby-LASIK approach pupil.
gives an annular ring in medium cornea for near
vision. Direct Q Value Adjustment with F-CAT
This profile is useful in case of small pupil, and In the F-CAT program allegretto we can choice a
for myopic eye. In myopic eye you have just to make a Q value target. If we choice the Q value = – 1.00, the
myopic treatment on a small OZ. It’s very tissue saving, results are the sames that the second technique. But
but the very oblate profile, can gives some halos. the real useful OZ will be smaller, and we must be
careful to compensate the hyperopic shift induce by
Near Vision in Central Cornea
this treatment. For a constant OZ of 6.50 mm, each
We make exactly the contrary; like some authors do variation of – 0.1 of Q value induce approximately
(1); at first myopic treatment and secondly hyperopic + 0.13 hyperopic shift.

Figures 34.12 and 34.13: Distant vision in central cornea is excellent, but near vision is only useful

Figures 34.14 and 34.15: Near vision in central cornea is excellent, but distant vision is only useful
318 Mastering Advanced Surface Ablation Techniques

Figures 34.16 and 34.17: If Q value decrease, OZ decrease also

Preferential Multifocality could be a Good CLINICAL EXAMPLES

Compromise
We show results in two examples of pseudophakic
Each eye see the both distant and near vision without patients with monofocal IOL.
glasses but the dominant eye get a better distant
vision that near vision, and the dominated eye can Distant Vision in Central Cornea
get a better near vision that distant vision. In this The first patient a 53 years old man has got
example right eye is treated with the first technique: hydrophilic STABIBAG IOLTECH laboratories in
Distant vision in central cornea, the left eye is treated the both eyes. In this case we remark some
with near vision in central cornea. It results a excellent irregularities in the topographic map due to the fact
binocular distant, near and intermediate vision, with in this first case studying we have not ever practice a
a good defocus curve, as we can see in the next previous A-CAT ( aberrometric customized ablation
chapter about clinical example. treatment ) treatment to make sure to get a free HOA

Figure 34.18: Preferential multifocality could be a good compromise

 Presby-Epi-LASIK in Pseudophakic Eyes with the Wavelight Allegretto 319
eye before performing presby-LASIK. The second Near Vision in Central Cornea
point is that this patient get in monocular vision very The both eyes have got a corneal excentricity = 1.00
good results on the defocus curve. That’s a proof of that’s mean that Q value = – 1.00.
very good depth of focus with this technique as so This patient previously emmetropic, obtained an
good than with MF IOL it is. excellent results with 20/20 j1 uncorrected binocular vision.

Figure 34.19: Bilateral distant vision in center

Figure 34.20: Excellent defocus cuve

320 Mastering Advanced Surface Ablation Techniques

Figure 34.21: Bilateral near vision in the very central cornea

T-CAT is the Clue at a point which is approximately the point of fixation

Topolink can compensate the angle kappa. Angle of the patient. In the case of a topographic
kappa is due to the difference between visual axis measurement, we consider that the point of fixation,
(object to macula) and the center of the pupil. This is the center of the very center ring of the machine.
angle is calculated by the topograph. The topolyzer If angle kappa it is more than 100 μ, the laser
wavelight gives the both angle kappa and the treatment, even in case of a spherical treatment can
dynamic pupillometry which can help surgeon to induce the both coma and astigmatism. Then we have
adapt the OZ of the treatment with the pupil size in to consider angle kappa especially in hyperopic eye,
mesopic and photopic conditions, especially in case with often nasal fixation, enhancement for
of presby-LASIK. The visual axis, crosses the cornea decentration, and dual treatment like presby-LASIK.

Figure 34.22: Angle kappa

 Presby-Epi-LASIK in Pseudophakic Eyes with the Wavelight Allegretto 321
Secondly presby-LASIK occurred generally in optional near and intermediate vision. At the contrary
older patient than in LASIK; it will be not logical to near vision in the center give only a useful distant
treat crystalline aberrations. Because after the vision. That’s the reason why, preferential
crystalline lens extraction reveal some others new multifocality could be a good compromise. The goal
HOA.Then it’s preferential to modify only the cornea of presby-lasik is not to completely erase spectacles
and do not compensate the crystalline aberrations. but to decrease the patient’s glasses dependency.
Finally in case of pseudophakic eye, the wavefront T-CAT treatment is the clue for preby-LASIK or
data are often not available, because there a capular presby-EpiLASIK in the both phakic and
fibrosis, and pupil distorsion, and a lot of reflexion pseudophakic eyes. Presby-LASIK seems to get as so
of the laser ray. Then often wavefront measurement good results as Multifocal IOL , especially in terms
are not valid in case of pseudophakic eye. on intermediate vision, and defocus curve. Is presby-
Therefore we have three reasons to use only T- LASIK will become a non-penetrative alternative of
CAT treatment for preby-LASIK or presby-EpiLASIK the clear lens exchange?
in the both phakic and pseudophakic eyes.
REFERENCES
CONCLUSION
1. Alio JL, Chaubard JJ, Caliz A, Sala E, Patel S. Correction
Presby-LASIK could be logically compensate of presbyopia by technovision central multifocal LASIK
presbyopia in emmetropic pseudophakic eye with (presby-LASIK). J Refract Surg 2006;22(5):453-60.
2. Cheng H, Barnett JK, Vilupuru AS, Marsack JD,
monofocal IOL, like the MF IOL do. The centered Kasthurirangan S, Applegate RA, Roorda A. A population
presby-lasik technique with distant vision in the study on changes in wave aberrations with
center give a very good distant vision and a useful accommodation. J Vis 2004 Apr 16;4(4):27.
322 Mastering Advanced Surface Ablation Techniques

CHAPTER
Advances in Epi-LASIK:
35 Surface Ablation Procedure

Vikentia J Katsanevaki, Maria I Kalyvianaki,

Ioannis G Pallikaris (Greece)

INTRODUCTION order to control the major drawbacks of PRK, i.e.

the postoperative pain and the risk of haze formation.
Since the introduction of excimer lasers for
The modification of the surgical technique as
photorefractive corrections the surgical trends are
compared to the conventional PRK, was the separation
continuously changing in order to achieve the best
of corneal epithelium as a sheet rather than its
possible clinical results with minimal complications.
scrapping prior to the photo ablation. This epithelial
Photorefractive Keratectomy (PRK) initially
sheet which is separated in toto and is replaced onto
introduced in the beginning of 90s1,2 was the first
the ablated cornea, is thought to act as a natural
technique to be used for photo refractive corrections.
contact lens on the operative eye10 is expected to
Despite its encouraging results for low and moderate
control the epithelial healing and thus provide better
myopia, during the evolvement of refractive surgery
postoperative results as compared to PRK.
PRK was partially abandoned mostly due to the
postoperative pain of the treated patients as well as EPI-LASIK: AN EVOLVING TECHNIQUE
the risk of corneal postoperative haze. Laser in situ
keratomileusis (LASIK),3,4 which involves the ablation The separation of the epithelial sheet in LASEK as
deeper in the stroma after the creation of a corneal described by Camellin, requires the preparation of
flap, soon became popular among refractive the cornea with a short-term exposure to a diluted
surgeons. Providing fast visual rehabilitation as well (18%-20%) alcohol solution. In order to avoid the
as the ability to correct higher degrees of ametropias probable toxic effect of alcohol on the epithelium and
LASIK is currently the undisputable leader within the underlying stroma13, 14 Pallikaris described Epi-
photorefractive treatments. However, LASIK is not LASIK.11,12 With this modality, the epithelial sheet is
without complications. Complications unique to separated mechanically with the use of a customized
LASIK such as those related to the use of the device (Centurion Epiedge Epikeratome, Ciba Vision
microkeratome,5,6 LASIK induced diffuse lamellar Surgical, GA) without the need of prior corneal
keratitis7 and the increasing reports of LASIK patients preparation with alcohol. This device has recently
that developed corneal ectasia8; have set the stage granted CE mark and 510K aproval for clinical use
for the revival of surface treatments. and is commercially available. Epi-LASIK, 11,12 is
Laser subepithelial keratomileusis9 (LASEK) was currently the treatment of choice for low myopia in
the first attempt to modify surface treatments in the University of Crete and up to now has been
 Advances in Epi-LASIK: Surface Ablation Procedure 323
performed in more than 400 eyes worldwide (Figure
35.1). Its name is derived from the Greek word
“epipolis’’ that means superficial and LASIK.

Figure 35.1

HISTOLOGICAL FINDINGS OF MECHANICALLY

SEPARATED EPITHELIAL SHEETS

Transmission electron microscopy of harvested

epithelial sheets in eyes that the treatments were
reversed to PRK demonstrated that the cleavage plane
of mechanical separation was located under the level
of the basement membrane.11 Basal epithelial cells
had normal morphology with minimal evidence of Figure 35.2

trauma and edema and rested upon the prominent EPI-LASIK: THE SURGICAL PROCEDURE
basal lamina, which consisted of an apparently
structure less lamina lucida and an electron-dense The operative eye is prepared with three drops of
lamina densa. Under the basal lamina an upper part topical tetracaine hydrochloride 0.5% (applied every
on Bowman layer was evident in the epithelial sheets 5 minutes before the procedure) and povidone-iodine
(Figure 35.2). Intracellular organelles and intercellular and is covered with a sterile drape. Before the
desmosomal connections, as well as hemidesmosomal epithelial separation the cornea is marked with a
connections with the basement membrane appeared customized Epi-LASIK marker (Epi-LASIK marker,
close to normal with only focal disruptions. Duckworth and Kent, Baldock, UK). This marker
Alcohol assisted epithelial separations are reported features two concentric circles crossed by 8 radial
to take place within the basement membrane thus arms. Upon the replacement of the epithelial sheet,
affecting its integrity. 11, 15,16 The presence of an intact any deformity of the preoperative marks dictates its
basement membrane has been shown to be important proper repositioning.
in the control of epithelial wound healing17 minimizing The Centurion EpiEdge Epikeratome is an
the fibrotic activation of keratocytes. Even though electrically powered device (Figure 35.3) that
alcohol solutions are not reported toxic in the specific operates under low suction similarly to a conventional
concentrations and exposure times that are advocated microkeratome. Instead of a blade it features a
for epithelial separations in LASEK18, 19, mechanical disposable, oscillating polymethylmethacrylate (PMMA)
separation appears to have the advantage of a deeper separator with an advance speed of 3.5 mm/sec.
cleavage plane over alcohol assisted separations thus The resulting separated epithelial sheet has a nasal
being expected to provide better control of corneal hinge and a diameter of 9.5 to 10 mm. Any
healing within the first postoperative days. manipulations of the epithelial sheet both for its
324 Mastering Advanced Surface Ablation Techniques
reflection and replacement, are performed with the constricted in the central area. Starting from its
use of a moistened sponge. The replacement of the peripheral part around the edges on the first
separated epithelial sheet is often achieved with a postoperative day the sheet becomes hazy in its total
single movement. Any inward or outward folds of area until about the third day after the treatment. At
its edges can be restored with the use of an anterior that time the hazy area measures about the central
chamber irrigation canula under constant irrigation. 1 to 2 mm whereas a front of newly synthesized,
Once the epithelial sheet is stuck to the underlying transparent epithelium migrates from the corneal
stroma, a therapeutic contact lens is applied onto the periphery towards the center of the corneal surface.
operative eye. After that stage, the transparency of the corneal
epithelium is restored within 24 to 48 hours and the
therapeutic contact lens is removed. The time of
epithelial healing ranges from 3 to 5 days between
the treated eyes.

CLINICAL RESULTS

Up to date we have performed 183 mechanically

assisted epithelial separations in the University of
Crete. 76 eyes were left to heal as Epi-LASIK whereas
the rest of the separated sheets underwent
Figure 35.3 histological evaluation and the treatments were
reversed to PRK. The preoperative spherical
equivalent of the treated eyes was up to –7.75 D,
POSTOPERATIVE TREATMENT
with cylinder up to –2.25 D. Postoperative pain of
Postoperative treatment includes eye drops of the treated patients was assessed subjectively with a
Diclofenac sodium 0.1% qid for two days and use of a questionnaire that graded pain in a scale
combined eye drops of tobramycin-dexamethasone from 0 to 4. The patients graded postoperative pain
qid until the removal of the therapeutic lens. After in two-hour intervals on the operative day and once
the removal of the lens all treated eyes receive daily in the following days. No patient reported pain
fluorometholone eye drops qid for five weeks in a after the operative day.On the operative day, the
tapered dose. Artificial tears are prescribed to be used mean scores remained below the threshold of pain
at the patients’ discretion. in the reported series of eyes (Figure 35.4). Similarly
as after LASEK,25, 26 epi-LASIK was not proved a
EARLY POSTOPERATIVE COURSE totally pain-free procedure. We observed that
At the end of the surgery, the replaced epithelial sheet discomfort or pain was mainly reported within the
often overlays its initial gutter probably due to the first postoperative hours. In order to deal with this
intraoperative mechanical stretch on the epithelial finding we included intraoperative corneal cooling
sheet upon separation. Immediately after the in the standard treatment of the last 20 eyes. We
operation the epithelial sheet is transparent. During cooled the cornea immediately before the separation
the healing process of the surface, slit lamp and after the ablation with the instillation of pre-
biomicroscopy reveals the borderline between the freezed balanced salt solution. After this alteration
migrating epithelium and the remnants of the of the technique, the reported discomfort was below
separated sheet. The migrating cells gradually replace the threshold of pain in all patients even in the first
the separated epithelial sheet, which is subsequently postoperative hours.
 Advances in Epi-LASIK: Surface Ablation Procedure 325
epithelial basement membrane. In contrast to the
varying solution dilutions and exposure times
required for alcohol assisted separations 20-22 the
epikeratome can achieve mechanically assisted
separations in a repetitive and fully automated way
with a short learning curve for experienced LASIK
surgeons. Preliminary clinical results are comparable
to that of LASEK15, 21,23,24 and suggest epi-LASIK as
an efficient and safe alternative surgical modality for
Figure 35.4: Mean pain scores (+SD) of the early postoperative low myopia. Given the preliminary encouraging
hours (n = 76)
results for low myopia the next goal will be to apply
During the early postoperative course, the mean this technique for higher myopic corrections. Intra-
uncorrected visual acuity (UCVA) of the treated eyes operative corneal cooling has an additive effect to
corresponded well with the progress of the epithelial the retained epithelial sheet minimizing discomfort
healing and the transparency of the replaced epithelial below the threshold of pain in all the treated eyes.
sheet. More particularly, UCVA was better on the Future randomised comparative studies between Epi-
first postoperative day, when the epithelial sheet was LASIK and PRK are expected to prove the advantages
transparent, to decrease around the third of the retained epithelial sheet in surface treatments.
postoperative day, as the epithelial sheet became
hazy, and, finally rise again, when the epithelial REFERENCES
healing was complete (Figure 35.5). On the sixth 1. Seiler T, Wollensak J. Myopic photorefractive keratectomy
month interval 94% of eyes had visual acuity of 20/25 with excimer laser; one-year follow up. Opthalmology
1991;98:1156-63.
or better whereas 48% of eyes have gained one or 2. Epstein D, Fagerholm P, Hamberg-Nystroem H,
two (8%) Snellen lines of best-corrected visual acuity. Tengroth B. Twenty four-month follow up of excimer
laser photorefractive keratectomy for myopia; refractive
and visual outcome results. Opthalmology 1994;101:1558-
63.
3. Pallikaris IG, Papatzanaki ME, Siganos DS, Tsilimbaris
MK. A corneal flap technique for laser in situ
keratomileusis. Human studies. Arch Ophthalmol 1991;
109(12):1699-702.
4. Hersh PS, Brint SF, Maloney RK, et al. Photorefractive
keratectomy versus laser in situ keratomileusis for
moderate to high myopia; a randomized prospective
study. Opthalmology 1998;105:1512-22.
5. Pallikaris IG, Katsanevaki VJ, Panagopoulou SI. Laser in
Figure 35.5: UCVA of the immediate postoperative period after epi- situ keratomileusis intraoperative complications using one
LASIK ( n = 75) type of microkeratome. Ophthalmology 2002; 109(1): 57-
63.
The vast majority of Epi-LASIK eyes had clear 6. Melki SA, Azar DT. LASIK complications: Etiology,
corneas or trace haze at three (96%) and six month’s management, and prevention. Surv Ophthalmol 2001(2);
46:95-116.
(100%) postoperative intervals. 7. Smith RJ, Maloney RK. Diffuse lamellar keratitis. A new
syndrome in lamellar refractive surgery. Ophthalmology
CONCLUSIONS 1998;105(9):1721-6.
8. Pallikaris IG, Kymionis GD, Astyrakakis NI. Corneal
Histological findings of mechanically separated ectasia induced by laser in situ keratomileusis. J Cataract
epithelial sheets have shown that mechanical Refract Surg 2001;27(11):1796-802.
9. Camellin M, Cimberle M. LASEK technique promising
separation preserves the epithelial cell viability, the after 1 year of experience. Ocular Surg News 2000;18(1):
stratification of the sheet and the integrity of the 14-17.
326 Mastering Advanced Surface Ablation Techniques
10. Lee JB, Seong GJ, Lee JH, Seo KY, Lee YG, Kim EK. 18. Chen CC, Chang JH, Lee JB, Javier J, Azar DT. Human
Comparison of laser epithelial keratomileusis and corneal epithelial cell viability and morphology after dilute
photorefractive keratectomy for low to moderate alcohol exposure. Invest Ophthalmol Vis Sci 2002;43(8):
myopia. J Cataract Refract Surg 2001;27(4):565-70. 2593-2602.
11. Pallikaris IG, Naoumidi II, Kalyvianaki MI, Katsanevaki 19. Gabler B, Winkler von Mohrenfelds C, Dreiss AK,
VJ. Epi-LASIK: Comparative histological evaluation of Marshall J, Lohmann CP. Vitality of epithelial cells after
mechanical and alcohol - assisted epithelial separation. J alcohol exposure during laser-assisted subepithelial
Cataract Refract Surg 2003; 29(8):1496-501. keratectomy flap preparation. J Cataract Refract Surg
12. Pallikaris IG, Katsanevaki VJ, Kalyvianaki MI, Naoumidi 2002;28:1841-6.
II. Advances in subepithelial excimer refractive surgery 20. Camellin M. Laser epithelial keratomileusis for myopia. J
techniques: Epi-LASIK. Curr Opin Ophthalmol. 2003;14(4): Refract Surg 2003;19:666-70.
207-12. 21. Chalita MR, Tekwani NH, Krueger RR. Laser epithelial
13. Kamm O. The relation between structure and keratomileusis: Outcome of initial cases performed by an
physiological action of the alcohols. J of the American experienced surgeon. J Refract Surg 2003;19:412-15.
Pharmaceutical Association 1921;10:87-92. 22. Litwak S, Zadok D, Garcia-de Quevedo V, Robledo N,
14. Kim SY, Sah WJ, Lim YW, Hahn TW. Twenty percent Chayet AS. Laser-assisted subepithelial keratectomy
alcohol toxicity on rabbit corneal epithelial cells: electron versus photorefractive keratectomy for the correction of
microscopic study. Cornea 2002 May; 21(4):388-92. myopia. A prospective comparative study. J Cataract
15. Azar DT, Ang RT, Lee JB, Kato T, Chen CC, Jain S, Gabison Refract Surg 2002;28:1330-33.
E, Abad JC. Laser subepithelial keratomileusis: electron 23. Anderson NJ, Beran RF, Schneider TL. Epi-LASEK for the
microscopy and visual outcomes of photorefractive correction of myopia and myopic astigmatism. J Cataract
keratectomy. Curr Opin Ophthalmol 2001;12(4): 323-28. Refract Surg 2002;28:1343-7.
16. Espana EM, Gruetereich M, Mateo A, Romano AC, Yee 24. Claringbold VT. Laser-assisted subepithelial keratectomy
SB, Yee RW, Tseng SCG. Cleavage plane of corneal for the correction of myopia. J Cataract Refract Surg 2002;
basement membrane components by ethanol exposure 28:18-22.
in laser-assisted subepithelial keratectomy. J Cataract 25. Shahinian L. Laser-assisted subepithelial keratectomy for
Refract Surg 2003;29:1192-97. low to high myopia and astigmatism. J Cataract Refract
17. Stramer BM, Zieske JD, Jung JC, Austin JS, Fini ME. Surg 2002;28:1334-42.
Molecular mechanisms controlling the fibrotic repair 26. Rouweyha RM, Chuang AZ, Mitra S, Phillips CB,Yee RW.
phenotype in cornea: implications for surgical outcomes. Laser Epithelial Keratomileusis for myopia with the
Invest Ophthalmol Vis Sci. 2003 Oct;44(10):4237-46. Autonomous Laser. J Refract Surg 2002;18:217-24.
 Angle Kappa Management 327

CHAPTER
Angle Kappa
36 Management

Frederic Hehn (France)

INTRODUCTION Then we have to consider angle kappa especially

in hyperopic eye, with often nasal fixation,
Coma is due to the difference between visual axis enhancement for decentration, and dual treatment
(object to macula) and optical axis (apex of cornea to like Presby-LASIK (Figure 36.4).
the center of crystalline lens). That’s the reason why We show a case of a big decentration, and we
we are thinking that presby-LASIK technique does analyze the reasons why.
not increase the natural existent coma. Then to avoid It’s about a 44 years old hyperopic female,
to increase coma presby-LASIK must be centered Preoperative refraction R+1.50 (93°–2.00) L+1.50(85°–2.75)
(Figure 36.1). Preoperative refraction R+0.75 (40°–0.75) L+0.25 (160°–0.50)
Angle kappa is due to the difference between Despite of a bad topographic final shape, the
visual axis (object to macula) and the center of the results would have been good enough for this patient,
pupil. with no complains even for night driving and
This angle is calculated by the topograph. The computer working. Helpfully in this case, the pupils
topolyzer wavelight gives the both angle kappa and were small, and the useful optical zone width enough
the dynamic pupillometry which can help surgeon to to give neither halos, nor loss of vision. Binocular
adapt the OZ of the treatment with the pupil size in UCVA final acuity was 20/20 and J2.
mesopic and photopic conditions, especially in case At this stage many questions can occurred
of presby-LASIK. The visual axis, crosses the cornea 1. Is there a loss of patient’s fixation during the
at a point which is approximately the point of fixation treatment ? No there is not
of the patient. In the case of a topographic 2. Is there a loss of eyetracker? No there is not
measurement, we consider that the point of fixation, because with the wavelight allegretto excimer
is the center of the very center ring of the machine laser, eye tracker is as fast as the treatment,
(Figure 36.2). secondly eyetracker is well calibrated by an
objective test, and it was a uneventful surgery.
PATIENTS AND METHODS 3. Is there a ocular cyclotorsion problema? No there
is not, because the new sytem of neurotrack has
If angle kappa it is more than 100μ, the laser been activated during this treatment, that’s give
treatment, even in case of a spherical treatment can a real time and permanent compensation of
induce the both coma and astigmatism (Figure 36.3). cyclotorsion (Figure 36.5).
328 Mastering Advanced Surface Ablation Techniques

Figure 36.1: Natural coma

Figure 36.2: Angle kappa

4. Has the laser well done on the pupil center or To verify this point, the fact that the eyetracker
not ? has well done, and the laser as perfectly treat on the
With the allegretto the default treatment is centred pupil center, we ask the patient to see a bit aside, in
of the pupil center (Figure 36.6). nasal position, to make artificially align the pupil
 Angle Kappa Management 329

Figure 36.3: Angle kappa induces astigmatism and coma

Figure 36.4: Decentration of left eye after hyperopic astigmatism treatment

Figure 36.5: Cyclotorsion control on allegretto Eye Q

330 Mastering Advanced Surface Ablation Techniques

Figure 36.6: Eyetracker is fixed on the very pupil’s center

center and the fixation point, during a new data HOW TO MEASURE AND COMPENSATE ANGLE
measurement with the topolyzer machine. We can KAPPA
see that what the laser has done is perfectly centred
The first point is that with dilatation there is a pupil
on the pupil center (Figure 36.7)!
shift, and then the pupil center shift also. The visual
5. The only possible response is the non
compensation of the angle kappa during the axis does not change a lot during dilatation, only the
treatment. center of the pupil moves. Therefore, pupil dilatation

Figure 36.7: What the laser has done is perfectly centred on pupil
 Angle Kappa Management 331
modified and often minimizes the angle kappa (Figure wavefront treatment, which is called A-CAT, pupil
36.8). has to be dilated (Figure 36.10).
Because we measure topography with non dilated In conclusion we have to treat what we have
pupil and aberrometry with dilated pupil, we have measured. Then in a standard treatment, the angle
to treat with the excimer laser with the same pupil kappa is not considered. The laser treatment is
condition. automatically centred on the pupil. In this case if
Then if we want to make a topolink treatment, necessary, we have to modify the target reference of
which is called T-CAT, pupil has not to be dilated the active eyetracker , by modifying the default center.
(Figure 36.9). At the contrary If we want to make a With the allegretto eye Q 400 Hz, we have to modify

Figure 36.8: Pupil dilatation minimizes angle kappa

Figure 36.9: Topolink with small pupil

332 Mastering Advanced Surface Ablation Techniques

Figure 36.10: Wavefront guided with large pupil

the dx dy Cartesian coordinates, in using the set-up visual axis (Figure 36.12). Angle kappa does not
menu in the panel with the joystick (Figure 36.11). change before and after laser treatment, like we can
see on this example (Figure 36.13).
DISCUSSION
CONCLUSION
It’s about a giant angle kappa of 800μ in a hyperopic If Kappa angle is more than 100μ on the topographic
female, with a very good results after excimer laser. measurement, his compensation has to be considered.
We can see the perfect centration of the OZ on her If not, some astigmatism or coma can be appeared.

Figure 36.11: Manually default center modification

 Angle Kappa Management 333

Figure 36.12: Hyperopic 800µ angle kappa

Figure 36.13: Angle does not change after laser

Especially in three cases: hyperopic patient, minimizes angle kappa with the induce shift of the
enhancement for decentration, and dual or sequential center of the pupil; we are thinking that topolink is
treatment like presby-LASIK. Because pupil dilatation the clue to well compensate the angle kappa.
334 Mastering Advanced Surface Ablation Techniques

CHAPTER

37 Pain Reduction after Epi-LASIK

Yutaro Nishi, Okihiro Nishi (Japan)

INTRODUCTION with adjacent epithelium, opacifies postoperatively,

perhaps as a result of apoptosis or necrosis resulting
Epi-LASIK was developed to avoid the serious flap in inflammation from ruptured cell contents. It is this
complications associated with LASIK. Since July, 2005, inflammatory response, we suspect, which may be
we have employed this technique in patients with the cause of the pain noted in the postoperative period
either a thin cornea or an extreme corneal curvature following epi-LASIK
who, were they to undergo LASIK, would stand a We, therefore, undertook to routinely excise the
high risk for flap complications. redundant corneal epithelium after epi-LASIK to
With an intact corneal epithelium, one would alleviate the postoperative pain.
expect that the pain after epi-LASIK should be much We performed a prospective observational case
less than the pain following PRK in which the corneal study, to investigate whether the reduction of pain
epithelium is disrupted. Likewise, wound healing and corneal opacification after epi-LASIK could be
should be quicker and corneal opacification should accomplished by means of an extremely simple
also be less. surgical procedure of redundant corneal epithelial
Nevertheless, despite the fact that the corneal bed excision.
after epi-LASIK is completely covered by an almost We evaluated the pain perceived by our patients
perfect epithelial flap, in contrast to LASEK in which by stages on a scale of 10, in which stage 1
the flap often displays a shabby and ragged margin represented a foreign body sensation without pain
within the corneal bed, it has been our impression and stage 10 an almost intolerable intense pain. Our
that the postoperative pain after epi-LASIK is more patients were requested to indicate their pain
intense than the pain following LASEK. discomfort accordingly.
In point of fact, the pain, rapidity of wound The surgical technique utilizing either the lower
healing, and corneal opacification after epi-LASIK is blade of a Vannas scissors or Uribe-Stern capsulotomy
more marked than after PRK, which begs the question scissors (ASICO, Westmont, IL) (Figure 37.1) carefully
why this should be the case? inserted beneath the extended epithelium without
Following epi-LASIK, redundant corneal flap the use of grasping forceps and quickly excised. We
epithelium overlies non-excised corneal epithelium recommend cutting the surplus epithelium slightly
beyond the margins of the corneal bed. This beyond its furthest extension, so that a small narrow
redundant epithelium which does not anastomose erosion or bare corneal bed is created (Figure 37.2).
 Pain Reduction after Epi-LASIK 335
Table 37.1: The BUVA represents at one month after surgery. From
the left eye of the 3rd patient, the surplus epithelium was snipped off.
Pain Perception after epi-LASIK
Patients Sex Age Best Uncorrected Pain Perception
Visual Acuity
R L R L
1. Y.T. M 36 1.5 1.2 6 7
2. M.N. F 55 1.0 N.A. 7 N.A.
3. K.R. M 32 1.5 1.0 8 2
4. Y.K. M 52 1.0 0.5 1~2 1~2
5. Y.S. F 38 1.5 1.0 3 3
6. Y.T. F 33 0.5 1.0 2~3 3
7. K.M. F 48 N.A. 0.7 N.A. 3
8. Y.T. M 26 1.5 1.5 3 3
9. M.S. F 27 1.5 1.2 4 4
10. M.Y. F 45 1.0 1.0 2 2

Figure 37.1: Curved Uribe-Stern capsulotomy scissors. It was

used for cutting the surplus epithelium
the right eye, and delay in wound healing, with a
resultant delay of 3 weeks for surgery for the left
eye at which time we elected to excise the redundant
epithelium from the left eye. Subsequently, we excised
the surplus epithelium in every case. The pain stages
recorded by the patients, as a result of this surgical
excision were uniformly lower and, subjectively, they
did not complain of postoperative pain. It was our
further impression that the epithelial wound healing
was more rapid and that the epithelium on the corneal
bed showed much less opacification.
The pain stages of the eyes that underwent the
normal epi-LASIK ranged from 6 to 8. In the eyes
Figure 37.2: The part of the corneal epithelium which was cut-off.
Cutting off the surplus epithelium slightly beyond its furthest extension that underwent the new procedure the stages ranged
(along the dotted line) is recommended from 1 to 4. The difference in the pain scale between
the eyes with and without epithelial trimming was
This erosion will be covered in the next day, and statistically significant (P <.01, Welch t test).
appears to cause no particular pain when covered by As a consequence of this simple supplementary
a scleral contact lens (SCL). surgical procedure the subjective pain and discomfort
From July 2005 to April 2006, we performed epi- experienced following epi-LASIK was dramatically
LASIK in 18 eyes of 10 patients (Table 37.1.). The reduced enabling us to perform epi-LASIK in one
first two patients underwent epi-LASIK without any session on both eyes. This simple technique can easily
trimming of the epithelium. They complained of be incorporated into the routine epi-LASIK surgery
intense pain, recorded as strage 6-8 for each eye, on and can prove beneficial to patient comfort.
the day following surgery. The third patient indicated The redundant epithelium overlies the nonexcised
stage 8 pain scale for the right eye the day after the epithelium adjacent to the corneal bed and opacifies
epi-LASIK procedure without epithelial excision, and postoperatively in several days. Our hypothesis,
stage 3 for the left eye with exsion of redundant borne out from our results, is that this phenomenon
epithelium. We do not perform epi-LASIK on both may represent apoptosis and/or necrosis of the
eyes in one session, rather at a one week interval. redundant epithelium and that the resultant
This third patient experienced such intense pain in inflammatory response from this necrotic epithelium
336 Mastering Advanced Surface Ablation Techniques
may be the cause of the pain in the postoperative postoperative refractive surgery pain is, likewise, an
period. important subject for further detailed investigation.
Further clinical randomized masked studies, with
appropriate patient consent, are needed to confirm REFERENCE
our observation of the effect of this simple surgical 1. Nishi Y, Nishi O, Nishi K, Auffarth G. Pain reduction after
procedure in significantly reducing post epi-LASIK epi-LASIK with a simple surgical procedure. J Cataract
pain and corneal opacification. The pathogenesis of Refract Surg 2007;33:555-557.
 Painless Epi-LASIK 337

CHAPTER

38 Painless Epi-LASIK

Chu Renyuan (China)

INTRODUCTION by balanced salt solution. The surgeon places the

suction ring on the cornea. Then start up the vacuum
In excimer laser surgery, surface ablation has always
so as to fix the eyeball. 20% alcohol solution is instilled
been a kind of surgery with high safety, high into the ring for about 15 seconds. The alcohol
efficiency and high stability. PRK was the initial solution is then absorbed by the vacuum,the trephine
representative surgery. But advanced surface ablation is used to delineate the margin of the epithelial sheet,
with epithelium being maintained has well developed then the cornea is rinsed thoroughly. Remove the
since 1999 when it was first performed. There are suction ring and detach the epithelial sheet gently
two methods of epithelium sheet creation, physical using an epithelial spatula. Pay attention to the
method with epikeratome and chemical method with integrity of the epithelial sheet. The hinge is placed
ethanol. We have accumulated experience during the superiorly at 11 to 1 o’clock. After laser ablation, the
seven years’ experimental and clinical researches of epithelial sheet is gently repositioned with the help
advanced surface ablation. Our technique of painless of BSS. Be sure not to overlap the epithelium or
advanced surface ablation, LASEK/Epi-LASIK is expose the stromal bed, especially at the peripheral
introduced as following. region of epithelial sheet.
A high-DK bandage contact lens is placed onto
SURGERY PROCEDURE the cornea. Subsequently, a topical corticosteroid and
antibiotic are instilled. The eyelid speculum is then
Epi-trephine Assisted LASEK Technique
removed carefully. The patient is examined with slit
Epi-trephine (KN5000E) is a precise device for lamp biomicroscopy before dismissal.
LASEK surgery. It is composed of a control panel,
epithelial cutting rings and epithelial separating Epi-LASIK Technique
instruments. Placed with a medical silicon rubber Epi-LASIK epikeratome (KM-5000D), invented and
washer inside the suction ring, the suction ring can manufactured by Department of Ophthalmology, Eye
firmly attract and fix eyeballs with different radius and ENT Hospital, Fudan University and Wuxi
of cornea when the electric pump starts up. Kangming Medical Device Corp, is a precise device
After topical anesthesia with eyedrops of 0.4% for epi-LASIK surgery. It is the unique rotational
oxybuprocaine hydrochloride, the cornea is rinsed epikeratome used to create epithelial sheet in epi-LASIK.
338 Mastering Advanced Surface Ablation Techniques
It is composed of a control panel and epithelium
separating system.
After topical aneasthesia with eyedrops of 0.4%
oxybuprocaine hydrochloride, the cornea is rinsed
by balanced salt solution. The surgeon places the
suction ring on the cornea. The size of the suction
ring is chosen according to the curvature of the
cornea. Then start up the vacuum so as to fix the
eyeball. When the vacuum reaches the target level,
the surgeon starts the automatic epikeratome. The
epikeratome rotates anticlockwise and creates a
smooth epithelial sheet with regular border and hinge
at superior 11 to 1 o’clock. It takes about 6 second in
average to make the epithelial flap. Remove the Figure 38.1: Slit lamp photo of one patient, 5 minutes after myopic
epi-LASIK
epikeratome slowly and place the epithelial sheet
aside. After laser ablation, the epithelial sheet is
gently repositioned with the help of BSS. Be sure not
to overlap the epithelium or expose the stromal bed,
especially at the peripheral region of epithelial sheet.
A high-DK bandage contact lens is placed onto the
cornea. Subsequently, a topical corticosteroid and
antibiotic are instilled. The eyelid speculum is then
removed carefully. The patient is examined with slit lamp
biomicroscopy before dismissal (Figures 38.1 to 38.3).

ADVANTAGES OF ROTATIONAL EPIKERATOME

The integrity, viability and stability of corneal

Figure 38.2: Pathologic photo of an epithelial sheet shows the
epithelial sheet are the most important elements of a entire basal membrane
painless Epi-LASIK surgery. How to get the perfect
epithelial sheet is undoubtedly a great challenge to
every designer of epikeratomes. Nowadays, there
are generally two different designs of epikeratomes
in the world, beeline design such as Moria
epikeratome and rotational design of KN5000D
epikeratome (Wuxi Kangming Medical Device Corp,
China). The beeline epikeratome creates nasal hinged
epithelial sheet, while the rotational one creates
superior hinged epithelial sheet. The superior hinged
sheet has the advantage of less movement with blinks,
thus assuring its stability. However, rotationally
seperating corneal epithelium is not as easy as
separating corneal stromal flap. Until now, KN5000D
epikeratome is the only one that has settled this Figure 38.3: Slit lamp photo of one patient, one day after myopic
problem. epi-LASIK
 Painless Epi-LASIK 339
How to ascertain the integrity and viability of can fit the oblate shape of central cornea surface and
corneal epithelial sheet is the key technique of provide the cornea with enough oxygen during the
epikeratomes. KN5000D rotational epikeratome is constant wearing period of 5 to 7 days.
characterized with pressure-free and flexible Good movement can prevent the contact lens from
seperating design that assures the integrity and adhering to the corneal epithelium and improve the
viability of corneal epithelial sheet. During the comfort of the eye. Therapeutic contact lens contains
seperating procedure, the corneal epithelium does big basic curve to ensure the movement of lens. Anterior
not receive any possitive pressure from the seperator, corneal curvature turns smaller postoperatively so lens
so the epithelial sheet is perfect without any with big basic curve fits the new curvature better. But
abnormalities such as tearing. The separator is a dock- lens with too big movement shifts easily, which cannot
styled flexible device, that is, separating piece in the protect the epithelium. Wu has compared lens with
separator is not rigidly connected, but with a suitable different basic curve and suggests the lens with basic
floating range. During the separating procedure, the curve of 8.7 mm shows good movement, good central
separating pressure is flexibly adjusted as the orientation and good tightness for postoperative
separator moves upward and downward on corneal treatment of excimer laser surgery.
surface, thus settling the problem of damage to Dk/t value is another important factor of bandage
corneal stroma. The procedure of creating corneal contact lens to promote postoperative epithelial
epithelial sheet by KN5000D epikeratome is the healing. Silicone hydrogel contact lens with high Dk/t
shortest, from 6 to 10 seconds, which is also important accelerates the corneal epithelial healing and reduces
for a viable epithelial sheet. Comparing with the applications related to anoxic. Wu reported
KN5000D epikeratome, beeline epikeratomes are all significant less pain, less foreign body sense and
pressure-relied and unflexible. The separating milder epithelial edema using contact lens with Dk/t
procedure of beeline epikeratomes is much longer of 86×10–9 barrer/mm than using month-wearing
than KN5000D (30 seconds in average). contact lens. On postoperative day 3, corneal
epithelium in 50% eyes with high Dk/t lens, 33% eyes
POSTOPERATIVE MANAGEMENT with month-wearing contact lens have healed well
enough to remove the lens.
Bandage Contact Lens The bandage contact lens should be removed off
Bandage contact lens is used to cover the exposed in 5 to 7 days postoperatively, depending on the
corneal nerves and to prevent the eyelids from healing process of epithelium. If the epithelium has
scraping the cornea so as to reduce the pain after been renewed and no edema can be detected, the
LASEK and Epi-LASIK. Decreased interference from contact lens is safe to be taken off. Studies have
the eyelids helps the stability of corneal epithelium, showed that cornea haze occurs at the place where
helps the healing process of epithelium and epithelial defect or edema. Once there is spot of
meanwhile, prevents the detachment of epithelium edema epithelium, contact lens is recommended to
layer from anterior stromal layer. remain for another 24 hours. Zhou has observed the
Disposable contact lens with Dk/t of 30×10 –9 epithelium healing process after LASEK and epi-
barrer/mm is widely used as therapeutic contact lens LASIK and suggests that in eyes with epithelium
after LASEK, but because of its poor oxygen healing delay, wearing contact lens longer can help
transmissibility, continuous wearing usually causes to prevent the postoperative pain and cornea haze.
hypoxia and edema of corneal epithelium.
Eyedrops
Considering the special condition after excimer laser
corneal surgery, the therapeutic contact lens ought While the bandage contact lens remains on cornea
to meet some special requirements in its basic curve for the first 5 to 7 days after surgery, the patient is
and oxgen transmissibility. Ideal bandage contact lens given topical corticosteroids (0.05-0.1% dexamethosone
340 Mastering Advanced Surface Ablation Techniques
eyedrops) to be used 6 times a day as a strike therapy the same effect and safety as flurbiprofen. Wang
to conquer the acute release of inflammation factors combined pranoprofen and steroid to control the
at the first several days after the surgery. After the inflammation reactivity after LASEK and found that
contact lens is removed, 0.1% fluorometholone pranoprofen can reduce the degree and period of
eyedrops is used 6 times a day for 5 days and then is postoperative uncomfort. No severe side effect was
reduced to 5 times a day for another 5 days. By then, reported. Topical NSAIDs such as pranoprofen and
the patient should have visual acuity and refraction flurbiprofen can be used 3 times a day for the first
examined. According to the cornea transparency and week if the patient complains of eye pain. Not like
refraction outcomes, the corticosteroid is adjusted corticosteroid, NSAIDs do not cause intraocular
and maintained for at least 3 months. The incidence pressure to rise. So they can also serve as substitutes
of haze on the cornea after LASEK and epi-LASIK is of corticosteroid to control the stromal proliferation
less, compared with PRK, however, continual and prevent corneal haze when the IOP has rise.
corticosteroids with slow taper prevent the likelihood The importance of a strong tear layer on the
of stromal haze. Subjective symptoms such as visual cornea allows proper healing and best visual outcome.
blur or residual myopia and objective signs such as Patients are advised a routine regiment of
the presence of stromal haze serve to guide the nonpreserved artificial tears to maintain a smooth
postoperative course of topical corticosteroids. Since tear film over the cornea. Persistent dryness or surface
steroid may raise the intraocular pressure (IOP) in irregularities secondary to tear deficiencies are cause
some patients, constantly check of IOP is necessary for considering punctal occlusion.
during the period of using steroid.
Topical antibiotics are recommended to be used 4 BIBLIOGRAPHY
times a day for the first two postoperative weeks, 1. Verugno M,Maino A, Quaranta GM, et al. A randomized,
unless there is any clue for infective inflammation. double-masked, clinical study of efficacy of four
Nonsteroidal anti-inflammation drugs inhibit nonsteroidal anti-inflammatory drugs in pain control after
epoxidase and stop the synthesis and release of excimer laser photorefractive keratectomy. Clin Ther
2000;22(6):719-31.
prostaglandin so as to achieve the strong effect of 2. WANG Xiao-ying, ZHOU Xing-tao, DAI Jin-Hui, et al.
diminishing inflammation and acesodyne. They are Clinical assessment of proanoprefen eyedrops on
commonly applied after PRK and LASIK to control postoperative inflammation from LASEK. Chinese Journal
of Optometry and Ophthalmology 2004; 6(3):150-2.
the postoperative reactivity. But indomethacin and
3. WU Ying, QU Xiaomei, ZHOU Xingtao, et al Clinical
diclofenac sodium are reported to cause epithelium evaluation of the Galyf ilcon A silicon hydrogel contact
dissolution or to influent the epithelium healing. lens as a bandage after LASEK or epi-LASIK. Chinese
Verugno reported that among four kinds of NSAIDs Journal of Optometry and Ophthalmology 2006;8(5):296-
8.
such as indomethacin, diclofenac sodium, ketorolac
4. ZHOU Xing-tao, CHU Ren-yuan, WANG Xiao-ying, et al.
and flurbiprofen, flurbiprofen has best effect but least The clinical study of the epithelial flap of painless LASEK
side-effect to control pain after PRK. Pranoprofen has and epi-LASIK. Chin J Ophthalmol 2005;41: 977-80.
 Epi-LASIK with Mitomycin C 341

CHAPTER

39 Epi-LASIK with
Mitomycin C

D Ramamurthy, Chitra Ramamurthy (India)

INTRODUCTION 2. Feasability to plan larger optic zones

Corneal refractive surgery has evolved through the corresponding to the mesopic pupil measurement.
last couple of decades. The radial keratotomy 3. The earlier broad beam lasers and central island
introduced by Fyodorov in 1980s followed by 1990s formation which brought disrepute to PRK gave
era of photorefractive keratotomy had their period way to sophisticated laser ablation profiles with
of glory. However, inconsistency in the predicted distinctively improved visual outcome for surface
outcome, the discomfort in PRK, the regression which treatment.
followed were the limiting features. 4. Thinner corneas, steep K’s with expectant
The need of the hour was a constant, predictable microkeratome complications were more ideal for
visual outcome and lasik emerged a winner in late surface ablations.
1990s with safety and reproducibility. With improved 5. Post flap complications with lasik could undergo
understanding of the bugbears inherent in lasik over enhancements with surface treatments with
the ensuing years, the occurrence of microkeratome- improved safety profile.
induced complications, the rare occurrence of DLK 6. Wavefront ablations was found to perform better
and the growing awareness of probable ectasia, a with surface ablations through various studies
rejuvenation of surface ablations occurred. This was conducted and the corneal biomechanical response
also the period of growing awareness of the wound was more predictable in surface procedures.
remodeling and the corneal biomechanical response. 7. Contrast sensitivity recovered faster than in lasik.
Resurfacing of surface ablations was initiated by Recovery from dry eye status was again speedier.1
the Lasek procedure with alcohol induced separation
of the basement membrane of the cornea. This was HISTOLOGICAL FINDINGS
followed upon by a more refined Epilasik procedure
described by Pallikaris in 2003. Transmission electron microscopy of the harvested
epithelial sheets showed minimal evidence of trauma
Reasons for Resurgence of in the basal epithelial cells, the intracellular organelles
Surface Ablations and intercellular desmosomal connections as well as
1. Conservation of corneal tissue by creating thinner the hemidesmosomal connections with the basement
flaps of 45 to 60 μ thickness depending on the membrane appeared closer to normal with only focal
thickness of the epithelium in that individual. disruptions.2
342 Mastering Advanced Surface Ablation Techniques
Alcohol assisted epithelial separations take place Different epikeratomes are presently available in
within the basement membrane affecting its integrity. the market. The popular epikeratomes are the
The intact basement membrane has been found to be Amadeus, Moria, Centurion and Nidek (Figure 39.2).
important to control the fibrotic activation of The Amadeus epikeratome allows a consistent flap
keratocytes and faster epithelial wound healing. To diameter of 9.0 mm, variable hinge width of 1.0, 1.1
this end, epi-LASIK with the clean cleavage at the level and 1.2 mm, 11,000 rpm with an advance rate of 3 to
of basement membrane faired better over LASEK. 5 mm/sec and a vacuum build up of 21.5 inches/Hg.
The epikeratomes include a blunt plastic separator
PRINCIPLE OF EPI-LASIK (Figure 39.3) instead of the blade in the lasik
microkeratome which have different angles of entry
A blunt epikerotome moves on the eye providing a
and slide along a path of least resistance.
clean cleavage between the basement membrane and
A speculum is placed on the eye and copiously
Bowman’s layer, lifting an epithelial sheet of 50 to
irrigated with chilled BSS or saline. Anesthetic drops
60 μ followed by surface laser ablation requisite for
are reapplied. The epikeratome assembly is placed
the refractive error (Figure 39.1).
on the eye and the vacuum built up. Following
PROCEDURE adequate vacuum build up signal and cross check with
applanation tonometer, the epikeratome is run on its
Icepacks need to be placed on either eye for 15 minutes track by pressing on the foot pedal. The assistant
prior to the procedure. This preoperative step should continuously irrigate with chilled BSS
contributes significantly in lessening the pain component throughout the forward and reverse run. (Figure 39.4)
following the surgery. The operative eye is prepared This crucial measure significantly alleviates pain in
with three drops of topical proparcaine hydrochloride the post operative period. The microkeratome pushes
(applied every 5 minutes before the procedure) and the thin epithelial sheet creating a nasal hinged flap.
povidone iodine and is covered with a sterile drape. The epikeratome is lifted off the eye and the thin
The epikeratome unit needs to be checked for all flap gently nudged to the periphery (Figure 39.5).
its parameters including vacuum build up and a trial The laser parameters fed in the laser machine for the
run prior to the procedure. The cornea could be requisite correction is activated, the usual precautions
marked with the usual markers as in all corneal for centered treatment applied and the surface
refractive procedures for a proper flap alignment. ablation is performed.

Figure 39.1: The red arrow indicates the plane of cleavage for epi-LASIK
 Epi-LASIK with Mitomycin C 343

Figure 39.2: Moria epi-K

Figure 39.3: Amadeus epi-keratome holders and separators

344 Mastering Advanced Surface Ablation Techniques
has been accepted to significantly retard the cytokine
induced inflammatory cascade in the tear film. The
exposed surface is then copiously washed to remove
any remnant of mitomycin. A blunt cannula is then
used to gently reposit the thin rolled up epithelial
flap opposed to the nasal hinge. The epithelium is
found to extend beyond the epithelial gutter because
of the mechanical stretch induced by the cut. The
periphery of the flap should be stroked smoothly to
remove all the folds. The epithelial flap should be
given adequate time to settle on the underlying
stroma. A bandage contact lens (preferably 8.6 to
8.7 mm diameter) is gently placed on the eye and
Figure 39.4: Copious chilled BSS irrigating the track during epi-
again given sufficient time to settle on the flap gently
keratome run nudging the air bubble away under the BCL (Figure
39.7). The speculum is removed once the flap integrity
is checked and BCL is left in place.

INTRAOPERATIVE COURSE

The sequence of events may not be smooth in all

situations. The flap may get torn or a buttonhole may
present. Attempts to salvage the flap, if failed, allows
removal of the flap in toto and gently scraping any
epithelial tags (Figure 39.8). Removal of this thin flap
is no quandary as in a Lasik flap. Surgeons at different
centres have studied the results with and without
the flap and the final visual outcome is comparable.
Rarely, a stromal incursion could occur (as low as 1%
incidence) because of high vacuum and the procedure
Figure 39.5: The thin epithelial flap is nudged to the nasal periphery needs to be aborted.

POSTOPERATIVE TREATMENT
After laser ablation, mitomycin C at 0.02%
concentration is applied with a merocoel sponge for The presence of the epithelial flap itself is understood
a duration of 12 sec (Figure 39.6). The concentration to act as a bandage contact lens preventing the
of 0.02% is arrived by a simple dilution measure. 2 mg marked inflammatory cascade of cytokine
of mitomycin is mixed with 5 ml of sterile water. production. However, the epithelium tends to die
2.5 ml of this reconstituted mixture is discarded. The out with the new epithelium migrating in from the
remaining 2.5 ml is further diluted with 2.5 ml of periphery replacing the separated epithelial sheet
sterile water. From this final reconstituted 5 ml (Figure 39.9). Significant epithelial haze is seen in the
solution, 1 ml is taken in a syringe to wet the merocoel first 3 days till a newly synthesized transparent
which is placed on the stromal bed. epithelial sheet is laid down. The time of epithelial
Different exposure times is suggested by different healing ranges from 3 to 5 days.
surgeons but a larger consensus favors 0.02% The patient is started off on a postoperative
mitomycin concentration. Application of mitomycin regime of frequent topical steroids coupled with
 Epi-LASIK with Mitomycin C 345

Figure 39.9: As re-epithelialization progresses, the separated epithelial

sheet shrinks in the central part and has a hazy appearance
Figure 39.6: Merocoel sponge soaked with mitomycin placed on the
stromal bed
fourth generation floroquinolones for the first couple
of weeks. The topical steroids are gradually tapered
off over the 6 weeks. Presence of a mild sub epithelial
haze may warrant continuation of steroid drops up to
3 months with complete clearing of the haze. Artificial
tear substitutes are maintained for 6 weeks or longer.
The bandage contact lens is removed after 5 days by
which time the epithelial healing is complete. Mild
analgesics are indicated for 3 to 5 days. Different
studies favor the usage of vitamin C (500 mg – bd
dosage) over the 6 weeks period.

CLINICAL DEDUCTIONS

The present generations of epikeratomes are very safe

Figure 39.7: Bandage CL placed on the reposited epithelium
involving intact epithelial flaps. The 60 μ thin flap expand
the range of correction leaving significant residual
stromal bed. However, as of, now, mild to moderate
myopes do perform favourably with epi procedures.3
The visual outcome is comparable to Lasik after the
initial 5 days. The wow effect of lasik, however, is
missing. The superficial lamellar fibres show a more
predictable biomechanical response than in the thicker
flaps. Wavefront ablation performs better as the flap
induced aberrations of a thick lasik flap are obviated.
The initial corneal thickness of 480 to 500 μ and the
residual bed of 300+ μ is a safe limit as of today.

CONCLUSION

The armamentarium of refractive surgery, at the

Figure 39.8: Damaged epithelial flap could be discarded present day scenario, provides varying options for
346 Mastering Advanced Surface Ablation Techniques
differing corneal parameters. The final onus falls on sensitivity and tear function following epi-LASIK or laser
in situ keratomileusis for myopia. Am J Ophthalmol 2006;
the surgeon to analyse the preset criteria and adopt
142(4):669-71.
a rational approach providing the requisite 2. Pallikaris IG, Naoumidi II, Kalyvianaki MI, Katsanevaki
customized treatment with optimal visual outcome. VJ. Epi-LASIK: comparative histological evaluation of
The future awaits for a customized biomechanical mechanical and alcohol-assisted epithelial separation J
Cataract Refract Surg 2003;29(8):1496-501.
wound response to be tailored to our treatment 3. Pallikaris IG et al. Epilasik: preliminary clinical results of
strategy.4 an alternative surface ablation procedure. JCRS–2005;
31(5):879-85.
REFERENCES 4. Netto MV, Mohan RR, Ambrósio R Jr, Hutcheon AE,
Zieske JD, Wilson SE. Wound healing in the cornea: a
1. Kalyvianaki MI, Katsanevaki VJ, Kavroulaki DS, Kounis review of refractive surgery complications and new
GA, Detorakis ET, Pallikaris IG. Comparison of corneal prospects for therapy. Cornea 2005;24(5):509-22.
Section
4

Advanced
Surface Ablation
Technique III:
LASEK
 CHAPTER

40 Advances in Excimer Laser

Subepithelial Ablation
(ELSA) or LASEK

Chris P Lohmann (Germany)

INTRODUCTION postoperative pain, slow visual recovery and corneal

haze) and LASIK (i.e. flap complications, interface
Refractive surgery is a field that is constantly changing
problems and possibly attenuated long time
with new technologies being developed and
biomechanical stability of the cornea) and combine
introduced routinely. Currently excimer laser
their advantages. Early studies suggest that refractive
photorefractive keratectomy (PRK) and excimer laser
and visual results, stability and safety of LASEK are
in situ keratomileusis (LASIK) are the surgical
comparable to those of PRK and LASIK, but haze
procedures most commonly being used to treat
levels and pain seem to be lower than PRK. Visual
myopia. PRK makes changes in the corneal curvature
recovery seems to be relatively faster after LASEK;
by ablating part of Bowman’s layer and anterior
approximately two-third of the treated eyes have an
corneal stroma tissue after removing the epithelium.
uncorrected visual acuity (UCVA) of 20/40 or better
In contrast, LASIK does not remove the epithelium,
at day three.
Bowman’s layer, or anterior stroma tissue but does
As there is some degree of similarity in
remove deep stromal tissue after making a cut into
pronouncing the names LASEK and LASIK and
the cornea stroma at approximately 160 microns using
therefore, confuse both the ophthalmic community
a microkeratome. Various peer reviewed studies have
and the patients we have re-named this procedure
shown that the refractive results and long time visual
to ELSA (Excimer Laser Subepithelial Ablation).
outcomes are good and similar for PRK and LASIK
in low to moderate myopia up to – 8 diopters (D).
SURGICAL PROCEDURE
A new keratorefractive technique, laser-assisted
subepithelial keratectomy (LASEK), was introduced Although various types of LASEK procedures have
by Massimo Camellin in 1999. LASEK is based on the been described the majority of surgeons are using
detachment of the epithelium using an alcohol the alcohol assisted classical Camellin technique which
solution, creating an epithelial flap that is then is illustrated in Figures 40.1A to E. The surgery is
repositioned after the laser ablation. The epithelium performed under topical anesthesia. After a lid
regenerates itself within a few days and in the speculum is applied to the patients eye the surgery
meantime the existing flap protects the ablated consists of the following steps:
corneal surface. This technique has the potential to 1. An incision of the corneal epithelium is performed
eliminate or reduce many disadvantages of PRK (i.e. using a 8.0 mm cornea trephine with a 70 microns
350 Mastering Advanced Surface Ablation Techniques

Figures 40.1A to E: The LASEK procedure (Camellin’s technique): (A) Trepnation of the epithelium; (B) 30 sec alcohol; (C) Mobilization of
the epithelium; (D) Excimer laser ablation; (E) Re-positioning of the epithelium
 Advances in Excimer Laser Subepithelial Ablation (ELSA) or LASEK 351
depth calibrated blade. The trephine is designed For astigmatic correction there are elliptical
to create a 280-degree epithelial incision leaving a instruments distributed by Geuder (Heidelberg,
blunt section of 80 degrees at the 12 o’clock Germany) which are shown in Figure 40.2.
position for the formation of a hinge. The trephine Just recently they have been disposable
is placed centrally on the papillary axis and instruments introduced to the ophthalmic
downward pressure of the trephine is evenly community. These are also been distributed by
applied to the blade and slight rotation of the Geuder (Heidelberg, Germany) and are shown in
blade (approximately 5 degrees in both directions) Figures 40.3A to D. The main advantage of these
is used to create the incision. disposable instruments that they are disposable and
2. An 8.5 mm LASEK alcohol cone is placed on the therefore reduces the risk of infection. There is no
corneal surface encircling the epithelial incision.
need for sterilization which may be of importance
This cone is filled with 20% ethanol (in distilled
for high volume clinic. You will always have an
water) and left for 30 seconds. After this time the
ultrasharp trephine for a good quality of the epithelial
alcohol is absorbed with a small sponge, the
incision. This is of importance for a reduced rate of
alcohol cone is removed and the cornea is
postoperative pain and haze.
thoroughly washed with BSS to remove all
remaining alcohol. The area of epithelial incision
is then dried with a small sponge. POSTOPERATIVE MEDICATION
3. To create the epithelial flap the pre-cut margin of A bandage soft contact lens is of critical importance
the epithelium is lifted using the sharp side of a
to keep the epithelium in place after the surgery. This
special epithelial peeler, starting at the edges of
contact lens should not be removed before the third
the epithelial incision and the epithelial flap is
postoperative day. Until the removal of the bandage
gently detached and folded-up at the 12 o’clock
contact lens the postoperative therapy should consist
position using the blunt side of the epi-peeler.
of a topical antibiotic agent and a corticosteroid 4
4. If the epithelium shows strong adherence, the
times daily and lubrication (we prefer carbomer 2.0
corneal surface is re-exposed to the alcohol for
additional 10 to 15 seconds. mg) 5 to 8 times a day. As there is a contact lens on
5. Then the laser ablation is performed and we are the eye, we recommend the use of non-preserved
using the normal LASIK normograms. eye drops. After the removal of the contact lens the
6. After the laser ablation the cornea is flooded with eyes should be treated with carbomer 2.0 mg 4 times
BSS and the flap is repositioned with the blunt daily and with topical corticosteroids 4 times daily
side of the epithelial peeler. A 14.0 mm soft for 2 weeks and twice a day for 2 weeks. All
bandage contact lens (we recommend Pure Vision medications should be withdrawn after 4 weeks.
Bausch and Lomb or Ciba Vision daily focus) is
applied for protection of the epithelial flap for 3 CLINICAL RESULTS
days.
So far there have been very few clinical studies
SURGICAL INSTRUMENTS published in peer-reviewed journals. In the following
we have summarized the results.
Almost all ophthalmic instrument companies have 1. Myopia: Up to a myopic correction of 8 D (spherical
LASEK instruments in their portfolio. The original equivalent, SE) between 81 and 97% are within
ones were from Janach (Como, Italy) which are shown +/– 0.5 D after 6 months. Uncorrected visual
in Figures 40.1A to E. The set of instruments usually acuity of 20/20 are between 73 and 92% of the
consists of a epithelial trephine and alcohol cone, and treated eyes, and between 96 and 100% are within
a peeler or microhoe to mobilize and push back the 20/40. None of the eyes have lost more than 1
epithelium. line of Snellen visual acuity.
352 Mastering Advanced Surface Ablation Techniques

Figure 40.2: Elliptical LASEK instrument for astigmatic corrections

Figures 40.3A to D: Disposable LASEK instruments: (A) The combined instrument; (B) Alcohol well; (C) The trephine;
(D) Disposable epi-peeler: i. Sharp part to mobilize the epithelium; ii. Blunt part to push back the epithelium

2. Astigmatism: Today there is only one larger studies 3. Hyperopia: So far no studies have been published
of the treatment of astigmatism. This have been in peer-reviewed journals on the treatment of
performed by our group. We have treated 60 eyes hyperopia using LASEK.
with a myopic astigmatism between –1 and – 4.5
D with a follow up of 12 months. All of these eyes ADVANTAGES AND DISADVANTAGES OF LASEK
were postoperatively within +/– 0.75 D of SE with
an astigmatic correction with less than 0.5 D. LASEK or ELSA is not as comfortable as LASIK but
None of the eyes lost more than 1 line of visual much less painful than PRK. In our experience 17% of
acuity, in contrast 39% gained 1 or 2 lines of visual our treated eyes have some kind of pain within the
acuity. No significant haze of greater 0.5 was seem first 4 hours which there after disappears. Visual
in these eyes. rehabilitation is faster in LASIK than in LASEK or
 Advances in Excimer Laser Subepithelial Ablation (ELSA) or LASEK 353
ELSA. But it seems to us, that using the new LASEK or ELSA. In particular we think of customized
microkeratom from Ciba or Gebauer (the procedure ablation just like wavefront- or topography-guided
called epi-LASIK) postoperative visual recovery is ablations LASEK or ELSA is obviously superior than
not much slower than in LASIK. The main advantage LASIK.
of LASEK or ELSA is that it does need a cut in the
stroma as with LASIK. Therefore, the LASIK flap CONCLUSION
related complications like diffuse lamellar keratitis,
free flaps, button holes, incomplete flap, flap LASEK or ELSA is a very good alternative for LASIK
wrinkles, epithelial ingrowth, microbiological corrections for myopia up to – 8.0 D and astigmatism
infections, biomechanical problems, and an increase up to – 5.0 D. In particular for customized ablations
in higher order aberrations are excluded with LASEK it is superior to LASIK.
354 Mastering Advanced Surface Ablation Techniques

CHAPTER

41 Pearls and Pitfalls of LASEK

Sanjay Chaudhary (India)

INTRODUCTION a. No flap related complications like buttonhole,

partial cut, free caps, flap wrinkling, epithelial
Excimer laser refractive surgery started with PRK down growth, etc.
and ushered in a revolution. The problem of painful b. Another 90 mic of stroma available for corneal
recovery, regression, coupled with corneal haze ablation thereby enhancing the limit of
especially when correcting higher diopters, led to an correction by approx another 5D over LASIK.
almost complete transition to LASIK. Lasik ruled for c. Less costly because the expense of a keratome
a few years till people saw in it a high rate of corneal and blades eliminated.
ectasia because of the 160 microns of corneal tissue d. In a better position to handle thin cornea. A
lifted as part of the flap. LASEK came in vogue as person with a corneal thickness of 490 mic may
the tissue saving procedure with less painful recovery still have an option of a 6 D myopia correction.
and lesser haze. 20% alcohol seemed to be a good e. Large zone treatments for better corneal
way to raise an epithelial flap. Since painful recovery prolacity and in hyperopia are now possible. This
persisted, doctors blamed the alcohol for the essentially means that in LASIK the flap size was
hyperemia and pain. A non-alcohol based procedure a restricting factor to the size of treatment. And
emerged to be called epi-lasik. It had less pain but it was seldom possible to go over a 9 mm
haze and regression were still an issue. The current treatment. The flap cornea which was a catch
situation in hyperopic patients who had a flat
trend is to look at sub-Bowman lasik flap as the best
cornea, a small flap and a need for a large
of both the worlds.
treatment zone. With LASEK there is no
limitation to the zone of treatment.
LASEK

The more the residual stromal bed one leaves behind, Surgical Considerations
the less the chances of ectasia was what makes LASEK LASEK involves the stripping of epithelium from the
ride the crest of popularity. Bowman’s membrane in a form of hinged flap.
LASEK has the following advantages to offer: An epithelial trephine of the required size is placed
1. More residual corneal bed thickness, so less on the center of the cornea after anesthetizing the eye
chances of ectasia. with 0.5 percent proparacaine eyedrops. A 4 mm
2. No flap to be lifted, so: segment of the trephine at the 12 o’clock is blunt. By
 Pearls and Pitfalls of LASEK 355
placing on the cornea with pressure, the trephine cuts generated from the edges of the wound. This usually
through the epithelium sparing the underlying stroma coincides on the fifth postoperative day. After
and the 12 o’clock epithelium. The diameter of the removing the bandage contact lens, FML eyedrops
trephine could vary from 8.5 to 10.5 mm. A similar are started to replace NSAID drops to contain the
sized alcohol well is now centered on the cornea. tissue edema and the subsequent fibroblastic reaction.
Twenty percent ethyl alcohol is filled in the well and In our clinical practice we use FML six times a day
kept in position for 60 sec. It is then removed with a for a week, and then taper it off by a drop every
cellulose sponge, the well taken off the eye and the week over the next six weeks. Antibiotic drops are
epithelium washed with BSS. After waiting another used for two weeks and lubricating drops for at least
minute to allow the alcohol to weaken the epithelial two and a half month or more as per requirement.
Bowman’s adhesions, a micro hoe is used to pick up
the epithelium from the edges of the trephine marks. Disadvantages of LASEK
A hockey shaped spatula is now used to roll the
These are similar to PRK with minor modifications.
epithelium slowly towards the hinge exposing a clean
Bowman’s to work on. Excimer laser is delivered to Postoperative Pain
the cornea surface to make a correction for the
refractive error. The corneal surface is washed This is a major setback of LASEK. The pain is intense
thoroughly and scrapped to rid of the debris and the on the day of LASIK and reduces over the next 2 to 3
condensed plume. The epithelium is carefully rolled days. This may be accompanied with hyperemia,
back with the help of an irrigating cannula. Because of chemosis of the conjunctiva, and lid edema. Strong
the loose elasticity of the tissue, the replaced epithelium analgesics and anti-inflammatory are required over
usually crosses over the natural edges to overlap some the first 2 to 3 days. The intensity of pain is definitely
of the healthy epithelium. A bandage contact lens is less than what is encountered in PRK. This is also in
now placed over the epithelium where it rests for the sharp contrast of LASIK where there is no pain and
next five days. The patient is sent home after instilling only an occasional irritation and watering on the day
a preservative free lubricating eyedrop, an antibiotic of the procedure.
and a NSAID eyedrop. There are used for the next
five days. Systemic antibiotic and strong pain killers Buttonholing
are prescribed for the next three days. Excess exposure to alcohol does help in easily picking
up the flap, but the resultant chemical trauma to the
LASEK with Mitomycin C epithelium results in greater tissue reaction, more
Here, all the above steps are the same. After corneal haze, pain and tissue edema. Less exposure to alcohol
ablation the treated area of the cornea is exposed to or less percentage of alcohol used prevents proper
0.02 percent mitomycin C for 30 seconds. The corneal loosening up of the epithelium resulting in single or
surface is then thoroughly washed with BSS for a multiple buttonholing. Excessive breaks in the
minute to remove all traces of mitomycin and then continuity of the epithelium make the flap useless and
the epithelium is reposited back. Mitomycin C is used have to be discarded. The situation then mimics a PRK.
in containing fibroblastic activity and thereby
reducing and delaying the chances of corneal haze, Blurred Vision
more so when attempting to treat high myopia. The patient encounters blurred vision for a week.
This is a result of epithelial haze as the new epithelium
Follow-up coming in from the sides replaces the old alcohol
The bandage contact lens is removed when the old treated epithelium. The vision clears up in a week’s
epithelium is replaced by the new epithelium time. This is in stark contrast to LASIK where the
356 Mastering Advanced Surface Ablation Techniques
patient has good vision within a few hours and has
total clarity by next morning (Figure 41.1).

Figure 41.1: Delayed epithelial healing with corneal haze on 9th

postoperative day after LASEK with mitomycin C. The eye was patched
with an antibiotic and lubricating ointment and the defect healed over
the next 3 days

Corneal Haze
This has become the most feared complication in a
long-standing follow-up of LASEK. The haze is similar
to the one encountered in PRK and can be graded
from I to IV (Figures 41.2A and B). The use of
mitomycin C is our routine clinical practice for myopia B
of over 4 D seems to have helped in the following
Figures 41.2A and B: The patient developed a grade I corneal haze
ways: in the right eye and a grade II haze in the left eye after one and a half
1. Haze is usually not encountered in myopia of up year of simultaneous LASEK with mitomycin C in both eyes
to 7.0 D as compared with PRK where it could be
encountered after 4 D. 7. The regression of haze sometimes results in some
2. Myopia of 8 to 12 usually results in grade I haze reversal of regression of the refractive error and
while 12 and above may result in grade II to III improvement in refractive error and vision.
haze. The above observations are not a rule but an
3. There have been situations where even – 18 D has indication of the surgeon’s experience with PRK of
had no haze and on the other hand, even a –5 over 10 years and of LASEK with and without
developed a mild haze. mitomycin on over 400 eyes in 4 years.
4. Haze usually develops after 6 to 9 months of the
procedure. LASEK IN RELATION TO PRK AND EPI-LASIK
5. Haze results in a regression of the refractive error
and the degree of regression depends on the PRK, LASEK and now epi-LASIK involve the
severity of haze. removing or stripping of the epithelium from the
6. Haze usually regresses spontaneously over a Bowman’s membrane. In PRK, it is mechanical
period of 2 to 3 years. Low dose topical steroids scrapping, in LASEK it is alcohol assisted while in
could assist resolution. epi-LASIK, it is again separation with a blade. Since
 Pearls and Pitfalls of LASEK 357
the three are essentially similar, they carry the same 3. Azar DT, Ang RT, Kee J-B, et al. Laser subepithelial
Keratomileusis: electron microscopy and visual
advantages and disadvantages with minor
outcomes of flap photorefractive keratectomy. Curr
modification. The postoperative pain has definitely Opin Ophthalmol 2001;12:323-8.
reduced from PRK to LASEK to epi-LASIK. This is 4. Camellin M. Laser epithelial keratomileusis for myopia.
attributed to a healthier flap over the cornea and less J Refract Surg 2003;19:666-70.
5. Claringbold TV II. Laser-assisted subepiehtlial
alcohol injury. The rate of epithelial healing has keratectomy for the correction of myopia. J Cataract
improved favoring epi-LASIK. This has also reduced Refract Surg 2002;28:18-22.
the blurring of vision to a shorter period. However, 6. Espana EM, Grueterich M, Mateo A, et al. Cleavage of
it postulates that the effect on corneal haze may be corneal basement membrane components by ethanol
in laser-assisted subepithelial keratectomy. J Cataract
similar in LASEK and epi-LASEK. Epi-LASIK is prone Refract Surg 2003;29:1192-7.
to buttonholing, and in such a situation, the entire 7. Le JB, Seong GJ, Lee JH, et al. Comparison of laser
epithelium has to be scrapped off to continue with epithelial keratomileusis and photorefractive
the procedure, and this then becomes a PRK. keratectomy for low to moderate myopia. J Cataract
Refract Surg 2001; 27:565-70.
8. Scerrati E. Laser in situ keratomileusis vs laser epithelial
BIBLIOGRAPHY keratomileusis (LASIK vs LASEK). J Refract Surg 2001;
1. Autrata R, Rehurek J. Laser-assisted subepithelial 178:S219-S221.
keratectomy and photorefractive keratectomy for the 9. Shah S, Sebai Sarhan AR, Doyle SJ et al. The epithelial
correction of hyperopia: results of a 2-year follow-up. J flap for photorefractive keratectomy. Br J ophthalmol
Cataract Refract Surg 2003;29:2105-14. 2001; 85:393-6.
2. Autrata R, Rehurek J. Laser-assisted subepithelial 10. Shaninian L Jr. Laser-assisted subepithelial keratectomy
keratectomy for myopia: two-year follow-up. J Cataract for low to high myopia and astigmatism. J Cataract Refract
Refract Surg 2003;29:661-8. Sur 2002; 28:1334-42.
358 Mastering Advanced Surface Ablation Techniques

CHAPTER

42 LASEK Procedure with the

Use of Mitomycin C

Iwona Liberek, Justyna Izdebska (Poland)

INTRODUCTION of spongostan impregnated with 5-FU at a

concentration of 50 mg/ml inserted for 5 min under
Antimetabolites are chemical compounds which, due sclera and conjunctiva flaps.
to the large similarity to body components Mitomycin C is widely used in glaucoma filtration
participating in metabolic processes, replace them in surgery, in pterygium surgery, in treating superficial
biochemical reactions. They act on the basis of neoplastic lesions in eye bulb, in mucosal pemphigoid,
competitive inhibition. They join specified reaction, in vernal keratoconjunctivitis, in strabismus surgery
causing disorder of cell functioning, including at and, from the last few years, in refractive corneal
times its death. During the last 15 years, use of surgery. Use of excimer laser in correction of
antimetabolites in wound healing became gradually refractive error by means of superficial methods leads
more popular. 1 These compounds, besides their to keratocytes activation and proliferation. Collagen
primordial use in treatment of neoplastic lesions, produced by keratocytes is abnormal, much less
were implemented also in ophthalmology. 5- organized with matrix-free areas and fibers with an
fluorouracil was used as the first one in treating irregular stereospatial relationship.2 Subepithelial
vitreoretinopathy. fibrosis is pathologic corneal tissue response,
Mitomycin C joined subsequently proliferate described by Waring and Rodriques,1 developed after
changes treatment. Comparing these two substances, refractive surgery conducts to haze creation inducing
mitomycin C on account of the greater efficacy after postoperative astigmatism and causing weakness of
an intraoperative application, seems to replace 5- vision. Before era of mitomycin C, the use of nothing
fluorouracil.1 5-fluorouracil is a pyrimidine analogue: but the steroid drops had been applied in order to
• Suppress cell proliferation through selective prevent subepithelial scarification. However, their
activity for the S phase (synthesis) of the cell cycle long-lasting administration causes rise in intraocular
• Is used in treatment of colorectal and breast pressure and cataract initiation. MMC is an antibiotic
carcinomas. derived from Streptomyces caespitosus. Its alkylating
In antiglaucoma procedures, mitomycin C is properties enable it to cross-link DNA between
administered: in the form of postoperative adenine and guanine, thereby inhibiting DNA
subconjunctival injections (0.5 ml of solution 10 mg/ synthesis through building crossed bonds within
ml); occasionally as well intraoperatively in the form DNA double helix.
 LASEK Procedure with the Use of Mitomycin C 359
Mitomycin C inhibits DNA, RNA and protein At 28 months’ follow-up, late haze had appeared
syntheses. It is an anti-cancer agent disturbing in 61 patients in the eyes not treated with MMC,
replication, transcription and translation processes, it reaching a maximum value of 1° in 23 patients, she
has an anti-proliferation property. Fast-dividing cells said, noting no patients required re-operation. All
are especially sensitive. Besides, MMC is a the patients achieved full re-epithelialization.
radiomimetic agent with long-term effects on tissues.3 The late haze appeared only at eyes not treated
After MMC application variable types of with mitomycin C (in 61 patients, 6.3%) reaching
complications were noted. Allergic diffuse maximum value of 1 degree in 23 operated patients
papillomatous conjunctivitis in pterygium surgery, (2.38%). None of the patients required re-operation.
corneal epithelium defect in case of local Full re-epithelialization was achieved after
administration (be prudent while using it because removal of the lens in all cases. No statistical
occasionally it may result from insufficiency of corneal differences in vision acuity between the groups in
limbal (stem) cells due to toxic action of mitomycin the 1 month after the procedure were observed.
C). Delayed wound healing may occur, as well as We achieved UCVA 24 months after the
closure of lacrimal points and lacrimal canaliculi procedure in total 558 patients (Figure 42.1).
(conjunctival neoplastic lesions treatment), iritis and Confocal microscopy examination with the use of
uveitis, scleritis, maculopathy caused by hypotension microscope ConfoScan 3 (Nidek Technologies) was
in filtration surgery, and finally endophthalmitis. performed in both eyes before the procedure and in
In the Microsurgery Eye Center LASER 0.02% the period of 2 weeks, 1, 3, 12 and 24 months after
solution (0.5-1 min) of mitomycin C was used in 968 the procedure (Figure 42.2). In examination under
patients at one eye with the corrected error of –6.0 confocal microscope considerably reduced signs of
to –9.5 spherical dioptres and spherical equivalent keratocytes activation, less needle like formations in
amounting to –7.65 +/–0.46 on average. The second the subepithelial area and in the anterior part of
eye or the eye with less refractive error was operated proper substance in the cornea after LASEK with
without MMC. The cornea thickness in these patients MMC were stated compared with the cornea that
did not allow performing the LASIK procedure. After underwent only LASEK procedure (Figure 42.3).
ablation cornea was cooled with 4°C BSS for 2 min. Important differences in the appearance of
Procedures were conducted by means of excimer laser epithelium, middle anterior, middle, and posterior
MEL 70 G-scan. parts of proper substance and endothelium within
Moist application of mitomycine C (0.2 mg/ml) compared eyes were not noticed.
applied from 30 seconds to 1 min. Subepithelial scar tissue revealed postoperatively
Contact lens remained on the eye during 6 days. in certain cases, had a reduced hiperreflectivity and
Identical postoperative treatment plan was was less firm and thinner in eyes that had undergone
implemented (antibiotics with steroids, artificial tears, LASEK procedure with the mitomycin use. Figures
topically and oral NSAID). 42.4 to 42.7 show photos of compared eyes of the
The follow-up period was between 13 to 28 months same patient. In following examinations, the scar
(24 month in 558 patients). tissue reflectivity was being decreased in a
The corneas were examined under a confocal comparable way in both eyes.
microscope Confoscan 3 (Nidek Laboratory) at the Research on the impact of MMC application on
following intervalls: before the surgery, 6, 12 and 24 the endothelium of cornea was made as well (Figure
months after surgery. In order to assess epithelial layer 42.8). The average density of endothelial cells before
status and any changes in the corneal endothelium. the procedure was comparable and stated 2968/ mm2
Over first days after the application of MMC the +/–347. After the LASEK and the LASEK with MMC
patients felt a greater discomfort than after the LASEK procedures it did not show statistically significant
procedure alone. differences (p > 0,05 T-Student test).
360 Mastering Advanced Surface Ablation Techniques

Figure 42.1: UCVA 24 months after the LASEK

Figure 42.2: Spherical equivalent after 24 months (number of eyes)

Figure 42.3: Unchanged mild stroma in patient 12 to 24 months after LASEK with adjunctive mitomycin C surgery
 LASEK Procedure with the Use of Mitomycin C 361

Figure 42.4: Subepithelial scar tissue two weeks after LASEK surgery Figure 42.7: Anterior stroma 1 month after LASEK with adjunctive
mitomycin C. No scar tissue remaining

Figure 42.5: Subepithelial scar tissue two weeks after LASEK with Figure 42.8: Unchanged endothelium in patient 12 months after
adjunctive mitomycin C surgery LASEK with adjunctive mitomycin C surgery

1. The use of mitomycin C allows qualifying for the

LASEK procedure patients with large errors for
whom it would be dangerous to undergo the
LASIK procedure due to insufficient cornea
thickness.
2. No side effects of mitomycin C on the eye
structure was observed in the studied group.
3. Based on the two years observation, the use of
mitomycin C seems to be a safe method to prevent
such complications as haze (confirmed by the
confocal microscope examination).
We did also research on the process of cornea
Figure 42.6: Anterior stroma 1 month after LASEK surgery. healing after the use of LASEK with the
Remains of scar tissue is visible
intraoperative MMC application in the correction of
On the grounds of the 2 years long observation remaining refractive errors persisting after the LASIK
we concluded as follows: procedure. We accepted the following indications for
362 Mastering Advanced Surface Ablation Techniques
the use of LASEK after LASIK method in the
correction of residual refractive errors:
1. Stable refractive error from –1.0 D, to –4.0 D,
astigmatism from –1.0 to 2.5 D.
2. Lack of patient’s acceptance of the offered optic
methods.
3. Symptoms of dry eye syndrome in the period of
3 months after the LASIK procedure (contraindi-
cated classic reoperation).
4. Massive DLK after the primary procedure.
5. Conditions after removal of epithelium in case of
ingrowth’s under the flap.
6. Irregular circular scar in the flap’s cut place.
Figure 42.9: Before LASEK surgery—very hyper-reflective deposits
Disorders of corneal structure were not at Lasik interface depth, the keratocytes density is locally decreased
demonstrated in preoperative confocal microscopy
examination excluding presence of deposits of
medium and high reflectivity on level of interface
and reduction of keratocytes density in this place. In
some of the cases anomalies in the course of nervous
fibres were stated (Figure 42.9).
Postoperative confocal microscopy examination
showed the presence of scar tissue under the
epithelium and in the anterior part of proper
substance in operated patients (Figure 42.10).
On examinations performed 3 months after the
procedure almost no scar formation war observed
(Figure 42.11).
Presence of pathological changes such as augmented Figure 42.10: Subepithelial opacities (scar tissue) is reflecting light
number of excited keratocytes, presence of needle-like under healthy basal epithelium—1 month after LASEK surgery
formations or infiltrative cells were not noticed either
in examination 3 months after the procedure.
Appearance of the epithelium did not differ from
the physiological one except from insignificant
thinning in the superficial layers in part of the cases.
It indicates the proper course of healing process
No corneal haze was noted in the slit-lamp examination
after LASEK reoperation in the analysed group.
LASEK with MMC in our opinion seems to be a
safe method for correction of residual errors after
previous LASIK (Figure 42.12).

SUMMARY

“According to Dr Liberek, they perform LASEK when Figure 42.11: Anterior stroma 3 months after LASEK surgery—no
the cornea is less than 500 μm thick, and they apply scar tissue detectable
 LASEK Procedure with the Use of Mitomycin C 363

“Without MMC, [LASEK] would not be possible

because [the case] would be high myopia, and with
high myopia, we observed haze,” If MMC is not
available, and the patient has more than –10 D of
myopia, phakic IOL use is indicated. “To choose the
phakic IOL or LASEK with MMC, so it depends on
the cornea and the pachymetry, and it depends on
the high refractive error.’’

REFERENCES

1. T J Liesegang, GL Skuta, LB Cantor (Eds). Basic and Clinical

Science Course. Section 13: Refractive Surgery. Elsevier
Inc 2005.
2. Gambato C, Ghirlando A, Moretto E, et al. Mitomycin C
modulation of corneal wound healing after
photorefractive Keratectomy in higly myopic eyes.
Ophthalmology 2005;112:208-18.
Figure 42.12: Comparison between BCVA before procedure and
UCVA after procedure 3. Carones F, Vigo L, Scandola E, et al. Evaluation of
prophylactic use of mitomycin C to inhibit haze formation
MMC when the patient is about –5 D and the ablation after photorefractive keratectomy. J Cataract Refract Surg
depth needs to be more than 60 μm. 2002; 28: 2088-95.
364 Mastering Advanced Surface Ablation Techniques

CHAPTER Corneal Permeability after

43 LASEK Measured
with Fluorophotometry

Marie-José Tassignon, Wim Weyenberg,

Patrick Schraepen, Grace Lie, Annick Ludwig,
Danny Mathysen, René Trau (Belgium)

INTRODUCTION the remaining Bowman’s membrane is completely

destroyed at the level of the treated zone.4
Several surgical techniques have been proposed The aim of this study is to assess whether the
during the last decade to correct refractive errors by corneal epithelial cells are capable to restore the
changing the corneal curvature with the excimer laser. physiological properties of the cornea after LASEK
Photorefractive keratectomy (PRK) was by studying corneal permeability measured with
introduced first and became popular because of the fluorophotometry. The study was performed in
simplicity of the surgical technique. The drawbacks, accordance to the basic principles of clinical research
however, became rapidly evident, e.g. postoperative as formulated by the World Medical Association
pain, slow visual recovery, and corneal haze. Declaration of Helsinki.
Laser in situ keratomileusis (LASIK) was proposed
as an alternative and appeared more successful in PATIENTS AND METHODS
reducing postoperative pain, haze and visual recovery
Eight patients (12 eyes) with a mean age of 38.8 years
period. 1 However, the flap complications have
(range 35 to 43) underwent LASEK treatment for the
considerably reduced the expansion of corneal flap
correction of mild to moderate myopia (mean SE –
laser refractive surgery until improvements in the
3.94 D, range –1.50 D to –6.50 D). The control group
laser technology and software made it possible to
consisted of nine healthy volunteers, matched for
return to the surface ablation techniques. Laser myopia (mean SE –2.14 D, range –1.50 D to –3.00 D)
epithelial keratomileusis (LASEK), first introduced and age (mean 35.8 years, range 24 to 62) to the
by Camellin,2 combines the advantages of both PRK LASEK treated group (Table 43.1). None of these
and LASIK: smooth corneal surface, fast recovery, volunteers had contact lens wear history, external
reduced pain and no flap complications.3 eye diseases or had previously ocular surgery. None
LASEK consists in trying to preserve the of them took any systemic or ocular medication. One
anatomical integrity of the epithelial flap by detaching female took oral contraception. During the follow-
it from the Bowman membrane by means of a 20 % up period no complications occurred.
alcohol solution (w/w) and repositioning it on the
corneal surface after laser ablation. The plane of LASEK
cleavage of this process is located between the lamina All treatments were performed by the same surgeon
lucida and the lamina densa. After laser treatment (RT) using an Inpro excimer laser (Germany),
 Corneal Permeability after LASEK Measured with Fluorophotometry 365
Table 43.1: Number, age, spherical equivalent (SE) and male/female ratio of the study and control group
1 Month 6 Months Controls with Controls without
post-LASEK post-LASEK eye drops eye drops
N 6 6 9 9
Age (years) 36.8 ± 4.3 39.0 ± 4.1 35.8 ± 15.4 35.8 ± 15.4
SE –3.96 D ± 1.99 D –3.92 D ± 1.93 D –2.10 D ± 0.82 D –2.19 D ± 0.69 D
Male/Female 3/3 4/2 6/3 6/3

featuring a ceramic laser cavity manufactured by recently in order to obtain a sustained drug release
Lambda-Physik (model 200i) and a broad-beam once in the conjunctival sac (Figure 43.1). According
Gaussian Delivery System (GDS). The procedure can to in vitro and in vivo studies,6,7 this device is very
be summarized as follows: suitable for clinical and diagnostical purposes. It has
1. A basket marker of 8 mm diameter is applied the advantage to obtain a sustained release of sodium
firmly on the cornea after careful centration, filled fluorescein in the tear film for at least 6 hours. One
with a 20% alcohol solution (w/w) and left in place batch of these minitablets was used in this study to
for 20 to 25 seconds. evaluate the corneal permeability after LASEK.
2. The alcohol is then absorbed by a cellular sponge
and rinsed thoroughly with BSS® solution, making
it possible to roll up the loosened epithelial layers at
the 12 o’clock position with an epithelial micro hoe.
3. After laser ablation, the epithelial flap is
repositioned using an irrigating cannula.
4. A therapeutic soft contact lens (Plano T, Bausch
and Lomb) is placed on the cornea and removed
3 days after the procedure.
Until the therapeutic lens was removed, the
therapy consisted in a topical instillation of ofloxacin
(Trafloxal®) every hour and diclofenac (Voltaren®)
four times a day. From then on, the eye was treated
with the following eye drops: chloramphenicol, Figure 43.1: Gelling minitablet in place in the inferior
dexamethason (DeIcol®) and Voltaren®. At one week conjunctival fornix
until the 4th or 5th postoperative month, the
treatment was tapered from three drops to one drop The following agents were employed to prepare
daily of both fluoromethalon (FML®) and Voltaren®. the ocular gelling minitablets: sodium fluorescein
The patients were examined daily until the (Sigma Chemical Co., St. Louis, MO, USA), Carbopol®
therapeutic lens was removed, and then at 1 week, 974 P (Noveon, Cleveland, Ohio, USA) and drum
1 month and 6 months postoperatively. dried waxy maize starch (DDWM) (Eridania Béghin-
Central corneal thickness, measured with Say Cerestar, Vilvoorde, Belgium). Sodium stearyl
ultrasonography, was within the physiological range fumarate was a gift of Edward Mendell Co. Inc. (New
in all eyes, before (545 μm ± 40 μm) and after LASEK York, USA).
(481 μm ± 30 μm).5 Carbopol® 974 P (5 %, w/w), DDWM (92 %, w/w),
sodium stearyl fumarate (1 %, w/w) and sodium
Preparation of Ocular Gelling Minitablets fluorescein (2 %, w/w) were homogeneously blended
A bio-erodible minitablet, containing the diagnostic in a laboratory mixer for ten minutes (Turbula T2A,
agent sodium fluorescein, has been developed Willy A. Bachoffen, Maschinenfabrik, Basel,
366 Mastering Advanced Surface Ablation Techniques
Switzerland). The powder mixture was then compressed served as control. This protocol was approved by
at 0.500 kN (range 0.475–0.525) into minitablets using the ethical committee of the hospital.
an eccentric tabletting machine Korsch (Type EKO,
Berlin, Germany) equipped with 5 concave punches Statistical Analysis
(Ø 2 mm). Afterwards the ocular minitablets were The study cases were divided in two main groups:
sterilized at an irradiation dose of 25 kGy, using a 60Co one comprising patients who had undergone LASEK
source (Gammir–I–Sulzer irradiator unicell, IBA– treatment and the other comprising controls. Both
Mediris–Sterigenics, Fleurus, Belgium). groups were compared for age distribution, spherical
equivalents (SE) and sex ratios by means of the
Fluorophotometry Kruskall-Wallis test (age and SE) and chi-square
To objectivate the presence of endogenous analysis (sex ratio).
fluorophores, three blank scans for each eye were For the analysis of the fluorescein concentration
performed to measure the autofluorescence in both in the different study groups the following statistical
the cornea-tear film compartment as well as the procedure was employed:
anterior chamber. After application of a minitablet 1. Outliers in fluorescein concentration were
in the inferior conjunctival fornix, the concentrations detected by means of the z-test and removed from
of sodium fluorescein were measured with a the analysis;
fluorophotometer FluorotronTM Master (Ocumetrics, 2. Homogeneity of variances was checked prior to
Mountain View, CA, USA). Autofluorescence values applying the unpaired, two-sided Student’s t-test.
were deducted from the values obtained after The results of the statistical analysis were
considered to be significant when the obtained p-
application of a minitablet.
value (cfr. Table 43.2) was equal or below 0.05.
The fluorescein concentrations in the anterior
chamber and in the tear film-cornea compartment
RESULTS
were measured as a function of time.7,8 The tear film
and the cornea were considered as one compartment, The fluorescein concentrations in the tear film-cornea
since it is impossible for the type of Fluorotron used compartment are 10-fold high compared to those
to measure both layers separately. found in the anterior chamber. The concentration in
The corneal permeability of twelve eyes of eight the tear film-cornea compartment presents a steady
patients who underwent a LASEK treatment was raise during the first three hours after application of
compared with the right eyes of nine volunteers the minitablet (Figure 43.2) to reach the highest
treated with the same topical medication for two days concentration five to five-and-a-half hours after
and the left eyes of the same nine volunteers serving application of the minitablet. Six to six-and-a-half
as controls. In the study group, a first measurement hours after application of the minitablet the
was performed at one-month post-LASEK. At that concentration decreases manifestly and reaches the
time the patients were still under topical medication baseline level after seven hours of application. This
(Voltaren® and FML®). A second measurement was is mainly the case for all groups considered.
performed six to ten months after LASEK whereby When looking at the concentration of fluorescein
topical medication was stopped for at least six weeks in the anterior chamber (Figure 43.3), it rises slowly
in all cases. during the first four hours after application of the
The influence of eye drops (Voltaren® and FML®) minitablet and reaches the highest concentration after
on corneal permeability was investigated in the six hours and decreases rapidly thereafter during the
control group by instructing the volunteers to apply following hour. This is the case for all groups studied.
Voltaren® and FML® in their right eye 3 times daily, Because of the slow fluorescein release in the
two consecutive days prior to the test. Their left eye tear film-cornea compartment, the concentration in
 Corneal Permeability after LASEK Measured with Fluorophotometry 367
Table 43.2: Significance rates (p-values < 0.05) of two-sided student’s t-test
Time CoND vs CoED 1MpL vs CoND 6MpL vs CoND 1MpL vs CoED 6MpL vs CoED 1MpL vs 6MpL
90 min NS (0.266) NS (0.418) 0.038 NS (0.830) 0.002 NS (0.074)
120 min NS (0.343) NS (0.450) NS (0.106) NS (0.814) NS (0.242) NS (0.616)
150 min NS (0.420) NS (0.234) 0.015 NS (0.498) 0.029 NS (0.208)
180 min NS (0.696) 0.048 NS (0.140) NS (0.065) NS (0.168) NS (0.531)
240 min 0.031 0.050 0.021 NS (0.123) NS (0.052) NS (0.781)
300 min NS (0.108) 0.035 0.011 NS (0.131) NS (0.265) NS (0.509)
360 min 0.005 0.024 0.008 NS (0.136) NS (0.587) NS (0.419)
420 min 0.000 0.008 NS (0.168) NS (0.175) NS (0.203) NS (0.203)
Legend:
CoND = Control group without eye drops
CoED = Control group with eye drops
1MpL = Study group 1 month after LASEK treatment
6MpL = Study group 6 months after LASEK treatment
NS = not significant (p > 0.05)
P-values indicated in italic are highly significant (p < 0.01)

Figure 43.2: Logarithmic fluorescein concentration measured during eight hours at the level of the tear film-cornea
compartment in the different groups studied:
CoND = Control group without eye drops
CoED = Control group with eye drops
1MpL = LASEK treated group 1 month postoperatively
6MpL = LASEK treated group 6 months postoperatively

the anterior chamber started rising significantly only minitablets so that the concentration measured in the
after three hours of application of the minitablet. anterior chamber after that time cannot be considered
Statistical study was therefore only considered from as a consequence of corneal permeability but
180 minutes on. However, the fluorescein release in corresponds mainly to the wash-out of fluorescein
the tear film-cornea compartment was significantly from the anterior chamber. Statistical study was
reduced seven hours after application of the therefore no longer considered after 420 minutes.
368 Mastering Advanced Surface Ablation Techniques

Figure 43.3: Fluorescein concentration measured during eight hours at the level of the anterior chamber in the different
groups studied:
CoND = Control group without eye drops
CoED = Control group with eye drops
1MpL = LASEK treated group 1 month postoperatively
6MpL = LASEK treated group 6 months postoperatively

The statistical analysis interval was thus performed DISCUSSION

between 180 and 420 minutes
LASEK is a surgical technique in which the corneal
The control eyes without instillation of any
epithelial layers of the cornea are detached from their
medication (CoND) were compared to the control
Bowman membrane by applying a 20% alcohol solution
eyes, which had two medications instilled for two
on the cornea. After the laser ablation, the epithelial
days (CoED). A statistically significant higher
layers are repositioned over the corneal wound. This
concentration of fluorescein was found in the CoED
technique presents the advantage to reduce the rate
at 4, 6 and 7 hours after application of the minitablet.
of postoperative pain and to decrease haze. LASEK
The patient’s eyes one month after LASEK (1MpL)
technique is as effective as LASIK9 concerning the
and six months after LASEK (6MpL) were compared
visual results at 6 months, and presents furthermore
with controls without eye drops (CoND). For both
the advantage over LASIK not to show flap-related
LASEK groups a statistically significant higher
and interface-related complications.
concentration of fluorescein was found at 3
Vitality of the epithelial cells after various exposure
(only 1MpL), 4, 5 and 6 hours after application of the
times to 20% alcohol was studied by Gabler.10 He
minitablet, while the significance lasted until 7 hours
concluded that vitality of the epithelial cells was
after application for only the 1MpL group.
preserved up to 30 seconds exposure times. This may
When comparing 1MpL and 6MpL, no statistically
explain why the wound response is dampened in
significant differences were found in the fluorescein
LASEK as compared to PRK.
concentration in the anterior chamber. This was also
Although the integrity of the epithelial cells is
the case when comparing CoED with 1MpL and CoED
preserved, the basement membrane is completely
with 6MpL.
 Corneal Permeability after LASEK Measured with Fluorophotometry 369
destroyed after LASEK over a corneal surface of at Postoperatively, a topical steroid (FML®) and a non-
least 6.5 mm of diameter. Electron microscopy and steroid anti-inflammatory medication (Voltaren®) were
immunofluorescence staining showed that the prescribed for several weeks, to prevent regression.
cleavage plane after alcohol exposure is located Diclofenac 24 and benzalkonium chloride (BAC),25,26 a
between the lamina lucida and the lamina densa of preservative added to FML®, have a known toxic effect
the basement membrane and that the remaining on the corneal epithelium resulting in a significant
lamina lucida presented significant interruptions after increase in permeability to fluorescein.24-27
LASEK.6,11 We found an increase in corneal permeability
The calculated permeability of the cornea using already two days after topical instillation of
fluorophotometry varies from one study to another preservative containing medication compared to the
according to the study protocol and the method of control group that did not receive topical instillation.
fluorescein administration. Permeability ranges from Because of objections of the ethical committee to treat
1.8 to 4.0 cm/min × 10–4.11-18 In this study a fluorescein volunteers with combinations of antibiotics and anti-
minitablet was used presenting the advantage of inflammatory drugs without medical indication, for
releasing fluorescein slowly for at least 6 hours. This longer than two days, we cannot answer the question
concept presents the advantage to be more whether corneal permeability would be disturbed
appropriate for the study of corneal permeability more after longer treatment times.
Fluorescein concentration was found statistically
compared to the monodosis instillation technique,
significantly higher 1 month and 6 months after
which generates a peak concentration at the time of
LASEK compared to the control group without drops.
application and a rapid gradual decrease after-
Although the difference between 1 and 6 months after
wards.6-7
LASEK was not significant, lower concentrations of
Studies on corneal permeability after LASEK have
fluorescein are measured after six months compared
– to our knowledge – not yet been published. Some
to one month, suggesting a slight decrease in corneal
studies on corneal permeability after PRK have
permeability to fluorescein six months after LASEK.
observed a permanent increase of diffusion after PRK
Although statistically not significant, the
in rabbits 19 and humans 20 or a transient increase for
concentration of fluorescein six months after LASEK
2 to 4 weeks.21-22 No studies have been performed
tends to be higher compared to the fluorescein
on corneal permeability after LASIK. Since we do
concentration in eyes after instillation of eye drops
not consider LASIK as treatment option for low to
containing preservatives only. This suggests that
moderate myopia, we were unable to compare corneal permeability is not influenced by topical
corneal permeability after LASEK and LASIK using medication alone but also by changes in the corneal
this sustained fluorescein-releasing device. tissue after LASEK, resulting in an increased corneal
There is no consensus about the effect of age on permeability to fluorescein starting at one month and
corneal permeability. According to Sawa,16 corneal remaining unchanged till six months after LASEK.
permeability is higher in younger subjects. Other
authors report no significant correlation with age.12,14 CONCLUSION
Bourne 12 did not observe any correlation between This study concludes that corneal permeability shows
corneal permeability and age, intraocular pressure increased permeability to fluorescein after topical
or anterior chamber volume. medication and after LASEK at one month till six
In a study on young myopic adults (mean age: months after surgery.
22.2 years, mean spherical equivalent: –4.17 D) there
appears to be no correlation between the corneal ACKNOWLEDGEMENTS
permeability and the corneal thickness, corneal The patients and the volunteers are acknowledged
curvature, axial length or the degree of myopia.23 for their contribution to this in vivo study. The
370 Mastering Advanced Surface Ablation Techniques
authors wish also to thank Prof. J.P. Remon 13. Coakes RL, Brubaker RF. Method of measurement of
aqueous humor flow and corneal endothelial permeability
(Pharmaceutical Technology, University Ghent) for
using a fluorophotometry normogram. Invest.
the use of the eccentric tabletting machine and Dr. Ophthalmol. Vis. Sci. 1979;18:288-302.
P. Dardenne (IBA–Mediris–Sterigenics, Fleurus, 14. De Kruijf EJ, Boot JP, Laterveer L, et al. A simple method
Belgium) for the sterilization of the ocular minitablets. for determination of corneal epithelial permeability in
humans. Curr. Eye Res 1987;6:1327-34.
15. Ota Y, Mishima S, Maurice DM. Endothelial permeability
REFERENCES of the living cornea to fluorescein. Invest. Ophthalmol
1974;13:945-9.
1. Azar DT, Ang RT, Lee JB, et al. Laser subepithelial 16. Sawa S, Araie M, Tanishima T. A fluorophotometric study
keratomileusis: electron microscopy and visual outcomes of the barrier functions in the anterior segment of the
of flap photorefractive keratectomy. Curr. Opin. eye after intracapsular cataract extraction. Jpn. J.
Ophthalmol 2001;12:323-8. Ophthalmol 1983; 27:404-15.
2. Camellin M. Laser epithelial keratomileusis for myopia. 17. Waltman SR, Kaufman HE. A new objective slit lamp
J. Refract. Surg 2003;19:666-70. fluorophotometer. Invest. Ophthalmol. 1970;9:247-9.
3. Vandorselaer T, Hermiat JJ, Schraepen P, et al. Lasek for 18. Yablonski ME, Zimmerman TJ, Waltman SR, Becker B. A
myopia: first results. Bull. Soc. belge Ophtalmol fluorophotometric study of the effect of topical timolol
2003;290:59-68. on aqueous humor dynamics. Exp. Eye Res. 1978;27:135-
4. Espana EM, Grueterich M, Mateo A, et al. Cleavage of 42.
corneal basement membrane components by ethanol 19. Chang SW, Tsai IL, Hu FR, et al. The cornea in young
exposure in laser-assisted subepithelial keratectomy. J. myopic adults. Br. J. Ophthalmol. 2001;85:916-20.
Cataract Refract. Surg 2003;29:1192-7. 20. Maitchouk D, Smirennaia E, Kourenkov V. Corneal
5. Doughty MJ, Zaman ML. Human corneal thickness and pharmacodynamics after photorefractive keratectomy
its impact on intraocular pressure measures: a review
and laser in situ keratomileusis in rabbits. J. Refract. Surg.
and meta-analysis approach. Surv. Ophthalmol.
2002;18:S382-84.
2000;44:367-408.
21. Kim KS, Lee JH, Edelhauser HF. Corneal epithelial
6. Ceulemans J, Vermeire A, Adriaens E, et al. Evaluation
permeability after excimer laser photorefractive
of a mucoadhesive tablet for ocular use. J. Control. Release
keratectomy. J. Cataract Refract. Surg 1996;22:44-50.
2001;77:333-44.
22. Kim JY, Heo JH, Park SJ, et al. Changes in corneal epithelial
7. Weyenberg W, Vermeire A, Remon JP, Ludwig A.
barrier function after excimer laser photorefractive
Characterization and in vivo evaluation of ocular
keratectomy. J. Cataract Refract. Surg. 1998;24:1571-4.
bioadhesive minitablets compressed at different forces.
23. Chang SW, Hu FR, Hou PK. Corneal epithelial recovery
J. Control. Release 2003;89:329-40.
8. Hornof M, Weyenberg W, Ludwig A, Bernkop- following photorefractive keratectomy. Br. J. Ophthalmol
Schnurch A. Mucoadhesive ocular insert based on 1996;80:663-8.
thiolated poly(acrylic acid): development and in vivo 24. Chetoni P, Burgalassi S, Monti D, Saettone MF. Ocular
evaluation in humans. J. Control. Release 2003;89:419-28 toxicity of some corneal penetration enhancers evaluated
9. Rouweyha RM, Chuang AZ, Mitra S, et al. Laser epithelial by electrophysiology measurements on isolated rabbit
keratomileusis for myopia with the autonomous laser. J. corneas. Toxicol. In vitro 2003;17:497-504.
Refract. Surg 2002;18:217-24. 25. Burstein NL. Preservative alteration of corneal
10. Gabler B, Winkler von Mohrenfels C, Dreiss AK, et al. permeability in humans and rabbits. Invest. Ophthalmol.
Vitality of epithelial cells after alcohol exposure during Vis. Sci. 1984;25:1453-7.
laser-assisted subepithelial keratectomy flap preparation. 26. Ramselaar JA, Boot JP, Van Haeringen NJ, et al. Corneal
J. Cataract Refract. Surg 2002;28:1841-6. epithelial permeability after instillation of ophthalmic
11. Jones RF, Maurice DM. A simple photographic method solutions containing local anaesthetics and preservatives.
of measuring the volume of the anterior chamber. Exp. Curr. Eye Res 1988;7:947-50.
Eye Res 1963;2:233-6. 27. Tognetto D, Cecchini P, Sanguinetti G, et al. Comparative
12. Bourne WM, Nagataki S, Brubaker RF. The permeability evaluation of corneal epithelial permeability after the use
of the corneal endothelium to fluorescein in the normal of diclofenac 0.1 % and flurbiprofen 0.03 % after phaco-
human eye. Curr. Eye Res. 1984;3:509-13. emulsification. J. Cataract Refract. Surg 2001;27:1392-96.
 CHAPTER Laser Epithelial
44 Keratomileusis (LASEK) for
the Correction of Hyperopia

David PS O’Brart (UK)

INTRODUCTION Published research has reported excellent outcomes

with LASEK for myopic and astigmatic corrections
Whilst comparative studies of photorefractive
with refractive and visual results comparable to those
keratectomy (PRK) and laser in situ keratomileusis
with PRK and LASIK. 18-20 There have been fewer
(LASIK) have demonstrated few differences in terms
studies reporting outcomes after hyperopic LASEK
of predictability and visual outcome,1-4 advantages
(H-LASEK). Those published in the peer-reviewed
in terms of minimal postoperative discomfort together
literature have been favorable with good outcomes
with rapid visual recovery have made LASIK the
equivalent to PRK and LASIK.21-23 The correction of
procedure of choice for the majority of refractive
hyperopia, however, remains problematic with poor
surgeons.(5) However, whilst outcomes after LASIK
predictability compared to myopic treatments and
are typically very satisfactory, serious site-
slower visual recovery and refractive stability.23-27 This
threatening, intra-lamellar complications may
chapter attempts to review the published literature of
occasionally occur.6-9 In addition, whilst long-term
H-LASEK in terms of refractive and visual outcomes,
data for PRK suggests good refractive and
potential complications and describe important aspects
biomechanical corneal stability,10-12 there is a paucity
of preoperative counseling and patient assessment,
of data concerning LASIK, which by its very nature
operative techniques and post-operative recovery and
of anterior stromal flap creation is more invasive in
care.
terms of biomechanical corneal disruption. What data
is available suggests uncertain refractive stability for REFRACTIVE AND VISUAL OUTCOMES OF
high myopic and hyperopic corrections.13-16 Such H-LASEK
concerns have led to renewed interest in surface
ablation and thin-flap LASIK techniques. In a recent study of H-LASEK, in 70 consecutive eyes
Laser epithelial keratomileusis (LASEK), which with 12-24 months follow-up we reported excellent
involves the fashioning of an intact epithelial sheet to refractive outcomes for hyperopic errors up to +5
cover the stromal bed after surface ablation, avoids diopters (D), with 98% of eyes within +/–1.0D and
the intralamellar complications associated with LASIK. 86% within +/–0.5D of the attempted correction.23
It has also been postulated that it might induce less These results compare favorably with published
haze and regression that occasionally limits the efficacy studies of H-PRK and H-LASIK11,15-16.24-31 and are
of PRK, as well as providing a faster visual recovery.(17) similar to those reported by Autrata and Rehurek
372 Mastering Advanced Surface Ablation Techniques
after H-LASEK.21 As expected, predictability in our for such extreme hyperopic corrections with only 50-
cohort was reduced for corrections between +2.625 90% of eyes within +/–1D of the attempted correction
to +5.0D compared to those between 0 and +2.50D. and more importantly a loss of 2 or more lines of
However, with 96% of eyes within +/–1.00D and 70% best spectacle corrected visual acuity (BSCVA)
within +/–0.5D at 12-24 months for corrections occurring in up to 7-10% of eyes. 11,15,16,21-31
>+2.50D, predictability was acceptable even with these Unpublished data from my own cohort of patients
higher order refractive treatments. indicates similar tendencies. In 21 eyes undergoing
Visual outcomes with H-LASEK in our study using corrections >+5D (range +5 to +7.375D) and reaching
a 7.0 mm optical zone were satisfactory.23 At 12-24 12 months follow-up, only 62% were within +/–1D
months uncorrected visual acuity (UCVA) was 20/ and 48% with +/–0.5D of the attempted correction.
20 or better in 78% of non-amblyopic eyes and 20/30 Refractive stability in these extreme hyperopic
or better in 98%. Such figures compare favorably to corrections took at least 6-9 months with a significant
published studies of H-PRK, H-LASEK and H-LASIK induction of myopia during the first few months
11,15,16,24-31
and are even comparable to myopic excimer following surgery. However, with the exception of
laser treatments.1-4,10,12-14,18-20 peripheral haze development complications were
Whilst LASIK offers advantages over surface insignificant and no eyes have lost 2 or more lines of
ablation techniques in terms of rapidity of post- BSCVA. Such results indicate that whilst H-LASEK
operative recovery, randomized, prospective and is effective for the correction of hyperopic errors up
bilateral studies comparing myopic PRK and LASIK to +5D, limited predictability and prolonged
show few differences in medium and long-term refractive stability (and therefore unaided visual
outcomes.1-4 Comparative studies of myopic PRK and recovery) limit its efficacy for corrections >+5D. The
LASEK indicate equivalent outcomes.20,32-35 In the use of antimetabolites such as mitomycin-C (MMC)
only published comparative study of hyperopic has been shown to improve the efficacy of high order
corrections, better refractive stability, contrast myopic corrections after surface excimer laser
sensitivity and predictability was reported with ablations.39-40 At present, there are no published
LASEK compared to PRK. 21 Published studies studies concerning its usage for routine H-LASEK
comparing LASEK and LASIK are few with no and H-PRK corrections. Whilst its use in higher order
published studies comparing hyperopic treatments. hyperopic corrections (>+5D) may be indicated as a
In two randomized investigations for low myopic means of improving predictability and preventing
corrections, 36-37 outcome measures indicated few peripheral corneal haze, the need to apply MMC to
differences, albeit with better contrast sensitivity the corneal periphery close to the limbal stem cells is
after LASEK. Kim et al,38 however, in a retrospective a cause for concern and requires further investigation.
analysis of high myopic corrections found that both The correction of astigmatism with excimer laser
techniques were safe and effective, although LASIK ablations remains challenging. Residual post-
appeared to provide superior results in terms of visual operative astigmatism is not infrequent, with axis
predictability and corneal transparency. Further misalignment very likely contributing to under- (and
studies, in particular randomized controlled over-) correction. In our published study23 we used
investigations of hyperopia, are required, but a Schwind ESIRIS laser which although it has a very
considering the published results, it is very likely that effective infrared tracker centering the ablation on
LASEK for hyperopia up to +5.00D is as effective in the entrance pupil center, has no system, as yet, for
terms of medium and long-term refractive outcomes accurate registration to account for cyclotorsion
as either LASIK or PRK. effects that commonly occur when vision is obscured
As yet there is no published data regarding and when the patient assumes a prone position.
H-LASEK for corrections greater than +5D. Studies Despite these limitations achieved outcomes in eyes
of H-LASIK and H-PRK indicate poor predictability where hyperopic cylindrical corrections were
 Laser Epithelial Keratomileusis (LASEK) for the Correction of Hyperopia 373
attempted were excellent with vector analysis biomechanical stability than surface ablation
demonstrating a mean 101% cylindrical correction for procedures. The LASIK flap once cut may contribute
corrections up to +5DC at 12-24 months, with only little to the mechanical stability of the cornea. It never
4% of treated eyes with cylindrical errors >+1.00DC completely adheres to the underlying stromal bed,
postoperatively compared 31% preoperatively and with late traumatic flap displacement being reported
none with more than +2DC of residual astigmatism. as an infrequent complication. 9 Certainly, two
As might be expected, predictability was less for high recently published long-term follow-up studies of
order hyperopic cylindrical corrections (>+2.00DC), H-LASIK indicate poor refractive stability over 5
although result were still very encouraging, with years, especially for corrections over +2.5D.15-16 This
vector analysis demonstrating a mean 93% correction. is in contrast to our study of H-PRK over 7.5 years.11
Interestingly, analysis of our published results of Thus, H-LASEK not only appears to offer excellent
myopic cylindrical corrections using the same laser refractive outcomes up to +5D of hyperopia and
show poorer cylindrical refractive outcomes, with +5DC of hyperopic astigmatism, but good long-term
vector analysis demonstrating a mean 85% cylindrical refractive and biomechanical stability.
correction.41 This suggests that hyperopic cylindrical
correction, where peripheral stromal tissue is POTENTIAL COMPLICATIONS
removed to steepen the flat cylindrical axis, may offer
Published studies of LASEK outcomes over the past
better refractive outcomes than myopic cylindrical
6 years have been very encouraging indeed.17-23,32-38,41
correction, where central stromal tissue is ablated
In a review article the cumulative reported safety
flatten the steep axis, and merits further
index (mean postoperative BSCVA/ mean
investigation.
preoperative BSCVA) of 11 peer-reviewed papers
REFRACTIVE STABILITY was 1.0, with only a single eye of nearly 1,500 studied,
losing two or more lines of BSCVA due to a macular
In our published study, following an initial myopic cyst unrelated to the LASEK procedure. 42 In our
overcorrection which settled towards emmetropia published study of 70 consecutively treated H-LASEK
during the first 3-6 months, refractive stability was eyes we reported a safety index of 1.06.23 Similarly,
achieved by 6-12 months with no significant Autrata and Rehurek reported a safety index of 1.03
differences in the refractive correction between 12 in 108 eyes 24 months after H-LASEK.21 BSCVA at
and 24 months.23 It is important to warn patient 12-24 months in our patients was unchanged or
preoperatively of the initial myopic overcorrection improved in 90% and no eyes lost more than 1 line of
and to inform them of blurred uncorrected distance decimal equivalent Snellen acuity. Similar outcomes
acuity during the first months following surgery. In have been reported by Autrata and Rehurek.21 Such
terms of long-term stability, further follow-up is results compare very favourably to other published
required, but in light of our recent publications of studies of myopic and hyperopic corrections either
long-term studies of myopic PRK up to 12 years12 with LASEK, LASIK or PRK.1-4,11-16,18-38,41 With respect
and H-PRK up to 7.5 tears11 which show excellent to BSCVA, our results and those of Autrata and
refractive stability for surface excimer laser Rehurek have to be interpreted with regard to an
procedures after 12 months, it is likely that stability expected reduction of retinal magnification when the
of the induced refractive correction will continue at correction is located at the corneal rather than the
least over the next 10 and probably longer. For LASIK spectacle plane in hyperopic eyes. In such a situation
long-term published data is somewhat limited and a slight reduction of BSCVA might be expected and
the refractive and biomechanical stability remains therefore the published results of H-LASEK indicate
uncertain. 13-16 By its very nature LASIK must be excellent safety in terms of visual performance. It is
regarded as more invasive in terms of corneal important to note than in our series, treatment was
374 Mastering Advanced Surface Ablation Techniques
centred on the entrance pupil center and in no eyes • Medium (weeks/months)
was the ablation decentred to take account of eyes – Over/under correction
with a large angle kappa. De-centration to take – Subepithelial corneal haze (peripheral
account of angle kappa is often important in paracentral ring)
hyperopic corrections in order to avoid the induction – Recurrent erosion syndrome
of high order wavefront aberrations and a reduction – Ptosis
in postoperative UCVA and BSCVA. However, we • Late (months/years)
found that with the use of a large optical zone – Over/under correction
(7.00 mm), such considerations are not important, – Corneal scarring (typically peripheral after
especially as hyperopic eyes have small corneas and H-LASEK)
with a mean age in our cohort of over 50 years, pupil – Recurrent corneal erosion syndrome
diameters were typically small (5.0 mm or less). Our – Ectasia * (very unlikely in hyperopic eyes
study demonstrated that with the use of a 7.0 mm especially with a with surface ablation
optical zone centred on the entrance pupil center very technique)
satisfactory visual outcomes can be achieved In our published study complications were few23
postoperatively and decentration to take account of and sight-threatening complications did not occur.
angle kappa is unnecessary. As a far as non-sight threatening complications, 2
Whilst such outcomes are very encouraging patients (3%) in our series experienced a single
adverse events after H-LASEK can and do occur. A episode of corneal erosion 4-6 weeks following
thorough knowledge of potential complications both- surgery, which settled with no further episodes.
sight-threatening and non-sight threatening, their Three patients (4 eyes) (6%) reported occasional minor
prevention and management is vital in order to pain on waking in the morning but have declined
minimize any adverse events postoperatively. This further treatments due to the infrequency of these
is particularly important considering the elective episodes and the mild nature of the symptoms. Whilst
nature of excimer laser keratorefractive procedures such outcomes are encouraging, they are the result
and accompanying extremely high patient of two decades of increasing knowledge of laser
expectations. A list of potential complications after tissue interactions and corneal wound healing
H-LASEK includes; responses, access to advanced technologies and
• Intraoperative meticulous attention to detail in regards to pre-
– Alcohol escape operative patient education and counseling, pre-
– Poor flap creation operative evaluation, operative procedures and post-
– Free flap operative care. Pearls for minimizing potential
• Early (hours/days) problems after H-LASK include;
– Pain • Preoperative
– Delayed epithelial healing
– Extensive patient counseling concerning
– Slow visual recovery
potential complications
– Sterile infiltrates
– Thorough medical history including
– Infectious keratitis *
- Ophthalmic and medical family history
• Early (days/weeks)
(keratoconus, diabetes, glaucoma)
– Corneal melt *
– Corticosteroid intraocular pressure response * - Past contact lens problems (infections,
– Corneal erosion preservative toxicity, dry eye, keratoconus)
– Delayed visual recovery - Past medical problems (connective tissue
– Herpes simplex keratitis * disorders, diabetes)
– Delayed infectious keratitis * * Potential sight-threatening complications
 Laser Epithelial Keratomileusis (LASEK) for the Correction of Hyperopia 375
– Thorough ophthalmic examination by – Be honest and keep patient informed at every
appropriately trained ophthalmologist/ stage.
optometrist
– Exclude all unsuitable and at risk patients, DISTURBANCES OF CORNEAL TRANSPARENCY
including: (HAZE) AFTER H-LASEK
- Form fruste/overt keratoconus (ectasia risk)
As excimer laser refractive surgery is undertaken on
- Active collagen vascular diseases (risk of
healthy eyes any deterioration in postoperative
corneal melt)
corneal transparency is of concern. In myopic PRK,
- Overt dry eye (slow healing, worsening of
subepithelial haze develops over the central cornea
symptoms)
- Conjunctival cicatrization (slow healing, by the 4th week postoperatively with maximal
corneal melt) disturbances at 3 to 6 months and is associated with
- Corneal limbal stem cell anomalies (slow increasing depths of stromal ablation.10,43 As the main
healing, corneal melt) site of ablation is in the corneal periphery in H-PRK
- Pre-existing active ocular pathologies and H-LASEK, disturbance of axial corneal
• Cataract (perform leenticular surgery transparency is rare. We have previously reported
• Glaucoma (inaccurate IOP assessment) that in H-PRK, no disturbances of the axial cornea
• Herpes simplex/zoster (reactivation) are detectable either by slit-lamp examination or
– Be suspicious in eyes with objective measurements after 6 months.11,25 As far as
- Unexplained corneal scars (herpes simplex) the corneal periphery is concerned, we have reported
- Abnormal corneal topography (forme fruste the appearance of a paracentral ring of haze (the
keratoconus, contact lens warpage) diameter of which relates to the size of the optical
- Central corneal thickness <500 um (ectasia zone) by the 4th week postoperatively, which reaches
risk) maximal intensity at 3-9 months and diminishes
– Be careful in eyes with thereafter. However, even at 7.5 years 25% of eyes
- High order corrections >+5.0D (regression, still show some remnants of paracentral haze material
haze, loss of BSCVA) especially in higher order corrections.11,25
- Central corneal thickness <500 um (ectasia In LASEK it has been postulated that the creation
risk) of an intact epithelial sheet to cover the ablated area
- Large scotopic pupil diameters (>7.00 mm)
might reduce epithelial-stromal cross-talk during the
(mesopic/scotopic vision problems)
early phases of postoperative wound healing and
– Treat pre-existing lid disease (reduce infection)
induce less haze that can occasionally limit the efficacy
– Treat mild dry eye preoperatively? punctal plugs
of PRK.17 Prospective bilateral comparative studies
(delayed healing)
of PRK and LASEK have produced conflicting results.
• Operative
– Meticulous attention to detail (flap loss irregular Whilst Hashemi 35 could find no differences,
ablation) Autrata20-21 and Lee 33 demonstrated less haze in
– Maintain sterile conditions (reduce infection LASEK treated eyes. In our study no eyes developed
risk) disturbances in central corneal transparency and 83%
• Postoperative showed no peripheral haze changes.23 Significant
– Careful patient monitoring (steroid response, paracentral corneal haze developed in only 3 eyes
infection) (4%), which was maximal at 6 months and thereafter,
– Ensure easy access emergency service is declined. This is encouraging given the degree of
provided hyperopic correction attempted in some eyes and the
– Discuss with patients potential problems and use of a large optical zone treatment of 7.0 mm with
ensure they understand the importance of calculated ablation depths up to 100 um. However,
attending out-patient follow-up visits such results have interpreted with regard to modern
376 Mastering Advanced Surface Ablation Techniques
flying-spot excimer laser technology, which provide visual outcomes, minimize adverse events and
wide diameter ablations with exquisitely smooth optimize patient satisfaction. In terms of patient
surfaces. Such factors are known to play an important assessment in addition to a complete and careful
role in the propensity to haze development after ophthalmic examination a full subjective and
surface ablation procedures.44-45 cycloplegic refraction is essential as it can be difficult
to obtain accurate manifest refractive data in
CORNEAL ABERRATIONS AFTER H-LASEK hyperopic patients, especially in younger individuals,
because of accommodative problems and latent
We have previously reported the induction of negative
hyperopia. In our own practice, during subjective
spherical aberration after H-PRK, using a 6.00 mm
refraction we place a great deal of reliance on fogging
optical zone and 1.5 mm transition zone.11,46 As expected
and duochrome techniques and in particular the
we have found similar changes after H-LASEK, analysis
+1.00D blur test, performing at least two measure-
of higher order aberrations of the anterior corneal
ments on separate occasions to ensure a consistent
surface, revealed a significant reduction of 4th order
end point. For low hyperopes and patients over 40,
spherical aberration for both 3.0 mm and 6.0 mm pupil
we have found this method to be reliable and
analysis.23 This is consistent with the nature of hyperopic
comparable to cycloplegic refractive measurements.
excimer ablations which increase the prolate nature of
In younger patients (aged less than 40) and high
the anterior corneal surface. None of our H-LASEK
hyperopes (SEQ greater than +3.00D) it is known that
patients have reported any problems with scotopic/
significant differences in the manifest and cycloplegic
mesopic vision and indeed night vision disturbances
refractive data can occur. However, in low hyperopes
would not be expected with the induction of negative
(less than +3D) even if patients are aged less than 40,
rather than positive spherical aberration. We found that
it is still the authors’ experience to base the correction
RMS values for high order aberrations were unchanged
on the manifest subjective refraction based on the
postoperatively,23 although there were small increases
+1.00D blur test and duochrome rather than the
in coma and quatrefoil. The lack of significant induction
cycloplegic refraction, as this avoids an overcorrection
of high order aberrations in our patients was probably
with induced myopia, which can be very
due the use of a 7.00 mm optical zone and the smooth
unsatisfactory for the younger patient. Indeed
ablation profile afforded by the Schwind ESIRIS flying-
cycloplegia can significantly alter the optical
spot laser with its 0.8 mm Guassian beam. As all our
properties of the eye and increase high order
treatments were based on Munnerlyn algorithms47 with
aberrations and may introduce errors of low order
attempted correction of only lower order aberrations,
aberrations, especially astigmatism. 50 Careful
this suggests that with large optical zone treatments
continuous, prospective audit of refractive outcomes
wavefront ablations are unnecessary for hyperopic
(as well as visual outcomes and adverse events) is
excimer laser treatments. This is in contrast to myopic
essential to optimize results and adjust treatment
corrections where the induction of 4th order spherical
algorithms based on factors such as age, degree of
aberration is almost invariable and can limit visual post-
attempted correction, optical zone size, preoperative
operative visual performance and where aspheric
subjective and cycloplegic refractive measurements.
ablation profiles48 and wavefront based surgery49 appear
Patients should be warned of the occurrence of
to limit these changes.
postoperative pain/discomfort following H-LASEK.
SPECIAL ASPECTS OF PREOPERATIVE ASSESS- Although comparative studies of PRK and LASIK have
MENT AND COUNSELING FOR H-LASEK demonstrated no differences in predictability and
visual outcome, 1-4 perceived advantages in the
As with any keratorefractive procedure, careful rapidity of postoperative recovery including very
ophthalmic examination and full and detailed patient little postoperative discomfort have made LASIK the
counseling is essential to optimize refractive and procedure of choice for most surgeons.5. It has been
 Laser Epithelial Keratomileusis (LASEK) for the Correction of Hyperopia 377
postulated that in LASEK the creation of an intact again is in contrast to our experience with myopic
epithelial sheet to cover the ablated area might LASEK corrections, where initial overcorrection is
provide a faster visual recovery than that seen after not seen and refractive stability rapid, even for high
PRK. 17 Comparative studies of myopic PRK and order corrections.41 At 1 week, the combination of
LASEK have demonstrated conflicting results in terms an initial myopic overcorrection (>-1.00D in 40% of
of early postoperative recovery. Whilst Leccisotti32 eyes) together ongoing epithelial healing, meant that
demonstrated no differences in terms of pain, UCVA was limited in most eyes, with only 26%
epithelial healing or visual recovery between PRK achieving 20/30 or better. Indeed in many cases it
and LASEK, Autrata and Rehurek20 and Lee33 in took several weeks for functional unaided distance
prospective bilateral studies found less postoperative visual acuity (20/30 or better) to be achieved. It is
pain and faster visual recovery after LASEK. In very important when counseling patients prior to H-
contrast, Litwak et al34 found more pain and slower LASEK to fully explain the nature of the early
epithelial healing after LASEK, although in their study postoperative recovery and its implications in terms
the epithelium was exposed to 20% alcohol for 45 of visual performance, both near and distance.
seconds, which would result in the death of virtually Because of the initial myopic over correction,
all the epithelial cells in the flap51 and might account patients undergoing H-LASEK often elect to have
for slower healing. In the only reported comparative unilateral treatments with the more hyperopic or non-
study of hyperopic corrections, Autrata and Rehurek21 dominant eye typically being treated first and the
reported less postoperative pain, faster visual second eye usually treated 6-10 weeks later. Patients
recovery and quicker refractive stability with LASEK who are contact lens intolerant and would therefore
compared to PRK. In our study most patients reported have considerable problems with aniseikonia with
some some ocular pain during the first 12-24 hours postoperative spectacle correction or who have a
following surgery, which typically settled over the strong preference for bilateral treatments can
next 12-48 hours.23 Although all our patients were undergo simultaneous bilateral surgery after careful
carefully counseled preoperatively concerning counseling concerning the elective nature of the
alternative treatment modalities such as LASIK, with procedure and the prolonged visual recovery. With
particular reference to improved postoperative simultaneous bilateral surgeries it is occasionally
discomfort, no patients declined LASEK treatment useful to prescribe temporary low prescription myopic
of the second eye because of pain experienced after spectacles of reducing powers. These can be lent to
the first eye. the patient in reducing powers and returned as the
Postoperative recovery in terms of refractive eyes settle towards emmetropia over the first
stability and visual recovery is delayed with surface 3 months following surgery.
ablation compared with LASIK techniques and is
generally slower with hyperopic compared to myopic OPERATIVE CONSIDERATIONS FOR H-LASEK
excimer laser corrections.1-4,10-38 In our published
study of H-LASEK, following removal of the bandage We have found flap creation to be relatively straight
contact lens at 3 days, a number of eyes still had forward in hyperopic eyes despite the relative ages
central epithelial defects. This is in contrast to our of the patients and the generally smaller corneal
experience with myopic LASEK corrections41 and may diameters compared to myopic eyes.23 It has been
be the consequence of the need to fashion a larger shown that with the administration of 20% alcohol
10.0 mm epithelial flap, which could result in a greater for a maximum of 20-30 seconds, the majority of the
propensity to epithelial flap loss and longer epithelial epithelial cells within the LASEK flap are viable.51 In
healing. All eyes had epithelial closure at 1 week, but our patients the application of 15% alcohol for 20
most experienced a myopic overcorrection which settled seconds with the preoperative administration of
towards emmetropia over the next 3 to 6 months. This Amethocaine 1% eye-drops allowed the creation of
378 Mastering Advanced Surface Ablation Techniques
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30. Carones F, Vigo L, Scandola E. Laser in situ keratomileusis photorefractive keratectomy. J Ref Surg 1996;12:50-60.
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31. Kermani O, Schmeidt K, Oberheide U, Gerten G. double-blind study. Arch Ophthalmol 1995;113:438-43.
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32. Leccisotti A. Laser-assisted subepithelial keratectomy optical aberrations induced by photorefractive
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E. Prospective randomized comparison of wavefront-
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2004;20:422-31. flap preparation. J Cataract Refract Surg 28:1841-6.
 CHAPTER
The Disruption and Healing
45 of Corneal Nerve Fibers
after Laser Subepithelial
Keratomileusis

Chu Renyuan, Zhou Xingtao, Wu Ying (China)

INTRODUCTION create a stromal flap but may have a beneficial effect

on corneal wound healing compared with conventional
Normal corneal innervation is essential to corneal
photorefractive keratectomy (PRK). Laser subepithelial
structure and function. Corneal nerves are disrupted
keratomileusis preserves a viable corneal epithelial
by different kinds of corneal surgeries and corneal
sheet and reposions it onto the ablated stroma. The
diseases. Corneal denervation can compromise the
viable epithelial sheet is thought to act like a barrier
protective blink reflex, reduce epithelial mitosis,
that reduces the migration of cytokines into the stroma.
delay wound healing, and result in decreased tear
Comparing with PRK, laser subepithelial kerato-
flow. Corneal refractive surgery using the excimer
mileusis has the advantage of less pain and formation
laser is currently the most popular approach for the
of corneal haze postoperatively. Comparing with
treatment of refractive errors. Laser in situ
LASIK, laser subepithelial keratomileusis has the
keratomileusis (LASIK) allows quick recovery of
advantage of avoiding stromal flap related
visual acuity with minimal or no postoperative pain,
complications. Laser subepithelial keratomileusis is
and is hence, the preferred procedure. These
thought to be the trend of laser refractive surgery.
advantages of LASIK are due to the removal of
According to the different way of creating the
corneal stromal tissue under a flap of superficial
epithelial sheet, laser subepithelial keratomileusis
corneal tissue. Creation of the corneal flap however,
includes LASEK (chemical way) and Epi-LASIK
results in flap related complications, including
(mechnical way). In this chapter, we will review the
transection of the nerves in the anterior cornea. Many
disruption pattern and healing process of corneal nerve
studies have confirmed the severe disruption to
fibers by different types of laser refractive surgery
corneal nerves caused by LASIK. Neurotrophic
and focus on LASEK and Epi-LASIK.
keratopathy and dry eye disease after LASIK are now
gaining more and more attention in the world. How DISTRIBUTION OF CORNEAL NERVES
to eliminate the degree of disruption to corneal
nerves and fasten its healing process are great Most corneal nerve fibres are sensory in origin and
challenge to all refractive surgeons. are derived from the ophthalmic branch of the
Advanced surface ablation is a recently evolved trigeminal nerve. Nerve bundles enter the cornea at
anecdotal term used to describe alternative surgical the periphery (mostly at 3 and 9 O’clock positions) in
approaches for photorefractive procedures that do not a radial fashion parallel to the corneal surface, and
382 Mastering Advanced Surface Ablation Techniques
then penetrate from the deep stroma into the surface o’clock. Second, laser ablation of the exposed stroma
by subdividing several times into smaller side results in damage to the deeper nerve fibers. So, most
branches. Most of the corneal nerve fibers locate in of the nerve fibers in ablated area and corneal flap
the anterior third of the stroma (Figure 45.1). The are damaged after LASIK.
stromal nerve fibers penetrate Bowman’s membrane Experimental studies on rabbit corneas using gold
and form sub-basal nerve bundles with beaded chloride staining have shown a great loss of epithelial,
structure. Beaded fibers separate from sub-basal subbasal and stromal nerve fibers except in the flap
bundles and course obliquely into the more superficial hinge at 1 day post-LASIK (Figure 45.2). The
epithelial cell layers where they eventually terminate. quantitive measurements of corneal nerves using in
Epithelial nerve endings are not uniformly vivo confocal microscope (IVCM) find the great loss
distributed in the whole cornea, but most densely of nerve fibers in both subbasal region and corneal
distributed in the centre. flap in the first month after LASIK and the
regenerating process is quite long. Lee BH et al
reported the number of subbasal nerve fiber bundles
remained less than half of the preoperative level by
1 year after LASIK. Erie JC et al reported the density
of subbasal nerves didn’t recover to its preoperative
level until 5 years after LASIK. Corneal sensation is
an important functional index that reflects the
condition of corneal nerves. In clinic, corneal tactile
sensation could be quantitively measured using
Cochet and Bonnet esthesiometer. After LASIK,
corneal sensation is severely decreased (mostly near
zero) in the first month, which is corresponding with
Figure 45.1: Schematic distribution of nerves in the stroma and the findings of IVCM. Corneal sensation returns
subbasal plexus in human corneas Adapted from D. Maurice after
data from R.W. Beuerman (1984)
slowly, from 6 to 18 months. Position of the hinge,
diameter and thickness of the flap, ablation depth
are reported to be the main correlation factors.
DISRUPTION PATTERN AND HEALING PROCESS
Superiorly hinged flap, thick flap, flap with large
OF CORNEAL NERVES
diameter, or high myopic correction result in slow
After LASIK recovery of corneal sensation.
Many patients after LASIK procedure complain
In LASIK, the disruption of corneal nerve fibers
about dry eye-like symptoms, such as fluctuating
occurs from two causes. First, a microkeratome is
vision that improves after blinking or instilling
used to cut a superficial corneal stromal flap, and it
severs superficial nerve fibers in the area of the flap. artificial tears, dryness, ocular fatigue. The severe
As the thickness of a corneal flap is mostly from 90 damage to corneal nerves by LASIK are thought to
to 160 (μm) and nerve fibers mostly distribute in the be the main reason. The recovery of dry eye-like
anterior third of the cornea (the thickness of cornea symptoms is often accompanied by the return of
is 550ìm in average), most of the nerve fibers are corneal sensation.
transected by the microkeratome. Fibers entering the
After Epi-LASIK or LASEK
corneal stroma in the region of the flap hinge tend to
be spared. However, if the hinge is positioned In Epi-LASIK/LASEK procedure, a corneal stromal
superiorly, considerable damage can result since most flap is not created, and the laser ablation is performed
of the fibers enter the corneal stroma at 3 and 9 under an epithelial sheet. Since the flap is just an
The Disruption & Healing of Corneal Nerve Fibers after Laser Subepithelial Keratomileusis 383

Figure 45.2: Gold chloride staining shows a great loss of stromal (left: magnification ×5), epithelial and
subbasal (right-inferior: magnification ×10) nerve fibers except in the flap hinge (right-superior:
magnification ×5) at 1 day post-LASIK. (Data unpublished, provied by Wu Y, Chu RY, Zhou XT, et al)

epithelial sheet, disrupted nerve fibers are limited –3.0 diopters, Ds). But, if the preoperative myopic
within the superficial stroma of the ablated area, error is high, especially with visible corneal haze
which is also the same in PRK. The degree of myopic formation, the recovery of corneal sensation after PRK
correction depends the depth of disrupted nerve becomes much longer. Nerve staining on rabbit
fibers. It is obvious that the extent of disrupted nerve corneas shows the formation of the subepithelial scar
fibers after LASEK/Epi-LASIK/PRK is much less due to the strong wound healing response may
than that after LASIK(Figure 45.3). influence the penetration of the regenerated nerve
fibers into subbasal and epithelial layers after PRK.
Kanellopoulos AJ reported a group of PRK patients
with the average myopic error of –7.5 Ds, the corneal
sensation still remained much lower at 6 to 12 months.
Kohlhaas et al reported the corneal sensation didn’t
recover even in 2 years after PRK if the preoperative
myopic error was more than –15.0 Ds.
Preserving a viable epithelial sheet during and
after epi-LASIK/LASEK procedure is believed to
result in reduced postoperative pain and corneal haze
formation compared with PRK. Horwath-Winter H
et al reported that low myopic LASEK resulted in a
one-month reduction in corneal sensation which was
Figure 45.3: Gold chloride staining shows the nerve fibers within the similar with the previous reports of PRK. Wu Y et al
ablation area disappear (magnification ×5). (Data unpublished, provied recently reported the recovery of corneal sensation
by Wu Y, Chu RY, Zhou XT, et al)
after LASEK was related to the preoperative myopic
The difference between LASEK/Epi-LASIK and errors, 3 months for eyes of less than –6.0Ds myopic
PRK is the wound healing process due to the epithelial eyes (average –3.73 ± 1.71Ds) and 6 months for eyes
sheet, which may greatly influence corneal nerve of more than –6.0Ds myopic eyes (average -10.70 ±
regeneration. Previous reports show corneal sensation 3.81Ds). In the group of eyes of more than -6.0Ds,
is less decreased and returns much quicker after PRK 12.96% had grade 1 haze and 3.71% grade 2 haze at
than after LASIK for low myopic correction (less than 3 months, 16.67% and 5.56% respectively at 6 months,
384 Mastering Advanced Surface Ablation Techniques
no eye had greater than grade 2 haze. It is obvious in higher attempted corrections comparing with PRK.
the recovery of corneal sensation is much quicker after Clinical studies have also confirmed the effectiveness
LASEK than that after PRK, especially in high myopic of reducing corneal haze formation by LASEK/Epi-
correction. Reduced formation of corneal haze after LASIK, especially in high myopic correction.
LASEK/Epi-LASIK may play a key role in it. One of Therefore, it is important to preserve epithelial
our unpublished recent study on rabbit eyes shows viability and integrity during the refractive surgery
most of the regenerated nerve fibers from ablated to achieve uneventful wound healing and optimal
stromal nerve trunks are seen penetrating into the visual recovery.
subbasal and epitheial layers in early post-Epi-LASIK Besides, corneal epithelium itself has important
stage (Figure 45.4), and subbasal nerve bundles have trophic fuction to nerve fibers. In vitro co-culture
reformed in 1 to 3 months which is much quicker studies have shown that neurons and corneal epithelial
than that after PRK (Wu Y, Chu RY, Zhou XT, et al). cells support one another trophically through the
The formation of corneal haze after surface mutual release of soluble substances. Corneal epithelial
ablation surgery is the result of wound healing. After cells release soluble factors (e.g. NGF and GDNF) that
PRK, cytokines such as TGFb1 are secreted by promote neurite extension and survival. In the early
damaged epithelium and from tear fluid. By cytokine period after LASEK/Epi-LASIK, viable epithelial cells
may secrete those trophic factors to support the
induction, the epithelium can activate the process of
damaged nerve fibers underneath them. The results
keratocyte apoptosis and myofibroblast transfor-
of one of our unpublished study supported this
mation, leading to keratocyte replenishment of the
hypothesis (Wu Y, Chu RY, Zhou XT, et al). The
anterior stroma. The epithelial sheet in LASEK/Epi-
expression of NGF is greatly increased in epithelial
LASIK acts as a barrier to tear fluid similar to applying
cells in early post-Epi-LASIK stage, which may be
a human amniotic membrane after PRK. Lee et al
beneficial to promote the regeneration of nerve fibers
underwent PRK in one eye and LASEK in the other
and also maintain corneal sensation (Figure 45.5).
eye in 15 patients and found less TGF-β1 released in
the early postoperative days following LASEK than DIFFERENCE BETWEEN EPI-LASIK AND LASEK
following PRK. This advantage of LASEK is more
obvious in high myopic correction. Experimental The difference between LASEK and epi-LASIK
studies have shown that LASEK induces less stromal procedure is the epithelium sheet preparation. LASEK
keratocyte apoptosis and myofibroblast uses chemical method (alcohol), while epi-LASIK uses
transformation and less chondroitin sulfate synthesis mechanical one (epikeratome). Epi-LASIK

Figure 45.4: Gold chloride staining shows the regenerated nerve fibers from ablated stromal nerve trunks penetrate into
the subbasal and epitheial layers with beaded structure in early post-Epi-LASIK stage (magnification ×20). (Data unpublished,
provied by Wu Y, Chu RY, Zhou XT, et al)
The Disruption & Healing of Corneal Nerve Fibers after Laser Subepithelial Keratomileusis 385
membranes, indicating that the point of separation was
likely within the basement membrane. Pallikaris et al
performed Epi-LASIK surgery using a linear advance
epikeratome, and histopathologic examination
revealed a cleavage plane between the basement
membrane and Bowman’s membrane with an intact
basement membrane. Dai JH et al obtained human
corneal epithelial sheets in low myopic PRK surgery
using a rotational epikeratome, and light and electron
microscopy observation revealed an almost entirely
intact basement membrane with normal lamina lucida,
lamina densa, and hemidesmosomes (Figure 45.6).
Because the basement membrane provides the stability
and support that keeps the epithelium intact and is
important for cell survival in other tissues, it is likely
that the mechanically separated sheets may retain
Figure 45.5: Immunohistochemical staining shows the greatly better function. Chen CD et al compared the effects of
increased expression of NGF in corneal epithelial cells in early period
post-Epi-LASIK (magnification ×20). (Data unpublished, provied by Epi-LASIK and LASEK on the corneal stromal cells
Wu Y, Chu RY, Zhou XT, et al). and evaluated their effects on cornea1 haze
histopathologically. The results show there are less
incorporates the advantages of LASEK and LASIK, stromal cell apoptosis,proliferation and myofibroblast
and hence avoids the alcohol-related side effects of generation after Epi-LASIK than that after LASEK,
LASEK. Alcohol has been proven to be have toxic therefore, Epi-LASIK induces less formation of corneal
effect to the viability of corneal epithelium. Chen et haze in correcting myopia (Figure 45.7). Long Q et al
al reported varying degrees of basement membrane estimated TGF-β1 levels in tear fluid after LASEK
alterations after alcohol application in vivo, including and Epi-LASIK, and correlated these values with
disruptions, discontinuities, irregularities, and the occurrence of corneal haze in the postoperative
duplication (specimens I-IV) of the basement period. The results show tear TGF-β1 levels are less
membrane and cellular destruction, and a time- and after epi-LASIK than LASEK and there’s a positive
dose-dependent effect in vitro in mono-layered, correlation between tear TGF-β1 levels and the
immortalized human cell cultures. In order to degree of corneal haze, which indicates the better
eliminate the toxic effect of alcohol, the treatment barrier fuction of epithelial sheet made in Epi-LASIK
time of alcohol used in LASEK procedure should be procedure.
as short as possible(within 20 seconds). However, The early clinical results of Epi-LASIK have shown
there’s always a learning curve to grasp the technique satisfactory surgical outcome. Epi-LASIK is
of making a LASEK flap with high quality. Epi- considered to be an encouraging new technique and
LASIK may offer further advantages as alcohol use a predictable and safe method for the treatment of
is not required. myopia. Dai JH et al reported a group of myopic
Histopathological studies have shown that the patients (range: –1.25 to –19.0 D) followed by 1 year
epithelial basement membrane in sheets made by Epi- after Epi-LASIK procedure. The results show only
LASIK appear to be more physiological than those after 2/72 eyes have grade 0.5 haze and others have no
LASEK. Azar et al found that the epithelial sheet haze. As the above has mentioned, the barrier and
removed by 18% ethanol applied for 25 seconds had trophic function of the epithelial sheet is also very
fragmented hemidesmosomes and basement important for the regeneration of nerve fibers. One
membrane remnants attached to basal epithelial cell of our unpublished study has found the recovery of
386 Mastering Advanced Surface Ablation Techniques

Figure 45.6: Histopathological findings of epithelial flap in Epi-LASIK. Left: Light microscopic specimen. The
basal epithelial cells maintain regular arrangement. The basal surface of the epithelial disk is continuous.
(Magnification, ×400) Right: Transmission electron microscopic specimen. The basement membrane (arrow) is
entirely intact. The lamina lucida, lamina densa and hemidesmosome appear normal. (magnification, ×15000)
(provied by Dai JH, Chu RY, Zhou XT, et al)

Figure 45.7: One day postoperatively, TUNEL staining shows less stromal cell apoptosis (arrow) after Epi-LASIK (1) than that after
LASEK (2). Three days postoperatively, immunohistochemical staining shows less Ki-67 positive cells (arrow) after Epi-LASIK (4)
than that after LASEK (5). One month postoperatively, less α-SMA positive cells (arrow) after Epi-LASIK (7) than that after LASEK
(8). (magnification ×100) (provied by Chen CD, Zhou XT, Dai JH, et al)

corneal sensation after Epi-LASIK seems to be more activity executed by Epi-LASIK and a lower
rapid than that after LASEK(Zhou H, Chu RY, et al). occurrence of haze may be one of the reasons for
Perhaps the intact epithelium sheet with high cell faster recovery of corneal sensation.
The Disruption & Healing of Corneal Nerve Fibers after Laser Subepithelial Keratomileusis 387
BIBLIOGRAPHY 13. Wu Y, Chu RY, Zhou XT, et al. Recovery of corneal
sensitivity after laser-assisted subepithelial keratectomy.
1. Müller LJ, Marfurt CF, Kruse F, et al. Corneal nerves: J Cataract Refract Surg 2006;32(5):785-8.
structure, contents and function. Exp Eye Res 2003;76(5): 14. Lee JB, Choe CM, Kim HS, Seo KY, Seong GJ, Kim EK.
521-42. Comparison of TGF-beta1 in tears following laser
2. Kohlhaas M, Klemm M, Böhm A, et al. Corneal sensitivity subepithelial keratomileusis and photorefractive
after refractive surgery. Eur J Implant Refract Surg 1994; keratectomy. J Refract Surg 2002;18:130-4.
6:319-23. 15. Kaji Y, Soya K, Amano S, Oshika T, Yamashita H. Relation
3. Kanellopoulos AJ, Pallikaris IG, Donnenfeld ED, et al. between corneal haze and transforming growth factor-
Comparison of corneal sensation following beta1 after photorefractive keratectomy and laser in situ
photorefractive keratectomy and laser in situ keratomileusis. J Cataract Refract Surg 2001;27:1840-46.
keratomileusis. J Cataract Refract Surg 1997;23:34–8. 16. Moller-Pederson T. The cellular basis of corneal
4. Pérez-Santonja JJ, Sakla HF, Cardona C, et al. Corneal transparency and haze development. Ophthalmic Res
sensitivity after photorefractive keratectomy and laser 2002;34:1-13.
in situ keratomileusis for low myopia. Am J Ophthalmol 17. Baldwin HC, Marshall J. Growth factors in corneal wound
1999;127:497-504. healing following refractive surgery: a review. Acta
5. Matsui H, Kumano Y, Zushi I, et al. Corneal sensation Ophthalmol Scand 2002;80:238-47.
after correction of myopia by photorefractive 18. Vesaluoma M, Teppo AM, Gronhagen-Riska C, Tervo T.
keratectomy and laser in situ keratomileusis. J Cataract Release of TGF-beta 1 and VEGF in tears following
Refract Surg 2001;27:370-3. photorefractive keratectomy. Curr Eye Res 1997;16:19-
6. Lee BH, Mclaren JW, Erie JC, et al. Reinnervation in the 25.
Cornea after LASIK. Invest Ophthalmol Vis Sci 2002;43: 19. Taneri S, Zieske JD, Azar DT. Evolution, Techniques,
3660-4. Clinical Outcomes, and Pathophysiology of LASEK:
7. Kumano Y, Matsui H, Zushi I, et al. Recovery of corneal Review of the Literature. Sur Ophthalmol 2004;49(6):576-
sensation after myopic correction by laser in situ 602.
keratomileusis with a nasal or superior hinge. J Cataract 20. Azar DT, Ang RT, Lee J-B, et al. Laser subepithelial
Refract Surg 2003;29:757-61. keratomileusis: electron microscopy and visual outcomes
8. Dennenfeld ED,Ehrenhaus M, Solomon R, et al. Effect of of flap photorefractive keratectomy. Curr Opin
hinge width on corneal sensation and dry eye after laser Ophthalmol 2001;12:323–8.
in situ keratomileusis. J Cataract Refract Surg 2004;30: 21. Pallikaris IG, Naoumidi II, Kalyvianaki MI, Katsanevake
790-97. VJ. Epi-LASIK: Comparative histological evaluation of
9. Erie JC, McLaren JW, Hodge DO, et al. Recovery of corneal mechanical and alcohol-assisted epithelial separation. J
subbasal nerve density after PRK and LASIK. Am J Cataract Refrac Surg 2003;29:1496-1501.
Ophthalmol 2005;140(6):1059-64. 22. Dai J, Chu R, Zhou X, et al. Histopathological study of
10. Tervo K, Latvala TM, Tervo TMT. Recovery of corneal epithelial flaps in Epi-LASIK. J Refract Surg 2007 (in print)
innervation following photorefractive keratoablation. 23. Long Q, Chu RY, Zhou XT, et al. Correlation Between
Arch Ophthalmol 1994;112:1466-70. TGF-â1 in Tears and Corneal Haze Following LASEK and
11. Trabucchi G, Brancato R, Verdi M, et al. Corneal nerve Epi-LASIK. Journal of Refractive Surgery 2006;22:708-12.
damage and regeneration after excimer laser 24. Chen CD, Zhou XT, Dai JH, et al. Stromal cells change
photokeratectomy in rabbit eyes. Invest Ophthalmol Vis after epipolis laser in situ keratomileusis and laser.assisted
Sci 1994;35:229-35. subepithelial keratectomy in rabbit. Chin J Ophthalmol
12. Horwath-Winter J, Vidic B, Schwantzer G, et al. Early 2006;42(9):796-801.
changes in corneal sensation, ocular surface intefrity, and 25. Dai J, Chu R, Zhou X, Chen C, Qu X, Wang X. One-year
tear-film function after laser-assisted subepithelial outcomes of epi-LASIK for myopia. J Refract Surg 2006;
keratectomy. J Cataract Refract Surg 2004;30:2316-21. 22(6):589-95.
388 Mastering Advanced Surface Ablation Techniques

CHAPTER

46 Update on LASEK

Chu Renyuan, Dai Jinhui, Wu Ying, Yao Peijun (China)

INTRODUCTION many youngsters like to join in army or take up police

or sport as career after undergoing excimer laser
Since LASEK was applied to correct refractive error
myopic surgery. In our practice, the youngsters are
in 1999, the new surgery, excimer laser assisted sub-
questioned about the aim of their surgery. If they
epithelial keractomeliusis (LASEK) has become well-
expect to remove spectacles so as to take furious
known in the world and added new concept to
activity as career, we take the corneal epithelial flap
excimer laser corneal refractive surgery. Along with
as first choice. (3) Either in LASEK, Epi-LASIK or
the prompting of LASEK, its advantages have been
PRK, even and thin corneal epithelial flap and the
recognized as: (1) LASEK reduces the amount of
tight attachment between the flap and beneath
corneal stroma ablation, which is suitable for those
stromal bed, make the postoperative visual quality
high myopic patients with thin cornea. This is very
better than that after LASIK. This has been a
helpful in China because incidence of myopia in
young people and incidence of high myopia are very consensus. We also observed the relationship between
high in China and have shown the trend of increasing the increment of higher-order aberrations and
every year. (2) After LASEK, corneal epithelium is thickness of corneal flap. Thus, to obtain good visual
tight adjacent to the beneath corneal stroma bed. quality after excimer laser refractive surgery, many
When cornea is punched, the two layers are not easy surgeons choose corneal epithelial flap.
to detach. But since corneal stromal collagen fibers LASEK also has some disadvantages which limit
align horizontally along the interface after LASIK, its application. So how to reduce or eliminate these
the corneal epithelium and corneal stroma bed are at disadvantages has become one of the hotspots in
the risk of detaching again. There has been several researches of LASEK. (1) Postoperative irritative
case reports in China. In our clinic, we also saw more symptom, less than that after PRK though, has been
than 10 cases of contusion induced corneal stroma complained of by many patients. (2) Postoperative
flap detachment 2 or 3 years after LASIK. Some were corneal haze still occurs, though better than after PRK.
hurt by the machine or instrument and some were In comparison, almost no corneal haze occurs after
hurt by fists. The longest postoperative time was LASIK. (3) Surgical technique of LASEK is difficult.
5 years. Since we started to perform LASEK in 2000 Surgical technique doesn’t mean the technique of
and perform Epi-LASIK in 2004, no such case has separating corneal basement membrane and
occurred. This is of great significance in China because Bowman’s membrane. It means to keep biological
 Update on LASEK 389
vitality of corneal epithelium when creating corneal preserved. Second, pathological study of epithelial
epithelial flap. 20% ethanol or other high osmotic flap shows basement membrane of epithelial sheet is
solution used by others both influences the biological more complete in epi-LASIK than in LASEK (Figure
vitality of corneal epithelium. In addition, individual 46.1). Entire epithelial basement membrane is believed
has different reaction to solution. The injury of corneal to be essential for the health of corneal epithelium.
epithelial flap during the creation and the reservation In clinic, less postoperative response and corneal haze
of biological vitality have direct relationship with formation have been observed after epi-LASIK than
postoperative irritative symptoms and corneal haze. that after LASEK. Third, negative pressure suction
If the injury of corneal epithelial flap is minimized is different. In LASEK, we usually don’t need negative
and the biological vitality is reserved to a good pressure to fix the eyeball, unless the patient has
extent, postoperative irritative symptoms are similar difficulty in eye fixation. Negative pressure used in
to that after LASIK and corneal haze seldom occurs. LASEK is usually below 30 mmHg. In epi-LASIK,
To achieve these, postoperative management plays however, 60 mmHg negative pressure is needed
an important role. According to our experience, during the procedure of creating corneal epithelial
wearing Galyfilcon A silicon hydrogel contact lens flap. As quick fluctuation of intraocular pressure
(ACUVE ADVANCE, Johnson and Johnson) and induced by negative pressure suction might interfere
frequent use of 0.1% tobramycin dexamethasone eye the balance of ocular physiology, LASEK is thought
drops (alcon) (replaced by 0.1% floromethosolone to
to be a better choice to patients who have
prevent steroidal high intraocular pressure) is very
pathological myopia or previous IOL surgery.
important. Recent reports good effect of removing
Epikeratomes are now the main factor that may
the corneal epithelial flap to reduce the postoperative
hinder the development of epi-LASIK. Relatively long
irritation and corneal haze after LASEK. But in our
operating time by beeline epikeratome (Figure 46.2)
opinion, the necessity of this technique is questioned
—at least 30 seconds after suction, makes epithelial
if we can ensure the integrity and vitality of corneal
flap easy to wrinkle. In contrast, rotational
epithelial flap. Our study indicates that reducing the
epikeratome (Figure 46.3) takes only 6 seconds to creat
contact between the TGF-β in tears and corneal
an epithelial flap, so flap shrinkage rarely happen. But,
wound can help to reduce the postoperative corneal
rotational epikeratome is not perfect yet, as the flap is
haze. But surely, if the biological vitality of corneal
too small-the diameter is always less than 10 mm.
epithelial flap has been badly damaged, removing
Whichever of the two epikeratomes has potential risk
the epithelial flap is a feasible management but should
not be a goal in creation epithelial flap. of cutting too deep and damaging Bowman’s
Epi-LASIK is now thought to be the improvement membrane. So, it is extremely important to the
of LASEK and differs from LASEK in many ways. development of epi-LASIK that unceasing endeavor
First, different method of creating corneal epithelial should be made to improve the fuction of
flap. In LASEK, corneal epithelial flap is created using epikeratomes.
chemical method, such as 20% ethonal or No matter which kind of laser subepithelial
hyperosmotic solution, to loosen the junction keratomileusis, laser damage to Bowman’s membrane
between epithelial basement membrane and is a formidable problem. As one of the five layers of
Bowman’s membrane, so the viability of corneal normal cornea, Bowman’s membrane has important
epithelial flap is inevitably destroyed. In epi-LASIK, physiological fuction. However, it is still unclear
corneal epithelial flap is created using mechnical which pathophysiologic changes of cornea will be
method, that is an epikeratome separates it between induced after loss of Bowman’s membrane. A new
epithelial basement membrane and Bowman’s corneal flap with the cleavage plane between
membrane. As no chemical solution is used in epi- Bowman’s membrane and stroma is thought to be
LASIK, the viability of corneal epithelial flap is better better than epithelial flap.
390 Mastering Advanced Surface Ablation Techniques

Figure 46.1: Pathological photo of epithelial flap created by

rotational epikeratome shows entire epithelial basement membrane

Figure 46.3: Rotational epikeratome

BIBLIOGRAPHY
1. Cheng ZY, He JC, Zhou XT, et al. Effect of flap thickness
on higher order wavefront aberrations induced by LASIK:
a bilateral study. J Refract Surg. 2007 (in print).
2. Dai J, Chu R, Zhou X, Chen C, Qu X, Wang X. One-year
outcomes of epi-LASIK for myopia. J Refract Surg 2006;
22(6):589-95.
3. Dai J, Chu R, Zhou X, et al. Histopathological study of
epithelial flaps in Epi-LASIK. J Refract Surg. 2007 (in print)
4. Liu WF, Du ZY, Zhao WX, et al. The structure and viability
analysis of corneal epithelial flap in the rabbit cornea after
epi-LASIK. Chin J Ophthalmol 2007;43(7): 651-57.
5. Long Q, Chu RY, Zhou XT, et al. Correlation Between
TGF-b1 in Tears and Corneal Haze Following LASEK
and Epi-LASIK. Journal of Refractive Surgery 2006;22:
708-12.
6. Nilforoushan MR, Speaker MG, Latkany R. Traumatic
flap dislocation 4 years after laser in situ keratomileusis. J
Cataract Refract Surg 2005;31(8):1664-65.
7. Pallikaris IG, Naoumidi II, Kalyvianaki MI, Katsanevake
VJ. Epi-LASIK: Comparative histological evaluation of
mechanical and alcohol-assisted epithelial separation. J
Cataract Refrac Surg 2003;29:1496-1501.
8. WU Ying, QU Xiaomei ,ZHOU Xingtao, et al. Clinical
evaluation of the Galyf ilcon A silicon hydrogel contact lens
as a bandage after LASEK or epi-LASIK. Chinese Journal of
Optometry and Ophthalmology 2006;8(5):296-8.
9. ZHOU Xing-tao, CHU Ren-yuan, WANG Xiao-ying, et al.
The clinical study of the epithelial flap of painless LASEK
Figure 46.2: Beeline epikeratome and Epi-LASIK. Chin J Ophthalmol. 2005;41:977-80.
 CHAPTER

47 Management of Corneal
Haze after LASEK with
Mitomycin C

Sanjay Chaudhary (India)

INTRODUCTION Operation Done

LASEK (E-LASIK) is an advanced surface ablation A simultaneous bilateral alcohol assisted lasek
procedure which has gained world wide acceptance surgery was done in both the eyes. The epithelial
in recent time with excellent visual results. Like other flap was loosened up using 20% ethyl alcohol. The
refractive procedure lasek has its own advantages cornea was ablated using the Nidek EC5000 laser
and disadvantages. In this chapter I shall discuss one system. After corneal ablation the cornea was cooled
of the important postoperative complication of using chilled BSS. The treated area of the cornea was
LASEK, i.e. corneal haze which is similar to PRK. Here, then exposed to 0.02% Mitomycin-C for 60 seconds.
The corneal surface was then thoroughly washed with
I am discussing an interesting case of lasek procedure
BSS for a minute to remove all traces of Mitomycin
with subsequent corneal haze and how to manage it
and then the epithelium was reposited back. A
for the benefit of refractive surgeons who shall
bandage contact lens was then placed on the eye.
encounter such problems while doing lasek procedure.
Complication
History
The epithelium healed in five days time. The vision
A 26-years old male presented with bilateral high
subsequently improved to unaided 6/9 in the right
myopia. The patient had a stable myopia for the past
eye and 6/9 p in the left eye. The patient was put on
3 years. The right eye had a refractive error of –11D FML starting at seven times a day for a week and
while the left eye had a refractive error of –15 D. His tapering off over the next seven weeks. Follow-up at
corrected visual acuity was 6/9p in the right eye and 3 months showed clear cornea and emmetropia.
6/12p in the left eye. The fundus had myopic changes Mitomycin–C is useful in containing fibroblastic
and retinal holes and lattice and an LIO was done to activity and thereby reducing and delaying the
seal the holes with double frequency Yag laser four chances of corneal haze, more so when attempting to
weeks prior to the procedure. The pachymetry was treat high myopia.
514 mic in the right eye and 520 mic in the left eye. The patient returned one and a half year later with
The average K reading was 44.5 D in right eye and diminishing vision. An examination showed myopia
44.75 D in left eye. He was scheduled for of -1.25 dioptre in the right eye and –2.75D in the left
simultaneous bilateral alcohol assisted lasek surgery eye with an associated corrected vision of 6/12 in
in both the eyes. the right eye and 6/18 in the left eye. A slit lap
392 Mastering Advanced Surface Ablation Techniques

Figure 47.1: The patient developed a gr. I corneal haze in the right eye and a gr. II haze in the left eye after
one and a half year of simultaneous lasek with mitomycin C in both eyes. The right eye had myopia of
–11D while the left eye had myopia of –15 D.

examination showed superficial corneal haze in the 4. Haze usually develops after 6-9 months of the
right eye grade I and left eye grade II. procedure.
5. Haze results in a regression of the refractive error
Management
and the degree of regression depends on he
The patient was put on low dose steroid drops three severity of haze.
times a day for three months and asked to report
6. Haze usually regresses spontaneously over a
after 3 months. There was a slight reduction in haze
period of 2-3 years. Low dose topical steroids
in these three months. It was not considered wise to
continue using steroid drops and they were taken could assist resolution.
off and patient sent back on lubricating eye drops 7. The regression of haze sometimes results in some
for the next three months (Figure 47.1). reversal of regression of the refractive error and
improvement in refractive error and vision.
DISCUSSION The above observations are not a rule but an
Corneal haze: This has become the most feared indication of the surgeon’s experience with PRK of
complication in a long-standing follow-up of LASEK. over 10 years and of lasek with and without
The haze is similar to the one encountered in PRK and mitomycin on over 400 eyes in 4 years.
can be graded from I to IV. It was a myth that mitomycin PRK, LASEK and now epi-LASIK involve the
prevents haze formation in Lasek while attempting removing or stripping of the epithelium from the
higher degree of corrections. The use of mitomycin C Bowman’s membrane. In PRK, it is mechanical
in our routine clinical practice for myopia of over 4 D scrapping, in LASEK it is alcohol assisted while in
seems to have helped in the following ways: epi-LASIK, it is again separation with a blade. Since
1. Haze is usually not encountered in myopia of up
the three are essentially similar and involve ablation
to 7.0 D as compared with PRK where it could be
of the Bowman’s membrane, they carry the same
encountered after 4 D.
2. Myopia of 8 to 12 usually results in Gr. I haze advantages and disadvantages, albeit with minor
while 12 and above may result in Gr. II to III haze. modifications. Therefore, it postulates that the presence
3. There have been situations where even –18 D has of corneal haze may be similar in PRK, LASEK and
had no haze and on the other hand, even a –5 epi-LASIK. Minor variations in the severity of haze
developed a mild haze. may be achieved with the help of mitomycin.
 CHAPTER

48 Advanced Surface
Ablations

Claes Feinbaum (Poland)

INTRODUCTION This technique may also be required for some

occupations.
Surface Ablation 2. Since laser treatment is done on the surface,
Any surgical procedure that ablates tissue at the LASEK preserves more corneal tissue. In
surface of the cornea, rather than under a LASIK or particular, patients who have thinner corneas may
All-Laser LASIK stromal flap. PRK, LASEK, and be more safely treated with a no flap technique
epi-LASIK are all surface ablation techniques. rather than LASIK
A cornerstone of refractive surgery is the concept 3. LASEK may be an option for patients who are
that corneal regularity is more important than its not good candidates for LASIK.
transparency. This can be easily clarified with an A number of often asked questions the practitioner
example. A window pane is transparent and is asked are the following:
raindrops on it are also transparent; however, a 1. Are results different from LASIK? No. Extensive
clinical trials which have been published show no
window pane covered with raindrops, even if
difference in outcomes. The only difference is
transparent, does not permit good vision quality
extended time for vision stabilization in surface
because of its lack of uniformity. Sunglasses, on the
laser procedures.
contrary, are not totally transparent, yet they permit
2. Is the laser different from LASIK? No. The same
good vision quality because of their regularity.
laser and technique is used.
Laser vision correction without preparation of a
3. Can a Custom Cornea Wavefront treatment be
LASIK flap goes by a number of names - LASEK (laser done? Yes. Again, the only difference from
epithelial keratomileusis, surface LASIK, epithelial Custom LASIK, is in the first step in the procedure.
LASIK, epi-LASIK, or Advanced Surface Ablation). 4. Aren’t surface procedures more uncomfortable
Although LASEK and LASIK sound the same, unlike than LASIK? Advances in surgical technique and
traditional LASIK, LASEK does not require the postoperative care have made the recovery period
preparation of a corneal stromal flap. This has three after LASEK quite comfortable as compared with
potential advantages: the original PRK procedure years ago.
1. Risks of making the corneal flap in LASIK are Dr. Massimo Camellin introduced LASEK in 1999
avoided. This may be important in some patients in an effort to overcome the limitations of surface
in whom there is an additional risk in making the ablation by PRK and also to eliminate potential
flap, or in patients who prefer a no-flap treatment. complications from use of a microkeratome in LASIK.
394 Mastering Advanced Surface Ablation Techniques
His original technique involved the use of alcohol to path of least resistance, leaving the basement
separate the corneal epithelium from the stroma and membrane intact. The instrument is designed not to
create an epithelial “sheet” that could then be engage stroma. Studies performed in pig eyes
repositioned over the ablated stroma. verified that this keratome left a smooth surface.
The advantages of LASEK vs PRK are that it can In one report, Dr Pallikaris reported on 34 myopic
provide a postoperative shield of epithelium over the eyes of 17 patients treated with epi-LASIK and stated
treated surface; it may prevent a wave of epithelial that epithelial separation was achieved in 100% of
migration in the first 48 post-op hours; it prevents cases. The postoperative regimen included bandage
interaction between injured stromal tissue and factors contact lenses, anti-infectives, steroids, and
released by corneal epithelial cells; and may have a nonsteroidal anti-inflammatories, but no “comfort
lower incidence of haze than PRK. drops” of dilute anesthetics. Only one of the 17
Alcohol toxicity is the greatest potential drawback patients reported moderate postoperative pain, and
to classic LASEK. This toxicity is both dose- and time- this was due to a tight bandage contact lens.
dependent. In vitro cell survival has been shown to
One advantage of this instrument and technique
be reduced when concentration exceeds 25% or
may be that it cleaves the basement membrane
exposure period is longer than 35 seconds. The upper
underneath the laminas lucida and densa, at the level
limit in which cells remain viable may be up to 45
where it contacts Bowman’s layer. Human
seconds in 20% solution.
histopathology studies have shown that epi-LASIK
There is also some patient variability regarding
leaves the basal cells and their hemidesmosomes
adhesion of the epithelium to basement membrane
(which act as mechanical “fasteners”) attached to the
and the effect of alcohol on the adhesion of epithelial
epithelium, which should improve the reattachment
cells. A solution of 20% alcohol applied for 20 seconds
of the epithelium. Alcohol splits the basement
is reportedly sufficient to create an epithelial sheet,
although Litwak et al. found that 20% alcohol needed membrane. Since the adherence of the basement
a minimum exposure time of 40 seconds in Hispanic membrane to the basal layer of the epithelium is
patients to loosen the epithelium. significant for the viability of an epithelial sheet, it is
Surgeons would like to eliminate the use of alcohol assumed that the cleavage plane of the mechanical
so that these variables will no longer be at issue. epi-LASIK separation might be superior.
Several approaches has been explored. Drs Rashid
and Langerman are working on a hydrodissection TECHNIQUES FOR ADVANCED SURFACE ABLATION
method. Dr Pallikaris has developed a technique he
calls epi-LASEK, which uses a keratome with a dull- Despite the popularity of LASIK, surface ablation
edged, flexible plastic separator designed to slide remains an attractive procedure. Surface ablation’s
under the epithelium without applanation of the appeal derives from two unique attributes. first, for
cornea. an equivalent correction, surface ablation leaves a
Now that interest in surface ablation is once again structurally stronger cornea than LASIK. Thus, the
increasing with the introduction of wavefront-guided incidence of corneal ectasia is lower with surface
ablation, the new frontier seems to be an automated ablation. From a corneal integrity standpoint, surface
LASEK procedure performed without alcohol. ablation is probably a better procedure than LASIK
Dr Ioannis Pallikaris developed a new keratome for high myopia or patients with atypical topography,
to perform a procedure that he called epi-LASIK. This such as inferior steeping, a steep central cornea
instrument uses a flexible plastic separator with a dull (>48D), or high oblique astigmatism. In these cases,
edge. No applanation of the cornea is necessary, and surface ablation offers a more conservative option
the separator slides under the epithelium along the than LASIK.
 Advanced Surface Ablations 395
Optical Issues 1. What changes are done to the stromal topography
after ablation?
Surface ablation may also provide superior optical 2. How big are these changes?
outcomes. Over the years there have been occasions 3. Is the change of the stromal topography
to use surface ablation to enhance post-LASIK transferred to the surface “epithelial” topography?
patients. (These patients had stromal beds too thin 4. Can steep and shallow pits be better identified?
for further ablation.) In 80% of these patients, multiple 5. If there are large irregularities in the stromal
wrinkles or folds were clearly present in Bowman’s topography, does this mean there will be greater
membrane, an observation that is consistent with aberrations and a worse visual outcome
other reports. 6. Flap shape/thickness
On slit lamp examination prior to enhancement, The importance of this Graph is evident: It seems to
all of these patients had very smooth corneas, with be a steepening of the unablated stroma compared to
no obvious striae. All had excellent best corrected the “epithelial topography. 42.18 > 43.15, 41.66 > 42.34
visual acuity. Wrinkling of Bowman’s membrane is Avg. rad. 7.95 > 7.58 or in D 42.45 > 44.51= 2.06D.
an inherent problem in myopic LASIK, especially high Steep RP 38.89 Flat RP 34.35 Tot.Ast. 4.54.
corrections, that derives from the geometry of the Steep Sim K 38.79 Flat Sim K 36.76 Avg. Sim K
flap and bed. That is, if one cuts a flap and no laser 37.77 Reg.Ast. 4.54.
ablation is performed, the flap will fit back on the There is a smaller change on stromal topography
bed perfectly; however, a myopic ablation removes created by an Intralase flap compared to that created
tissue and decreases the surface area of the bed. The by a mechanical microkeratome. The stromal bed is
result is a flap that is now slightly too large for the smoother and less irregular., and thus there will less
bed. In a high percentage of patients, the result is disturbance in the optical outcome.
wrinkling of Bowman’s membrane. A further Fortunately the epithelium undergoes hyperplasia
explanation to wrinkling is the change of the stromal and/or hypoplasia to smooth the anterior surface,
topography. Why stromal topography? and although best corrected visual acuity is

Figure 48.1: Unablated stromal topography: Flap created by a mechanical microkeratome

396 Mastering Advanced Surface Ablation Techniques

Figure 48.2: Ablated stromal topography for the same eye as in Figure 48.1

Figure 48.3: Comparison unablated and ablated stromal topography

 Advanced Surface Ablations 397

Figure 48.4: Flap created by intralase 30 HZ and appearance of stromal topography

preserved, the question remains whether the all has been to use chilled or frozen balanced salt
wrinkling of Bowmans membrane produces more solution (BSS) or tears. The surgeons interviewed for
subtle effects, such as the induction of higher order the story offered their pain management
aberration. I suspect that there is subtle effect on pharmacological regimen.
vision, the size and nature of which are unpredictable. One could make the distinction to use 40 to 50
In FDA studies of wavefront-customized ablation, drops of partially frozen BSS immediately before the
the PRK outcomes were often superior to the LASIK epikeratome pass and not afterwards like many
outcomes in comparable eyes, perhaps for the reasons surgeons do.
just outlined. Also give patients 40 mg of prednisone 45 minutes
preoperatively.
Haze and Pain Management Another way to go is for patients to use chilled
Haze had initially been an issue for surface ablation tears. Use Acular LS (ketorolac tromethamine,
patients, but doctors are including mitomycin C in Allergan) QID starting the day before the surgery.
their regimens to alleviate this complication. For all Postoperative, soak the contact bandage lens in Acular
surface ablation patients who are more than –6 D or PF.
their ablation is over 75 microns, mitomycin C 0.02% Yet another option is to freeze the cornea after laser
could be used for 10 seconds intraoperatively. treatment with a frozen Weck-Cel sponge. Use Xibrom
Having an ablation depth of over 75 microns, use (bromfenac ophthalmic solution, ISTA Pharma-
mitomycin C for somewhere between 20 and 30 ceuticals) BID, Pred Forte (prednisolone acetate,
seconds, and with that (regimen) there risk of haze Allergan) and one of the fluoroquinolones QID.
is minimized. Further patients could be started on systemic anti-
While surgeons vary in their pharmacological inflammatories preoperative. Prescribe Celebrex
regimens to mitigate pain, one common routine for (celecoxib, Pfizer) 200 mg p.o. q.d.starting 3 days prior
398 Mastering Advanced Surface Ablation Techniques
to surgery and continues 3 days postoperative. For LASEK to be a safe and effective method for the
patients who may not want to take Celebrex, suggest correction of myopia. Lee et al reported their results
Motrin (ibuprofen) TID 3 days preoperative and then after treating 27 myopic patients comparing LASEK
4 days postoperative. Also uses Acular PF BID or performed in one eye and PRK in the other eye of
QID 3 days preoperative. each enrolled patient. LASEK treatments were
Further a Weck-Cel sponge with frozen BSS could performed with the use of a 20% alcohol solution
be used on the cornea for 1 minute after ablation. applied for 30 seconds to the cornea. In this series, the
This “frozen popsicle” has really alleviated patient mean epithelial healing time was 3.18 ± 0.50 days in
pain postoperative, rotate Pred Forte, Acular, and PRK-treated eyes and 3.64 ± 0.63 days in LASEK-
Zymar (gatifloxacin, allergan). treated eyes; the difference was not statistically
significant. The investigators reported a statistically
Ectasia significant (P = 0.047) difference of subjective pain
The reports of an increasing incidence of iatrogenic scores in favor of LASEK-treated eyes. At 1 month,
ectasia, the evolution of wavefront aberrometry, and there was a statistically significant difference in the
the suggestion that the laser in situ keratomileusis mean corneal haze score between PRK- (0.86 ± 0.45)
flap could lead to unpredictable biomechanical corneal and LASEK-treated eyes (0.46± 0.24). This difference,
changes have renewed interest in surface ablation however, was not detected by the third postoperative
and have set the stage for the introduction of month. In this series, 63% of patients (P > 0.05%)
alternative photorefractive treatment modalities. preferred the LASEK procedure because of the faster
The theoretical advantage of surface procedures, visual rehabilitation and painless recovery. The
such as laser epithelial keratomileusis that preserve investigators concluded that the epithelial flap could
the epithelial button, stems from the repositioning act as a natural contact lens that decreases postoperative
of the epithelial flap over the laser-ablated corneal pain and haze formation. Similarly, Shah et al.
surface. This epithelial sheet is thought to act as a compared LASEK and PRK in 36 myopic patients and
natural contact lens that decreases postoperative pain reported significantly less haze in eyes treated with
and haze formation. Epipolis laser in situ LASEK 1 year after the treatment. Litwack et al., in a
keratomileusis is an alternative modality of epithelial prospective, randomized trial that compared PRK with
separation with the use of a device that features a LASEK in 25 myopic patients, did not confirm these
blunt oscillating blade. This surgical approach does results. They reported faster epithelial healing of the
not require the use of alcohol for epithelial loosening. PRK-treated eyes, whereas LASEK-treated eyes
demonstrated greater discomfort and poorer unaided
LASER EPITHELIAL KERATOMILEUSIS: CLINICAL vision within the first 3 postoperative days. Because
RESULTS
alcohol toxicity on corneal epithelium is both dose and
Laser epithelial keratomileusis evolved from PRK after time dependent, one possible explanation of their
alcohol-assisted epithelium removal. Initial studies results could be the application of a 18% alcohol
have shown that exposure of the corneal epithelium solution for 40 seconds compared with shorter
to 18 to 25% alcohol solutions for 20 seconds to 3 application times by other investigators. Compared
minutes allowed fast and easy that was compared with with laser in situ keratomileusis (LASIK), LASEK
alternative methods of epithelial debridement. The seems equally effective, but does not carry the risks
theoretical advantage of LASEK over PRK is supposed of flap-related complications. Scerrati et al compared
to be the repositioning of the epithelial flap over the two groups of 15 patients, in which one eye underwent
laser-ablated corneal surface. Clinical trials by myopic LASIK and the other LASEK. Contrast
numerous investigators using various alcohol sensitivity data in the LASEK group were better than
concentrations and exposure periods have shown. in the LASIK group.
 Advanced Surface Ablations 399
LASEK 20% alcohol solution. Espana et al (Paper presented
at the Association for Research in Vision and
Effect of Corneal Exposure to Alcohol Solutions
Ophthalmology Annual Meeting, Ft. Lauderdale, FL,
Epithelial Cleavage May 2002) confirmed these results. They found no
statistically significant differences in viability between
Despite the increasing number of patients undergoing
exposed and non-exposed cells after the application
LASEK worldwide, the exact mechanism of action of
of 20% alcohol solution for 20 seconds. Chen et al.
the brief alcohol exposure on the corneal epithelium is
confirmed that the effect of alcohol solution on corneal
not completely clear. In a recent study, Azar et al.
epithelial cell viability is both dose and time
found that corneal flaps removed by 18% ethanol
dependent. They reported high percentages of cell
applied for 25 seconds showed fragmented
survival for dilutions of less than 24% applied for
hemidesmosomes and basement membrane remnants
less than 35 seconds. Similarly, Gabler et al. reported
attached to basal epithelial cell membranes, indicating
that after 15 and 30 seconds of exposure to 20%
that the point of separation was likely to be within the
alcohol solution, most epithelial cells were vital. This
basement membrane. The basement membrane layer
changed substantially after 45 seconds when vital and
showed discontinuous and irregular extracellular
dead cells were almost equal. Longer exposure times
fragments. As shown by transmission electron
(60 and 120 seconds) showed predominantly dead
microscopy, neither the Bowman membrane nor the
cells. These studies suggest that brief exposure of
corneal stroma was found in the epithelial flap.
the corneal epithelium to low concentrations of
Similarly, Espana et al. carried out immunofluore-
alcohol is not toxic.
scence studies to determine the corneal epithelial
anatomic cleavage plane after alcohol-assisted epithelial
MARKET DEVELOPMENT OF EPI-LASIK
removal in both cadaver and living eyes. Applying a
20% solution of alcohol for 20 seconds in a technique When new products or technologies are introduced
described by Camellin and results showed that the into the market, it can take considerable time before
cleavage plane of the alcohol-induced corneal epithelial they achieve widespread market adoption. Such is
flap was located between the lamina lucida and lamina the case with epi-LASIK.
densa of the basement membrane. Epi-LASIK accounted for only approximately 1.5%
Using transmission and scanning electron of all refractive procedures in the United States in
microscopy, Browning et al examined epithelial flaps 2005, according to David Harmon, president and
from six patients who underwent alcohol senior editor of Market Scope. “The movement you
delamination before PRK and from three eye bank see is relatively small,” says Harmon when asked
donor eyes. The cleavage plane was determined to about epi-LASIK’s place in the refractive market
be at the hemidesmosomal attachments, including the today.
most superficial part of the lamina lucida of the While this is a seemingly small number, surface
basement membrane. ablation as a whole is on the rise. Market Scope
The component of the basement membrane that surveys ophthalmologists on a variety of refractive
remained attached to the epithelial sheet after alcohol surgery issues, and they reported 9.6% of refractive
delamination showed a mean thickness (± SD) ranging surgeries performed in 2005 employed surface
from 31.9 to 56.4 nm (± 8.0 to 22.8) among the six ablation techniques, which is up from a reported 7.2%
different samples. in the 2004 survey. This continues a pattern of surface
ablation growth over the last several years.
Epithelial Cell Viability after Alcohol Exposure
Most see epi-LASIK eventually grabbing a greater
Dreiss et al reported that epithelial cells remained piece of the refractive market pie. Dave Fancher,
viable after as much as 45 seconds of exposure to president of CooperVision Surgical, believes
400 Mastering Advanced Surface Ablation Techniques
consumers will demand it once they realize it offers inclined to compare it to LASIK. The conventional
a better quality of vision, and that it is safer than wisdom has been that LASIK offers faster visual
LASIK and other surface ablation treatments. recovery and less pain than surface ablation. With
“Quality of vision and safety are going to be the two LASIK, patients can see quite well in 1 to 2 days post-
key issues that will drive this,” he notes. operative epi-LASIK cannot make that claim yet.
Diane Appler, senior global marketing manager, Surgeons who are performing epi-LASIK are
Laser Vision Correction Group, Advanced Medical making great inroads in mitigating pain, and they
Optics (AMO), says epi-LASIK is finding a middle say the discomfort difference between epi-LASIK and
ground between being a niche and a large, growing LASIK might be negligible at this point.
market. “I think it is somewhere in the middle. It is One area where epi-LASIK is more advantageous
increasing in popularity, and our market research has than LASIK today is fewer complications.
shown that about one third of all laser vision “If you are going to do refractive surgery, why
correction procedures in the U.S. will probably be not do a procedure where the complications are
done with a surface ablation (method) by the end of extraordinarily low and the outcomes are fairly
2007.” predictable?” asks Lamar Chandler, vice president,
Don Mikes, vice president, Global Marketing, Marketing, for the United States and Europe,
Moria, says the aforementioned numbers from the Norwood.
Market Scope survey validate Moria’s observations Surgeons who have implemented epi-LASIK into
that there is an increasing interest in surface ablation their practices are reporting patient safety as a
among refractive surgeons. “We are continually paramount reason for doing so.
monitoring trends and see a steady increase in the “I am becoming much more cautious in terms of
percentage of surface ablation procedures being whom I will perform any procedure on, but more
performed.” importantly, whom I will perform a LASIK flap on,”
While there was initially pent-up demand for epi- says Bruce Larson, MD, principal, Larson Eye Center,
LASIK, performances issues with earlier versions of Hinsdale, Ill.
competitive epikeratomes, as well as “market inertia,” Dr Larson attributes his initial interest in epi-
have kept industry sales at a modest level, says Mikes.
LASIK to his own personal experience with LASIK
It appears that many surgeons have been waiting to
and suffering from halos. In fact, his wife had LASIK
hear more about epi-LASIK before investing in the
as well and suffers from the same problem. His
technology.
personal experience, compounded by concerns about
Nonetheless, Mikes is confident epi-LASIK will
ectasia and kerataconus, has motivated him to
have a prominent role in the refractive market. “I don’t
perform more epi-LASIK.
see it as a niche; I see it as fulfilling a significant need
Dr Larson estimates about 60% of his laser vision
and that it will eventually become a major segment of
patients still undergo LASIK, but the remaining 40%
the laser vision correction market,” says Mikes. “The
of them now undergo epi-LASIK. He has been using
surgeons will eventually decide, but there is enough
the EpiVision system (Gebauer/CooperVision
in the literature and the experience indicating that
Surgical) in his practice.
surface ablation has distinct advantages, and I believe
Eric Donnenfeld, MD, partner, Ophthalmic
that epi-LASIK will ultimately emerge as the preferred
Consultants of Long Island and Connecticut, also says
surface technique.”
patient safety has influenced him to introduce epi-
LASIK, EPI-LASIK LASIK into his practice. “My use of surface ablation
has increased as the indications have increased, and
When considering the integration of epi-LASIK into as my concerns for complications with LASIK are
their practices, some surgeons may be naturally increasing,” says Dr Donnenfeld.
 Advanced Surface Ablations 401
He says the wider and deeper ablations associated this method has allowed many of his patients to go
with custom LASIK reduce the residual stromal beds out and function the next day after surgery, and he
available and create concerns about ectasia. In has not had one patient who has not been able to
addition, irregular topographies, which he would return to work after 3 days.
have treated with LASIK years ago, are now more Dr Milne is now performing KAASA exclusively
suited for surface ablation. on his surface ablation patients after having a similar
So the question remains will epi-LASIK be an complication arise in three patients who had epi-
alternative to LASIK or a replacement to it? Fancher LASIK. On these patients, there was what he
thinks that while some practices may go totally over described as multiple layers of epithelial growing,
to surface ablation, most surgeons will adopt epi- so it caused a refractive effect that delayed the
LASIK to go along with their LASIK procedures. “I recovery. In these patients it appears that the flap
think most practices will offer both and it will depend was so viable that a second layer of epithelium had
on the profile of the patients as to which they’ll grown over or under the flap. All three patients
choose,” predicts Fancher. “I don’t think this is a eventually resolved to corrected visual acuities in 6
takeover; I think it is a complementary way of meeting weeks to 2 months.
patient needs.” Warren Cross, MD, principal, Warren Cross and
Associates, Houston, Texas, performs conventional
FLAP REMOVAL epi-LASIK in most of his surface ablation patients, but
he also utilizes a flap-removal technique, which he calls
One significant area of ongoing debate in epi-LASIK
Epi-PRK. He says modifying his Epi-PRK over the last
has been whether or not to leave the epithelial flap.
year and a half has led to faster visual recoveries in
Surgeons have been reporting success with both
patients. “We are using less fluid during the surgery
techniques, but some say flap removal procedures
and lifting a dry flap,” says Dr. Cross. “We actually
outperform standard epi-LASIK.
have some of our patients 20/25, 20/30 the next day.”
Dr Donnenfeld has been having success with flap
He has observed that his Epi-PRK patients see better
removal, and he and colleagues use the term lamellar
faster than his conventional epi-LASIK patients.
epithelial debridement (LED) to describe the
technique. They began using the term when doing a OTHER SURFACE ABLATION MODALITIES
comparative study with epi-LASIK and LED.
“We have evaluated LED and epi-LASIK, and we Traditional PRK is still the number one surface
have found LED provides more rapid visual ablation technique, according to Market Scope. Their
rehabilitation than epi-LASIK, while epi-LASIK is survey asked surgeons about their plans for 2006.
more comfortable,” says Dr. Donnenfeld. He has been Those respondents who planned on performing
using the Amadeus II system with surface ablation surface ablation, said they expected to perform
module (AMO). traditional PRK in 4.2% of cases, epi-LASIK in 2.7%
HL “Rick” Milne, MD, president, The Eye Center of cases and LASEK 1.4% of the time.
PA, Columbia, S.C., is an Epi-K user and an advocate While this does not appear to bode well for LASEK
of removing the flap. In referring to the procedure, supporters, it does leave a question about how PRK
he uses the term first coined by Raymond Stein, MD, will be performed in the future.
Bochner Eye Institute, University of Toronto: Dr Larson still performs the traditional PRK
Keratome-Assisted Advanced Surface Ablation method with the Amoils brush and has not used his
(KAASA). epikeratome for the modified PRK because he sees it
Dr. Milne says all of his KAASA patients thus far as too expensive. He does concede, however, that
have been fully healed and their bandage contact using an epikeratome to do PRK would create “a
lenses removed by 3 days postoperative. He also says beautiful surface’’.
402 Mastering Advanced Surface Ablation Techniques
Some surgeons take a contrary viewpoint and “We have seen a dramatic reduction in
believe flap removal with the epikeratome will replace postoperative pain,” says Dr. Larson. He also gives
traditional PRK. “LED and epi-LASIK are replacing patients 40 mg of prednisone 45 minutes
(traditional) PRK,” asserts Dr Donnenfeld. He says preoperatively.
LED and epi-LASIK are more comfortable, reliable Dr Donnenfeld has his patients use chilled tears.
and faster healing procedures than traditional PRK. He uses Acular LS (ketorolac tromethamine,
Dr Milne says KAASA outperforms LASEK and Allergan) QID starting the day before the surgery.
traditional PRK. “It [KAASA] brings a very quick Post-op, he soaks the contact bandage lens in Acular
epithelial re-covering of the stromal bed, much PF. Dr Donnenfeld also writes a prescription for
quicker than you get with other methods such as Vicodin (hydrocodone, Abbott Laboratories), which
alcohol or with a brush,” states Dr Milne. “The key he says patients rarely ever use.
here is the epithelial cells right next to where they Dr Milne freezes the cornea after laser treatment
have been lifted, are completely untraumatized, so with a frozen Weck-Cel sponge. He also uses Xibrom
they heal very quickly and without a leading edge of (bromfenac ophthalmic solution, ISTA
devitalized cells. None of these patients have had a Pharmaceuticals) BID, Pred Forte (prednisolone
central dendritic accumulation of these devitalized acetate, Allergan) and one of the fluoroquinolones QID.
cells as you can sometimes see in PRK or LASEK.” On the morning of surgery, Dr Milne initiates
Neurontin 300 mg (gabapentin, Pfizer) TID for 3 days.
HAZE AND PAIN MANAGEMENT “It is an analgesic drug that has mild sedative
properties. It really mutes nerve-ending pain used
Haze had initially been an issue for surface ablation
to treat post-herpetic neuralgia.” He writes a
patients, but doctors are including mitomycin C in
prescription for a stronger pain medication, but he
their regimens to alleviate this complication. For all
advises patients not to get the prescription filled
of his surface ablation patients who are more than -6
unless they get what he calls “breakthrough pain.”Dr
D or their ablation is over 75 microns, Dr Donnenfeld
Milne reports that less than 5% of patients need the
has been using mitomycin C 0.02% for 10 seconds
additional medication.
intraoperatively.
Dr Cross starts patients on systemic anti-
“I want to minimize the risk of haze, and by using
inflammatories preoperative. He prescribes Celebrex
mitomycin I can almost eliminate it,” explains Dr.
(celecoxib, Pfizer) 200mg p.o. q.d. starting 3 days prior
Donnenfeld.
to surgery and continues 3 days post-operative. For
Dr Milne also utilizes mitomycin C. “If I have an
patients who may not want to take Celebrex, Dr Cross
ablation depth of over 75 microns, I use mitomycin C
will suggest Motrin (ibuprofen) TID 3 days pre-
for somewhere between 20 and 30 seconds, and with
operative and then 4 days postoperative. He also uses
that [regimen] I have not had haze (with any of his
Acular PF BID or QID 3 days preoperative.
KAASA patients),” reports Dr Milne.
He uses a Weck-Cel sponge with frozen BSS on
While surgeons vary in their pharmacological
the cornea for 1 minute after ablation. This “frozen
regimens to mitigate pain, one common routine for
popsicle” has really alleviated patient pain according
all has been to use chilled or frozen balanced salt
to Dr Cross. Postoperative, he will rotate Pred Forte,
solution (BSS) or tears. The surgeons interviewed for
Acular, and Zymar (gatifloxacin, Allergan).
the story offered their pain management
pharmacological regimen. SUMMARY
Dr Larson makes the distinction to use 40 to 50
drops of partially frozen BSS immediately before the Laser Assisted Sub-Epithelial Keratomileusis
epikeratome pass and not afterwards like many other (LASEK) is a refractive surgery technique developed
surgeons do. by Italian doctor, Massimo Camellin, MD and first
 Advanced Surface Ablations 403
publicized in 1999. The motivation behind LASEK rule, if there is a need of less than 6.00 diopters of
was to find a surface ablation technique like PRK that correction, LASEK will not offer a risk of corneal
induced less discomfort, offers a lower incidence of haze any different than PRK. Above 6.00 diopters,
corneal haze, and provides the patient with faster LASEK may have an advantage.
vision recovery time.
To understand LASEK, one needs to understand Old Reliable Vitamin C
a little about PRK and conventional or custom It has been found that having a patient take 500 mg
wavefront Lasik. of vitamin C twice a day for a week before PRK and
at least two weeks after surgery significantly reduces
Hazy View of Things
the incidence of corneal haze. Isn’t it always the simple
A major problem with PRK in its early development answer that is the best. This appears to be helpful,
was corneal haze. Corneal haze is caused by the but more study is needed to determine just how much
cornea’s wound response. Surgery is an insult to the help is provided with oral vitamin C supplements. It
cornea, and the cornea really doesn’t care, it is going is really not known if vitamin C is enough for
to respond as if it has been wounded. A part of that someone who needs 8.00 diopters of correction, but
wound response causes opaque cells to form. This is not enough for someone who needs 10.00. The
presents as white hazing of the cornea, restricting limits need to be determined.
light from passing through, and reducing the quality
of vision. Strong Medicine
The use of the topical eye drop Mitomycin C
Combine Old with New
dramatically reduces the probability of haze, and can
It was noted that wound response to PRK laser be used to treat haze when it occurs, but this is a
ablation deeper in the cornea is significantly different rather strong medicine. Mitomycin C is appropriate
than when the ablation is performed at the outer when required, but probably needs to be avoided if
surface of the cornea. The idea was formed to possible.
creating a flap of corneal tissue using ALK methods,
perform the PRK ablation under the flap and deeper It’s All in the Flap
in the cornea, then returning the flap over the ablated The concern between LASEK and LASIK is the LASIK
area. Thus LASIK was created as a combination of flap. Although it provides the patient with more
ALK and PRK. LASIK literally “fools” the cornea into comfort, virtually eliminates the probability of haze,
not knowing it has been wounded. This is why LASIK and offers very quick visual recovery, if the flap exists,
normally provides virtually no pain, has an almost there will be the possibility of flap related problems.
instant vision recovery, and almost never causes Once LASIK is performed there will always be LASIK
corneal haze; the cornea almost doesn’t know it has and the eye is fundamentally and forever changed.
had surgery. Change can be a good thing, but sometimes not.
Another potential problem with LASIK is that
Moderate Correction = No Haze
severing the corneal nerves deeper in the cornea often
PRK haze does not normally form for corrections that will temporarily induce dry eyes. The signals from
require a moderate amount of tissue removal, the cornea are interrupted until sensation returns
generally less than about 6.00 diopters of refractive with healing. That can be weeks to months. Although
error. That is good news for moderate and low fewer than 3% of refractive surgery patients have
myopia (nearsighted, shortsighted) and virtually all any kind of unresolved complication at six months
hyperopes (farsighted, longsighted), but bad news postoperative, dry eyes is the temporary problem
for those needing higher corrections. As a general most prevalent with LASIK.
404 Mastering Advanced Surface Ablation Techniques
Yet another issue with the thicker LASIK flap solution, they will quickly regenerate. After the
relates to the ability to create more detailed ablation epithelial flap is moved out of the way, excimer laser
profiles with newer technology like flying spot energy is then applied through the Bowman’s Layer
gaussian beam excimer lasers and wavefront-guided and into the upper stroma to reshape the cornea. When
ablations. The wavefront ablation profile of where the cornea has been reshaped by the laser, the
more tissue needs to be removed here, and less tissue epithelium flap is returned back to its original
needs to be removed there, is very nuanced with position.
tiny changes across the treatment area. The limitation A contact lens is placed on the cornea shortly after
with LASIK is that you are putting a relatively thick surgery as a bandage for several days to aid in the
100-180 micron flap of corneal tissue on top of this healing and the reduction of pain. It normally takes
fancy nuanced ablation. Like too many blankets on three to ten days for the epithelium to heal and
the bed, you lose some of the detail of the shape of resurface the cornea. This healing time varies
who is in that bed. Also, the Bowman’s layer and depending on a number of factors such as the size of
uppermost layer of cells of he cornea are more dense the area treated, the health of the patient’s cornea,
than the deeper stromal layer. It is opined that ablation the individual’s in healing rate, and the toxicity of
in Bowman’s layer may help in creation of better and the medications and solutions applied to the surface
better ablations. of the cornea.
And if that was not enough, the LASIK flap is Neither a mechanical nor laser microkeratome is
from 100 to 180 microns thick. If the patient has a used in LASEK.
thin cornea, there may not be enough room for the
LASIK flap, the tissue ablation, and the 280 to 300 LASEK Flap Loss Means PRK
microns of untouched cornea that is needed to keep Sometimes when LASEK is attempted, the 50-micron
stability and reduce the probability of ectasia. thin epithelium flap is not strong enough to be laid
back over the treatment zone. In these cases, the
A Flap That’s Not a Flap epithelium will be removed as it would have been in
The desire to eliminate potential LASIK flap related PRK. In this situation the LASEK procedure becomes
problems brings us back to PRK, but PRK is not a PRK procedure. If this happens and the patient was
terribly comfortable for the patient, has a longer within the parameters for PRK, there is no cause for
recovery period, and there is that problem with haze concern because it will normally not adversely affect
for higher myopes. The idea that Dr. Camellin had the visual result. If the patient was a high myope and
was to create an “epithelial flap” that would fool the LASEK was being used as a technique to reduce the
cornea the way the thicker Lasik stroma flap does, probability of corneal haze, then there may be a
but not be subject to the same complications as a problem. Most doctors will tell a LASEK patient that
LASIK flap. LASEK will be attempted but it cannot be guaranteed
During PRK, the epithelium is removed and the that the LASEK will be completed - the epithelium of
excimer laser treatment occurs on the underlying each individual behaves differently.
outermost surface of cornea. Rather than removing
the epithelium, LASEK attempts to save the epithelium Advantages and Disadvantages
by using an alcohol solution to cause the epithelial Visual recovery after LASEK is generally faster than
cells to weaken. After removing the solution from in PRK, a little slower than Epi-Lasik, but significantly
the eye, the edge of the weakened epithelial flap is slower than Lasik.
lifted and gently folded back out of the way. The The potential advantages of LASEK over PRK are
corneal epithelial cells are the fastest reproducing cells a reduction of postoperative discomfort, a decreased
in the human body. Even if destroyed by the alcohol risk of infection, and decreased incidence of corneal
 Advanced Surface Ablations 405
haze. Advantages of LASEK over LASIK include 5. Fasano AP, Moreira M, McDonnell PJ, Sinbawy A.
Excimer laser smoothing of a reproducible model of
elimination of the possibility of any stromal flap anterior corneal surface irregularity. Ophthalmology.
complications during surgery or throughout the 1991;98:1782-5.
patient’s lifetime, including striae, DLK, and others, 6. Fratzl P, Daxer A. “Structural transformation of collagen
fibrils in corneal stroma during drying. An x-ray
a decreased risk of temporary induced dry eyes, and
scattering study.” Biophys J. 1993 Apr;64(4):1210-4. PMID
an increase in the overall thickness of the untouched 8494978.
area of the cornea. Advantages of LASIK over LASEK 7. Hersh PS., Brint SF, Maloney RK, et al. Photorefractive
keratectomy versus laser in situ keratomileusis for
include virtually no pain with LASIK and almost
moderate to high myopia. A randomized prospective
instant clear vision, often called the “WOW!” effect. study. Ophthalmology 1998;105 (8):1512-22 (pubmed).
A progression of LASEK is Epi-LASIK. Epi-LASIK 8. Kornhehl EW, Steinert RF, Puliafito CA. A comparative
study of masking fluids for excimer laser photo-
uses a mechanical microkeratome with a blunt blade
therapeutic keratectomy. Arch Ophthalmol. 1991;109:
to slide across Bowman’s and lift up a flap of epithelial 860-3.
cells. This flap is not reduced in strength by an alcohol 9. Lombardo M, De Santo MP, Lombardo G, Barberi R,
Serrao S. Roughness of excimer laser ablated corneas
solution and tends to be more stable than a LASEK
with and without smoothing measured with atomic force
flap. microscopy. J Refract Surg. 2005; 21(5):469-75.
As with nearly all excimer laser based refractive 10. Netto MV, Mohan RR, Sinha S, Sharma A, Dupps W,
surgery, correction can be performed with both Wilson SE. Stromal haze, myofibroblasts, and surface
irregularity after PRK. Exp Eye Res. 2005; (in press).
conventional ablation and wavefront-guided 11. Serrao S, Lombardo M, Mondini F. Photorefractive
ablation. keratectomy with and without smoothing: a bilateral
Primum Non Nocere! study. J Refract Surg. 2003;19:58-64.
12. Serrao S, Lombardo M. Corneal epithelial healing after
phorefractive keratectomy: analytical study. J Cataract
BIBLIOGRAPHY Refract Surg. 2005;31:930-37.
13. Vinciguerra P, Azzolini M, Airaghi P, Radice P, De
1. Carones F, Vigo L, Carones AV et al. Evaluation of Molfetta V. Effect of decreasing surface and interface
photorefractive keratectomy retreatments after irregularities after photorefractive keratectomy and laser
in situ keratomileusis on optical and functional outcomes.
regressed myopic laser in situ keratomileusis.
J Refract Surg. 1998;14:S199-203.
Ophthalmology 2001;108(10):1732-37 (pubmed).
14. Vinciguerra P, Azzolini M, Radice P, Sborgia M, de
2. Daxer A, Fratzl P. “Collagen fibril orientation in the
Molfetta V. A method for examining surface and interface
human corneal stroma and its implication in
irregularities after photorefractive keratectomy and laser
keratoconus.” Invest Ophthalmol Vis Sci. 1997;38(1):121- in situ keratomileusis: predictor of optical and functional
9. PMID 9008637. outcomes. J Refract Surg. 1998;14:S204-6.
3. Daxer A, Misof K, Grabner B, Ettl A, Fratzl P. “Collagen 15. Vinciguerra P, Cro M, Giuffrida S, Airaghi P, De Molfetta
fibrils in the human corneal stroma: structure and aging.” V. A new strategy in excimer laser PTK: use of hyaluronic
Invest Ophthalmol Vis Sci. 1998;39(3):644-8. PMID acid solution as masking fluid. Inv Ophthalmol Vis Sci.
9501878. Annual Meeting Sarasota, FL, 1994;1-6.
4. El-Agha MS, Johnston EW, Bowman RW et al. Excimer 16. Vinciguerra P, Prussiani A. Fotocheratectomia
laser treatment of spherical hyperopia: PRK or LASIK? terapeutica (PTK). In: Chirurgia Refrattiva: Principi e
Trans Am Ophthalmol Soc 2000;98:59-66 (pubmed). Tecniche. Asti: Fabiano, 2000;439-62.
406 Mastering Advanced Surface Ablation Techniques

CHAPTER

49 Pitfalls in Advanced Surface

Ablations

Claes Feinbaum (Poland)

INTRODUCTION Despite the popularity of LASIK, surface ablation

remains an attractive procedure. Surface ablation’s
Various refractive eye surgery techniques change the
appeal derives from two unique attributes. first, for an
shape of the cornea in order to reduce the need for
equivalent correction, surface ablation leaves a
corrective lenses or otherwise improve the refractive
structurally stronger cornea than LASIK. Thus, the
state of the eye. In many of the techniques used today,
incidence of corneal ectasia is lower with surface
reshaping of the cornea is performed by
ablation. From a corneal integrity standpoint, surface
photoablation using the excimer laser.
ablation is probably a better procedure than LASIK for
Laser vision correction without preparation of a
high myopia or patients with atypical topography, such
LASIK flap goes by a number of names - LASEK (laser
as inferior steeping, a steep central cornea (>48D), or
epithelial keratomileusis, surface LASIK, epithelial
high oblique astigmatism. In these cases, surface ablation
LASIK, epi-LASIK, or Advanced Surface Ablation).
offers a more conservative option than LASIK.
Although LASEK and LASIK sound the same, unlike
A viable surface ablation technique changes the over-
traditional LASIK, LASEK does not require the
all refractive landscape. Until recently, the belief was
preparation of a corneal stromal flap. This has three
that the safe upper limit for laser vision correction was
potential advantages:
in the vicinity of -8 D. for higher corrections, it looked
1. Risks of making the corneal flap in LASIK are
as if the best solutions were intraocular, most often with
avoided. This may be important in some patients
a phakic intraocular lens (IOL). However, with advances
in whom there is an additional risk in making the
in laser technology and the use of mitomycin-C, now
flap, or in patients who prefer a no-flap treatment.
the feeling is that surface ablation up to -12 D could be
This technique may also be required for some
occupations. performed, using either a wavefront-guided or a
2. Since laser treatment is done on the surface, wavefront-optimized approach.
LASEK preserves more corneal tissue. In If laser vision correction becomes the norm up to,
particular, patients who have thinner corneas may say, – 12 D, that has the potential to significantly
be more safely treated with a no flap technique diminish the phakic IOL market — the number of
rather than LASIK candidates with corrections greater than –12 D is very
3. LASEK may be an option for patients who are small, especially compared to the number of potential
not good candidates for LASIK. patients between – 8 and –12 D.
 Pitfalls in Advanced Surface Ablations 407
Outcomes with advanced surface ablation have keratectasia) the initial problems of PRK did not seem
improved with advances in laser technology and too severe. That is the reason for the revival of PRK.
pharmaceutical management, but surface ablation still Haze formation, pain and slow recovery have almost
lags behind LASIK in the areas of comfort and speed of disappeared by the introduction of Advanced Surface
visual recovery. One development that holds great Ablation (ASA). This method is basically the PRK
potential is the epithelial separator that would allow us technique with the following modifications:
to make an epithelial flap without alcohol (epi-LASIK). development of a special distribution pattern of laser
At this point, it looks as if the future of corneal shots and various postoperative treatment
refractive surgery is a race between epi-LASIK and modifications.
LASIK. If surface ablation is to challenge LASIK in a
meaningful way, however, we will have to find a THE BOTTOM LINE
way to deal with the pain and recovery-time issues.
Although surface ablation has advantages in terms
If epi-LASIK can reduce pain and speed recovery to
of safety and visual outcome, it has been associated
the point where it rivals LASIK, then it has a bright
with some significant problems, including haze, pain,
future. However, the jury is still out.
slow visual recovery, and regression. The
Although lasers have been in use around the world
combination of frozen BSS to chill the cornea after
since 1964 for various scientific and medical purposes
surgery, a tight bandage contact lens, and aggressive
it was not until 1987 that an ophthalmologist first
pharmaceutical management has reduced the
used the laser for refractive purposes. Applying
incidence of pain to the point where 85% of surface
excimer laser photo ablation directly to the central
ablation patients have roughly the same comfort level
surface of the cornea became known as “photo
as LASIK patients. Use of mitomycin-C has removed
refractive keratectomy” or PRK and became widely
significant haze as a complication of surface ablation.
used around the world to correct nearsightedness.
The smooth ablation surface that current flying spot
The first PRK procedure on a patient was performed
lasers deliver speeds recovery following surface
in 1987 at Columbia University and was on a blind
ablation, although the pace of visual recovery is still
eye. Photorefractive Keratectomy (PRK) was born.
significantly slower than with LASIK. Larger optical
The accuracy of the laser led to more accurate results
zones have greatly diminished the incidence of
than previous techniques. But in the beginning of
regression following surface ablation, to the point
Photorefractive Keratectomy in 1988 this method
where enhancement rates for surface ablation are
suffered from 2 severe complications: severe
lower than for LASIK. Visual outcomes have been
postoperative pain and increased corneal haze
stellar. Advanced surface ablation opens up the
formation. These factors limited its effectiveness and
possibility of extending the range of laser vision
reputation ever since. So as a matter of fact, the
correction to –12D.
popularity of PRK, however, was slow to catch on. It
wasn’t until the development of microkeratome ADVANCED SURFACE ABLATION TECHNIQUES
technology and introduction of laser-in-situ
keratomileusis (LASIK) in 1991 for vision correction ASA is nothing more than PRK or epi-LASIK using
that popularity soared. With LASIK, patients the newer more advanced excimer laser
experience little if any pain and see well quickly. Due CustomCornea treatment. Every cornea has it is own
to the fact that the LASIK procedure has its fingerprint that makes it different than any other
complications and disadvantages, like e.g. cornea in the world.
intraoperative microkeratome-related complications
Laser
(thin, irregular, dislocated, free or perforated flap;
entry into eye; diffuse intralamellar keratitis; An acronym for Light Amplification by the
epithelial ingrowth; interface problems and corneal Stimulated Emission of Radiation. Laser light is
408 Mastering Advanced Surface Ablation Techniques
different from ordinary light in that it is composed more curved surface for people who are hyperopic.
of one color (wavelength) traveling in one direction Photorefractive Keratectomy techniques may also be
and each light wave is traveling in step with the used to correct astigmatism.
adjacent wave making the laser light more powerful
by a factor of millions. This energy is carried by the Point Spread Function
wave in “packets” called photons. Often used in wavefront diagnostic analysis. A single
round spot of light becomes diffused when it passes
Laser Assisted in situ Keratomileusis
through an aberrated element such as a human eye.
An advanced laser procedure combining ALK and Aberrations cause some of the light to spread beyond
PRK to reshape the central cornea, thereby decreasing the boundaries of the light source, causing the dot of
or eliminating myopia (nearsighted, shortsighted light to appear fuzzy. Analysis of the diffusion of
vision), hyperopia (farsighted, longsighted vision), light (spread) helps doctors determine what changes
and astigmatism (irregular cornea). The refractive may be made to remove aberrations causing the
surgeon uses an automated microkeratome to shave diffusion.
off a thin, hinged layer of the cornea. This flap is
then lifted like a hinged door and the exposed surface Surface Ablation
is reshaped using the excimer laser. After altering Any surgical procedure that ablates tissue at the
the corneal curvature, the flap is replaced and adheres surface of the cornea, rather than under a Lasik or
without stitches. All-Laser Lasik stromal flap. PRK, LASEK, and Epi-
Lasik are all surface ablation techniques. Several
Laser Assisted Epithelium Keratomileusis
studies have shown that surface ablation techniques
Laser Assisted Sub-Epithelium Keratomileusis provide better refractive surgery outcomes than
(LASEK) is the detachment of the epithelium with Lasik or All-Laser Lasik, for patients who are
the use of an alcohol solution that softens the appropriate candidates for both types of surgery.
epithelium and allows it to be rolled back into a flap.
The flap of epithelium is then be repositioned over CORNEAL TOPOGRAPHY AND THE TEAR FILM
the cornea following excimer ablations.
The epithelial surface of the cornea is naturally
Automated Lamellar Keratoplasty hydrophobic. Therefore, for a tear layer to be able
to remain on the corneal surface without rolling off,
An incisional refractive surgery technique for low to the hydrophilic mucoid or mucin layer of the tear
moderate myopia (nearsighted, shortsighted vision). film is laid down onto the surface of the cornea by
In the procedure, the refractive surgeon places an Goblet cells. On the other hand, the lacrimal layer of
instrument called an automated microkeratome on the tear film located above the mucoid layer, can defy
the eye which removes, in a shaving motion, a thin gravity and remain in front of the eye.
layer of cornea only microns thick. An even thinner A further important factor for the tear film to
layer of cornea underneath this top cap is removed, remain stabile on the corneal epithelial surface is the
and the top cap is replaced. The procedure does not glycocalix – this substance is found in the surface cells
require sutures. of the corneal epithelium and acts like a glue to the
mucoid layer. However, this substance is extremely
Photorefractive Keratectomy
sensitive and any disturbance to the corneal surface
Abbreviated as PRK. A surgical procedure using an will cause a disappearance of the glycocalix. This
excimer laser to reshape the central cornea to a disturbance could for example be a surgical
flattened shape for people who are myopic and a intervention or contact lens wear.
 Pitfalls in Advanced Surface Ablations 409
Measurements of the tear film thickness in vivo quality. It is therefore necessary to change strategy
are limited and cannot easily be applied in a clinical in these cases and use alternative methods.
setting. The studies on tear film thickness at Ohio 26 eyes from 13 patients interested in refractive
State University (Columbus, Ohio) did not confirm surgery, were examined by the same investigator
Prydal´s estimate of approximately 40 μm. Nor were (author), a normal ophthalmological protocol was
there prominent peaks near Danjo´s value of followed for the examination. For topography a
approximately 11 μm, except in cases of probable topographer manufactured by BON was used.
reflex tears. Because the reflection of the aqueous-
mucus boundary would be expected to be weaker
than that from the epithelial surface, the 3 μm peak is
unlikely to correspond to the aqueous layer rather
than the complete tear film. The proposal that the
3μm peak corresponds to a reflection from the front
of the cornea is supported by the demonstration of a
peak of similar contrast from the back of the cornea.
Thus, the current evidence consistently supports a
value of approximately 3 μm for the thickness of the
human precorneal tear film.
A deficient tear film will cause discomfort and a
deficiency in any of the three layers of the film can
lead to a dry eye condition, causing anything from
mild eye irritation to severe pain. Interestingly, in
some cases, excessive tearing or watering of the eyes
can be a symptom of a dry eye condition. This is
because when, for whatever reason, there is an
inadequate normal tear layer on the eye, irritation
results; the later causes an overproduction from the
Figure 49.1: BON topographer
lacrimal gland and resulting in a flooding of lacrimal
fluid onto the anterior surface of the eye. Two measurements of corneal topography were
With the irregular changes occurring when made namely:
performing corneal topography, as indicated above, 1. In wet state just after blink without anesthetic
the outcome of ablation surface techniques like PRK, 2. In dry state 15 seconds after blink without
LASEK, EpiLASIK and LASIK will vary considerably anesthetic
and cause: Four measurements sites:
1. Higher order aberrations 1. Steep central meridian
2. Dry eyes or better ocular surface syndrome 2. Flat central meridian
3. Variable uncorrected and corrected visual acuity. 3. Steep meridian at 3 mm zone
If there are changes in corneal topography of more 4. Flat meridian at 3 mm zone
than than 1 D in more than 3 out of 4 meridians And the results were as follows:
measured, the outcome of surface ablation techniques There was a change of corneal curvature from wet
will vary considerably due to totally different surface to dry state in more than 3 out of the 4 meridians in
topographies in wet and dry state and the changes the following eyes of more than 1D:
are the same in all directions. These surface 1, 3, 5, 6, 8, 9, 10, 11, 13, 18, 21 and 23. Thus 12 out
discrepancies will cause higher order aberrations, dry of the 26 eyes showed changes from wet to dry
eyes and variable visual acuity and poor optical topography.
410 Mastering Advanced Surface Ablation Techniques
Further it is also important to have a close look at Better and more refined ablation algorithms mean
the topographies for other corneal diseases like more accurate and predictable postoperative
keratoconus, as the following topographies will outcomes, and aberrometer improvements have
show: enhanced the precision with which refractive errors
This is the cornea in wet state with hardly any are captured. Two innovations come to mind. Iris
indication of keratoconus, the topographer did not registration technology and pupil centroid
indicate keratoconus. compensation work hand-in-hand to ensure more
And here it is clearly indicated keratoconus, also precise delivery of the ablation.
from the topographer. Please note, that it is the same The salient element of a wavefront-guided
eye, there was a mistake done in marking OD and procedure is the wavefront capture. The quality of
OS. the laser ablation, which is directly related to the
Thus always perform corneal topography in wet visual outcome, depends on an accurate assessment
and dry state. of the aberrations of the eye. Mathematical formulas
Since the FDA approval of wavefront-guided ‘describe’ these aberrations to the excimer laser, which
LASIK 3 years ago, significant advances have taken then uses the information as a roadmap to correct
custom procedures further along the evolutionary the optical errors.
pathway. With expanded indications — wavefront In the evolution of wavefront-guided LASIK, we
is now approved for hyperopia and mixed started with — and still use — Zernike polynomials
astigmatism, as well as myopia with astigmatism — to describe optical aberrations. Zernike polynomials
more people are candidates for custom procedures. are useful because they can be used to describe not

Figure 49.2: Corneal topography wet state

 Pitfalls in Advanced Surface Ablations 411
only sphere and cylinder — what we now term lower- basis of the aberrometer measurement, can change
order aberrations — but also other types of optical positions up to 0.7 mm as the pupil dilates or
aberrations, called higher-order aberrations (HOAs). constricts. Accordingly, it is important to compensate
We are beginning to appreciate the visual significance for this centroid shift to avoid a decentered ablation.
of some of these HOAs, particularly coma and sphere. Iris registration systems do this by using the limbus
While Zernike polynomials are useful to clinically as a reference point. Effective centroid shift
describe the wavefont, an improved method to compensation technology is a critical component of
mathematically describe optical aberrations is Fourier treatment registration.
transformations. This upgraded wavefront
reconstruction is currently available for custom IOP AND REFRACTIVE SURGERY
treatments with the AMO VISX Advanced
CustomVue system. By now nearly everyone recognizes that the current
The alignment of the eye as measured by the gold standard for measuring IOP, the Goldmann
aberrometer must match the alignment when surgery tonometer, has considerable flaws. The GAT and
is performed. Similar to astigmatism, most HOAs tonometers calibrated to “read” like GAT are affected
require precise torsional alignment. Torsional by corneal properties including rigidity, thickness,
misalignment during surgery can result in hydration, curvature, and perhaps other factors not
undercorrection of the aberration or even induced yet identified. Dr. Goldmann designed his tonometer
aberrations. There can be as much as 10 degrees of to provide accurate measurements in eyes with
cyclorotation measured on the aberrometer when a “average” corneas. But we now know that many
patient goes from a seated position to a prone corneas vary more significantly from average than
position under the excimer laser. Even small amounts previously thought.
of misalignment can result in significant It is well documented that there is an apparent,
undercorrection of astigmatism and HOAs. but artificial, reduction in post-LASIK GAT-measured
The most basic technique for alignment is to mark IOP. However, this anomaly cannot be explained by,
the limbus, typically at the 3 o’clock and 9 o’clock or corrected for, using CCT data or any currently
positions, while the patient is seated prior to surgery. known parameter. This is because the LASIK
These marks are then used to align the head when procedure not only thins the cornea, it induces
the patient is under the excimer laser. A greatly complex biomechanical changes which are not really
improved technique is iris registration technology. measurable by any previously available device.
This helps ensure the eye alignment during A meta-analysis of 134 published papers between
aberrometry precisely matches the alignment under 1968 and 1999 concluded that IOP and CCT were
the laser. Iris landmarks, such as crypts, are captured interrelated, and that a 10% change in CCT in eyes
and recorded by the aberrometer. A sophisticated exhibiting no corneal pathology would account for a
camera and computer system in the excimer laser 1.1 (+-0.6)mmHg change in IOP. However, CCT alone
records and matches iris details to the aberrometer. cannot account for all the variation in measured IOP
Cyclotorsional compensation is provided to precisely amongst individuals, and it is likely that more
align the treatment. complex biomechanical properties have an important
Proper centration of an ablation is crucial to good influence on IOP measurement.
outcomes. Decentration of 0.5 mm or less can result All tonometers measure IOP indirectly through
in visual symptoms. Accurate centration is even more the cornea. Thus, their accuracy relies on certain
important when treating HOAs. This is done by assumptions about the cornea – not just about its
matching the aberrometer-derived ablation profile curvature and thickness but also subtler aspects of
to correct position on the cornea under the laser. The the eye wall tissue, which we are only beginning to
problem is that the center of the pupil, which is the understand.
412 Mastering Advanced Surface Ablation Techniques

Figure 49.3: Corneal topography dry state

Figure 49.4: Wavefront aberrometer by VISX

 Pitfalls in Advanced Surface Ablations 413

Figure 49.5: Centration and cyclotorsion

Figure 49.6: Visual outcomes on centration and cyclotorsion

GAT is based on application of the Imbert-Finck a. Surface tension of the tear film, which tends to
principle to the cornea. He states that the force of draw the tonometer head toward the cornea.
flattening (F) equals the pressure (P) multiplied by b. Corneal rigidity, the force of the cornea which
the surface area flattened (A) or F = P×A. However, resists flattening.
this principle assumes that we are examining a dry, In theory, using the 3.06 mm diameter of
perfectly flexible, infinitely thin spherical surface – applanation in the Goldmann tonometer, surface
in other words, a cornea that does not exist. tension of the tear film and corneal rigidity cancel
Goldmann´s derivations attempted to take into each other out. But this occurs only under the
account these two additional factors: following circumstances:
414 Mastering Advanced Surface Ablation Techniques
• In corneas which are exactly 500 microns thick second, several measurements are needed to obtain
• If corneal rigidity is constant and equal in all an accurate reading. The software is pre-programmed
corneas for six measurements, but the result can be seen from
• When anterior corneal curvature is normal and the first successful measurement.
posterior corneal curvature parallels anterior The Icare is a highly repeatable instrument for
surface. Again, this is not something we see in measuring IOP with a variablitiy of ± 1mm Hg per 6
the real world, and certainly not after laser measurements.
refractive surgery.
In the normal population, CCT ranges between GLAUCOMA AND REFRACTIVE SURGERY
420 and 620 microns. Thicker corneas typically yield
higher IOP readings, and thinner corneas yield lower Steroid induced pressure elevation:
readings when measured by GAT and other devices. • Most frequent cause of glaucoma after RS
Few, if any corneas are perfectly spherical. High • More frequent after superficial procedures (PRK,
levels of astigmatism introduce artifacts when LASEK) to avoid or treat haze.
• After DLK treatment
measured with a large diameter applanation device
• Pressure-induced stromal keratopathy (PISK):
like the GAT or Perkins.
condition similar to DLK but unresponsive to
steroids. Occurs later in the postoperative period.
Responds to IOP-lowering agents.
After LASIK, in a small number of patients, fluid
can accumulate in the flap interface resulting in a
condition similar to DLK, but with a later onset,
usually after the first postoperative week. In such
eyes, elevated IOP drives fluid across the corneal
stroma toward the epithelium. However, before
reaching the epithelial layer, the fluid enters the
interface beneath the LASIK flap.

Figure 49.7: The IC are tonometer by Tiolat,Finland

The ICare fromTiolat is a rebound tonometer,

which combines the advantages of existing
technologies: the tonometer is cell-phone-sized,
lightweight, battery-operated which makes it truly
portable. The manufacturer claims that it is extensively
tested, and the measuring probe touches the eye so
gently that it is barely noticeable. No topical
anesthetic is required. There is no risk of
microbiological contamination, as one-use probes are
Figure 49.8: Fluid accumulated in the interface
used in the instrument.
IOP changes due to the effects of pulse, breathing, As such, IOP is grossly underestimated. This
eye movements, and body position. Because the underestimation of IOP may mask markedly elevated
measurement is made handheld in fractions of a IOP.
 Pitfalls in Advanced Surface Ablations 415
There are several names for this occurrence: Check-list Postoperatively for IOP
• “Interface fluid syndrome”
• Measure IOP early in post-operative period
• “Interface stromal cyst”
(within 1–3 days)
• “PseudoDLK”
• Monitor IOP carefully during steroid therapy
• Keep postoperative steroid therapy brief if
possible
• Document ablation depth and change in CCT in
chart
• Consider a warning label in conspicuous place on
chart: “Caution: IOP Underestimated”
• Monitor angle depth, especially in hyperopic
patients
• Patient education regarding need for life-long
follow-up.

Remember:
Glaucoma is linked to refractive surgery as well
as refractive surgery is linked to glaucoma.

Figure 49.9: Interface fluid syndrome or interface stromal cyst or

pseudoDLK SURGICAL PROCESSES AND PROCEDURES

CHECK-LIST Equipment used in Clinic

Check-list Pre-Operatively for IOP

• IOP (mean of several measures at different times)
• Central corneal thickness
• Baseline optic nerve and/or nerve fiber layer
imaging
• Visual field studies
• Baseline gonioscopy, especially important for
hyperopic patients
• Patient education regarding importance of life-
long follow-up and surveillance for glaucoma.

Check-list Intraoperatively for IOP

Figure 49.10: Amadeus II microkeratome
• Minimize vacuum time (experienced surgeon)
• Record Duration of maximum vacuum The Amadeus II Microkeratome is the first and
• (Consider avoiding LASIK in presence of a only microkeratome with completely customizable
filtration bleb. Suction may be unpredictable or parameters for both LASIK and surface ablation
bleb damage may occur. PRK, LASEK, spectacles, procedures. Featuring computer-controlled intelligent
or contact lens wear may be better options design, the Amadeus II provides surgeons with the
depending on the severity of the glaucoma or safety and confidence of voice-confirmation of flap
nature of the bleb.) parameters and instrument readiness. Experience
416 Mastering Advanced Surface Ablation Techniques
using the epikeratome configuration of the Amadeus dilated. Because clinical research has shown that
II shows that it creates epithelial flaps with highly dilation distorts and decenters the pupil relative to
smooth edges and consistently maintains Bowman’s its natural position during surgery.
membrane integrity. The Amadeus II travels more Moreover, dilation slows recovery and adds to
slowly across the eye. Settings for the epikeratome patient discomfort during surgery.
consist of 1.5 mm/sec for translation speed, 11,000 The VISX S4 laser has been FDA-approved for
rpm for oscillation speed, and 840 mbar Hg for Wavefront-guided LASIK, using its CustomVue
suction. WaveScan technology.

Step by Step Procedure

Pre-and Postoperative Procedures

Before the laser surgery with the VISX S4 laser,

Novesine 0.4% (Oxybuprocain-HCl 4 mg) eye-drops
are applied for topical anesthesia. A lid speculum is
inserted. The eye has to be marked with an optical
zone marker. The diameter of this marker depends
on the pupil diameter of the patient. The epithelium
is then removed mechanically with an Amoil epithelial
scrubber.This Brush should be moisturized with 1 or
maximum 2 drops BSS with room temperature before
being used. Afterwards an epithelium spatula is used
Figure 49.11: VISX S4 laser
immediately to clean any debris from the stromal
The VISX is the laser of choice for patients with surface. The stroma is then ablated using a treatment
thin corneas. It is a leading technology in laser vision diameter of 5.5 to 8.0 mm. If the pupil diameter is
correction – more than 4 million procedures have very large, we rather prefer a treatment diameter of
already been performed on a VISX laser worldwide! up to 8.0 mm. In order to prevent an increase of
3-D Active Infrared Eye Tracking, the only FDA – corneal temperature we have developed a special
approved system that allows the surgeon to track distribution pattern of laser shots.
eye movements in all three dimensions (left and right The complete procedure should be performed
movements of the eye as well as the up and down continuously because the longer the procedure, the
movements naturally occur when you breathe), for higher the risk for the cornea to dehydrate and to
greater control. This tracker was designed specifically get traumatized with the consequence of more haze
to address patient eye movement during surgery: formation. This is also a decisive factor for minimizing
the patient’s eye position is verified and safety the dehydration of the cornea. Following the ablation
checked before every laser pulse and the laser is the corneal treatment zone has to be cooled with –8 °C
repositioned to match eye movements. In this way, chilled BSS which has to be applied 3 to 4 times onto
the tracker assists the surgeon, rather than taking the corneal surface for the duration of 10 seconds
away control during the actual surgery. Seven each. The solution is sucked away by a sponge after
Variable Sized Beams, to give greater flexibility and each cooling procedure. It is most important, that
allow for faster, smoother treatment with precise before the cooling procedure a metal ring or funnel
corneal shaping. No dilation required! Unlike laser is applied to the treatment zone to ensure, that only
platforms used by other vision correction providers, this area is being cooled in order to avoid spill-over
the VISX Star S4 does not require the pupils to be onto the adnexa due to the fact, that if the chilled
 Pitfalls in Advanced Surface Ablations 417
BSS gets in contact with the conjunctiva the patient 4. Do not drive immediately after surgery, distance
would suffer from pain due to coldness of BSS. judgement might be changed and adaptation to
Then we apply one drop of NSAID (Non- this normally takes a week.
Steroidal-Anti-Inflammatory-Drugs) such as Voltaren 5. Sunglasses with proper UV-protection are
(Diclofenac Sodium 0.1%, Ciba Vision). Voltaren is recommended to be used outdoors for protection
an anti-inflammatory drug to reduce pain and the from glare, trauma, and drying of the eyes.
initial inflammatory response. 6. Vigorous excercises, swimming, and contact sports
A bandage contact lens is applied (disposable soft should be avoided for 1 month post-operatively.
contact lens,
1-Day-Acuvue® Johnson and Johnson Vision Primum Non Nocere!
Products, Inc.). With one hand we use a Merocel
sponge to remove the bandage lens from its BIBLIOGRAPHY
packaging. With the other hand we use another 1. Abad JC, An B, Power WJ, et al. A prospective evaluation
sponge to correctly position the lens onto the eye. of alcohol assisted versus mechanical epithelial removal
The aim of this technique is to minimize potential before photorefractive keratectomy. Ophthalmology
sources of infection to the corneal wound by avoiding 1997;104:1566–75.
2. Abad JC, Talamo JH, Vidaurri-Leal J, et al. Dilute ethanol
any contact with the surgeon’s glove and to apply versus mechanical debridement before photorefractive
the lens a traumatically. Since the cornea surface gets keratectomy. J Cataract Refract Surg 1996; 22:1427–33.
flatter with higher myopic corrections, we hold the 3. Stein HA, Stein RM, Price C, et al. Alcohol removal of the
epithelium for excimer laser ablation: outcomes analysis.
opinion, that one should develop bandage lenses
J Cataract Refract Surg 1997;23:1160–63.
especially for refractive surgeries with high oxygen 4. Shah S, Doyle SJ, Chatterjee A, et al. Comparison of 18%
permeability as well as a plainer base curve. ethanol and mechanical debridement for epithelial
After the lens is positioned the lid-speculum has removal before photorefractive keratectomy. J Refract
Surg 1998, 14:S212–S14.
to be removed.
5. Carones F, Fiore T, Brancato R: Mechanical vs. alcohol
Postoperatively all patients should be treated with epithelial removal during photorefractive keratectomy.
Ofloxacin 0.3% eye drops 4 times a day until complete J Refract Surg 1999;15:556–62.
re-epithelialization (usually on the second 6. Kanitkar DK, Camp J, Humble H, et al. Pain after epithelial
removal. Ethanolassisted mechanical vs. transepithelial
postoperative day). During this time you must not excimer laser debridement. J Refract Surg 2000;16:519–
give any therapeutic ointment. After removing the 22.
contact lens, fluorometholone eye drops 0.1% are 7. Gimberle M: LASEK may offer the advantages of both
instilled 3 times a day for 1 month, tapered by 1 drop LASIK and PRK. Ocul Surg News 1999;Mar:28.
8. Lee JB, Seong GJ, Lee JH, et al. Comparison of laser
every month over the next 3 months. epithelial keratomileusis and photorefractive keratectomy
Postoperative management of the patients: we for low to moderate myopia. J Cataract Refract Surg 2001;
emphasize the following outpatient handling: all 27:565–70.
patients can reach us 24 hours a day for the following 9. Scerrati E. Laser in situ keratomileusis vs. laser epithelial
keratomileusis (LASIK vs LASEK). J Refract Surg 2001,
3 days to ensure, that we can treat any unexpected 17(suppl 2):S219–S221.
circumstance such as infiltrates as well as answer all 10. Shah S, Sebai Sarhan AR, Doyle SJ, et al. The epithelial
questions of the patients during this time. flap for photorefractive keratectomy. Br J Opthalmol 2001,
85:393–6.
Additional Post-Operative Instructions 11. Azar DT, Ang RT, Lee JB, et al. Laser subepithelial
keratomileusis: electron microscopy and visual outcomes
1. it is recommended that eye make-up is avoided 1 of photorefractive keratectomy. Curr Opin Ophthalmol
week before surgery and one week after surgery. 2001;12:323–8.
2. It is important to rest the eyes as much as possible 12. Rouveyha RM, Chuang AZ, Yee RW: LASEK: outcomes
in high myopia. Invest Ophthalmol Vis Sci 2001;42:S599.
during the first 24 hours postoperatively. 13. Lohmann CP, Von Mohrenfelds W, Gabler B, et al. LASEK:
3. Try to avoid rubbing or squeezing the eyes for 1 a new surgical procedure to treat myopia. Invest
week postoperatively. Ophthalmol Vis Sci 2001;42:S599.
418 Mastering Advanced Surface Ablation Techniques
14. Kornilovski IM. Clinical results after subepithelial 19. Chen CC, Chang JH, Lee JB, et al. Human corneal
photorefractive keratectomy (LASEK). J Refract Surg epithelial cell viability and morphology after dilute alcohol
2001;17(suppl):S222–S23. exposure. Invest Ophthalmol Vis Sci 2002;43:2593–2602.
15. Claringbold VT. Laser-assisted subepithelial keratectomy 20. Gabler B, Winkler von Mohrenfelds C, Dreiss AK, et al.
for the correction of myopia. J Cataract Refract Surg 2002; Vitality of epithelial cells after alcohol exposure during
28:18–22. laser-assisted subepithelial keratectomy flap preparation.
J Cataract Refract Surg 2002;28:1841–6.
16. Shahinian L. Laser-assisted subepithelial keratectomy for
21. Browning AC, Shah S, Dua HS, et al. Alcohol debridement
low to high myopia and astigmatism. J Cataract Refract
of the corneal epithelium in PRK and LASEK: an electron
Surg 2002;28:1334–42.
microscopic study. Invest Ophthalmol Vis Sci 2003; 44:510-13.
17. Anderson NJ, Beran RF, Schneider TL: Epi-LASEK for the 22. Dreiss AK, Winkler Von Mohrenfels C, Gabler B, et al.:
correction of myopia and myopic astigmatism. J Cataract Laser epithelial keratomileusis (LASEK): histological
Refract Surg 2002;28:1343–47. investigation for vitality of corneal epithelial cells after alcohol
18. Litwak S, Zadok D, Garcia-de Quevedo V, et al.: Laser- exposure. Klin Monatsbl Augenheilkd 2002; 219:365–9.
assisted subepithelial keratectomy versus photorefractive 23. Pallikaris JG, Naoumidi II, Kalyvianaki MI, et al. Epi-
keratectomy for the correction of myopia. A prospective LASIK: comparative histological evaluation of mechanical
comparative study. J Cataract Refract Surg 2002; and alcohol-assisted epithelial separation. J Cataract
28:1330–3. Refract Surg 2003, (in press).
436 Mastering Advanced Surface Ablation Techniques

CHAPTER

51 Advances in Epi-LASIK
and LASEK

Bojan Pajic (Switzerland)

INTRODUCTION palpebral fissure, ecurrent erosio syndrome, dry eyes

and for patients who are predisposed to trauma, such
Photorefractive keratectomy (PRK) was the most
as military personnel and athletes.
commonly performed surgical procedure until the
introduction of laser in situ keratomileusis (LASIK)
METHODS
in the mid nineties. While PRK is safe and effective,
the risk of corneal haze, especially in high myopia, is Patients
significant. Postoperative pain and slow visual
A total of 140 eyes of 70 patients were matched. In
rehabilitation are other limiting factors in PRK. LASIK
has minimal postoperative pain, faster visual recovery, the right eye a LASEK and in the left eye a PRK
less regression, and no haze even in high myopia. treatment was done. All patients were 27 years of
However, cations (free cap, incomplete flap, button- age and had between –0.5 and –6.0D SE of myopia
holes and lost flaps), interface related complications with up to –4.0D of astigmatism.
(epithelial ingrowth, deep lamellar keratitis and
interface debris), flap-related corneal biomechanical Examination
instability and iatrogenic keratectasia have been Preoperative evaluation included uncorrected visual
reported1-3. Laser epithelial keratomileusis (LASEK) acuity (UCVA), best spectacle-corrected visual acuity
and Epi-LASIK may combine the advantages of PRK (BSCVA), manifest and cycloplegic refractions, ocular
and LASIK while avoiding the disadvantages of both. dominance, slit-lamp examination, keratometry,
It avoids all of the flap-related complications and
tonometry, pachymetry, computerized videokerato-
reduces the risk of keratectasia associated with
graphy (Orbscan II), mesopic pupil size measurement
LASIK. In addition, it has relatively faster recovery
using a pupillometer, and dilated fundus examination.
periods with slightly less pain and haze than PRK4.
LASEK and epi-LASIK may be considered in patients
Surgery Procedures
with low to moderate myopia and myopic
astigmatism, thin corneas with no signs of LASEK and epi-LASIK surface are techniques in
keratoconus, extrem keratometric values (such as refractive surgery of surface ablation, it is said, that
steep or flat corneas), deep set eyes and small the epithelium is separated from the cornea.
 Advances in Epi-LASIK and LASEK 437
Surgery Procedure LASEK
After topical anesthesia and lid speculum application,
a semi sharp circular well is used to administrate 20%
alcohol is used for 25 to 35 seconds on corneal surface.
Prior to alcohol exposure, positioning marks were
used to mark the corneal surface. The margins of the
delineated area were freed using a hockey knife and
leaving up to three clock-hours of intact margins for
hinge. The loosened epithelium was then peeled back
using a Merocel sponge. After standard laser ablation,
the epithelial sheet was gently repositioned using
intermittent irrigation. The epithelium was carefully
realigned using the preplaced positioning marks and Figure 51.2: Porcin eye
allowed to dry for three to five minutes. A
100 μm extra microns available for performing the
combination of antibiotics and steroids eyedrops was
correction, more versatile for thin. The disadvantage are
applied, followed by placing a bandage contact lens
that in average patients have more pain during the first
to reduce the mechanical friction by the eyelid and
5 days post OP, it is more difficult to handle a surface
to reduce postoperative pain.
ablation flap than a Lasik Flap and the visual recovery
Epi-LASIK Surgery Procedure need more time. Surface ablation does not substitute the
LASIK. It is a complementary method to LASIK.
The separation of epithelium in the Epi-LASIK Epi-LASIK is similar to ‘standard’ LASEK, except
technique is done mechanically with a keratome. The no alcohol is applied. Epi-flap is made with a
epithelium is separated from the cornea just over the keratome-like equipment. Cleavage of epithelial basal
Bowman’s Layer. The flap thickness is given from cells from basement membrane is performed along
the thickness of the patient’s epithelium, not from plane of least resistance (Figure 51.3). Epi-tome is
the Blade Holder. The human epithelium thickness similar to microkeratome, but blunt separator is used
is about 40–50 μm (Figure 51.1). The pig epithelium instead of a sharp blade. The forward speed is more
is about 50–70 μm (Figure 51.2). slow (Figure 51.4). A suction unit is proposed of 8.5
mm for a k-reading over 45 D, 9.0 mm for a k-reading
between 42 and 45 D, and 9.5 mm for a k-reading
below 42 D (Figure 51.5).

Figure 51.1: Human eye

Comparison of the Different Techniques

The advantages of the LASEK/Epi-LASIK technique
comparison to LASIK is no flap related complications, Figure 51.3: Basement membrane with least resistance
438 Mastering Advanced Surface Ablation Techniques

Figure 51.4: Epi-tome: Blunt separator

Figure 51.5: Suction unit choice regarding K-reading for surface ablation
 Advances in Epi-LASIK and LASEK 439
In the study epithelial separation was done with RESULTS
Amadeus II Epikeratome (AMO) (Figure 51.6).
The mean age was 35 years (with a range of 21 to 69
years). 35 patients (50%) were male and 35 (50%) were
female. The differences of preoperative visual and
refractive values between LASEK and PRK were not
statistically significant for mean spheres, cylinders,
spherical equivalents, and BSCVA. The mean
preoperative sphere was –1.81 ± 0.83 D for LASEK
and –1.92 ± 1.18 D for PRK (P = 0.27). The mean
preoperative cylinder was –0.55 ± 0.71 D for LASEK
and –0.92 ± 0.79 D for PRK (P = 0.39). The mean
follow-up period was for all patients 6 months.

Efficiency
Figure 51.6: Amadeus II epikeratome (AMO) 93% of patients had an UCVA of 0.5 or better at one
month, where 73% had 0.8 or better. At three months
Data Analyisis
respectively at six months, 90% respectively 100% of
Statistical analysis was performed using SPSS 14.0 eyes examined had UCVA of 0.8 or better in the
software. Paired-samples t-tests, independent samples LASEK eyes (Figure 51.7). 93% of patients had an
t-tests, and Chi-squares were applied. A P-value of UCVA of 0.5 or better at one month, where 86% had
less than 0.05 was considered statistically significant. 0.8 or better. At three months respectively at six

Figure 51.7: UCVA versus percentage efficacy in LASEK eyes

440 Mastering Advanced Surface Ablation Techniques
months, 82% respectively 100% of eyes examined had DISCUSSION
UCVA of 1.0 or better in the PRK eyes (Figure 51.8).
Several reports have investigated the safety, efficacy,
Predictability predictability, and stability of LASEK. Azar and
associates found that all patients had an UCVA of
For all LASEK and PRK eyes, the mean postoperative 0.5 or better at one week, where 64% had 0.8 or
spherical equivalent was 0.04 ± 0.28 D. for LASEK better. At one months, 92% of eyes examined had
and –0.13 ± 0.5 D for PRK. 93% respectively 100% of UCVA of 0.8 or better5. Taneri et al. reported that
LASEK-treated eyes were within ± 0.50 D at one approximately 95% of the eyes were ±1.0 D of
months respectively three months of the intended emmetropia after four weeks. At one year not loss
correction (Figure 51.9) compared with 94% of BSCV was present6. Partal et al. Found that 66%
respectively 93% for PRK (Figure 51.10). and 98% of the eyes had postoperative UCVA of 1.0
or better and 0.5 or better, respectively7. Claringbold
Safety
found that the UCVA was 0.5 or better in 83.8% of
At six months the safety index which is the ratio of eyes at day 4. At two weeks, all eyes were completely
mean postoperative BSCVA to mean preoperative epithelialized, and the UCVA was 0.5 or better in
BSCVA was 0.98 for LASEK and 1.02 for PRK. 91.8% of the eyes8. In a large series, Anderson et al.
Relevant haze was seen in the LASEK eyes in 2 cases found that patients with a preoperative SE between
and in the PRK eyes in 8 cases, what is statistically 0 and 6.0D had better UCVA at three months than
significant. those with a preoperative SE between 6.1 and 12.0D.

Figure 51.8: UCVA versus percentage efficacy in PRK eyes

 Advances in Epi-LASIK and LASEK 441

Figure 51.9: Refractive outcome—percentage within attempted in LASEK eyes

Figure 51.10: Refractive outcome—percentage within attempted in PRK eyes

442 Mastering Advanced Surface Ablation Techniques
Clinically significant haze was observed in 1.6% of of the intercellular spaces, and extensive
eyes9. In our study we observed, where one eye was discontinuities in the basement membrane, which was
treated with PRK and the other with LASEK excised at the level of the lamina lucida. Mechanical
technique, that the re-epithelialisation time was separation did not affect the normal cell morphology
significant longer in the LASEK eye than in the PRK of the excised epithelial disks. Transmission electron
eye. Further there was more pain in the LASEK eye microscopy of the specimens proved the manual
compared with PRK. The reason could be in the technique is less invasive to epithelial integrity than
alteration of alcohol with the conjunctiva and in the LASEK using either alcohol concentration15. Recovery
induction of apoptosis of epithelial cells by alcohol. of corneal sensitivity began 1 month after LASEK
The incidence and degree of corneal haze and was completed by 3 months in eyes treated for
formation were compared following laser low-moderate myopia and at 6 months in eyes with
subepithelial keratomileusis (LASEK) and epithelial high myopia. The depth of ablation during surgery
laser in situ keratomileusis (epi-LASIK), and affected the recovery of corneal sensitivity16. The
examined its correlation with tear film transforming greater decrease in the number of subbasal nerve
growth factor-beta1 (TGF-beta1) levels. Less corneal fibers in the LASIK group compared with the LASEK
haze was noted after epi-LASIK than LASEK. A group may relate to the greater decrease in corneal
positive correlation between corneal haze and tear sensitivity. The pattern of corneal nerve regeneration
fluid TGF-beta1 levels on the first postoperative day and the recovery of corneal sensation after LASEK
suggests a possible mechanism for the observed did not differ greatly from that after photorefractive
difference10. Prophylactic use of intraoperative MMC keratectomy in previous studies17. Epi-LASIK-treated
in LASEK significantly decreases haze incidence11. eyes had faster rehabilitation of corneal sensitivity
Epi-LASIK is a safe and efficient method to correct and tear function than LASIK-treated eyes 18 .
myopia with the advantage that it has only mild Histological examination of specimens in four eyes
symptoms and mild haze12. At higher attempted showed that 24 hours after mechanical separation the
corrections, LASEK-treated eyes showed less epithelial cells’ morphology was close to normal19.
keratocyte apoptosis, myofibroblast transformation, Epi-LASEK appeared to be a safe and effective
and up-regulation in the synthesis of chondroitin treatment for the correction of myopia and myopic
sulfate than PRK-treated eyes. These differences may astigmatism. Most patients achieved postoperative
account for better visual acuities and less stromal haze visual acuities comparable to those with laser in situ
in higher attempted corrections in LASEK-treated keratomileusis and photorefractive keratectomy.
eyes 13 . Reduced subepithelial stromal tissue There was a low incidence of haze and pain
deposition was observed in LASEK-treated eyes postoperatively20. Keratocyte density in the anterior
compared with PRK-treated eyes. Postoperative retroablation area recovers during the first year after
preservation of the epithelial basement membrane LASEK for the correction of myopia, but does not go
and survival of epithelial cells in LASEK and possibly back to preoperative values 21 . Laser in situ
in epithelial laser in situ keratomileusis may keratomileusis and LASEK did not significantly affect
contribute to this phenomenon. An advantage of the RNFL thickness parameters postoperatively22.
LASEK over PRK is the reduction of postoperative
ACKNOWLEDGMENTS
haze14. The basal epithelial cells of the separated
epithelial disks showed minimal trauma and edema. I thank for distinct support of Dr. Gerhard Youssefi,
Specimens obtained using 15 and 20% alcohol Anton Hilger (Technolas) and Dr. Anton Wirthlin,
concentrations showed formation of cytoplasmic Fritz Meyer (Ziemer Ophthalmology) for personal
fragments of the basal epithelial cells, enlargement and technical advice.
 Advances in Epi-LASIK and LASEK 443
REFERENCES 12. Dai J, Chu R, Zhou X, Chen C, Qu X, Wang X. One-year
outcomes of epi-LASIK for myopia. J Refract Surg
1. Kohnen T. Iatrogenic keratectasia: current knowledge, 2006;22(6):589-95.
current measurements. J Cataract Refract Surg 2002;28: 13. Esquenazi S, He J, Bazan NG, Bazan HE. Comparison of
2065-6. corneal wound-healing response in photorefractive
2. Teichmann KD. Bilateral keratectasia after laser in situ keratectomy and laser-assisted subepithelial keratectomy.
keratomileusis. J Cataract Refract Surg 2004;30:2257-8. J Cataract Refract Surg 2005;31(8):1632-9.
3. Lifshitz T, Levy J, Klemperer I, Levinger S. Late bilaterale 14. Javier JA, Lee JB, Oliveira HB, Chang JH, Azar DT.
Basement membrane and collagen deposition after laser
keratectasia after LASIK in low myopic patient. J Cataract
subepithelial keratomileusis and photorefractive
Refract Surg 2005;21:494-6.
keratectomy in the leghorn chick eye. Arch Ophthalmol
4. Lee JB, Seong GJ, Lee JH, et al. Comparison of laser
2006;124(5):703-9.
epithelial keratomileusis and photorefractive keratectomy 15. Pallikaris IG, Naoumidi II, Kalyvianaki MI, Katsanevaki
for low to moderate myopia. J Cataract Refract Surg 2001; VJ. Epi-LASIK: comparative histological evaluation of
27:565-70. mechanical and alcohol-assisted epithelial separation. J
5. Azar DT, Ang RT, Lee BJ, et al. Laser subepithelial Cataract Refract Surg 2003;29(8):1496-501.
keratomileusis : electron microscopy and visual outcomes 16. Wu Y, Chu RY, Zhou XT, Dai JH, Qu XM, Rao S, Lam D.
of flap photorefractive keratectomy. Curr Opin Recovery of corneal sensitivity after laser-assisted
Ophthalmol 2001;12:323-8. subepithelial keratectomy. J Cataract Refract Surg
6. Taneri S, Feit R, Azar DT. Safety, efficacy and stability 2006;32(5):785-8.
indices of LASEK correction in moderate myopia and 17. Lee SJ, Kim JK, Seo KY, Kim EK, Lee HK. Comparison of
astigmatism. J Cataract Refract Surg 2004;30:2130-7. corneal nerve regeneration and sensitivity between LASIK
7. Partal AE Rojas MC, Manche EE. Analysis of the efficacy, and laser epithelial keratomileusis (LASEK). Am J
predictability,and safety of LASEK for myopia and Ophthalmol 2006;141(6):1009-15.
myopic astigmatism using the Technolase 217 excimer 18. Kalyvianaki MI, Katsanevaki VJ, Kavroulaki DS, Kounis
laser. J Cataract Refract Surg 2004;30:2138-44. GA, Detorakis ET, Pallikaris IG. Comparison of corneal
8. Claringbold TV II. Laser-assisted subepithelial sensitivity and tear function following Epi-LASIK or laser
in situ keratomileusis for myopia. Am J Ophthalmol
keratectomy for the correction of myopia. J Cataract
2006;142(4):669-71.
Refract Surg 2002;28:18-22.
19. Katsanevaki VJ, Naoumidi II, Kalyvianaki MI, Pallikaris
9. Anderson NJ, Beran RF, Schneider TL. Epi-LASIK for the
G. Epi-LASIK: histological findings of separated epithelial
correction of myopia and myopic astigmatism. J Cataract sheets 24 hours after treatment. J Refract Surg
Refract Surg 2002;28:1343-7. 2006;22(2):151-4.
10. Long Q, Chu R, Zhou X, Dai J, Chen C, Rao SK, Lam DS. 20. Anderson NJ, Beran RF, Schneider TL. Epi-LASEK for the
Correlation between TGF-beta1 in tears and corneal haze correction of myopia and myopic astigmatism. J Cataract
following LASEK and epi-LASIK. J Refract Surg. Refract Surg 2002;28(8):1343-7.
2006;22(7):708-12. 21. Herrmann WA, Muecke M, Koller M, Gabel VP, Lohmann
11. Argento C, Cosentino MJ, Ganly M. Comparison of laser CP. Keratocyte density in the retroablation area after
epithelial keratomileusis with and without the use of LASEK for the correction of myopia. Graefes Arch Clin
mitomycin C. J Refract Surg 2006;22(8):782-6. Exp Ophthalmol, 2006.
444 Mastering Advanced Surface Ablation Techniques

CHAPTER

52 One-shot Epithelium-Rhexis:
Personal Technique

Roberto Pinelli (Italy)

INTRODUCTION Alcoholic solution is another technique which is

able to separate the epithelium from the Bowman’ s
The surface ablation technique through excimer laser
membrane and consequently to remove it more easily.
is a procedure in use since long time. Once that the epithelium is treated with the alcoholic
In the last 25 years this technique has had an solution, the problem is how to remove it: again it is
evolution and many surgeons in the world gave their possible to remove it with more soft instruments,
contribute to develop different sub-techniques of not necessarily surgical.
surface ablation. Epi-LASIK and LASEK1,2 are two techniques able
The most important issue is to remove regularly to remove the epithelium and then, after the ablation,
the epithelium and obtain a smooth surface in order to put the epithelium again in its natural position.
to perform excimer laser in a safe and effective way.
Description
Questions
In our experience at Istituto Laser Microchirurgia
1. How to remove the epithelium in order to obtain Oculare, Brescia (Italy), surface ablation is around
a regular surface and perform the excimer laser 10% of the procedure, being the 90% of our corneal
and obtain a pure ablation without central islands procedure the thin-flap LASIK.
or irregularity? Our favorite approach to surface ablation, called
2. How to manage the postoperative phase? “Epithelium-rhexis ASA” (Advanced Surface
3. Is the postoperative pain related to the removal Ablation) is to remove the epithelium with a
of the epithelium? maneuver that we call “epithelium-rhexis”. This
4. The re-epithelization depends on the technique? technique is very similar to the Capsulorhexis
At the beginning of this procedure, the most Technique in the cataract surgery.
common technique was to remove the epithelium As you can see in the images we usually use a dry
mechanically with surgical instruments: different merocel after 25 seconds application of alcohol
spatulas to remove the epithelium were designed by solution on the epithelium (Figure 52.1) and we detach
a lot of surgeons but the problem of the technique is epithelium with one circular induced maneuver
the timing of this maneuver and the elegance of this (Figure 52.2) in order to have only one single
delicate part of the surgery. approach to the epithelium and less trauma.
 One-shot Epithelium-Rhexis: Personal Technique 445

Figure 52.1: The metal ring surgical instrument is Figure 52.3: The epithelium-rhexis is performed with merocell in an
applied on the cornea anti- clockwise movement

An interesting question can be: why we remove

the epithelium at 8 mm optical zone and we do not
go to the limbus?
In our experience we compared one eye ( 8 mm
optical zone disepithelization treated) with another
(10 mm optical zone of disepithelization) and as far
as transparency of the cornea, visual acuity post laser
excimer and absence of haze is concerned, we can
observe that the refractive result was in the two eyes
very similar.
The eye treated with 8 mm optical zone
epithelium-rhexis was significantly better as far as
less pain for the patient and more fast re-
Figure 52.2: The alcoholic solution is administered on the cornea epithelization: 3 days only compared to the 5 days of
with a metal ring surgical instrument the collateral eye with the disepithelization at 10
If we are able to remove the epithelium circularly mm optical zone.
in one maneuver we will have not only less problems We think that touching the cornea with the merocel
but even an optical zone around 8 mm ready to the and not with a surgical instruments we cause less
ablation with a perfect smooth surface. trauma to the ephithelium: less surgery in the classic
The epithelium detachment from Bowman’s meaning of the word is giving to the eye less
membrane is very crucial in this technique; after the microtraumas and consequently less complain as far
alcohol solution treatment the epithelium is more soft as pain is concerned.
and once broken the epithelium membrane with the The procedure to epithelium-rhexis and the surface
merocel (Figure 52.3) we can choose a clockwise ablation is in our Institute always bilateral and in
movement or an anticlockwise movement (it depends topical anesthesia (Figure 52.4).
on the surgeon’s attitude), and in one circular shot To perform a correct epithelium-rhexis very
we can remove the epithelium at 8 mm optical zone. important are:
As you can see by the Figure 45.s and in the CD ROM • the quality of the alcoholic solution,3
the maneuver is relatively simply and clean. • the timing of preparing the solution;
446 Mastering Advanced Surface Ablation Techniques

The patient is prepared before with three drops

of Propacaine and three drops of Tetracaine in each
eye at the following intervals of time:
• 10 minutes before surgery
• 5 minutes before surgery
• Some seconds before the surgery.
The alcoholic solution is administered on the
cornea with a metal ring (E. Janach srl, Como – Italy),
a surgical instrument, actually very easy to find in
the surgical instruments market
After we drape the eye lashes (the upper and not
the lower eyelashes).
After the classical bilateral ephithelium-rhexis ASA
Figure 52.4: “One-shot” epithelium rhexis is totally performed (in the CD-rom you can see all the maneuvers) we
• the concentration of alcohol in the solution (with put in the eye some drops of Oftacilox (SA Alcon-
BSS - balanced salt solution, we use 20% solution Couvreur NV- 2870 Puurs - Belgium) and then the
of alcohol). soft contact lens (Figure 52.5).
 One-shot Epithelium-Rhexis: Personal Technique 447
hours, this technique can be easily performed by every
refractive surgeon.
It is easy, simply and well accepted by the patients.
In the last five years of use of this technique no
haze was detected in our patient, no problems of re-
epithelization and no central islands were observed
on the surface of the cornea and the new epithelium
was extremely regular. Also the satisfaction
questionnaire of the patient reported a high
satisfaction level very close to LASIK procedure.
So the patients are accepting this technique
of Advance in Surface Ablation with great
confidence.
We started to perform this technique five years
Figure 52.5: After the Laser ablation, a contact lens is applied
ago because the classical mechanical epithelial removal
After the excimer laser ablation, a soft contact lens was not well accepted by the patients although the
is enough to protect the ablation, and contact lenses visual acuity post operative was extremely positive:
after a bilateral treatment are removed usually on the satisfaction questionnaire of this patient by the
day 4th postoperativly (Figure 52.6). classical surface ablation without epithelium-rhexis
Second eye is performed immediately after the was very different from the satisfaction questionnaire
first eye just operated. of LASIK procedure; now the satisfaction
Finally, we check the both operated eyes at the questionnaires of LASIK procedure and of Advanced
slit lamp in the consultation room in order to be sure in Surface Ablation Technique through epithelium-
that the contact lenses are in the properly position. rhexis are very close.
When the patient will come back to the Institute, In our Institute the popularity of this surface
on day 4th post-operatively, we remove the two technique is very high and also the patient’ s reaction
contact lenses, and we check the complete re- to it: when we decide for this technique, generally
epithelization of the cornea. due to the pachymetry < 500 microns (which is
After a learning course, which can be different the limit of our thin flap LASIK and our Advances
from surgeon to surgeon, usually not more than 10 in surface Ablation Technique) results are very
positive.
Patient selection of one-shot-epithelium-rhexis
compare to the LASIK thin flap technique is
substantially focused on the visual defect and the
pachymetry:
• if the pachymetry is < 500 microns we decide for
Advanced in Surface Ablation Technique;
• if the visual defect is from - 0.5 to -6D of myopia,
with or without astigmatism and from + 0.5 to + 3
of hyperopia, with or without astigmatism, as far
as myopic population, and we have > 500 microns
we switch to thin flap LASIK Technique;
• in hyperopia also, when we have central
pachymetry of > 500 microns, we switch to thin
Figure 52.6: Speculum removed. At this point the surgery is over flap LASIK Technique.
448 Mastering Advanced Surface Ablation Techniques
• Phachik IOL’s also, and their implantations, are In the CD-rom you can see all the maneuver of
covering the population ACD with higher visual this technique, from the beginning of the surgery to
defects in presence of an anterior chamber the end and in the box you will see a summary of
(minimum 3 mm). the most important phases in order to perform a
correct epithelium-rhexis in one shot and in order to
CONCLUSION obtain a perfect advanced disablation.

We will see in the next years what will be the destiny REFERENCES
of the surface ablation being thinner and thinner the
1. Pallikaris IG, Katsanevaki VJ, Kalyvianaki MI, Naoumidi
flap of the LASIK and growing the implantation of II: Advances in subepithelial excimer refractive surgery
Phachik IOL. techniques: Epi–LASIK. Curr Opin Ophthalmol
2003;14:207-12.
But we think that the surface ablation with soft
2. Hoang-Xuan T, Arnaud D, Souissi K, Cornu S. Epi-LASIK,
and nice ephithelium-rhexis ASA technique is a novel surface photoablation technique. J Fr Ophalmol
reducing the pain and giving to the eyes of our 2007;30:535-8.
patients brilliant and visual acuity and the regular 3. Sharma N, Sony P, Prakash G, Jhanji V, Sinha R, Titiyal JS,
Vaypayee RB. Influence of epi-LASIK and alcohol-assisted
absence of hazes still remains an issue and an option LASEK on retinal nerve fiber layer thickness. J Refract
for our patients. Surg 2007;23:431-2.
 CHAPTER
Transepithelial Cross-linking
53 for the Treatment of
Keratoconus

Roberto Pinelli, E Milani (Italy)

INTRODUCTION The cause of keratoconus is unknown, but it seems

that enzymatic changes in corneal epithelium, such
Keratoconus is a non-inflammatory cone-like ecstasia
as a decrease of the levels of the inhibitors of
of the cornea, which is usually bilateral and progress
proteolytic ezymes and an increase of the lysosomal
over time, with consequent central or paracentral
enzymes can be involved in the cornea degradation.
thinning of the stroma and irregular astigmatism.
At the beginning, glasses are sufficient to correct
myopia and astigmatism still regular or slightly
irregular; successively, in cases of high astigmatism,
it becomes necessary to apply hard contact lenses.
Epikeratoplasty is efficacious in patients which do
not endure contact lenses and which do not show a
significant central corneal opacity, but, due to its
visual outcomes not perfect, it was dropped.
Intracorneal rings also can be an option,2 but all
these described techniques unfortunately only correct
refractive errors and do not treat the cause underlying
the corneal ecstasia and, therefore, they do not permit
to stop the progression of keratoconus.
In 1996 3 , some theoretical studies started
investigating more deeply the underlying causes of
keratoconus and the possible parasurgical techniques
Figure 53.1: Keratoconus
to stop its progression. In all patients affected by
The relevance of keratoconus in the general keratoconus a reduced degree of cross-links in the
population seems to be relatively high, with corneal collagen fibers has been observed; that is,
approximately 1 in 2000,1 even if the diffusion of new the aim of those studies was firstly to determine how
diagnostic means will permit to find prevalence rates to increase those crosslinks to obtain an improved
certainly greater. In nearly all cases both eyes are mechanical stability of the cornea and increase the
affected, at least from a topographic point of view. resistance against enzymatic degradation.
450 Mastering Advanced Surface Ablation Techniques
CORNEAL COLLAGEN NETWORKS Cheratansulphate type I is the most important
mucopolysaccaride present in corneal stroma: it plays
Collagen is a structural protein organized in fibers.
an important role for the orientation of collagen
Those fibers are responsible of limiting the tissue
mashes and lamellae (corneal clarity, tensile strenght)
deformations and preventing mechanical brakes. The
and for corneal hydration (corneal edema).
collagen fibers are chemically stable and have high
mechanical properties. Inside the connective tissue,
PHOTOCHEMICAL CROSS-LINKING
fibroblasts synthetize tropocollagen molecules, the
base blocks of collagen fibers. Those molecules have There are many different possibilities of crosslinking:4
a typical weight of 300 kDa, a length of 280 nm with • Lysyl oxidase (LOX) crosslinks collagen
an average diameter of 1.5 nm. The molecule is enzymatically
composed by 3 helicoidal chains (alpha-chains) • Transglutaminase (12h, pH=3)
interlaced each other like a rope (Figure 53.2) • Sugar aldehydes (diabetes - Advanced Glycation
Endproducts AGEs)
• Chemical crosslinking (glutaraldehyde,
formaldehyde, DPPA)
• Photochemical crosslinking (UV, ionizating
radiation)
The interaction between organic tissues and
radiation depends on the type of radiation used. The
ionizing radiation has enough energy to turn out
electrons from the atoms of the tissues. Other types
of radiation, i.e. UV radiation, have not enough
energy to turn out electrons but to make them jump
to higher energy levels (exciting radiation).
In the human biologic tissues, water molecule is
present at a rate of 70 to 90% so it is clearly the main
target of radiation. During the water radiolysis
process, the energy applied to water molecules
ionizes them ad generate free radicals molecules. Free
radicals are continuously produced in tissues and
quickly inactivated by chemical or enzymatic
Figure 53.2: Collagen triple helicoidal chain transformation.
The factors of stabilization of those collagen In the eye, ascorbic acid absorbs UV radiation (at
molecules are related to the interactions between the cornea, lens and vitreous body districts); it is a
3 helics and are due to Hydrogen links, Ionic links cofactor of several enzymes, the best known of which
and intra-chain reticulations (cross-links). are prlyne hydroxylase and lysine hydroxylase,
The stroma, composed mainly by collagen enymes involved in byosinthesis of collagen. In
lamellae, gives to cornea 90% of its thickness. vitreous body, after cataract surgery (absence of
Between the lamellae keratocites can proliferate, glutathione), ascorbic acid (in ascorbate form)
migrate and turn into their active state. Integrity of absorbs UV not stopped by lens, resulting in the
corneal epithelium for the switch of keratocites formation of free radicals, disaggregation of
(resting cells) in fibroblasts (active cell) is very hyaluronic acid and increase in cross-linking of
important. collagen fiber networks.
 Transepithelial Cross-linking for the Treatment of Keratoconus 451
RIBOFLAVIN-UVA TREATMENT

A photo sensitizer is a substance which is activated

by the absorption of light at a given wavelength and
which can induce free radical reactions in its activate
form. This substance can amplify light radiation
effects on biologic tissues.
The basic mechanism of the photochemical
treatment of keratoconus is to use Riboflavin as a photo
sensitizer and apply on it UV irradiation at a
determined wavelength to induce free radicals
reactions and increase this way the cross-links in the
collagen fibers. Riboflavin has a high UV absorption
between 360 and 450 nm; due its additional shielding
all structures behind the corneal stroma, including
corneal endothelium, anterior chamber, iris, lens and
retina, are exposed to a residual UV radiant exposure
less than 1J/cm2 (in accordance with safety guidelines). Figure 53.4: Photochemical induction of cross-links
The UV source is typically a group of 3 to 5 Light
Emitting Diodes producing a radiation of 370 nm
wavelength and 3 mW/cm2 intensity (Figure 53.3). damage. Keratocytes showed (in both laboratory and
clinical studies in epithelium-removed eyes) cells
death up to a 350 μm depth. After 6 months the area
is repopulated by keratocites which, differently from
corneal endothelium, can reproduce. To preserve the
endothelium a minimum corneal thickness of 400 nm
should be assured.
The news in this treatment is represented by the
possibility of realizing cross-linking keeping the
epithelium unaltered. This natural barrier protect the
Figure 53.3: UVA source (Courtesy of Peschke GmbH) cornea but it is not an impermeable stratus: it is an
osmotic membrane through which the riboflavin can
The cross-linking effect is obtained in 3 steps penetrate to the cornea. Of course, the riboflavin itself
(Figure 53.4): can’t penetrate easily so the question is, at this stage,
about the real effectiveness of the treatment,
CORNEAL EPITHELIUM
compared with the “official” one. If we combine the
The widespread technique of cross-linking is based riboflavin drops with a tense-active substance, we
on a central corneal abrasion (with a diameter of can have a more efficient penetration to the cornea.
8 mm). This abrasion is made because the epithelium This substance act as a vector for riboflavin, with a
is believed to be a barrier to the correct diffusion of double effect: reaching the cornea and filling the
riboflavin so a possible factor of decreased epithelium, contributing so far to its strengthening
effectiveness of the treatment. (Figure 53.5).
What has been observed during the different The advantages of this particular technique is that
studies 5,6 is that free radicals mediated by the all the macroscopic side effects related to the
riboflavin irradiated with UV light can create cell epithelium-removal technique are not present: no
452 Mastering Advanced Surface Ablation Techniques
rigidity of the corneal epithelium, thus a decreased
instability in visual acuity of the patient.
The real question is about the effectiveness of the
treatment, as the safety issues are not a worry of this
technique: keeping the epithelium unaltered means
reducing most of the side effects of the treatment
(included the death rate of keratocites and the
number of endothelial cells). We continue our studies
in this way because we believe that the epithelium
removal is something that could be avoided in the
treatment and transepithelial technique will become
the standard in Crosslinking treatments.

REFERENCES
Figure 53.5: Patient eye under C3-R treatment
1. Rabinowitz YS. Keratoconus - Surv Ophthalmol, 1998.
pain, no stromal edema (due to the abrasion) and, 2. Colin J et al. Correcting keratoconus with intracorneal
more important, the possibility to treat both eyes in rings, JCRS, 2000.
the same session (85% of patients has bilateral 3. Seiler T, Spoerl E. et al. Conservative therapy of
keratoconus by enhancement of collagen cross-links, 1996.
keratoconus, so the treatment is in most cases 4. Spoerl E. Physical background of the riboflavin/UV
necessary in both eyes). crosslinking of the cornea. World Vision Surgery
Even if we assume that the riboflavin cannot Symposium, 2007.
penetrate efficiently the epithelium, we think that as 5. Wollensak, Spoerl, et al. Keratocyte apoptosis after collagen
cross-linking using riboflavin/UVA treatment, 2004.
the photo sensitizer is distributed homogeneously 6. Spoerl E, Seiler T et al. Safety of UVA-Riboflavin Cross-
on the treated eye, we can at least obtain an increased Linking of the Cornea. Cornea, 2007.
 CHAPTER cTEN™ - Custom

54 Transepithelial “No-touch,
One-step, All-laser” Refractive
and Therapeutic Ablations with
the IVIS™ Suite
Carlo Francesco Lovisolo, Charles WM Stewart (Italy)

INTRODUCTION pupil. The ultimate design of the surgical profile is

based upon a synthesis of corneal shape, pupil
After more than a decade of attempts to identify the
dimensions, and refractive data.
optimal strategy to perform customized excimer laser
treatments on the basis of corneal anterior surface Precisio™ - High Definition Corneal and Anterior
elevation data with different technological means1-13, Chamber Tomography
a new generation of ophthalmic surgical products first
became commercially available in Europe in the Real, repeatable measurements of corneal shape
spring of 2006: a single platform for both custom based upon corneal elevation, is fundamental to the
refractive and custom therapeutic surgery14. The iVIS design of a new, postoperative ideal aconic surface.
Suite is the first system designed, engineered and Based upon the Scheimpflug principle (Figure 54.1),
manufactured for the rigorous demands of Precisio™ measures over 39,000 data points for each
customized corneal refractive and therapeutic surface: anterior cornea, posterior cornea, and iris
surgeries. The iVIS Suite includes three synergistic plane / anterior lens surface. A 3-D pachymetry map
applications areas: Diagnostic – to collect high is derived from the differences in elevation from
precision, highly repeatable biometric measurements; anterior to posterior corneal surfaces.
Design – to develop surgical profiles to treat both
stable and unstable corneas; and Delivery – to
implement the desired corneal surgery with a high
performance, high resolution laser delivery system.

DIAGNOSTIC PRODUCTS

The iVIS Suite’s diagnostic products provide the

surgeon with accurate and highly repeatable data as Figure 54.1: Precisio’s horizontal scan of dr. Lovisolo’s left eye
a fundamental for design of the surgical profiles.
Importantly, this data is used to regularize the cornea Precisio’s data acquisition is from a rapid series
thusly correcting high and low order corneal of 50 high resolution Scheimpflug images recorded
aberrations while respecting the unique character- in only one second from a tandem cameral system. A
istics and dimensions of the eye’s diaphragm, the specialized eye-tracking subsystem is used with in
454 Mastering Advanced Surface Ablation Techniques
conjunction with a 4 axis automated positioning
system. Additionally, ocular features including limbal
vessels and iris features are recorded for use as the
basis of data registration during surgery and active
rotational tracking. In vivo, repeatability is the only,
though indirect way to assess accuracy (corres-
pondence to true dimensions) of measurements, and
Precisio’s anterior corneal surface measurements are
repeatable with precision exceeding 1.5 microns
centrally and the posterior surface (and 3-D
pachymetry) exceeding 10 microns. To achieve these
levels of surgical precision, the Precisio system has Figure 54.2: Precisio™ high definition corneal and anterior
been engineered to be very stable and damp to chamber surgical tomographer
motion and vibration (Figure 54.2).
Precisio allows the operator to select one of two the operator to acquire at least two sequential
modes, Surgical and Diagnostic. Diagnostic mode examinations, with a subsequent automated
utilizes single examination view of the described differential analysis of the data sets validating that
anterior segment surfaces. The Surgical mode requires the data is repeatable (Figure 54.3).

Figure 54.3: Precisio’s point-by-point difference map obtained by subtraction of two consecutive acquisitions of corneal anterior surface
elevation. The vast majority of the 8 mm central area data points lie within the less than 2 µm range
 cTENTM-Custom Transepithelial “No-touch” One-step, All-laser” 455
Precisio’s proprietary data validation removes optical zone dimension adequately covers the pupil,
subjective bias out of a critical process that with other but does not needlessly remove tissue because a
systems may require the surgeon to visually standard size optical zone was used by default
determinate whether or not the data is repeatable without thought as to if was really “right sized”.
and accurate enough to be used as the basis of pMetrics™ (Figure 54.4) provides critical pupil
surgery. Importantly, the validation process does not dimension data from analyzing dynamically the pupil
use multiple averaged data sets assuming that the sizes from scotopic to photopic in controlled and
average would be acceptable. Upon completion of calibrated lighting scenes (a true pupillography). This
the statistical analysis of two or more data sets with important data not only describes pupil dimensions
low variability, Precisio will prompt the operator that in commonly encountered lighting conditions, but
the data may be exported for surgical planning. The also provides new insight into to qualitatively
surgical data is comprehensive and includes patient understand the pupil’s relative reactivity.
ID, multiple elevation data sets, pupil dimension at
examination and with its relative location to the data
sets for data registration during surgery, and
additional ocular features mapping that is used for
intra-operative eye registration, identification, and
active rotational tracking.

Clinical Applications
Precisio provides surgical grade data which must be
highly accurate and repeatable data. This data is
designed to be used as the basis of custom refractive
surgery and custom therapeutic surgeries. Examples
Figure 54.4: pMetrics™ dynamic pupillometer
of these surgical applications are to correct prior
refractive surgery failures from too small optical pMetrics utilizes binocular eye-tracking with
zone, decentered ablations, induced irregular elliptical fitting, tele-centric optics with constant
astigmatism, or lamellar procedures such as laser deep magnification within the depth of focus of the system,
lamellar keratoplasty or epikeratophakia. The Precisio 30 micron precision of pupil dimensions, and internal
tomographer also provides useful data for phakic and testing scenes that can be either standardized with
aphakic IOL implantations such the 3-D anterior calibrated illuminations, or custom defined environ-
chamber dimensions. ments by the operator.

pMetrics™ - Dynamic Pupil Assessment and Ideal The Ideal Pupil

Pupil Determination
The examination data is collected binocularly and
It is essential that any surgical plan developed for includes pupil dimensions (minimum, maximum, and
refractive, therapeutic, or cataract surgery must fully mean) for each lighting scene (Figure 54.5). Uniquely,
consider the patient’s pupil sizes with respect to the the data is statistically analyzed with a lifestyle
balance of the overall visual system. In the past, weighting to determine an ideal pupil dimension that
surgeries were designed with a standard size optical will cover two standard deviations of all of the visual
zone that may or may not have any size relationship conditions that the patient could be expected to
to the dynamic diaphragm limiting the patient’s encounter based upon a clinical assessment of typical
refractive system. To provide a surgical plan that is visual environments. The 95% criterion is deemed to
truly customized to the patient demands that the be a safe value. The ideal pupil dimension may be
456 Mastering Advanced Surface Ablation Techniques
used by the surgeon as a basis for determination of CIPTA™ – Corneal Interactive Programmed
the ablative optical zone and may also have useful Topographic Ablation
indications for selection of IOL dimensions including CIPTA™ is a fundamental departure from refractive
the appropriateness of a particular multi-focal lens only treatments that have been marketed either as
design. standard refractive treatments, wavefront adjusted
or wavefront guided refractive treatments. As a
synthesis of high definition elevation data, dynamic
pupil dimensions, and refractive data, CIPTA includes
corneal lower and higher order aberrations. This data
synthesis is used to create a proprietary ideal aconic
surface that uniquely covers the projection of the Idea
Pupil dimension onto the surface of the postoperative
cornea (Figure 54.6). The volume of this ablation is
defined by the intersection of the real corneal surface
(measured by elevation topography) and the ideal
aconic surface that is limited to the ideal pupil
dimension (Figure 54.7). As an important point of
differentiation, this is not derived from a single lens
formula or matrix of lens formulas (spatially
resolved) as with wavefront. This method also does
not suffer from the spatial limitations of refractive
only based ablations that only have information
within the pupil at whatever illumination happened
to be present when the refractive data was acquired,
nor is it applied without specific knowledge or
without regard to the underlying corneal shape.

Figure 54.5: pMetrics data report including ideal pupil calculation

SURGICAL DESIGN PRODUCTS

The iVIS Suite incorporates new intelligent design

tools that extend the surgeon’s capabilities to design
physiologically sound, customized surgical plans.
These surgical plans cover a much broader range than
any other refractive platform, for example primary
fully customized refractive surgery, complex corneas
that are resultant from prior refractive surgery
failures, and unstable corneas that prior would have
been relegated to a more serious, full cornea
transplantation. Figure 54.6: The ideal pupil
 cTENTM-Custom Transepithelial “No-touch” One-step, All-laser” 457

Figure 54.7: Since 1997, the original CIPTA (Corneal Interactive Programmed Topographic
Ablation)1 considers the volume of the ablation as described by the intersection of the
anterior surface of the cornea and the ideal aconic corneal surface. Ablation takes into
account the patient’s real anterior corneal surface, not derived from mathematical calculation
based upon lens application

Morphologic Axis vs. Optic Axis performed by adding a fixed width to the optical
zone regardless of the slope from treated to untreated
Refractive based treatments are by definition
tissue. The CIPTA transition zone is developed as an
acquired and calculated only along the optical axis.
additional customized element of the treatment. The
Uniquely, CIPTA utilizes a proprietary method to
acceleration of the slope from the optical zone to the
decouple the Morphologic Axis from the optic axis.
untreated cornea is controlled as a constant slope in
The Morphologic Axis can dramatically minimize the
each radial direction (Figure 54.8). This produces a
total amount of tissue that is surgically removed, but
variable width to accommodate changes is power
generally incrementally spares more tissue with the
from astigmatism or local irregularities. The constant
higher the degree of irregularities present in the pre-
slope, variable width transition minimizes risk of
operative condition1.
regression by producing a physiologically smooth and
cTEN™ - Custom Transepithelial “No-touch, One- constant shape as opposed to a sharply accelerated
step, All-laser” Treatment Strategy “blend zone” widely used with legacy laser systems.
This is especially dramatic with high amounts of
CIPTA provides multiple surgical planning strategies,
astigmatism and hyperopic refractive corrections.
inclusive of cTEN, a single step, transepithelial
approach which eliminates mechanical touching of the
cornea. There is a resurgence in interest with many
well known surgeons claiming a steady increase in
the percentage of surface ablations performed due
to safety, better results, and improved medical
regimens.15 With CIPTA, the surgeon has a choice in
selecting LASIK, LASEK, PRK, or the new cTEN
procedure. cTEN eliminates any mechanical or laser
keratome induced aberrations that are unmeasured
and unaccounted for with LASIK, in addition to any
safety concerns with the use of microkeratomes. Figure 54.8: Variable width constant slope transition zone

Variable Width Constant Slope Transition Zone CLAT™ – Corneal Lamellar Ablation
for Transplantation
The CIPTA custom treatment includes a transition
zone strategy with patented characteristics that are Keratoconus patients have historically required
novel to the industry. Treatment plans commonly are corneal transplantations when no standard optical
458 Mastering Advanced Surface Ablation Techniques
treatment will allow functional vision and the patient the cornea. As opposed to lamellar keratoplasties that
has become contact lens intolerant with concomitant are being attempted with mechanical or laser
resultant corneal scarring. A penetrating keratoplasty keratomes, CLAT creates a uniform thickness
(“PK”) was the last resort and left the patient with receiving bed in which the new normal thickness
an additional set of significant risks, complications, transplant is placed (Figure 54.9). This eliminates most
variable clinical results and patient satisfaction issues. serious residual irregularities of the keratome
With CLAT™ the surgeon may choose to utilize a prepared bed and thusly improves the resultant
fully automated, custom lamellar transplantation of corneal optics.

The receiving bed is created by calculating the The surgeon resizes the donor cornea
intersection of the pachymetry map and the ideal thickness with the iRES laser from the
corneal bed for the patient. This irregular volume is endothelial surface by the amount of the
removed with the iRES laser. residual cornea receiving bed thickness.

The new uniform thickness receiving bed now A trephine will cut the cornea of the donor to
takes on membrane properties ... an equal (or slightly larger) diameter than the
diameter of the receiving bed.

.. with no cross sectional rigidity. The donor is positioned ...

... on the receiving bed, on which a peripheral pocket

may be created, and then secured with conventional
sutures or tissue glue.

Figure 54.9: CLAT surgical process

 cTENTM-Custom Transepithelial “No-touch” One-step, All-laser” 459
iRES™ - High Resolution, Ultra-fast Custom The treatment position is continuously monitored
Refractive and Custom Therapeutic Laser and corrected using a high-speed eye-tracker
iRES™ (Figure 54.10) is the first refractive laser system including active rotational tracking. The system unit
specifically developed to perform customized includes dual monitors with, the surgeon centric
refractive and therapeutic corneal surgeries. Surgical monitor displaying eye tracking and surgical
computer-aided design and planning using the information, and the main system monitor displaying
principles of CIPTA™ and CLAT™, integrates the overall system and ablation details.
real corneal shape, dynamic pupil assessment, and
Constant Frequency per Area™
refractive aberrations to define the ablation profile.
Unique to the iRES laser is a patented beam delivery
method, Constant Frequency per Area™ (“CF/A”)
(Figure 54.12). CF/A tunes the 1 KHz delivery
frequency so that regardless of the ablation layer area
treated, the delivered frequency remains constant per
area. With lasers that only randomize the laser spots,
as the ablation layer becomes smaller in size, the
affect of the plume becomes substantially higher,
absorbing an undetermined amount of the laser
energy. Legacy laser systems typically provide a
compensation or algorithm to minimize the
reductions in energy delivered as extra shots
delivered compensate for energy absorbed by plume.
Additional physician maintained nomograms may be
further applied to lessen variability of clinical results.
Figure 54.10: The iRES laser system
By maintaining the same frequency per area both
The iRES laser features a 1,000 Hz delivered throughout the entire ablation profile and from
frequency utilizing a proprietary dual beam system, patient to patient, the laser benefits from improved
each operating at 500 Hz. The micrometric 0.65 mm predictability, improved ablation smoothness, and
spots each have a highly symmetric, Gaussian shape without extra shots delivered to the cornea. An
(Figure 54.11). additional benefit for custom and highly irregular

Figure 54.11: Highly homogeneous, symmetric, Gaussian shaped 0.65 mm spot of the iRES
460 Mastering Advanced Surface Ablation Techniques

Figure 54.12: Constant frequency per area

ablation shapes is highlighted by lasers without CF/ pupil diameter (Figure 54.14), and irregular
A: the unpredictability of the plume effect becomes astigmatism secondary to infective or immunological
more unwieldy with no well defined algorithm for stromal keratitis like DLK (Figure 54.15) may now be
asymmetric and irregular shapes. more easily managed. Uniquely, regular or irregular
ametropias that may be residual after lamellar or
CLINICAL APPLICATIONS penetrating keratoplasties (Figure 54.16 and 54.17),
thermokeratoplasty (Figure 54.18), radial or arcuate
With the iVIS Suite, complications such as decentrations keratotomy (Figure 54.19), cicatricial sequelae of
(Figure 54.13), optical zones smaller than the entrance contact lens-induced bacterial keratitis (Figure 54.20)

Figure 54.13A
 cTENTM-Custom Transepithelial “No-touch” One-step, All-laser” 461

Figure 54.13B
Figure 54.13 A and B: Example of successful repair of a decentration and induced irregular astigmatism following LASIK for a -7.00 D. After
2 years, the patient presented to us complaining of severe night vision disturbances. On examination, the UCVA in the right eye was 20/40
improving to 20/25 with +1.50 -1.00 x 10°. The contrast sensitivity was below the normal range for 3, 6, and 12 cpd. Topography showed a
significant decentration (lower left, A) and the wavefront analysis showed that the eye had significantly raised spherical aberrations with
increased coma and higher order aberrations. The patient was treated utilizing a transepithelial surface ablation strategy with the iRES laser
implementing a topographically guided treatment designed using CIPTA software. The intended post-operative refraction was plano. Four
months post-operatively (top left, A), the UCVA was 20/20+, with a gain of 3 lines of BSCVA. The patient reported that the haloes and the
starburst had disappeared. The post-operative topography was well-centred with a large optical zone. The topography difference map (right,
A) clearly shows the areas of temporal flattening and central and nasal steepening that were achieved corresponding to the ablation profile
generated by the CIPTA algorithm (B)

Figure 54.14: Example of a laser enhancement of small optical zone typical of older generation excimer laser ablations. The original
treatment was performed to correct –5.00 D of myopia. The 31-year-old patient complained of severe halos during night driving. The
anterior surface of the cornea was highly oblate (quotient of asphericity Q = +1 in the pupillary area). On examination with the pMetrics
pupillometer, the patient’s mesopic pupil size was 8.8 mm! The UCVA was 20/20 improving to 20/15 with +1.50. Cycloplegic refraction
was +3.00 and the contrast sensitivity below the normal range. The eye was treated as transepithelial surface ablation with the iRES
excimer laser using a topographically guided treatment designed using CIPTA software (ablation profile: A). The intended post-
operative refraction was +0.75. Four months post-operatively, the UCVA was 20/20, cycloplegic refraction +0.25 +0.25 x 10°.
Complaints of serious night time visual problems had disappeared. The topography difference map (right, A) shows the enlargement
of the optical zone with a restoration of a more physiological profile (Q = 0.03)
462 Mastering Advanced Surface Ablation Techniques

C
Figures 54.15A to C: A 39-year-old male patient underwent three consecutive laser procedures (PTK), after a viral
keratitis complicated the original AK procedure for a +0.25 – 4.00 x 90° mixed astigmatism in the right eye. On an
examination performed 15 years after the first procedure, the UCVA was 20/400, improving to 20/80 with –2.75 –2.00 x
110° and to 20/25 with pinhole. Haze 2+ and slight basement membrane dystrophy was found as partially responsible of
the irregularities of the anterior corneal surface. CSO corneal topography (bottom left, A) and corneal wavefront analysis
(B) showed that the eye had significantly raised higher order aberrations. The eye was treated with transepithelial
surface ablation procedure, using a topographically guided treatment designed with the CIPTA software (C, postoperative
ideal shape and ablation profile) and the iRES laser system. 0.02% Mitomycin C was applied for 15 seconds at the end of
the procedure. The intended post-operative refraction was plano. One month post-operatively, the UCVA was 20/20,
improving to 20/15 with +0.75 -1.00 x 102! All haloes and starbursts disappeared with an impressing subjective and
objective improvement. The post-operative topography was well-centered with a large optical zone
 cTENTM-Custom Transepithelial “No-touch” One-step, All-laser” 463

Figure 54.16: Corneal topography (CSO) shows irregular astigmatism in the left eye of a 37 year old male patient, 6 years
after 7-mm penetrating keratoplasty for keratoconus (bottom left). BSCVA was 20/40 with –2.25 –4.25 x 80°, 20/25 with
pinhole. Wavefront analysis showed that the eye had significantly raised higher order aberrations. The eye was treated
with transepithelial surface ablation procedure, using a topographically guided treatment designed with CIPTA software.
0.02% Mitomycin C was applied for 120 seconds at the end of the procedure20-21. The intended post-operative refraction
was plano. Six months post-operatively, the UCVA was 20/30, improving to 20/20- with -1.00 x 100°. The post-operative
topography (top left) was regular, with a large optical zone and a physiologically normal asphericity

Figure 54.17A
464 Mastering Advanced Surface Ablation Techniques

Figure 54.17B
Figures 54.17A and B: Corneal topography (CSO) showing irregular astigmatism in the right eye of a 19 year-old-male patient, 40
months after 7.5 mm penetrating keratoplasty for keratoconus (bottom left, A). BSCVA was 20/30 with +3.50 x 165°, 20/20 with pinhole.
The eye was treated with transepithelial surface ablation procedure, using a topographically guided treatment designed with CIPTA
software (ablation profile, B). 0.02% Mitomycin C was applied for 120 seconds at the end of the procedure. The intended post-
operative refraction was +1.00. Six months post-operatively, the UCVA was 20/25, improving to 20/20- with +1.25 x 165°. The post-
operative topography (top left, A) was regular, with a large optical zone and a physiologically normal asphericity

Figure 54.18: 10 years after 6 corneal procedures (one exagonal keratotomy, three holmium laser thermokeratoplasty and two conventional
PRK) for hyperopic astigmatism, the right eye of a 44 year old male patient showed a BSCVA of 20/50 with +0.50 +4.50 x 85°. The eye was
treated with transepithelial surface ablation procedure, using a topographically guided treatment designed with CIPTA software. 0.02%
Mitomycin C was applied for 120 seconds at the end of the procedure. The intended post-operative refraction was plano. Four months post-
operatively, the UCVA was 20/30, improving to 20/30+ with +0.75 x 85°. Preoperative (bottom left), post-operative (top left) and differential
(right) topography maps are shown
 cTENTM-Custom Transepithelial “No-touch” One-step, All-laser” 465

B
Figures 54.19A and B: 14 years after a combined RK-AK procedure complicated with an ectasia of the inferior
astigmatic cut, the right amblyopic eye of a 36 year-old man showed a BSCVA of 20/70 with +0.50 +7.00 x 5°, not
improving with pinhole. Disabling visual symptoms, mainly glare and monocular diplopia, were described under
mesopic light conditions. Corneal topography (bottom left, A) showed the ectatic changes of the inferior incisions.
The eye was treated with transepithelial surface ablation procedure, using a topographically guided treatment
designed with CIPTA software (ablation profile, B). 0.02% Mitomycin C was applied for 120 seconds at the end of
the procedure. The intended post-operative refraction was plano. Six months post-operatively, the UCVA was 20/
30, improving to 20/30+ with +1.00 -2.00 x170°. The post-operative topography (top left, A) shows a partial
restoration of the corneal physiology

can be surgically corrected with optimized of its aspherical profile and the volume of ablated
predictability, efficacy and safety ratios.16-19 tissue. This translates in extraordinary outcomes, as
For conventional cases, the CIPTA customization can be seen in the contrast sensitivity charts at six
allows the surgeon an unprecedented capability to months postoperatively, for the high myopia group
control the width of the optical zone, the preservation in particular (Figure 54.21).
466 Mastering Advanced Surface Ablation Techniques

Figures 54.20A and B: 23 years after a Pseudomonas aeruginosa corneal infection in a contact lens wearer, the
topography of the left eye (bottom left, A) of a 47 year-old lady showed the irregularity caused by a deep stromal scar
in the supratemporal quadrant. BSCVA was 20/50 with -4.50 -6.00 x 165°. Disabling visual symptoms were described
under mesopic light conditions. The eye was treated with transepithelial surface ablation procedure, using a
topographically guided treatment designed with CIPTA software (ablation profile, B). 0.02% Mitomycin C was applied
for 120 seconds at the end of the procedure. The intended post-operative refraction was -0.50. Six months post-
operatively, the UCVA was 20/25, improving to 20/20 with -0.25 -0.50 x 138°. The post-operative topography (top left,
A) shows an almost complete restoration of the anterior surface corneal profile
 cTENTM-Custom Transepithelial “No-touch” One-step, All-laser” 467

A B

C
Figures 54.21A to C: Postoperative contrast sensitivity curves of ‘conventional’ myopic patients treated with the iVIS Suite Platform,
as divided in overall (A), low myopia (B) and high myopia (C). Courtesy of Alessandro Mularoni, MD

REFERENCES postkeratoplasty astigmatism Ophthalmology

2001;108:2029-37.
1. Stojanovic A, Suput D. Strategic planning in topography- 5. Hjortdal JO, Ehlers N. Treatment of post-keratoplasty
guided ablation of irregular astigmatism after laser astigmatism by topography supported customized laser
refractive surgery J Refract Surg 2005;21:369-76. ablation Acta Ophthalmol Scand 2001;79:376-80.
2. Alessio G, Boscia F, Tegola MG, et al. Topography-driven 6. Mularoni A, Laffi GL, Bassein L et al. Two-step LASIK with
photorefractive keratectomy: results of corneal topography-guided ablation to correct astigmatism after
interactive programmed topographic ablation software penetrating keratoplasty J Refract Surg 2006;22:67-74.
Ophthalmology 2000;107:1578-87. 7. Alio JL, Belda JI, Osman AA, et al. Topography-guided
3. Alessio G, Boscia F, La Tegola MG, et al. Topography- laser in situ keratomileusis (TOPOLINK) to correct
driven excimer laser for the retreatment of decentralized irregular astigmatism after previous refractive surgery J
myopic photorefractive keratectomy Ophthalmology Refract Surg 2003;19:516-27.
2001;108:1695-703. 8. Rajan MS, O’Brart DP, Patel P, et al. Topography-guided
4. Alessio G, Boscia F, La Tegola MG, et al. Corneal interactive customized laser-assisted subepithelial keratectomy for
programmed topographic ablation customized the treatment of postkeratoplasty astigmatism J Cataract
photorefractive keratectomy for correction of Refract Surg 2006;32:949-57.
468 Mastering Advanced Surface Ablation Techniques
9. Jankov MR 2nd, Panagopoulou SI, Tsiklis NS et al: 16. Lovisolo CF. Topography vs. wavefront-guided Excimer
Topography-guided treatment of irregular astigmatism laser Custom treatments in secondary cases. Presented
with the wavelight excimer laser J Refract Surg at the 10th ESCRS Winter meeting Montecarlo 2006.
2006;22:335-44. 17. Lovisolo CF. Topo-guided transepithelial surface ablation
10. Toda I, Yamamoto T, Ito M, et al. Topography-guided
+ MMC safer and more effective than wavefront-
ablation for treatment of patients with irregular
astigmatism. J Refract Surg 2007;23:118-25. based LASIK. Presented at the Eye Advance 2006 Mumbai
11. Knorz MC, Jendritza B. Topographically-guided laser in 2006.
situ keratomileusis to treat corneal irregularities 18. Lovisolo CF. The iRES laser platform, a breakthrough
Ophthalmology 2000;107:1138-43. for custom therapeutic corneal surgery. Presented at the
12. Wygledowska-Promienska D, Zawojska I, Gierek- AIRS meeting Aspen 2007.
Ciaciura S, et al. Correction of irregular astigmatism using 19. Lovisolo CF. CTen: Custom Trans-epithelial No touch
excimer laser MEL 70 G-Scan with the TOSCA program- surface laser ablation with the iRES platform (LIGI).
introductory report. Klin Oczna 2000;102(6):443-7. Presented at the 8° Curso Sevilla Refractiva 2007.
13. Mattioli R, Camellin M. La aberrometria corneale ed il 20. Abraham LM, Selva D, Casson R, Leibovitch I. Mitomycin:
link ‘topoaberrometrico’. Cap. 18 in Camellin M. LASEK
clinical applications in ophthalmic practice. Drugs
& ASA, Fabiano Ed. Canelli 2004;232-53.
14. LIGI Tecnologie Medicali, S.p.A (www.ivistechnologies.com). 2006;66:321-40.
15. McDonald MB. Use of Surface Ablation Increasing; 21. Lacayo GO 3rd, Majmudar PA. How and when to use
Experts Debate It’s Future. OSN. Retrieved on Febr, 2007 mitomycin-C in refractive surgery. Curr Opin Ophthalmol
from www.osnsupersight.com/view.asp?rID=19948. 2005;16:256-9.
 CHAPTER

55 Ocular Pharmacokinetics in
Advanced Surface Ablations

Ashok Garg (India)

INTRODUCTION Preoperative Ocular Therapeutics

Even since Theo Seiler in 1987 and Marguerite Pre-operatively patient is given combination of topical
McDonald in 1988, did the first corneal ablation in antibiotic (Moxifloxacin (0.5%) and NSAID diclofenac
normal sighted eye, Excimer laser refractive surgery (1%) sodium drops. Twenty-four hours prior to
has produced revolutionary changes in the field of procedure, this combination is started at 4 hourly
ophthalmology. Refractive surgery is certainly a high- interval. A mild oral sedation with valium (diazepam
tech advancement in the field of ophthalmic surgery 5-15) helps the patient to overcome the anxiety to
since the last decade of this millennium which has the procedure.
come as a great boon to spectacle weary patients all
around the world. Topical Anesthesia
In this chapter, I will discuss the preprocedure For PRK surgery, topical anesthesia is the best
and postprocedure considerations of ocular anesthesia selected worldwide.
therapeutics in detail in PRK as well as in epi-LASIK 2-5 minutes before operation patient is given any
and LASEK surgery. Every refractive surgeon should of the following topical anesthetic agents.
have clear concept of ocular therapeutics in his mind - Proparacaine HCl 0.5 percent
before starting the procedure to ensure better clinical - Benoxinate HCl 0.4 percent
results to the patients. - Tetracaine HCl 0.5 percent
Proparacaine is used most commonly followed by
PHOTOREFRACTIVE KERATECTOMY (PRK)
benoxinate and tetracaine. Other topically applied
The PRK is most commonly performed refractive anesthetics (Xylocaine 4%) are used for less commonly
surgery for low to moderate myopia worldwide. It due to problems with irritation, allergy, etc. Both
is now gradually becoming a safe procedure due to proparacaine and benoxinate have a rapid onset of
newer technologies and the availability of the better action and cause little discomfort making them
anti-inflammatory drugs both steroidal and non- excellent choices.
steroidal to reduce corneal scarring and haze. As Onset of anesthetic action starts within 15-20
patient selection criteria and other technical modes seconds with proparacaine, benoxinate and tetracaine
have been discussed in other chapters of this book, I and effects last for 15-20 minutes enough for
am discussing ocular therapeutics section here. completion of PRK surgery.
470 Mastering Advanced Surface Ablation Techniques
Dosage decreasing corneal haze and increasing refractive
stability.
Topical proparacaine, benoxinate or tetracaine are
Standard modality for the management of patients
given in the dosage of 2 drops in each eye 2-3 times
undergoing PRK, the major considerations are:
repeated at the interval of one minute.
a. Closure of epithelial defects.
After topical anesthesia patient is carefully
b. Post PRK pain management
centered and local preparation with iodine solution
c. Modulation of refractive and visual results.
(Betadine) is done and the operative eye is given a
sterile plastic ophthalmic drape that covers the eyelid Epithelial Defect Closure
margins and the cilia.
It is recommended that the size of epithelium to be
Postoperative (Postprocedure) Therapeutic removed to be kept to the minimum. The best
Management possible methods to facilitate healing of corneal
epithelium are :
Corneal wound healing and its modulations after
- Patching
excimer laser PRK surgery are complex phenomenon.
- Bandage contact lens
In PRK the corneal epithelium is debrided after which
- Collagen shield.
stromal ablation is performed. A 7-10 day epithelial
healing phase follows with the final stromal effects Patching
being observed weeks to month later.
Ocular therapeutics are given post PRK according The common practice among ophthalmologists to
to phases and course of corneal wound healing. The patch the eye for 24 to 48 hours following laser
temporal response of cornea to PRK can be divided procedure. Operated eye is padded putting topical
into three phases. antibiotic and mydriatic eyedrops and an antibiotic
1. Acute (1 to 3 weeks) ointment. The next day padding is changed. Some
2. Intermediate (3 weeks to 6 months), and refractive surgeons prefer to give oral antibiotic
3. Long-term (6 months or more). (Ciprofloxacin/Levofloxacin 500 mg bd for 5 days).
During the acute phase cornea mounts its initial After 48 hours patching is removed and eye is kept
response to epithelial removal and photoablation. The open.
earliest phase involves the healing of epithelial injury
Bandage Contact Lens
and is characterized by migration of epithelium which
occurs 12-24 hours after injury, 2-3 days after the Contact lens fitting is dependant on the
insult, epithelial cell proliferation is evident. - Standard of care
Endothelial migration and possibly epithelial cell - Better patient compliance
proliferation also begins this time. The acute phase - Better comfort
corresponds to a clinical appearance of general - Earlier return to normal activities
corneal clarity. Despite the advantage one needs to be cautions
In the intermediate phase the epithelium remodels of the following complications due to contact lens
itself to normal thickness if the surface contours are fitting which are:
gradual and regular. Type VII collagen is produced - Infectious keratitis
and large number of fibroblasts populate the anterior - Tight lens syndrome
stroma. This phase corresponds to a clinical phase of - Problems with patient compliance
subepithelial haze and loss of initial refractive effect. - Contraindicated with the use of topical NSAIDs
In the long-term phase development of fibrous
Collagen Shield
metaplasia is complete. Subepithelial stroma remodels
itself. Clinically, this corresponds to a phase of Some refractive surgeons advocate the use of collagen
 Ocular Pharmacokinetics in Advanced Surface Ablations 471
shield instead of patching or contact lens but this ii. Molecular and cellular inflammatory response.
modality is not very popular. iii. Activation, proliferation and migration of
corneal cells to wound.
Post PRK Management
Corneal Haze (Post PRK)
One of drawbacks of the PRK procedure is problem
of pain caused by the exposure of nerve endings due i. Incidence depends on:
to the loss of epithelium. - Time post-treatment
The causes of pain are: - Size of ablation
- Mechanical - Depth of ablation
- Epithelial defect - Excimer laser used
- Thermal - Individual wound healing variability.
- Acoustic ii. Haze occurs in 2 phases.
Course of post PRK pain is most intense during - Early (within 2 weeks of procedure)
the first 24-36 hours followed by dramatic reduction - Decreased transparency associated with
but foreign body sensation may persist epithelial reduced optical performance due to
closure. Once the exposed nerves are covered epithelial and surface irregularities
- Late (2-6 months postprocedure)
by healing epithelium patient experience no more
- Subepithelial deposit on the layer at epithelial
pain.
and stromal junction.
Following PRK corneal sensation returns to
- May peak at 3 months and then decrease.
baseline within 12 weeks. The various modalities
iii. Therapeutic considerations should work
for managing the pain are:
towards.
- Oral analgesic (Preferably oral diclofenac or
- Reducing haze or scarring.
nimesulide for 5 days. Tab diclofenac sustained
- Improving predictability of refractive
released 75 mg bd or tab. Nimesulide 100 mg bd
outcome.
for 5 days continuously relieve the patient of PRK
- To prevent regression.
pain to great extent.
For this refractive surgeon prefer to give a
- Topical non-steroidal anti-inflammatory drugs
combination of topical NSAIDs and topical steroids.
like.
Combination is preferred because topical NSAIDs
- Topical diclofenac 1 percent 4 times a day or
reduce corneal haze while topical steroids have a
- Topical Ketorolac — Topical 0.5 percent 4 times a
day helps in reducing the pain. certain role to prevent regression.
- Topical Nepafenac – 0.1% four times a day. The regimes of choice are:
- Topical lubricant eye drops 4-5 times a day gives i. Topical dexamethasone eyedrops (0.1%)
the patient a soothing sensation. Polyvinyl alcohol starting from 3rd post PRK procedure day 3-4
liquifilm tear drops helps in post PRK pain. times a day upto 2 weeks followed by switching
- In excessive pain, topical anesthetics like to topical FML (0.1%) (Fluorometholone drops)
proparacaine 0.5 percent drops 3-4 times a day or topical Rimexolone (1%) drops from 15th day
helps the patient to overcome the pain. of 6 months with the same dosage. It is gradually
tapered off.
Modulation of Refractive and Visual Results ii. Topical NSAIDs like ketorolac 0.5 percent
solution or diclofenac 1 percent/Topical
Corneal wound healing following excimer laser ablation
Nepafenac 0.1% solution 4 times a day for
i. The refractive outcome is dependant upon the 6 months and gradually tailed off. Topical
balance between initial ablation depth and the NSAIDs and topical steroids is an ideal
healing and remodeling of the epithelium and combination and have maximum effect on
the stroma. corneal haze and visual outcome. Some
472 Mastering Advanced Surface Ablation Techniques
refractive surgeons prefer to give topical FML i. Topical NSAIDs like diclofenac sodium (1%) or
or topical rimexolone eyedrops straight from ketorolac (0.5%) reduces the accumulation of
3rd post PRK day instead of topical prostaglandin E and inflammatory cells in the
dexamethasone for initial 15 days (because of corneal stroma but on the other hand has been
greater side effects of topical dexamethasone associated with the development of sterile
drops). Topical FML (0.1%) or topical infiltrates following PRK.
rimexolone (1%) have greater effectiveness in ii. The combination of mitomycin C with topical
controlling corneal inflammation and have steroids like FML (0.1%) or rimexolone (1%)
better ability to inhibit leukocyte accumulation decreases the sub-epithelial fibrosis associated
in the cornea. Their potency as an powerful anti- with healing after PRK surgery.
inflammatory agent is similar to iii. Application of cytokines to reduce corneal haze
dexamethosone. and scarring has been demonstrated recently.
Combination of topical non-steroidal and steroidal Cytokines are proteins secreted by cells that
therapy is given for 6 months post PRK and then regulate important biological properties of target
gradually tapered off. When topical steroids are cells. Cytokines act by an exocrine pathway to
given for an extended period of time after PRK an influence corneal wound healing.
important consideration is possibility of steroid iv. Topical interferon eyedrops given four times
induced rise in intraocular pressure. Because all daily for 5 weeks reduces the corneal haze
wound healing activity after wide area ablation occurs remarkably in eyes following a 6.00 D excimer
within the superficfial cornea, it is probably preferable laser PRK.
to minimize the amount of corticosteroid within the v. Topical dexamethasone (0.1%) in combination
aqueous humour. with interferon a2 produces less haze.
It is essential for the regular check-up of the vi. Topical b FGF treatment applied four times daily
operated patient. until complete epithelial wound healing occurred
PRK patient is usually called for follow-up by significantly reduces corneal haze 5-13 weeks
refractive surgeon on following deep stromal laser ablations.
- 2nd post PRK day vii. Application of topical anti TGF-b1 antibody
- 10th day reduces corneal fibrosis remarkably.
- 20th day viii. Treatment of corneas following excimer PRK
- 4th week with a synthetic MMP inhibitor reduces
- 8th week intrastromal epithelial migration after laser
- 12th week ablations.
- 18th week The above mentioned topical agents are in
- 24th week advanced stage of research and sometime more will
be needed to be available as commercially.
On each follow-up following examination is done:
So the present option for PRK medication is
- Visual check-up
combined therapy of topical NSAIDs and steroids.
- IOP with non-contact tonometer
Refractive surgeon has to keep strict watch on the
- Slit lamp examination for haze
potential adverse effect of topical steroids. Inspite
- Topography to see central profile
of the use of topical FML or rimexolone which have
RECENT UPDATE IN POST PRK MEDICATIONS less propensity to raise IOP than comparable dose of
dexamethosone. Practically patients with IOP rise are
Several topical agents have been used in an attempt seen by every refractive surgeon in their practice. It
to modify the stromal wound healing following PRK is worthwhile to mention here complications of topical
surgery. steroids following post PRK phase.
 Ocular Pharmacokinetics in Advanced Surface Ablations 473
It has been commonly observed even in educated onset of action and lesser irritation to the patient.
people that even after the stoppage of topical steroid 2-5 minutes prior to the surgery any of the
therapy by ophthalmologists after a specific duration following topical anesthetic agent can be safely used.
patients continue to put these drops for indefinite time - Proparacaine HCl - 0.5%
without the consultation of the doctor. It is essential - Benoxinate HCl - 0.4%
to inform the patient well in advance about the - Tetracaine HCl - 0.5%
potential adverse effects of topical steroids so that Proparacaine is most commonly used anesthetic
patient may not go for self medication in future. agent followed by benoxinate and tetracaine. Other
Broadly complications of topical steroids are as topical agent like Xylocaine (4%) is less commonly
follows: used due to problems of irritation, allergy, etc.
- Steroid induced glaucoma. Proparacaine, benoxinate and tetracaine have rapid
- Cataract onset of action and cause little tingling sensation and
- Delayed wound healing irritation to the patient.
- Infection and ulceration. Onset of anesthetic action starts with in 15-20
- Periocular dermatitis.
seconds with these agents and effects last for 15-20
minutes sufficient for the completion of epi-LASIK/
EPI-LASIK AND LASEK
LASEK surgery. Proparacaine or benoxinate are given
Epi-LASIK and LASEK provides an extra-ordinary topically in the dosage of 2 drops in each eye 2-3
accurate method of tissue removal (0.20-0.25 um tissue times repeated at the interval of one minute.
per pulse). The extreme pain, haze, regression and After topical anesthesia some refractive surgeon
slow in visual rehabilitation of PRK are absent thus prefer to instill pilocarpine 1% in the eye to aid in
the minimum use of postprocedure medications marking the optical axis.
specially topical steroids and its potential adverse Pachymetry is performed and patient is carefully
effects. centred and eyelids are cleaned with betadine
Although pre-procedure medications are same in solution (Iodine solution) and operative eye is given
epi-LASIK and LASEK as those in PRK surgery while a sterile plastic ophthalmic drape to cover the eyelid
post-procedure medications are drastically reduced margins and the cilia.
in epi-LASIK and LASEK surgery leading to quick
visual rehabilitation of patient postoperatively. Postprocedure Therapeutic Medications
Here now I shall discuss the ocular therapeutics The biggest advantage of epi-LASIK and LASEK over
used in epi-LASIK and LASEK surgery before and PRK is the minimum use of ocular therapeutic in post-
after the procedure. operative phase. The visual recovery in epi-LASIK
and LASEK is virtually immediate owing to the
Pre-procedure Therapeutic Medications
preservation of the epithelium of the cornea.
Pre-operatively patient is given broad range. Topical Typically, recovery is painless and postprocedure
antibiotic eye drops, Preferably Gatifloxacin (0.3%) refractions and vision are remarkably stable during
or moxifloxacin (0.5%) at 4 hourly interval starting the postoperative period. Postprocedure medications
24 hours prior to surgery. are quite significant for early visual rehabilitation and
A mild oral sedation (diazepam 3-10 mg) is given recovery of the patient. During the initial active
in all cases. Bilateral simultaneous surgery is done in postoperative phase. Refractive surgeons prefer to
all cases. give:
a. Oral antibiotic (Gatifloxacin 400 mg OD or
Topical Anesthesia
levofloxacin 500 mg OD for 5 days).
For epi-LASIK/LASEK surgery, refractive surgeon b. Topical fluorometholone (FML, 0.1% eye drops
prefer to give topical anesthesia because of rapid four times a day for two weeks.
474 Mastering Advanced Surface Ablation Techniques
c. Topical lubricant like polyvinyl alcohol liquifilm Corneal healing following epi-LASIK/LASEK
tear drops 4 times a day for two weeks. should be considered as a combination of events
d. Topical antibiotic (Moxifloxacin 0.5%) QID for a involving the response to injury of the epithelium
week. Immediately after epi-LASIK/LASEK and stroma.
procedure some surgeon prefer to give patch for Understanding these events and the molecules that
2-3 hours. While other view is to ask the patient regulate the wound healing response should enable
to wear a clear eye shield nightly for a week. the refractive surgeon to induce fewer complications
e. Oral analgesic (Tab. diclofenac 75 mg SR BD for and aid in developing therapeutic modalities to alter
three days if needed but not in routine). would healing prercisely.
Patient operated for epi-LASIK/LASEK surgery Close follow-up and attention to postoperative
is called for follow-up on: medications and surface lubrication will enable the
- 2nd day postprocedure surgeon to achieve better results.
- 1st week
- 2nd week
BIBLIOGRAPHY
- 3rd week
1. Agarwal Amar, Textbook of ophthalmology, Jaypee
On each follow-up following examination are Brothers Medical Publishers, New Delhi 2002;1.
done 2. Bartlett JD. Clinical Ocular Pharmacology, Boston:
- Vision check-up Butterworth-Heinemann 2001;4.
3. Bartlett JD. Ophthalmic Drug facts: Lippincott – William
- IOP with noncontact tonometer
and Wilkins 2001.
- Slit lamp examination for haze 4. Crick, RP, Trimble RB. Textbook of clinical ophthalmology:
- Topography to see corneal profile. Hodder and Stoughton 1986.
Corneal wound healing and its modulations after 5. Duane TD. Clinical ophthalmology, Butterworth –
Heinemann 1999;4.
epi-LASIK/LASEK surgery have multiple
6. Duvall. Ophthalmic Medications and Pharmacology : Slack
components. Epi-LASIK/LASEK is a refractive Inc. 1998.
surgical procedure that is performed in several steps 7. Ellis PP. Ocular Therapeutics and Pharmacology, CV
and each step involved a different structure of cornea. Mosby 1985;7.
8. Fechner. Ocular Therapeutics : Salck Inc. 1998.
9. Fraunfelder. Current Ocular Therapy, WB Saunders 2000; 5.
Phases of Healing 10. Garg Ashok. Current Trends in Ophthalmology, Jaypee
Brothers Medical Publishers, New Delhi 1999;1.
Following epi-LASIK/LASEK injury healing occurs
11. Garg Ashok. Manual of Ocular Therapeutics, Jaypee
in several phases. The earliest phase involves the Brothers Medical Publishers, New Delhi 1996; 1.
healing of epithelial injury and is characterized by 12. Garg Ashok. Ready Reckoner of Ocular Therapeutics,
the migration of epithelium which occurs New Delhi 2002;1.
13. Goodman LS, Gilman A. Pharmacological basis of
12-24 hrs after procedure 2-3 days after the insult, Therapecutics, New York: Macmillan 1985;7.
epithelial cell proliferation is evident. Six months after 14. Havener’s, Ocular Pharmacology, CV Mosby 1994; 6.
the surgical insult the development of fibrous 15. Kanski. Clinical Ophthalmology, Butterworth-Heineman
1999;4.
metaplasia is complete. Throughout these phases of
16. Kershner. Ophthalmic Medications and Pharmacology:
healing the types of cytokine communication are Slack Inc. 1994.
operating to create an integrated repair of injured 17. Olin BR, et al. Drugs Facts and Comparisons: Facts and
corneal areas. Comparisons, St. Louis 1997.
18. Onofrey. The Ocular Therapeutics; Lippincott, William
Although epi-LASIK/LASEK is safe and reliable and Wilkins 1997.
procedure yet it is susceptible to all the complications 19. Rhee, The Wills Eye Drug Guide: Lippincott, William and
noted in PRK procedure which includes over- Wilkins 1998.
20. Steven Podos, Textbook of ophthalmology, Jaypee
correction, undercorrection, decentration, infection,
Brothers Medical Publisher, New Delhi 2001.
loss and displacement of flap, central islands and 21. Zimmerman. Textbook of the Ocular Pharmacology:
epithelial ingrowth. Lippincott and William and Wilkins 1997.
 CHAPTER

56 Theoretical Aspects of
Customized Surface
Ablation

JT Lin (Taiwan)

INTRODUCTION REFRACTION POWER IN HUMAN EYE

The combined technologies of scanning laser, eye Total power of human eye (Lin, 2005):
tracking, topography and wavefront sensor advance P = Dc + ZP’ (1)
the corneal reshaping (the refractive surgery) one step Z = 1 – S(Dc/1336).
further from the conventional ablation of spherical Corneal power:
surface to the customized ablation of aspherical Dc = 377/r1 – 41/r2 + at (2)
surface. Therefore, the theory (or mathematics) Lens power:
behind LASIK is also expanded from the simple P’= 84 (1/R1 – 1/R2) – bT (3)
paraxial formula to the high-order nonlinear formulae The corneal power (Dc) is also related to the
involving the change of the corneal asphericity and keratometry power (K) by Dc=1.117K–41/r1. The
the LASIK-induced surface aberrations. This Chapter effective anterior chamber depth is given by S = ACD
provides a summary of the classical and modern + 2.4 mm for a typical lens thickness of 4.0 mm; and
formulae with comprehensive examples to illustrate refractive indexes of 1.377, 1.42 and 1.336,
the application or clinical aspects of LASIK. The respectively, for the cornea, lens and aqueous
mathematics (formulae) for the following subjects
(vitreous). (r1, r2) and (R1, R2) are the (anterior,
(principles) is covered:
posterior) surface radius for the cornea and lens,
• Refraction power of human eye including corneal
respectively (in mm). The small correction terms due
and lens, definition of refractive error
to the corneal thickness “at” is about 0.25% of Dc
• Ablation rate of LASIK (a thermal model)
• Mixed (compound) astigmatism (may be ignored for small thickness t = 0.5 mm), but
• Bifocal (or presby-LASIK) the lens thickness term (–bT) about 1.5% of P’ can
• LASIK ablation profiles for both spherical and not be ignored (since T = 4.0 mm).
aspherical surface.
• Second-order (paraxial) and high-order REFRACTIVE ERROR (D)
approximation
• Prediction and control of corneal asphericity. In LASIK procedure, the refractive power change
Greater detail of the derivations of the formulae (error) is defined by the difference of the preoperative
presented in this Chapter may be found in the cited (R) and postoperative (R’) front surface radius of the
references. cornea
476 Mastering Advanced Surface Ablation Techniques
D = 377(1/R – 1/R’), (4) normally measured by a spectacle power, Ds, (at a
where D in diopter (or 1/m) and R and R’ in mm, typical vertex distance of V=12 mm) related to D (or
therefore as shown Figure 56.1. the contact-lens power) by
D = Ds/ [1 – V Ds] (5.a)
= Ds/ [1– 0.012 Ds] (5.b)

Ds –20 –15 –10 –5 +5 +10 +15 +20

D –16.1 –12.7 –8.9 –4.7 +5.3 +11.4 +18.3 +26.3

The refractive error may be also calculated from

the axial length (L) given by Lin’s Effective Eye Model
(EYM, Lin, 2004) as shown in Figure 56.2.
qD = 1336/X – Dc/Z – P’ (5.c)
Z = (1 – SDc/1336) (5.d)
where q=1/Z 2 and for emmetropia (D = 0),
X = FZ, that is the focal point matching the retina
position as shown by Figure 56.2. The axial length
L = S + X + aT, with a = 0.045 and T = 4.0 mm (lens
Figure 56.1: The corneal post-LASIK front surface radius vs.
refraction correction power (D), for initial radius R=7.7 mm
thickness) and S = ACD = gT, with ADC being the
anterior chamber depth (Lin, 2004).
myopia (D<0), R’>R,
LASIK PROCEDURE TIME
hyperipia (D>0), R’<R.
EXAMPLE (for preoperative R=7.7 mm), By defining T*=T/D, or the procedure time (in
D -1 -5 -10 0 +2 +5 +10 seconds) per diopter correction (D), one may obtain
————————————————————
R’ 8.0 8.6 9.7 7.7 7.4 7.0 6.4 the following scaling law (Lin, 2007):
T * ~ W2/[AHPR2], (6)
It should be noted that in LASIK procedure the where, W is ablation effective zone diameter, A
change on the corneal (front) surface represents the is the ablation rate (um/pulse), P is laser power (in
refractive errors of the treated subject which is W), and R is the laser spot size (radius). The laser

Figure 56.2: An effective eye model showing the refractive error (D) vs. axial length L = X + S = at
 Theoretical Aspects of Customized Surface Ablation 477
fluence is defined by the laser energy/pulse per unit A = b In (F/F∗), (7.a)
area F=E/(πR2). The following examples may be b= (0.616/n) (λ/a) 1/2
(7.b)
obtained from above equation. F*= (ΔT/a1/2 ) [πm3 C3K tp]1/4 (7.c)
For a typical system parameters of W=6.0 mm, ∗
where F, F are the true and threshold fluences,
H=100 Hz, P=100 mW, E=1.0 mJ/pulse and spot size ΔT is the temperature increase needed for tissue
of R=1.0 mm (diameter) and ablation rate of A=0.5 thermal destruction per laser pulses, a is the linear
microns/pulse, we define a typical T*=5.0 seconds in absorption coefficient, m is the density, C is the heat
myopia correction. capacity, K is the thermal conductivity, λ is the
1. For fixed (A,H, R, W), T* is linear propositional wavelength, and n is the refractive index (n=1.52 at
to 1/P, that is T*=(2.5, 10) seconds for P=(200, 50)
193 nm) and tp is the laser pulse duration. For a square
Hz. Therefore for H<100 Hz, a larger spot size of
pulse the maximum surface temperature increase is
R>1.2 mm would be needed for reasonable T*.
given by an analytic form of (Lin & George, 1983)
2. For fixed (A,P,R,W), T* ~ W2, therefore
T*=(3.5, 5.8, 6.8) seconds, for W=( 5.0, 6.5, 7.0)mm, ΔT = 2Io (1-Re) tp1/2 (π m CK) 1/2 , (8)
in single-zone method. The procedure is faster in where Io is the laser intensity, Re is the surface
a multi-zone method which has a smaller effective refection loss. Combining Eq. (2) and (3.2.c), one
inner zone size. further obtains F* ~ tp3/4 that is for a given laser
3. For fixed (A,P,H,W), T* ~ R2, therefore energy (or intensity) longer pulse requires a higher
T*=(20, 13.9, 3.47) seconds, for R=(0.5, 0.6, threshold fluence to achieve the temperature needed
1.2) mm. This is the major reason that a small spot for thermal destruction/evaporation of the corneal
system such as a diode-pumped laser system made tissue. One may also re-write Eq. (2) as following
by CustomVis having a small energy/pulse about F = F* exp (A/b) (9.a)
1.0 mJ and spot size of 0.6 mm, requires a very = F* exp [A a1/2 /(0.616/n) λ1/2], (9.b)
high repetition rate of > 500 Hz. On the other
which implies that for a given laser fluence, the
hand, for lower H,100 Hz, larger spot of >1.2 mm
ablation rate (A) is inverse proportional to the
is needed.
4. For a limited available energy/pulse, say < 1.0 absorption coefficient (a); and to achieve the same
mJ, a small spot is required in order to have F > ablation rate, high fluence (F) is needed for a higher
150 mJ/cm2. absorption coefficient (a). As shown in Figure 56.3,
If none of the laser parameters are limited, then the relationships of A, F and F* are presented in the
the sole limiting parameter determining T* is the laser normal scale and in the natural log (In) linear scale,
power (P) and T* ~ P, where typical P is 200mW to where A = 0, when F = F*. Typical values are: a = 2.9
340mW. On the other hand F value can not be too (1/um), A = 0.3 to 0.5 um and F* = 40 to 60 mJ/cm2.
for the sake of ablation depth precision, say 0.2 to Other factors may influence A or T include:
0.5 micron/pulse. This is another limiting factor for • re-absorption of the laser energy by the tissue
T*, even laser power is not limited. The current plume
systems in the market having H=(100-500) Hz, and • corneal (or stroma) hydration (or BSS) level
unlimited laser power (>500mW), the typical range • non-normal incident angle of the beam (in
of T*=(3.5 – 7.0) seconds have been used based on peripheral area)
the issues discussed above. • PMMA calibration reading error
• Ablation nomogram (or algorithm) used in the
LASIK ABLATION RATE
system (to be detailed later).
Based on the thermal model of Pursikov et al (1990), Most of the manufacturers of LASIK systems use
the ablation rate (A), or the laser ablation/ a fudge factor (m) to clinically adjust the conversion
penetration depth per pulse (A) is given by between in the PMMA power and the corneal
478 Mastering Advanced Surface Ablation Techniques

Figure 56.3: The ablation rate (A, in microns) vs the laser fluence (F)
and its threshold value (F*) in normal and natural log scales

correction power with m = (0.3 to 0.35) depending Table 56.1: Strategies of presbyopia-LASIK using either a center-
myopia island (CM) or peripheral-myopia ring (PM) to see both near
on laser systems and algorithm used. and far.
For example, –5.0 diopter in PMMA ablation Preoperative Correction diopter (zone size)
corresponding to about –1.5 diopter in actual corneal cases PM CM
power change, that is, the corneal tissue ablation rate (a) Plano +2.0 (W = 7.0) +2.0 (W = 4.0)
NA* = +2.0 D - 2.0 (W = 4.0) No Wring needed
is about 3 times of the PMMA. This m-factor may
(b) Hyperope +1.0 +4.0 +1.0 (Wring)
smear out part of the factors affecting the ablation NA = +3.0 D - 3.0 +4.0 (W = 4.0)
rate or errors from algorithms.
(c) Myope -2.0 D +3.0 -2.0
NA = +3.0 D - 5.0 +1.0
BIFOCAL (PRESBY-LASIK) (d) Myope -4.0 D +2.0 -4.0
NA = +2.0 D -6.0 -2.0
Bifocal Presby-LASIK may be achieved either by
* NA stands for the near addition power of a presbyopic eye.
central-myopia (CM) using the central cornea to see ** Each treatment consists of two steps: for PM, a large (W=7.0
near, or by peripheral myopia (PM) using the mm) followed by a small (W=4.0 mm) zone correction; for
peripheral to see the near, as shown by Figure 56.4. CM, a ring-zone Wring(4/7 mm) followed by a central zone W
= 4.0. CM has the advantage of less tissue removed comparing
The correction powers shown in Table 56.1 below to PM, however, it may suffer worse contrast (Lin, 2006).
are based the following general formulas developed
by Lin (2006) for general case of (spherical, Asphericity Comparison
presbyopia) = (a, NA), where NA = near addition.
The difference of shape factor (dP) or asphericity (dQ)
For CM: W(ring) needs D = a (to achieve plano at between CM and PM depends on the areas of the
peripheral) and W(center 4.0 mm) needs D’ = a + NA cornea.
(for myopia to see near) which corrects with the a. Central zone (within W = 4.0 mm)
spherical error and presbyopia (or NA). The net refractive error pf PM is given by a (for
For PM: W(7.0 mm) to see near needs D = a + NA both a > 0 and a < 0), whereas CM has (a + NA).
(if a > 0), NA (if a < 0); and D’ (for W = 4.0 mm to Therefore, the p-factor difference, defined as
achieve plano) = NA (if a > 0), (a – NA) (if a < 0). dp = p’(PM) may be derived from Eq.(4.a) with C
 Theoretical Aspects of Customized Surface Ablation 479

Figure 56.4: Presbyopia-LASIK using bifocal corneal profile for (a) center-myopia (CM)
and (b) peripheral myopia (PM)

defined by a (for PM) and (a + NA) (for CM) as The above comparison implies that CM offers
follows: better image quality (by smaller SA) in the central
(dp)/p = 0.0408(NA) – 0.0612[(a + NA)2 – a2], zone for near, but worse than PM in the peripheral
where NA > 0 (the presbyopia near addition zone far vision whereas the reversed benefits offered
power), therefore dp > 0, or CM always has a by PM.
smaller p-factor (or more prolate) than PM.
b. Peripheral zone (between W = 4.0 to 7.0 mm) MIXED ASTIGMATISM
In this area, CM has the refractive error of D1 = a
It was known that (Lin, 1994) the strategy of using
and PM has D2 = (a + NA) (for a > 0), NA (for
positive cylinder correction (followed by spherical)
a < 0). The refractive error difference is D12 =
for the treatment of compound (mixed, toric)
D1 – D2 = a – (a + NA) (for a > 0), or D12 =
astigmatism and benefiting less corneal tissue removal
(a – NA) (for a < 0). Therefore,
and faster procedure. As shown in Figure 56.5, a
dp = 0.0408 d12 – 0.0612(D12 – D22).
negative cylinder of 180 may be converted to a
In contrast to the central zone, the peripheral zone
positive cylinder rotated to 90.
shows p’(CM)>p’(PM), that is, the CM has less
The corneal shape change of the above 2-step
prolate than PM in the peripheral, as opposed to
sequential ablation (with correcting powers of D and
the central zone.
D’) is given by the formulas below. As shown in Table
Above formulas allow us to calculate dp for all
56.2, case (a) and (b) are equivalent having the same
the cases or shown in Table 56.1.
SE; and (c) = (d). They are converted by the formula
Case (a) (b) (c) (d) for a general case of [spherical, Cylinder, Angle],
(dp/p)(A) -0.08 -0.1 -0.13 -0.09 noting that the negative and positive cylinder are
(B) +0.08 +0.1 +0.2 +0.26
rotated by 90 degrees. The shape factor (P) change
Note: (A) for central zone, (B) for peripheral zone of above 2-step procedure is given by:
Comparisons of CM and PM for the corneal shape ———————————————————————
Δ = [1/(1+B)2 - 1]P, (10.a)
and spherical aberration (SA)
CM PM Δ > 0 (less prolate, after myopic LASIK)
Corneal shape (A) Central large small Δ < 0 (more prolate, after hyperopic LASIK)
(degree of prolate)(B) Peripheral small large B = (D’ + D)R/377, (10.b)
——————————————————————————— R = preoperative corneal front surface radius
Spherical aberration (A) Central small large
(B) Peripheral large small D and D’ = correction power in sequential ablation
———————————————————————
480 Mastering Advanced Surface Ablation Techniques
• Effect of ablation diameter (W) (for fixed D= -
5.0 diopter, C=0)
W (mm) 4.0 5.0 6.0 6.5
———————————————————
H’o (μm) 26.7 41.7 60.0 70.4

• Effect of high-order term (C) (for r1=7.7 mm,

or K=43.2 D):
W (mm) 6.0 6.5 7.0
————————————————
C (%) 11.2 13.2 16.5
b. Central ablation depth for multi-zone
Figure 56.5: Ablation profiles of negative and positive Ho (3-zone) = Rd Ho (single-zone),
cylinder correction where the reduction factor Rd=(0.70 to 0.85)
depending on the algorithms used
which define the power and radius of each zone.
Table 56.2: Converting mixed astigmatism For example, comparing to a single zone with W=6.5
Conversion formula: mm, a multizone depth will reduces to 71.6% (or
[a, b x A1] = [1+b, -b x(A1 - 90)] Rd=0.716) when a smaller inner zone of 5.5 mm is
Spherical equivalent (SE) = (a + b)/2
(a) [+5.0, -3.0 x 180] = (b) [+2.0, +3.0 x 90] (SE = +3.5) used.
(c) [-3.0, -2.0 x 180] = (d) [-5.0, +2.0 x 90] (SE = -4.0)
Aspherical Surface
LASIK ABLATION NOMOGRAMS As shown in Figure 56.6, the human eye typically has
a negative Q for corneal surface and positive Q for
Most of the existing LASIK monograms are based on
the lens surface, in which whole eye optical aberration
spherical corneal surface. The customized nomograms
may be partially balanced by these two opposite
require aspherical surface in order to minimize the
components, particularly in young eyes. The shape
optical oberrations. Both cases are analyzed as
factor (p) is related to the asphericity (Q) by p = Q +
follows.
1, where Q = 0 (or p = 1) representing a spherical
Spherical Surface surface. Greater detail of Q may be found in the book
of Atchison (2002).
• Paraxial (second-order): a. Conicoid surface
hyperopia: H(y) = 4 Dy2/3 (11.a)
Z(y) = [R – (R2 –py2)1/2]/p (13)
myopia: H’(y) = H(y) – H(d)
where:
• High-order
Z: distance along the optical axis
hyperopia: H”(y) = H (1+C) (11.b)
y: distance from the optical axis
myopia: H”(y) = H”(y) - H”(d)
R: vertex radius of the corneal front surface
where:
P: shape-factor, P = Q + 1.
C = 0.19 (W/R)2 is the high-order term
Q: corneal asphericity, Q = P – 1.
d = ablation radius (in mm)
b. Polynomical expansion of Z(y)
W= ablation zone (W = 2d)
Z(y) = Zo + Z2 + Z4 + Z6 + .... (14)
a. Central ablation depth of single-zone
c. LASIK ablation profile
H’o = H’ (y = 0)
Hyperopia:
= -(DW2/3)(1 + C) (12)
H(y) = Z(R’, p’, y) – Z(R, p, y)
• For fixed W=6.0 mm (C = 0 case)
= H2 + H4 + H6 + ···· (15.a)
D -2 -5 -10 (in diopter)
——————————————— Myopia:
H’o 24 60 100 (in μm) H’(y) = H(y) – H(d) (15.b)
 Theoretical Aspects of Customized Surface Ablation 481
For myopia (R’>R): p’ > p (more prolate)
For hyperopia (R’<R): p’< p (less prolate)
* where the measured values M’ are assumed to
be 30% higher or lower than the nth-order
approximation A(1), that is, M’(m=2) = 1.3M”
(m=measure) for myopia and M’=0.7 M” for
hyperopia correction. These values also allow us to
calculate the corresponding power m=4.5 (myopia)
and 6.0 (hyperopia).
Figure 56.6: The Q-value of human eye Example, for typical value of R=7.7 mm, the slope
function is given by (for various correction power D
H2 = (4D/3)y2 (16.a) and m=2 case)
H4 = –(1/8R3)y4(p–Bp’)
D –2 –5 –10 +2 +5 +10
H6 = –(1/16R5)y6 (p2-B5/3 p’2) —————————————————————
B = (R/R’)3 =[1 + RD/377]3 (16.b) M’ 1.1 1.24 1.58 0.92 0.82 0.65
d. Central depth (myopia)
Figure 56.8 shows the chart for Q’ vs. Q based on
Ho = –(DW2/3)(1+C’), (17)
C’ = 0.19p(W/R) ,2 m=2 case, where (+, -) stands for (oblate, prolate).
which reduces to that of spherical case when p=1.0 b. Change of Q values
(or Q=0). Transition point defined by p’=1.0, or post-LASIK
asphericity Q’=p’-1=0, or the pre-LASIK value of
Asphericity Control Q*=(R/R’) m -1. It also provides the extra
It was well known that the shape factor (p) or Q information of the post-LASIK corneal shape
increases after myopic-LASIK and decreases after depends on the initial shapes. Examples are shown
hyperopic-LASIK. The amount of these changes also in Figure 56.7 for myopic and hyperopic LASIK.
an increasing function of the power of corrections as These trends are consistent with the measured
shown in Figure 56.7. the non-linear behavior is due data of Marcos et al (2003).
to the non-linear dependence of B=(R/R’) 3 =
(1+0.0204 D )3.
a. Correlated case
The shape factor post-LASIK (p’=Q’+1) is
correlated to its initial (or preoperative)
value (p) by
p’ = B-Np = (R’/R)mp = M’p,(18.a)
M’= 1/(1 + RD/377)m, (18.b)
= 1/(1 + 0.0204 D)m,
for typical R=7.7 mm.
where the m-power depends on the ablation
algorithms used:
——————————————————————
m = 2 (for nth-order approx of Lin.)
m = 3 (for second-order approx of Jimenez.)
m = (4.5 to 6.0) (fit to measurements)* Figure 56.7: The increase (and decrease) of the pre-operative p
(or Q) after myopic (and hyperopic) LASIK
——————————————————————
482 Mastering Advanced Surface Ablation Techniques
c. Non-correlated case
If p’ and p are not correlated, particularly for
actual LASIK procedures in which the ablation rate
(and profile) affected by biomechanical factors,
then the ablation for myopia LASIK is given by
H(y) = H2(y) + H4(y) (19.a)
H2 = – (4D/3) (d2-y2), (19.b)
H4 = (1 – B)CP + M ?P (19.c)
C = 10 [(d -y )/(8R )] , (19.d)
3 4 4 3

where ΔP = p’ – p, B=(R/R’)3 and d is the ablation

radius. A negative slope function is defined by M =
– CB representing the reduction of profile depth (in
micron) per 1.0 increase of the shape factor (ΔP). In
the above expression, H in micron, D in diopter and
R, R’, d, y in mm.
Note that the M-function has a strong D
dependence of via B given by B = (1 + 0.008RD) (1 +
Figure 56.8: A code chart for the predicted post-LASIK corneal 0.02D).
asphericity (Q’) versus the preoperative value (Q). Curve (1) (2) (3) For example, B = (0.59, 0.72, 1.34, 1.57) for D = (–
(4) are for LASIK correction power of –8.0, –5.0, +5.0 and +8.0
diopter, respectively. It shows four areas defined by notations of 8.0, –5.0, +5.0, +8.0) diopers, for d = 3.0 mm, R = 7.7
(+, +) stands for both preop and postop surface are oblate (with Q, mm. The associate M (at y = 2.0 mm) is calculated M
Q’>0), (+, –) for preop is oblate and postop is prolate, etc.
= (10.5, 12.8, 23.9 and 27.9) um.
d. Maximum ablation depth (Ho)
Defining : Q1 = pre-LASIK, Q2 = post-LASIK Ho defined by H(y) at y=d for myopia), or at
EXAMPLE # 1 y=d (for hyperopia) can be derived from Eq. (19)
For myopia –5.0 D correction, Q2 = 1.23 (Q1 + 1) to be
–1. Ho = (4D’/3)d2 [ 1+ C’] – BC’ ΔP (20.a)
Therefore an initial Q1 = – 0.1 (prolate) will result C’ = 0.75 P(d/R)2, (20.b)
in Q2 = + 0.11 (oblate); and initial Q1 = – 0.4 result where D’ is defined as the absolute value of the
in correction power (D). The significance of above new
Q2 = – 0.26 (less prolate). formula may be summarized as follows.
EXAMPLE # 2 For spherical surface (with P = P’ = 1.0, ΔP = 0 ),
For hyperopia +0.5 D correction, Q2 = 0.826 (Q1 + Ho = Hparax(1 + C), with C= 0.75 (d/R), reduced to
1) –1. Therefore an initial Q1 = + 0.1 (oblate) results that of the so-called paraxial approximation(PA)
in Q2 = – 0.09 (prolate); and Q1 = + 0.4 results in Hparax when the second-order is ignored (C=0).The
Q2 = 0.16 (less oblate). existing laser ablation algorithms are believed to rely
Depending on the initial corneal shape (p or Q), on the PA of Munnerlyn formula which provides no
information about the change of the corneal
the post-LASIK corneal shapes are shown in Table
asphericity (or its shape) even high-order or exact
56.3.
Table 56.3: Prediction of corneal surface shape formula is used. Discrepancy was found in measured
(asphericity, Q) after LASIK postoperative corneal asphericities and predictions
LASIK Pre-operative Post-operative based on several proposed algorithms including the
Q1 < Q1* Q>Q* optical surface loss of laser energy and other
Myopic PRO less PRO OB biomechanical effects.
OB —— more OB
Hyperopic PRO more PRO —— SURFACE ABERRATION
OB PRO less OB
* where Q* is a transition value defined by when Q’=0. As shown in Table 56.4, optical aberration may be
Shorthand notations used: PRO for prolate and OB for oblate defined by the Zernike polynomials which are similar
 Theoretical Aspects of Customized Surface Ablation 483
Table 56.4: Summary of optical aberration defined by Zernike c. Refractive error (De)
coefficients
Defocusing due to myopic-shift induced by corneal
(A) Monochromatic
Defocus (second-order) Coma (third-order)
positive SA for optimal image (Atchison and Smith,
Spherical (fourth-order) Field curvature (second- 2000)
order) De = –2Wb2, (23.a)
Astigmatism (second-order) Distortion (first-order) W = (198.6 + 376Q)/R 3
(23.b)
(B) Chromatic
Longitudinal, Transverse for W’ in the unit of um/mm 4 and R in mm.
(1) Seidel Aberration (surface contribution, relaxed eye)
Therefore an idea corneal surface W’=0 is defined by
Cornea (+80%, -10.4%), cornea-lens separation (-5.6%) Q = Q* = –0.527. However, for minimal whole eye
Lens (+13.1%, +22.9%), total power 60.29 diopter. PSA or W(whole) = 0, one shall have W’ = –W”, or
For (r1, r2) = (7.8, 6.5), (R1, R2) = (10.5, 6) and S = 6( all in
Q* = (-R3W” – 198.6)/376, (24)
mm)
which depends on the lens SA (or W”) and Q* is
(2) Typical aspherical data (Q-value) for (front, back) surface
Cornea (–0.3, –0.66), ideal surface Q=–0.527 larger than its ideal value (–0.527).
Lens (–0.94, +0.96), for relaxed eye (Louis & Brennar) As reported by Smith et al 23 that lens has negative
SA, however, it is not clear what the causes are. They
to the expansion coefficients of the Z(y) defined by proposed three sources of SA: the front, back surface
Eq. (13) and (14) asphericity and the bulk refractive index distribution
a. Prime spherical aberration (PSA) in addition to the age-related factors. Therefore,
For a given final state asphericity (Q’) and corneal customized change (or control) of the corneal
anterior surface radius R2, the PSA is given by asphericity for minimal SA depends on the individual
(Manns et al, 2000) lenticular SA (W”). For higher negative W”, smaller
Sj = Wjb4, (21.a) Q* (of the cornea) would be needed as shown by
W1 = –0.046 (0.535 + Q’)/R3, (21.b) Eq.(7). This optimal value (Q*) for minimal whole
where j = 1, 2, 3, 4 stands for the PSA of anterior eye SA also depends on the corneal front surface
and posterior surface of the cornea and lens, b is the radius (R) and the contribution from its posterior
ray height on the corneal surface. Therefore, the surface which has a typical value about –0.6. For a
change of corneal PSA is given by typical value of W = +0.038, De = –0.29 diopter at
dS1 = 0.046(b4/R3)(dp’), (21.c) pupil diameter (b) of 6.0 mm comparing to b=2.0 mm.
b. Change of shape-factor The ideal corneal surface with W = 0 gives Q = Q* =
It may be derived from Eq. (19) and M=-CB, with –0.527 as seen from above formula.
R = 7.7 mm, d. Whole eye aberration
dp’ = dH/M (22.a) It was known that the PSA contributed from the
M = 0.274B(d4-y4), (22.b) lens is normally negative, whereas cornea has
where dH is the ablation depth change. As an positive contribution and has larger value than
example, for d = 3.0 mm and D1 = –2.0 diopter, B = that of lens. Therefore, the PSA of the whole eye
0.882, M = (19.3, 15.7) microns at y = (1.0, 2.0) mm. in general is positive and may be expressed as
Therefore, the PSA change due to corneal shape follows
change at y = 2.0 mm, and for post-myopic LASIK W(whole eye) = W’(cornea) + W”(lens), (25)
radius of R = 8.15 mm as an example, dS1 = 0.254(dH), For typical mean value of W” = –0.026 (range
that is a positive PSA increase of 0.254 microns per –0.015 to –0.04) and W’ mean of +0.032 (range of 0.02
1.0 micron corneal surface ablation depth which causes to 0.04), one expects W(whole eye) is a positive mean
the increase of the corneal asphericity. This is in value of 0.005 (range of 0.002 to 0.02) depending on
consistent with the reported data that induce positive the shape of the cornea and lens which are also age
PSA were found in myopic LASIK procedures. dependent.
484 Mastering Advanced Surface Ablation Techniques
As reported by Smith et al that lens has negative 8. Gatinel D, T Hoang-Xuan, Azar D. Determination of
corneal asphericity after myopia surgery with the excimer
SA, however, it is not clear what the causes are. They
laser: a mathematical model. Invest Ophthalmol Vis Sci
proposed three sources of SA: the front, back surface 2001;42:1736-42.
asphericity and the bulk refractive index distribution 9. Gatinel D, Joang-Xuan T, Azar D. “Analysis of cuotomized
in addition to the age-related factors. Therefore, coreal ablations: theoretical limitations of increasing
negative asphericity. Invest Ophthalmol Vis 2002;43:
customized change (or control) of the corneal 941-8.
asphericity for minimal SA depends on the individual 10. Gonzalez-Meijome JM, Villa-Collar C, Montes-Mico R,
lenticular SA (W”). For higher negative W”, smaller Gomes A. Asphericity of the anterior human cornea with
different corneal diameters. J Cataract Refract Surg 2007;
Q* (of the cornea) would be needed as shown by 33:465-73.
Eq.(25). This optimal value (Q*) for minimal whole 11. Jimenez JR, Anera RG, Diaz J, Diaz A, Perez-ocon F.
eye SA also depends on the corneal front surface Corneal asphericity after refractive surgery when the
Munnerlyn formula is applied. J Opt Soc Am. (A)
radius (R) and the contribution from its posterior
2004;21:98-103.
surface which has a typical value about –0.6. 12. Koller T, Iseli HP, Hafezi F, Mrochen M, Seiler T. Q-factor
customized ablation profile for the correction of myopic
CONCLUSION astigmatism. J Cataract Refract Surg 2006; 32:584-9.
13. Lee H, Oh JR, Reintein DZ, et al. Conservation of corneal
The formulas presented in this Chapter for LASIK tissue with wave-front-guided laser in situ keratomileuse.
J Cataract Refract Surg 2005;31:1153-8.
procedures are based on the available, published 14. Lin JT. Multiwavelength solid state laser for ophthalmic
articles. They may be revised, updated or even applications. Proc SPIE 1992;1644:266-75.
corrected by further newer developments. New 15. Lin JT. Mini-excimer laser corneal reshaping using a
scanning device. Proc SPIE 1994;2131:228-36.
information may become available by contact the
16. Lin JT. Scanning laser technology for refractive surgery.
author at his email address: [email protected]. In: Garg et al. Mastering the techniques of corneal
refractive surgery. New Delhi, India, Jaypee Brothers;
BIBLIOGRAPHY 2005;20-36.
17. Lin JT. Critical review on refractive surgical lasers. Opt.
1. Anera R, Jimenez JR, Barco LJ. Equation for corneal Engineer 1995;34:668-75.
asphericity after corneal refractive surgery. J Refract Surg 18. Lin JT. Bifocal profiles and strategies of presbyopic-LASIK
2003;19:65-9. for pseudo-accommodation. J. Refract Surg 2006;22:736-
2. Anera RG, Jimenez JR, Barco LJ, Hitta E. Change in corneal 8.
asphericity after laser refractive surgery, including 19. Lin JT. A new formula for ablation depth in 3-zone LASIK.
reflection loss and nonnormal incidence upon the anterior J Refract Surg 2005;21:413-4.
cornea. Opt Lett 2003;15:417-9. 20. Lin JT. The generalized refractive state theory and
3. Atchison DA, Smith G. Optics of the human eye. Boston, effective eye model. Chinese J Optom & Ophthal 2005;7:
MASS: Butterworth Heinemann 2000. 1-6.
4. Avalos G, Silva A. Presbyopia LASIK-the PMMA 21. Lin JT. Prediction and control of corneal asphericity after
technique. In: Agarwal A. ed. Presbyopia, a surgical refractive surgery. J Refract Surg 2006;22:848-9.
textbook. Thorofare NJ: SLACK; 2004;139-46. 22. Lin JT. A New Algorithm for Controlling Corneal
5. Azar DT, Primack JD. Theoretical analysis of ablation Asphericity in LASIK. In: Garg A Lin JT (Ed) “Mastering
depths and profiles in laser in situ keratomileusis for the Techniques of LASIK, EpiLASIK and LASEK
compound hyperopic and mixed astigmatism. J Cataract (Techniques & Technology)”. New Delhi: Jaypee
Refract Surg 2000;26:1123-36. Brothers, 2006, Chapter 35.
6. Cantu R, Rosales MA, Tepichin E, et al. Objective quality 23. Manns F, Ho A, Parel JM, Culbertson W. Ablation profile
of vision in presbyopic and non-presbyopic patients after for wavefront-guided correction of myopia and primary
pseudoaccommodative advanced surface ablation. J spherical aberration. J Cataract Refract Surg 2002;28:766-
Refract Surg 2005 (Suppl.); 21:S603-5. 74.
7. Deutsch TF, Geis MW. Self-developing UV photoresist 24. Pinelli R, Ngassa N, Scaffidi E. Sequential ablation
using excimer laser exposure. J Appl Phys 1983;54: approach to the correction of mixed astigmatism. J Refract
7201-4. Surg 2006;22:787-94.
 CHAPTER
Clinical Aspects of High-
57 order Aberration after
Myopia LASIK

JT Lin (Taiwan), FJ Zhang, Lu Yang (China)

INTRODUCTION

Customized corneal surface ablation may be achieved

by either topography-guided ablation (TGA) or
wave-front-guided ablation (WGA), where supper
vision is achievable via various techniques 1,2
including:
ƒ minimized high-order surface aberrations (SA),
ƒ using TGA to correct the corneal front surface
irregularity,
ƒ using WGA to correct the internal SA from the
lens and from the whole eye (cornea plus lens),
ƒ using aspherical surface ablation based on the
initial corneal conditions including the high-order
nonlinear profile, where the pre-operative
parameters of the cornea shall include the anterior
(or K-reading), posterior surface radius, and the
shape factor.
Figure 57.1: The age dependence of spherical aberration of the
It has been known3-11 that a myopic correction cornea (W’), lens(W”) and the whole eye (W).
produces higher Q-value, or the corneal surface
becomes less prolate or even oblate; whereas a of the lens, particularly during youth.12,13 When one
hyperopic correction produces an opposite effect. ages, the surface aberration of the lens changes from
Therefore, it is desired to calculate and control the about –0.25 micron to about +0.25 micron and results
postoperative anterior corneal shape (or its in an increased total positive spherical aberration.
asphericity) with aberrations that can either In this Chapter, we shall present the additional
compensate the LASIK-induced increase of SA or clinical aspects of the individual SA and the overall
slightly more prolate than necessary to account for SA which may be influenced by the pupil sizes and
age effects of the lens. the age. Results based on myopic and astigmatism
It was known Figure 57.1 that in normal eyes, the LASIK will be shown. Analysis will be presented by
aberration of the cornea tends to balance with that the age and pupil size dependence of the root-mean-
486 Mastering Advanced Surface Ablation Techniques
2square (RMS) values of selected Zernike terms of Table 57.2: The RMSh of left and right eyes at different pupil (x ± SD,
n = 180)
C12 (spherical), C7 (vertical coma), C8 (horizontal
pupil
coma) and the total SA.14 4 5 6 7
left eyes 0.088±À0.049 0.125±À0.068 0.170±À0.071 0.225±À0.098
METHODS right eyes 0.091±À0.040 0.129±À0.053 0.175±À0.071 0.227±À0.098
F 0.001 0.198 0.095 0.305
P 0.970 0.657 0.758 0.581
LASIK patients were diagnosed with myopia and
3. There was a negative relationship between C7 and
myopic astigmatism and having no indications of any
BCVA ( r = – 0.147, P = 0.05) in the 4 mm pupil,
other ocular diseases. The LASIK procedures were
but there was no significant relationship between
conducted at the Refractive Center, the First Hospital
C8 and BCVA. There was a negative relationship
affiliated to the Dalian Medical University (China).
between C12 and BCVA ( r = –0.151 , P = 0.044) in
There were 142 cases (273 eyes), 40 males (80 eyes),
6 mm pupil .
and 102 females (193 eyes). The average age was
4. There was no significant difference between the
(29 ±9.50) years, range of 19–40 years. Spherical
left and right eyes for higher order aberrations in
refraction was (–5.36 ±1.57) D, range of –2.25 to myopia (P > 0.05) nor was there a significant
–7.00 D; and cylindrical refraction was (–0.72 difference between males and females (P > 0.05).
±0.47)D, range from –0.25 to –2.75 D. Best corrected 5. There was a significant negative relationship
visual acuity (BCVA) was 0.99 ± 0.11 (0.8~1.2). between C7 and age (P < 0.01) , but there was no
Aberration analysis was based on the Tscherning relationship between C8 and age (P > 0.05).
theory with system made by WaveLight (Germany). However , there was a positive relationship
All the wave-front data were taken by the same between C12 and age (P <0.01).
operator, each subject was measured four times and 6. There was a positive relationship between RMS3/
the set of data having the most repeatable RMS, high- RMSh and astigmatism (P < 0.05) and between
order SA and minimum refractive measured RMS5 and astigmatism when the pupil was larger
difference was recorded. For each subject, the than 6 mm (P < 0.05). There was also a positive
individual RMS SA (RMS 3–6), C7, C8 and C12, and relationship between RMS6 and sphere when
the total RMS (RMSh) were recorded and analyzed the pupil was larger than 6 mm (P < 0.05) (Table
by SPSS 10.0 software. 57.3).
Table 57.3: The relationship between RMS3, RMS4, RMS5, RMS6,
RESULTS *
RMSh and astigmatism(n=180)
RMS3 RMS4 RMS5 RMS6
1. The gender dependence (as shown in Table 57.1),
*

r P r P r P r P
is not significant.
*

4 0.169 0.024* 0.172 0.021* - -

2. As shown in table 57.2, There was no significant
*

5 0.187 0.012* 0.178 0.017* 0.069 0.357 - -

*

difference between the left and right eyes for 6

*
0.210 0.005 **
0.221 **
0.003 0.184 0.013 *
0.245 0.001 **

higher order aberrations in myopia ( P> 0. 05) nor *

7 0.220 0.003 **
0.241 **
0.001 0.197 0.008 **
0.191 0.010

was there a significant difference between males

DISCUSSIONS
and females ( P> 0. 05).
Table 57.1: The RMSh of male and female at different pupil (x ± SD)
Data Analysis
pupil Our clinical data showed that there is no significant
n 4 5 6 7 difference of the high-order SA (HoA) between male
male 54 0.092±À0.057 0.129±À0.078 0.169±À0.078 0.218±À0.103 and females. The high HoSA symmetric between left
female 126 0.088±À0.038 0.126±À0.052 0.170±À0.068 0.228±À0.095
F - 0.021 0.356 0.923 0.667 and right eyes are consistent with that of Mrochen
P - 0.567 0.722 0.673 0.506 et al.5,8
 Clinical Aspects of High-order Aberration after Myopia LASIK 487
For pupil size of 4 mm, There was a negative produces an opposite effect. This general trend may
relationship between C7 and BCVA ( r = –0.147, P be easily realized by the following.
=0. 05), but there was no significant relationship The shape factor preoperative (p) and
between C8 and BCVA. These results imply that the postoperative (p’) is correlated by1,2,9
negative C7 will have improved BCVA for pupil size p’=(R’/R)mp, (1)
4 mm. However, there was no significant relationship where m=1.0 in first-order approximation 9,10
and
between C7, C8, C12 and BCVA for larger pupil size 1,2
m=2/3 in high-order. R and R’ are the corneal front
of 6 mm. This implies that the BCVA at larger pupil surface radius pre- and post-operatively. For myopic-
size is influenced by mutiple factors and can not be LASIK, R’>R, therefore p’>p, that is, an increase of p
described by any single factor. or the asphericity (Q). In contrast, hyperopic-LASIK,
There was a significant negative relationship
R’<R, therefore p’< p or a decrease of p (or Q). The
between C7 and age, but there was no relationship
above trend also explains the clinically measured
between C8 and age. However, there was a positive
increasing of positive spherical aberration (SA) after
relationship between C12 and age. These results may
myopic LASIK and vice versa after hyperopic LASIK.
be analyzed as follows.
The conical shape of the anterior corneal surface
Age-dependence may be described by the asphericity Q or the shape
factor p=Q+1, where Q equals –0.18 to –0.3 for a
It was reported by Mrochen et al5,8 that for patients
typical natural prolate cornea,13 and about 1% of the
older than 40, their normal wavefront aberration
population may have positive Q-value (or oblate
increases as ages grow. They proposed that this age-
surface).
induced phenomena may resulted from the lens
It was known that the SA contributed from the
density continuing increasing and the change of the
lens is normally negative, whereas cornea has positive
refractive index gradient and the increase the positive
contribution and has larger value than that of lens.
lens spherical aberration, which in turn, break the
Therefore, the SA of the whole eye in general is
balancing relationship of the SA between the lens and
positive and may be expressed as follows:
cornea surfaces. In addition, for pupil size larger than
6 mm, the RMS6 is significantly influenced by the W(whole eye) = W’(cornea) + W”(lens), (2)
lens power, however the total RMS remains For a typical mean value of negative W”(in lens)=-
unchanged. This also implies that there is a balancing 0.026 (range –0.015 to –0.04) and positive W’ (in
relationship for the whole eye which reduces the cornea) mean of +0.032 (range of 0.02 to 0.04), one
increase of SA due to myopia. expects W(whole eye) is a positive mean value of 0.005
It was calculated by Lin and Jiang (by ray-tracing (range of 0.002 to 0.02) depending on the shape of
method, unpublished data) that each 1% increase (or the cornea and lens which are also age dependent
0.142) the refractive index of the lens will result in a (see Figure 57.1).
refractive power about (2.0 to 2.5) D increase. For a relaxed eye, the corneal SA (with refractive
Therefore the age-induced refractive index increase index of 1.376) may be expressed by:13
of the lens may result in defocusing and/or change W’(cornea) = (198.6 + 376Q)/R3, (3)
the overall SA compensation (balancing) with the for W’ in the unit of um/mm 4 and R in mm.
cornea. Therefore an idea corneal surface W’=0 is defined by
Q=Q*=-0.527. However, for minimal whole eye SA
Whole-eye Spherical Aberration or W(whole)=0, one shall have W’ = –W”, or
It was known2-8 that a myopic correction produces Q* = (–R3W” – 198.6)/376, (4)
higher Q-value, or the corneal surface becomes less which depends on the lens SA (or W”) and Q* is
prolate or even oblate; whereas a hyperopic correction larger than its ideal value (–0.527).
488 Mastering Advanced Surface Ablation Techniques
As reported by Smith et al12,13 that lens has negative and general higher order aberrations become
SA, however, it is not clear what the causes are. They larger.
proposed three sources of SA: the front, back surface ƒ Coma is mainly affected by astigmatism, and
asphericity and the bulk refractive index distribution spherical aberration(C12) is mainly affected by
in addition to the age-related factors. Therefore, age.14
customized change (or control) of the corneal ƒ Complex factors such as C7, C12 and age, etc.
asphericity for minimal SA depends on the individual should be analyzed before customized corneal
lenticular SA (W”). For higher negative W”, smaller laser ablation surgery is performed.
Q* (of the cornea) would be needed as shown by ƒ Eyes with higher order aberration values, corneal
Eq.(4). This optimal value (Q*) for minimal whole eye irregularity, a larger pupil or enhancement are
other factors that should also be taken into
SA also depends on the corneal front surface radius
consideration.
(R) and the contribution from its posterior surface
ƒ The age-dependent SA of the lens should be
which has a typical value about –0.6.
included in customized LASIK, such that the
It was known (Figure 57.1) that in normal eyes,
balance between the SA of the cornea and lens
the aberration of the cornea tend to balance with that
may be achieved for minimum whole-eye SA,
of the lens, particularly during youth.12,13 When one
when eye ages.2-4
ages, the surface aberration of the lens changes from
about –0.25 micron to about +0.25 micron and results
REFERENCES
in an increased total positive SA. It is possible to
calculate and control the postoperative anterior 1. Lin, JT. Prediction and control of corneal asphericity after
corneal shape (or its asphericity) with aberrations that refractive surgery. J Refract Surg 2006;22:848-9.
2. Lin, JT. The mathematical handbook of LASIK. In:
can either compensate the LASIK-induced increase
Mastering the techniques of customized LASIK”, In: Garg
of SA or slightly more prolate than necessary to A, Rosen E, Lin JT, et al, eds. New Delhi: Jaypee Brothers
account for age effects of the lens. A controlled 2007, Chapt. 8.
ablation algorithm can also produce the desired 3. Lin, JT. A refined algorithem for controlling post operative
corneal asphericity in Lasik, same as above, Chapt. 35.
corneal shape to compensate the aberrations resulted 4. Lin, JT. Customized aspherical ablation for minimal
from other optical factors such as laser power aberration. Same as above, Chapt. 50.
reflection loss, reduced laser fluence due to abnormal 5. Mrochen M, Kaemmerer M. Increased high-order optical
aberrations after laser refractive surgery. J Cat Refract
incidence, and other tissue related factors such as Surgery 2001;27:362-9.
wound healing, epithelial hyperplasia and other 6. Manns F, Ho A, Parel JM, Culbertson W. Ablation profile
biomechanical effects.8,11 for wavefront-guided correction of myopia and primary
spherical aberration,”. J Cataract Refract Surg 2002;28:766-
74.
CONCLUSION 7. Berrio E , Guirao A , Redondo M. The contribution of the
corneal and internal optics aberrations changes with age.
Based on our studies, we may address the following Invest Ophthalmol Vis Sci 2000;41:545.
conclusion regarding the SA: 8. Seiler T , Kaemmerer M, Mierdel P, et al . Ocular Optical
ƒ For higher order aberrations, there are no Aberrations after Photorefractive Keratectomy for
Myopia and Myopic Astigmatism. Arch Ophth 2000;118:
significant differences between the left and right
17-21.
eyes; there is also no significant difference 9. Jimenez JR, Anera RD, Diaz JA, Perez-ocon F, “Corneal
between genders. asphericity after refractive surgery when the Munnerlyn
ƒ With an increase in age, higher order spherical formula is applied”, J. Opt. Soc. Am. (A) 2004;21:98-103.
10. Anera RG, Jimenez JR, Barco LJ, Hitta E. Change in corneal
aberrations become larger while the value of
asphericity after laser refractive surgery, including
vertical coma becomes smaller. With an increase reflection losses and nonnormal incidence upon the
in refractive astigmatism, the values of the coma anterior cornea”, Opt. Lett 2003;15:417-9.
 Clinical Aspects of High-order Aberration after Myopia LASIK 489
11. Marcos S, Cano D, Barbero S. Increase in corneal 13. Atchison DA, Smith G. Optics of the human eye. Woburn,
asphericity after standard laser in situ keratmileusis for MA: Butterworth-Heinemann 2000;14-16,143-7, 160-2.
myopia is not inherent to the Munnerlyn algorithm. J 14. Zhang Feng-ju, Yang Lu, Yu Fang-lei, et al. A study of
Refract Surg 2003;19:S592-6. higher order aberrations in myopia and myopic
12. Smith G. et al. The spherical aberration of the crystalline astigmatism. Chinese J of Optometry & Ophthalmology
lens of the human eye. Vision Res 2001;41:235-43. 2006;8:112-4.
490 Mastering Advanced Surface Ablation Techniques

CHAPTER

58 Solid State Lasers for

Advanced Surface Ablation

Emanuel Rosen (UK), Tarak Pujara (Australia)

BASIC LASER BACKGROUND Laser Pumps

Light Amplification by Stimulated Emission of Lasers need to consist of a ‘pump’ (a source energy
Radiation to energize the atoms) a ‘medium’ that contains the
atoms that do the lasing, and a cavity consisting of
What is Light? Sometimes light behaves as if it is
mirrors to direct that light backwards and forwards
composed of waves and at other times as if it is
through the energized media to allow the ampli-
composed of particles. For this reason, the nature of
fication process to grow to a useful level.
light is often difficult concept to grasp. Light is a
There are many different methods for pumping
transverse electromagnetic wave, the energy ‘waves’
lasers ranging from chemical reactions to electron
as it oscillates between an electric field and magnetic
beams. Probably two of the most common forms of
field. For light to also have the properties of a particle,
pumping involve either electrical discharge or current,
it is useful to consider these waves to come in packets
and light energy produced by either flash lamps,
of a limited size (photons).
diodes or another laser.
When the electrons spinning around an atom are
energized to a higher energy orbit and then decay
Laser Media
back to lower energy orbit, they can give off a photon
of a light. The wavelength of this light is inversely The laser medium also comes in a large number of
proportional to the energy lost by the electron, which variations covering all the states of matter. Lasers
in turn dependent up on the type of atom. This with a gas medium include CO2 lasers, excimer lasers
process of light generation is called spontaneous and argon lasers; dye lasers have a liquid medium,
emission, where stimulated emission occurs when while neodymium:YAG (Nd:YAG) and diode lasers
this event is triggered by another photon that has an are examples of solid medium lasers.
identical wavelength to that which the atom will Nd:YAG lasers are solid medium lasers that are
produce. The amplification process is thus one photon often pumped with flash lamps. In the laser, the
triggering the release of a second, nearly identical medium is neodymium atoms. The YAG crystal holds
photon. In a laser, each photon may then go on and the neodymium atoms in place and help to transfer
trigger two more photons and so on. the flash lamp pump energy to the neodymium atoms.
 Solid State Lasers for Advanced Surface Ablation 491
It is vital that the pumped medium be in a state of At one end of the box, aligned with the gap between
population inversion for lasing to occur. Population the electrodes, a minor is mounted and at the other
inversion is when more than half of the atoms in the end a window. The window is usually an uncoated
medium are energized to an excited state. An atom optic. The small amount of reflection that normally
that is capable of being excited and then stimulated occurs from each surface is enough to provide laser
to emit a photon of light will also resonantly absorb action.
a photon of the same wavelength when not excited. Outside the box there is usually a large bank of
Hence, it is easy to perceive that unless there are capacitors and these are charged using a high voltage
more atoms in an excited state than in a non-excited power supply to several tens of kilovolts. A special
state, then the absorption process will exceed the switch (thyraton) is used to dump the energy stored
stimulated emission process and amplification will in these capacitors across the electrodes inside the
not occur. box. The electrical discharge through the gas between
the electrodes ionizes the gas and allows the excimer
Common Properties of Lasers molecules to form. Lasing action usually occurs within
Light from a laser has a number of properties that nanoseconds.
make it different from other light sources. Firstly,
Disadvantages of Excimer Laser
the divergence of a laser beam is much, much lower
than that of other light sources. This allows the laser High Voltage Requirement
beam to be confined to very narrow beams and to be
The amount of energy involved and the rate with
focused to very small spot sizes. Secondly, laser light
which it needs to he delivered across the electrodes
is usually monochromatic, that is, the light is of a
to make excimer laser work is very high. With
single very pure color (single wavelength). Thirdly,
voltages around 30,000 volts and currents of
laser beam light is usually coherent, that is, all the
approximately 10,000 amps reached within 50 ns, the
waves of the photons are oscillating in phase with
electrical characteristics are like a bolt of lightning.
each other.
Early Replacement of Special Switch
EXCIMER LASER
A thyraton is usually used as a special switch to
Basic Concepts quickly initiate the discharge and carry the high
‘Excimer’ is a contraction of the term ‘excited dimer’. currents. Thyraton failures were quite common and
Dimers are usually considered to be molecules made they were costing many thousands of dollars.
up of two identical atoms. However the term However, modem excimer lasers, with improved
‘excimer’ has subsequently been extended to include discharge circuit designs and using techniques such
other excited molecules (though usually diatomic). If as electrical pulse compression and insaturable
two systems (atoms or molecules) do not form a inductors, have significantly reduced the load on
strong chemical bond when one of them is in an those switches and thyraton failures are now
excited state, then the bound excited state is called relatively uncommon.
an excimer.
Corrosiveness and Toxicity of Fluorine Gas
Currently ArF gas is used to generate 193 nm
wavelength for corneal ablation in Laser Vision To maintain the quality of the gas within the cavity
Correction. is another major problem. Excimer lasers are usually
Excimer lasers usually consist of a large, elongated specified to run at purities of 99.99995%. The fluorine
aluminum box. This box is filled with the appropriate in the gas usually makes up to 0.1% to 0.2% of the
gas mixture. Running the full length of this box is gas volume. However fluorine is an extremely reactive
two metal electrodes spaced about 2 to 3 cm apart. gas and can react with most materials that make up
492 Mastering Advanced Surface Ablation Techniques
the components inside the excimer laser cavity and High cost for Proper Storage of Toxic Gases and
will also react with most impurities that have either Training of a Technician
entered with the gas or are out–gasses from the High-pressure excimer gas cylinders are contained
material inside the laser cavity. These reactions not in a protected compartment in any excimer system.
only use up some of the fluorine gas, so that the lasing Storage of additional cylinders and the replacement
action becomes very inefficient, but also create of used cylinders must be done in accordance with
products that can absorb the laser radiation, interfere “Gas Safety’ and “Gas Maintenance” rules applicable
with the energy transfer process to the argon fluoride to each country.
excimers and form deposits on the laser cavity optics. The premix (argon/fluorine) gas mixture used in
These processes can also significantly interfere with this laser system is highly toxic. It is always
the lasing action. To make matters worse, the intense recommended that anyone working with the gas
UV and hot plasma which is formed by the electrical cylinders: 1) be trained in the proper handling of toxic
discharge between the electrodes helps to initiate and compressed gases, 2) know the location of the
many of the reactions that occur. emergency exhaust fan/room purifier switch, 3) have
Gas leakage (fluorine) is also a major problem. It easy access to all required protective equipment, and
may cause serious health problem. Gas discharge into 4) be familiar with safety procedures.
the atmosphere may be evident by a sharp,
penetrating odor and by eye, nose, and throat irri- Hydration Dependence of 193nm
tation.
Fluid on the cornea can result in a reduction of the
Recurrent Expenses of Excimer Gases ablation rate during refractive surgery procedures
with 193 nm laser pulses. This reduction in ablation
Argon and Fluorine have a shelf-life. Surgeries need rate is evidenced by the high degree of absorption
to be completed within a certain period of time after of 193 nm light in balanced salt solution (BSS).
the gas charge is dispensed to the laser head. This Underlying tissue, therefore, is effectively masked
results in restrictions on using the laser to maximize from incident radiation. An unknown reduction of
the usage of the gas charge. Consequently treatments the ablation rate can result in undercorrection or
are usually grouped together in a “List” and refractive errors or irregular ablations, such as the
performed on only one or two days a week. This formation of corneal island.
results in a lack of flexibility for patient treatment.
You cannot efficiently do treatments ‘as required’. Other Disadvantages of Excimer Laser
As the laser operates, fluorine is lost from the
• Large and bulky size of excimer laser will require
mixture and thus the fluorine must be replenished.
a big room to accommodate. This means higher
A common practice called “boosting”, is a process, in cost in develop cities to buy more space
which a small amount of the dilute fluorine/buffer • Excimer lasers create loud noises during operation
gas mixture is added to the laser to make up for the – may frighten patients
depletion of fluorine that occurs during normal • High power consumption to charge gases. It will
operation. This method can only be used for a given increase electricity bill
number of cycles after which the gas composition has • Small flying spot is very difficult to obtain and
been so altered the laser will not operate satis- custom surgeries require small flying spot for best
factorily. The gas charge must then be vented and results
the laser re-charged with a new gas mixture. • Longer warm up time
If not followed properly it will result in unwanted • Mature technology – little chances for further
downtime and increased gas expenditures. development.
 Solid State Lasers for Advanced Surface Ablation 493
SOLID STATE LASERS IN REFRACTIVE SURGERY progress much further and stopped production and
Over the years, there have been several attempts to dissolved.
develop and market solid state lasers for use in
refractive surgery. Currently only one company Present Situation
manufactures a solid state refractive laser and that is Currently the only company in the Solid State Laser
CustomVis, based in Perth, Australia. Pulzar Z1 is a in the Refractive market is the Pulzar Z1
trade name for their commercial solid state laser. It manufactured by CustomVis based in Perth, Western
is now clinically proven that it is an equivalent or Australia. CustomVis, founded in March, 2001, is
superior to available excimer refractive lasers in terms aiming to be a major force in the refractive surgery
of simplicity, safety, predictability and reliability, industry over the coming decade. It has installations
which will take refractive surgery to the next level. in 9 countries including Europe, South America and
The current excimer technology is approaching the Asia pacific. The company has a strong financial
end of its product development cycle and will be position from which to develop and move ahead
replaced by Solid State Laser. It resolves all the (Figure 58.1).
disadvantages of excimer laser and gives a definite
and reliable refractive system in the hands of a
surgeon.

SOLID STATE LASER

History
Attempts had been made in the late 1980s included
nanosecond and picosecond YAGs or YLFs that
operated in the near infrared (IR) or at green wave
lengths. Phoenix Laser Systems, headed by Alfred
Sklar, attempted to take advantage of photo-
disruption with a doubled YAG. Intelligent Surgical
Lasers, under Josef Bille, used fast-pulsed near IR to
vaporize tissue. Both lasers attempted to perform
intrastromal ablation within the cornea without
affecting a corneal surface. The results were not very
good and not reproducible.
Figure 58.1: PULZAR Z1 (Solid State Refractive Laser)
In the early 1990s, other companies tried to
develop solid state lasers. Two of these were the CustomVis has a very skilled Research and
Laserharmonic quintupled YAG from JT Lin at Laser Development team. The company spent around
Sight and the LightBlade from Shui Lai at Novatec. 20 million US$ on research and development, and Dr.
Neither system made it to the market. The LaserSight Paul van Saarloos, Chief Scientist and Research and
system never got beyond the experimental stage. The Development Manager is has developed a vast experience
Novatec system after some human clinical trials in the refractive industry since beginning in 1986.
simply ran out of money. Another company, Q-Vis, The PULZAR Z1 (Solid State Refractive Laser), is
had developed the Quantum 213 solid state laser, designed specifically for custom surgery, permitting
and also started FDA trials. After Dr Paul van an accurate approach to correcting both standard and
Saarloos, co-founder of Q-Vis and developer of solid non-standard vision disorders. The PULZAR Z1’s
state laser left the company; they were unable to small 0.6 mm Quasi Gaussian spot size, stable
494 Mastering Advanced Surface Ablation Techniques
homogeneous beam energy, fast closed loop eye a series of three nonliner optical (NLO) crystals
tracking, advanced solid state scanning technology (Figure 58.1) Figure 58.2, which are used to facilitate
and sophisticated proprietary surgical planning harmonic generation processes to produce the surgical
software, all contribute to the system’s ability to beam with a wavelength of 213 nm.
overcome the traditional limitations of excimer lasers The first NLO crystal doubles the fundamental
in performing custom surgery. 1064 nm Nd:YAG infrared beam to green light at
The Solid State Laser differs from all other 532 nm. The second crystal doubles the green light
commercially available Excimer lasers. It uses a to ultraviolet light at 266 nm. The final crystal mixes
213 nm wavelength as opposed to the common the 266 nm ultraviolet beam with residual Nd:YAG
193 nm wavelength used for Excimer lasers, and it infrared light to produce far ultraviolet light at
does not utilize gas as Excimer lasers do. 213 nm. This wavelength, close on the spectral scale
The 213 nm wavelength delivers a number of to the clinically well accepted 193 nm ArF excimer
potential benefits over the 193 nm wavelength of laser beam, is used to perform the surgical treatment.
traditional excimer lasers, including reduced
dependence on tissue hydration, less thermal effect Advantages of Solid State Laser
and more efficient tissue ablation.
• Stable homogenous beam energy
Future of Solid State Laser • Longer laser source lifetime
• Improved reliability and efficiency
Today’s ophthalmologists use three different lasers • Low power consumption
for different surgical procedures, i.e. UV laser to • Improved beam quality
correct refractive disorders, Nd:YAG for capsule • Greater pulse to pulse stability
operations and a green laser to coagulate blood • Extremely fast ‘Turn on’, to ‘Ready’ period
vessels in the retina. It is possible to develop a laser • Fewer consumables, (i.e. gas, & fluence plates, not
using one solid state sources to produce a combined required)
laser which will offer all three types of beam. This • No purchase or handling of toxic gas required
will reduce cost and space requirements for doctors • Long optic life – fewer optic changes required over
and clinic. life of laser
The solid state diode pumped Nd:YAG (1064 nm) • Extremely fast and accurate eye tracking (1000 hz
laser is frequency doubled in to green (532 nm) and closed loop)
passes through further frequency conversions to • Faster patient turn around due to automated
produce the 213 nm wavelength for refractive routine set up and calibration needs.
surgery. The multipurpose laser will be able to take
advantage of these wavelengths used for other
ophthalmic surgeries, in particular, YAG lasers which
are currently used in post cataract surgery to remove
the posterior opacity of capsule. Whilst, green lasers
are used for treatment of various retinal conditions,
such as, retinal photo coagulation, age related macular
degeneration and ocular vein occlusion. Green lasers
are also used to treat open angle glaucoma.

Technical Advantages of Solid State Laser

Solid State Technology
The laser system is based on a quintupled Q-switched
Nd:YAG laser. The 1064 nm Nd:Yag laser is flash
lamp or diode pumped and frequency converted via Figure 58.2: Creation of 213 nm wavelength
 Solid State Lasers for Advanced Surface Ablation 495
213 nm Wavelength wavelength proves to be very good for laser vision
correction as it has a very little effect from hydration
The 213 nm wavelength of the Pulzar Z1 is generated
(Figures 58.3 and 58.4).
by transmitting the 1064 nm Nd:YAG laser beam
through three nonlinear crystals.

Benefits of the 213 nm Wavelength Include

• Less dependence on tissue hydration
• Production of clean and smooth ablated surface
• Reduced thermal effect and collateral damage
• More efficient tissue ablation
• Less damage to optics due to humidity issues.

Tissue Hydration Study

Absorption coefficients were obtained for sodium
chloride solution (saline) and balanced salt solution
at 193 nm and 213 nm laser wavelengths. This was
Figure 58.3: Transmissions through 0.9% of NaCl
achieved by measuring laser pulse transmission
through both solutions. Results were used to obtain
an overall absorption coefficient and penetration
depth for balanced salt solution and 0.9% sodium
chloride.
Absorption coefficients in balanced salt solution
for the 193 nm and 213 nm wavelengths were found
to be 140 and 6.9 cm–1, respectively. In 0.9% sodium
chloride solution, the absorption coefficient was
81 cm–1 at 193 nm and 0.05 cm–1 at 213 nm. Penetration
depth of 193 nm in BSS is 72 μm and in 0.9% sodium
chloride is 123 μm, while penetration depth of
213 nm in BSS is 1450 μm (almost 20 times higher
than 193 nm) and in 0.9% sodium chloride is 2 × 105
μm (over 1000 times higher than 193 nm). (Table 58.1)
Table 58.1: Absorption Coefficients and Penetration Depths of Figure 58.4: Transmissions through 0.9% of NaCl
various fluids
193 nm 213nm
Clinical Advantage
Absorption Penetration Absorption Penetration
Solution Coefficient Depth Coefficient Depth This feature of 213 nm has an important clinical
BSS 140 72 6.9 1450 advantage. Fluctuations in corneal hydration or
0.9% Sodium 81 123 0.05 2.0 x 105 environmental humidity are unlikely to have a signi-
Chloride
ficant effect upon the performance of the solid state
During refractive surgery, fluid placed on the laser. The subtle effects of these conditions upon
surface of the cornea proved to be a barrier to excimer laser performance are the primary reason
ablation for the 193 nm wavelength. The increased most refractive surgeons have personalized nomo-
penetration depth through sodium chloride and grams. These allows us to compensate as best we can
balanced salt solution for the longer 213 nm laser for hydration issues related to surgeon technique
496 Mastering Advanced Surface Ablation Techniques
(e.g. wet vs dry technique, duration of bed exposure) important contributors to haze are cell proliferation,
and localized climatic conditions. By taking theses migration and morphological changes.
variables, the outcome of solid state procedures Study was performed to examine the short-term
should be more practical. time course of live cells (keratocytes) and apoptosis
in the cornea of adult rabbits following PRK treatment
HISTOPATHOLOGICAL COMPARISION OF using a 193 nm or 213 nm laser (Figure 58.5).
PHOTOREFRACTIVE KERATECTOMY (PRK) IN
RABBITS WITH 193 NM AND 213 NM Methods
Introduction New Zealand White rabbits underwent PRK (-5
diopters, 6.5 mm optical zone, 7 mm transition zone)
The cornea is commonly reshaped by photorefractive
laser surgery with the 213 solid state laser or the 193
keratectomy (PRK) which ablates the cornea by
excimer laser. Corneas were evaluated after 3 days
removing micron-thick layers of tissue from Bowman’s
(Figure 58.6).
layer and the anterior stroma. PRK is typically
performed using a 193 nm Excimer laser. However,
Analysis
there are concerns about the practicality and safety of
the excimer (193nm) laser for corneal surgery. To Photographs of the sections were taken with a
address these concerns, a solid state 213 nm fluorescence microscope. Sx photographs of each
(5th harmonic) Nd:YAG laser has been developed. section were taken, two inside the crater, two at the
Programed cell death, or apoptosis is particularly edges of the crater within the transition zone and
important to measure as it is a precursor for post- two from the nonlasered portions of the cornea
operative corneal opacification, or haze. Other outside of the ablation zone.

Figure 58.5: TUNEL staining of Rabbit Cornea following PRK

 Solid State Lasers for Advanced Surface Ablation 497

Figure 58.7: Histological similarity of 193 nm and 213 nm

It is also the range where cells exposed to these

wavelengths are less susceptible to cellular in-
activation and mutation, this is due to a screening or
protecting intervening layer of cytoplasm before
DNA located in the core produces a similar clinical
and histopathology course to the excimer 193 nm laser
Figure 58.6: Total live Cells and Apoptotic cells in Crater on Day 3 in a vivo rabbit study and produces a clean, smooth
ablation surface on in vitro porcine tissue.
Discussion
The Pulzar Z1’s 213 nm wavelength is close to the
There was no difference in the amount of apoptosis absorption peak of collagen and has low absorption
induced by both lasers. in fluid. These contribute to its high corneal ablation
The increased number of live cells (keratocytes) efficiency.
in the crater of the 193 nm lasered corneas suggests It proves that the Solid State 213nm laser produces
cell proliferation and/or migration. It also suggests a similar clinical and histological course to the excimer
that 193 nm lasered cornea has more inflammation 193 nm laser.
than 213 nm lasered cornea.
In conclusion these results demonstrate that the 0.6 MM FLYING GAUSSIAN BEAM SPOT
213 nm solid state laser has similar cell death inducing
A beam size of less than 1mm is essential for the
properties, but causes less cell proliferation/
creation of a superior customized profile.
migration (inflammation), to the currently used
The current Solid State Laser available in market
193 nm excimer laser, therefore making it a potentially
(PULZAR Z1, CustomVis, Australia) has a 0.6 mm
superior tool for refractive surgery (Figure 58.7).
Gaussian shaped flying spot, which is one of the
SCIENTIFIC BENEFITS smallest spot sizes on the market in the refractive
industry. 0.6 mm is also considered as an ideal spot
The UV wavelengths within 190 nm – 220 nm size for customised surgery.
represents the acceptable ‘window of ablation’ within The Gaussian beam profile with smaller spot size
which photo-ablation of corneal tissue can occur with permits fine sculpting of corneal tissue producing
a high degree of precision and minimal collateral/ smooth ablation surfaces. The flying spot ablates the
thermal damage to adjacent areas. cornea in a nonsequential pattern to avoid the effects
498 Mastering Advanced Surface Ablation Techniques
of laser plume and enables tissue thermal relaxation CORNEAL HYDRATION DURING ABLATION
(Figure 58.8).
213 nm has a special characteristic. As 213 nm lasered
These improvements therefore follow,
• Improved pulse to pulse energy stability pulse is delivered onto the corneal bed it will produce
• Minimal thermal heating of the cornea a fluid over the corneal surface. 193 nm laser (excimer
• Precise customised ablation profile. laser) behaves in the exact opposite way by drying
out the cornea.
CRYSTALSCAN As 213 nm is less affected by the hydration or
fluid on the cornea, there is no need to continuously
The currently available Solid State Laser (PULZAR wipe accumulated fluid. Fluid over cornea will allow
Z1) is equipped with CRYSTALSCAN high per- patient to have a more clear view of the fixation target
formance ultra fast solid state scanning technology. than 193 nm lasered dry cornea. It will allow patient
This advance solid state scanning technology is to fix their eye very well during whole treatment
significantly faster than galvanometer based systems reducing chances of decentered treatment and
used in conventional laser systems, which is very increases comfort for patient and surgeon.
important for achieving a 1kHz closed looped
response. NOMOGRAM ADJUSTMENT
CRYSTALSCAN has following advantages:
• Allows much faster response time to eye The 213 nm laser wavelength has increased penetration
movements depth through sodium chloride and balanced salt
• High reliability, efficiency and accuracy solution. It proves to be very good for laser vision
• Allows true flying spot scan patterns and complex correction as it has very little effect from hydration.
custom surgery without increasing treatment time These allow us to compensate as best we can for
• Co-axial scan path eliminates ablation errors due hydration issues related to surgeon techniques.
to elevation misalignment of the eye While 193 nm excimer laser results depend on the
• Greatly reduced ‘overshoot’ and settling times of corneal hydration or environmental humidity
scanners = less positioning error. requiring personalized nomograms for every
surgeon.

ANYTIME SURGERY – FREEDOM TO DO

SURGERIES AT YOUR CONVENIENCE

Anytime Surgery is possible only with the Solid State

Laser as there is no need to charge or refill gases.
You can just switch on the laser and start doing
surgeries within 5 minutes (dramatically reduced
warm up time). There is a no need to keep special
surgery days, as there is no extra cost involved in
doing surgery at any time and any number of eyes,
may be even a single eye.

LESS MAINTAINANCE AND COST

Electricity – 10 Amp supply with a maximum of 2400

watts is the requirement to run Solid State Laser.
This is much less than excimer lasers enabling a
Figure 58.8: 0.6 mm flying gaussian beam spot and crystalscan reduction in energy bill.
 Solid State Lasers for Advanced Surface Ablation 499

A. Dry Bed – Before Laser Firing B. Wet Cornea – After laser fired

C. Wet Cornea – After laser fired D. Wet Cornea – Wetness Increases

Figures 58.9A to D: Clearly show the production of fluid over corneal bed as 213nm laser fires

Gas – No need to use any toxic and expensive gases THE BOTTOM LINE
any time for refractive surgery. No more worries for
transport and storage of ArF gases. It will save a huge Solid State technology promises to meaningfully
amount of money over a period of time. advance the state of the art in refractive laser surgery
Replacement of Optics – Absorption peak of optics by streamlining design, increasing predictability of
is near 185 nm. 193 nm is close to 185 nm causing results, improving results and eliminating the need
damage to optics more frequently than 213 nm which for high voltage power sources.
is little longer wavelength and away from 185 nm. It The clinical advances that stand to be gained are
will allow us to replace optics less frequently than related to precision and predictability. Predictability
with excimer lasers. will be enhanced, in the larger part because the laser
Less Downtime—The long-term stability of the Solid energy at 213 nm can pass through the NaCl 0.9 %
State Laser indicates a minimum down time over the year. and BSS (Balanced Salt Solution) with very little energy
500 Mastering Advanced Surface Ablation Techniques
loss. As a result, a 213 nm laser’s performance is less 4. Lembares A, Hu X, Kalmus, GW. Far ultraviolet
absorption spectra of porcine and human corneas. SPIE
susceptible to variations in humidity or corneal
1997;2971:277-786.
hydration. 5. Dair, GT, et al. Investigation of Corneal Ablation Efficiency
The precision of the solid state laser system, now Using Ultraviolet 213 nm Solid State Laser Pulses.
clinically proven, is a result of enhanced tracking and Investigative Ophthalmology and Vision Science 1999;40
(11): 2752-6.
ultrafast scanning, which also supports a faster pulse 6. van Saarloos PP, et al. Bovine corneal stroma ablation
rate. rate with 193 nm excimer laser radiation: quantitative
Clinical results from all international sites are measurement. Journal of Cataract and Refractive Surgery
1990;424-9.
promising, exceeding the expectations of patients and 7. Vukich John, Solid state lasers may shape future of custom
surgeons. Solid State Laser is a good alternative to ablation, Refractive Eyecare for Ophthalmologists 2003.
the current excimer laser. It also looks to be the future 8. Vukich John, Promise shown in initial results from new
device trials, Eye world 2003.
of refractive laser surgery.
9. Barbara Boughton, Euro Times, 2003, Solid State laser
promising in early cases.
BIBLIOGRAPHY 10. Talia E Sanders, Jennifer Rodger, Serge Camelo, Paul van
Saarloos, School of Animal Biology, The University of
1. Guirao A, Williams DR, MacRae SM. Effects of Beam Size Western Australia, Corneal Refarctive Surgery using the
on the Expected Benefit of Customized Laser Refractive solid state 213 nm laser causes less apoptosis than the
Surgery. Journal of Refractive Surgery 2003;19,15–23. excimer 193 nm laser.
2. Ren, Q, G. Simon, et al. Ultraviolet Solid-state Laser 11. Paul van Saarloos, Physical Principles of Excimer Lasers
(213 nm) Photorefractive Keratectomy in vivo Study. 12. Irving J Arons, 2003, Ocular Surgery News, New Solid
Ophthalmology 1993;101:883-9. State refractive surgery laser system emerges.
3. Dair, GT, RA Ashman, et al. Absorption of 193- and 213 13. Ocular Surgery News, 2003, CustomVis laser features
nm Laser Wavelengths in Sodium Chloride Solution and promising technologies.
Balanced Salt Solution. Archives of Ophthalmology 14. Perfect Vision, UWA News, The University of Western
2001;119:533-7. Australia, 2000.
 CHAPTER
Advances in
59 Femtosecond Laser

David Donate, Jean-Marc Legeais (France)

INTRODUCTION contained in a cavitation bubble.9 When ultra-short

pulses are used, the cavitation bubbles generated
The development of femtosecond lasers for use in
combine to produce an incision. 10 It is therefore
ophthalmology is based on the hope that it will be
possible to focus the laser beam accurately within
possible to use high-precision robotic microsurgery
the cornea and to create a flap without affecting the
to carry out all routine procedures.1 The femtolasik,
neighboring tissues. 11 In order to develop the
a procedure that involves excising the flap using a
applications of the femtosecond laser for refractive
femtosecond laser is currently being assessed by the
surgery and flap or transfixing corneal transplants it
FDA in the United States, where more than 500,000
seems to be necessary to identify some factors that
patients have undergone the procedure. 2 These
are still unknown, such as the amount of tissue
femtosecond lasers can already be used to carry out
vaporized per laser pulse, the exact kinetics of the
flap excisions on healthy corneas,3 but used alone they
cavitation bubbles within the cornea and differences
do not yet constitute a reliable tool for the treatment
in the effects of the femtosecond laser on the cornea
of myopia.4,5 Similarly, the possible applications of
depending on its degree of hydration and trans-
this technology to carrying out lamellar corneal graft
parency. We first determined the minimum incident
or suture-free transfixing transplants have yet to be
energy required to reach the plasma threshold as a
perfected.6, 7 This is probably because all the factors
function of the hydration of the corneas. It is essential
involved in the cornea/laser interaction are far from
to determine the minimum energy levels required to
being fully understood. There have been a few
create a corneal flap, in order to be able to compare
publications. The principle underlying the interaction
the impacts of laser pulses on the cornea. We then
of the femtosecond laser with tissue is that of
investigated the difference in the sizes of the
photodisruption.8 The wavelengths of these lasers
cavitation bubbles depending on the degree of
are in the near-infrared range. This makes it possible
hydration and of the cornea.
to focus them within the thickness of a transparent
medium. When the energy applied to the focal point METHODS
is great enough, the tissue is destroyed and vaporizes
to form a high-density gas known as «plasma». The The minimum incident energy of the femtosecond
minimum energy required to produce this plasma is laser required to generate plasma at various depths
known as the «plasma threshold». This gas is within the cornea was determined by detecting the
502 Mastering Advanced Surface Ablation Techniques
formation of cavitation bubbles using a confocal supplied had been eliminated from the transplant
microscope. The confocal microscope was also used circuit either because they displayed endothelial
to determine the diameter of the cavitation bubbles insufficiency (group 1) or gave inconclusive virus test
produced. results (group 2). They were stored in the storage
Three groups of samples were prepared: fluid for no more than two weeks. The pachymetric
— Group 1: the corneas were stored in storage fluid thicknesses were determined using an ultrasound
(CorneaMax®). Ten corneas were included in this pachymeter (Quantel Medical, Pocket model).
group. They had a mean pachymetric thickness of The experimental system used includes a
1000 ± 75 μm. femtosecond laser sample cutting system and a
— Group 2: the corneas in this group underwent
confocal microscopic observation system (Figures 59.1
deturgescence for 48 h in Corneajet® (the usual
and 59.2).
preoperative transplant deturgescence protocol).
The femtosecond laser system used consisted of
The ten corneas in this group had a mean
pachymetric thickness of 700 ± 53 μm. a laser oscillator delivering femtosecond pulses
— Group 3: this group consisted of ten identical (1fs=10–15s) followed by an amplifier providing the
samples of silicone dioxide. These samples had energy required for incising transparent biological
fixed degrees of transparency and hydration, and tissues. The laser oscillator and the amplification
constitute the reference sample used to assess the medium consisted of a glass matrix containing
results (thickness of 700 μm). Neodyme. Pumping was carried out by laser diodes
The human corneas were supplied by the French with an emission wavelength (900 nm) centered on
Eye Bank (Banque Française des Yeux). The corneas the absorption peak of Neodyme. The spectrum of

Figure 59.1: Femtosecond experimental set up

 Advances in Femtosecond Laser 503

Figure 59.2: Femtosecond laser system

the laser was centered at 1.065 nm and was several The samples were fixed in an anterior chamber
tens of nanometers in width. The CPA system mobilized by a motorized system of micrometric
(chirped pulse amplification) consisted of a single precision. Movement through the three dimensions
diffraction system and was used to stretch the pulse of space was computer controlled (Labview, National
out over time and then, after amplification, to re- Instrument) to ensure the complete reproducibility
compress it to its original duration. When it emerged of the incisions. Using this anterior chamber made it
from the compressor system, the pulse had a duration possible to control the hydration and pressure so as
of 500 fs, a peak energy of 60 μJ and a frequency of to maintain stable conditions throughout the
10 KHz. The stability of the amplified pulses was experiment. The infusion bag was fixed at a height
excellent, with peak-to-peak fluctuations of less than of 2 m in all the experiments, thus ensuring that the
1%. The 10-KHz frequency of the pulses permitted intraocular pressure remained stable. For each group,
very rapid incisions. The beam was Gaussian in form, the infusion was administered in the appropriate
TEM00. The crest power density obtained was of the preparation fluid in order to ensure stable corneal
order of 1015W/cm2. hydration.
The laser beam was directed onto the samples by The distance between the sample and the last
a set of mirrors and lenses. This system made it focalizing lens being fixed throughout the laser
possible to regulate both the horizontal and vertical treatment, in order to administer the treatment at a
alignments of the beam, and to obtain a focal distance constant depth in the stroma it was necessary to
of 5 cm, with a focal spot of 3 to 4 μm. flatten the surface of the cornea. The cornea was
The beam delivery system is currently fixed in flattened by a 1 mm thick glass plate held in a ring
order to achieve the best possible optical quality and fitted to the articial anterior chamber.
to ensure that there is a focal spot of a fixed size. To The minimum incident energy required to produce
carry out the incision, the samples were moved in plasma was achieved by delivering laser pulses at
front of the laser beam. The energy of the laser was decreasing energies of between 100 J/cm² and
controlled by means of a calibrated photodiode. 5 J/cm². During the first phase, the energy was
504 Mastering Advanced Surface Ablation Techniques
decreased in steps of 5 J/cm², and then the exact thickness of the cornea in real time. These cavitation
threshold was pinpointed by successive adjustments bubbles, which are produced by the laser pulses are
of 1 J/cm² around the threshold. The threshold was hyper-reflective. They can be clearly distinguished
defined as the minimum energy required to produce from the less reflective corneal stroma.
cavitation bubbles visible under the confocal
microscope. Each flux was tested by creating a flap Minimum incident energy required to produce
in order to minimize the impact of any local plasma
differences. The determinations of the threshold at For all three groups: the plasma threshold at the
the two depths were carried out on the same cornea surface of the samples was 5 J/cm².
in order to minimize inter-sample variability. The For a given treatment depth, the minimum incident
threshold was determined in the deep layers before energy required to generate plasma was always
the surface layers. The distance separating the higher in the group-1 corneas, than in those of group-
successive treatment zones was set at 100 μm to avoid 2 and was higher in the group-2 corneas than in the
inducing cumulative effects. The laser treatments were silicone dioxide samples (Figure 59.3).
all carried out in the central zone of the cornea. In groups 1 and 2, the incident energy required
The diameter of the cavitation bubbles was to generate plasma increased linearly with the
determined for each group during the creation of a treatment depth, by 10 J/cm² and 5J/cm² respectively
flap located in the center of the cornea, with an area per 100 μm of cornea crossed (Figure 59.3).
of 4 cm², and at a depth of 200 μm. The incident energy
used was equal to twice that required to generate Size of the Cavitation Bubbles
plasma at this depth . Silicone dioxide samples (Figure 59.4)
A confocal microscope (ConfoScan Model P4; The laser treatment was carried out with a flux
Tomey, Erlangen-Tennenlohe, Germany) was used equal to double the minimum incident energy
to detect the cavitation bubbles and measure their required to generate plasma at a depth of 200 μm,
diameter. The treated samples were not taken out of i.e. 10 J/cm².
the artificial chamber but the chamber itself was then It was difficult to assess the size of the bubbles.
rapidly transferred from the motorized support Most of the bubbles measured 1 μm. The spatial
system to the support system fixed to the confocal distribution of the cavitation bubbles was very unfirm
instrument. This made it possible to relocate the and close to the theoretical distribution pattern.
treated zone of the sample within the axis of the
confocal microscope within a few seconds. The Group-2 Corneas
corneas were not subjected to any change, and were The laser treatment was carried out with a flux equal
examined immediately. A single drop of Goniosol® to double the minimum incident energy required to
was used as the immersion fluid. The lens used was generate plasma at a depth of 200 μm in this group of
an Achroplan (Zeiss, Oberkochen, Germany), corneas, i.e. 30 J/cm².
immersion lens, 40x/NA= 0.75 with a working The cavitation bubbles had a mean diameter of 25
distance of 1.98 mm. The time between the end of μm (± 1.7 microns). The spatial distribution was fairly
the treatment and inputting the appropriate reference uniform. A comparison of this photo and the
image for the measurements was 30 seconds for all theoretical distribution pattern shows that most of
the samples. the laser pulses produced cavitation bubbles.

RESULTS Group-1 corneas (Figure 59.5)

The confocal microscopic observation system makes The laser treatment was carried out with a flux equal
it possible to visualize the cavitation bubbles in the to double the minimum incident energy required to
 Advances in Femtosecond Laser 505

Figure 59.3: Comparison of the mean minimum incident energy required to generate plasma as a
function of the depth of treatment (all three groups)

Figure 59.4: Cavitation bubbles on a sample of silicone dioxide, Figure 59.5: Cavitation bubbles on group 1 cornea, confocal
confocal microscopy microscopy

generate plasma at a depth of 200 μm in this group of bution. When the image obtained by confocal
corneas, i.e. 50 J/cm². microscopy is compared to the theoretical dis-
The confocal microscopic measurement of the tribution, we can see that there is a shortfall of a
bubbles found at the same depth and at the same considerable number of bubbles.
time, sizes ranging from 1 to 20 μm, with a mean
DISCUSSION
value of 6 μm (± 7 μm). There were very wide dis-
parities in the diameters of the cavitation bubbles The use of the femtosecond laser to carry out corneal
and above all in the pattern of their spatial distri- excision is based on photodisruption. When this laser
506 Mastering Advanced Surface Ablation Techniques
beam is focused in a micrometric fashion on the energy levels used to carry out flap keratectomy on
cornea, an ionized form of material is produced that healthy corneas in refractive surgery (of the order of
is known as plasma. The minimum energy required 2 to 3 μJ11,15 are just not high enough. In order to
at the focal point to generate plasma is known as the carry out flap or transfixing keratectomies, the
“plasma threshold”. Plasma is a high-density gas (a incident energy of the laser beam has to be increased
mixture of ions and electrons), and when this and adjusted to suit the degree of edema of the flap
expands, it forms a cavitation bubble. When ultrashort or of the ailing cornea. The appropriate energy
laser pulses are administered, the cavitation bubbles intensity may be more than ten times higher than the
generated by the pulses merge and an excision can plasma threshold. It is accepted that femtosecond
be carried out.12 We have shown that the plasma lasers do not produce heat damage as long as the
threshold determined at the surface of the samples energy used is similar to the plasma threshold.11,16
does not depend on the degree of hydration of the Further experiments, similar to those carried out for
sample. Data in the literature reveals similar values the Excimer laser,17,18 will be required to confirm the
for various materials.13 The value we found for our safety of energy levels that are considerably greater
threshold is slightly higher than those in the literature, than this.
and this was probably attributable to the attenuation The cavitation bubbles, measured using the
caused by the glass plate placed in front of our confocal microscope, have a more regular diameter
samples. Our findings show that for a given depth, and arrangement on the silicone dioxide samples and
the minimum incident energy required to produce on the corneas with hydration levels close to normal
plasma was higher for more edematous corneas and (group 2) than on the more edematous corneas (group
that, for a given group, it increased linearly with the 1). Corneal edema, which attenuates the beam, is
corneal thickness crossed. This shows that the probably the cause of these disparities between the
attenuation of the energy of the incident beam was cavitation bubbles. This feature also has repercussions
proportional to the corneal thickness crossed in when femtosecond lasers are used for corneal
reaching the focal point. This attenuation per cm of transplant surgery; excisions are performed by
cornea was greater in more edematous corneas. The combining a series of cavitation bubbles, and so will
be less regular if these bubbles are not uniform in
attenuation of the energy of the incident beam is
diameter. This lack of uniformity results in the
produced by three mechanisms: reflection, absorption
formation of bridges of residual material. It is
and diffusion. Diffusion seems to be the main
probably necessary to adjust the intervals between
mechanism of attenuation, and is linked to the
pulses to offset the lack of uniformity of the bubbles
disruption of the collagen plates in edematous
and to make it possible to carry out flap keratectomies
corneas. The attenuation by reflection, from the glass
or suture-free transplants.
plate or corneal surface, is the same in the various
In view of these findings, it seems likely that it
sample groups, and cannot account for any differences
will not be possible simply to transpose the
observed. The wavelength of the laser in the near
femtosecond laser treatment parameters currently
infrared range limits the attenuation of the beam by
used in refractive surgery to cornea transplant
water. Even if we assume that this is the main
surgery. Further studies are necessary to identify the
mechanism of attenuation, since the coefficient of
parameters appropriate for cutting the transplants
absorption is 0.34/cm at the wavelength of the laser,
and for the various corneal disorders that make a
then the thickness of the cornea, taken to consist of
transplant necessary.
100% water14, required for the complete extinction
of the beam would appear to be 7 cm!
ACKNOWLEDGMENTS
This attenuation of the energy of the laser beam
in edematized corneas has a direct impact on the use This study was supported in part by « Fondation de
of femtosecond lasers in corneal transplants. The l’Avenir, l’Etablissement Français des Greffes « . We
 Advances in Femtosecond Laser 507
thank Pr Gerard Mourou from the Center for 2. Ratkay-Traub I, Ferincz IE, Juhasz T, Kurtz RM, Krueger
RR. First clinical results with the femtosecond neodynium-
Ultrafast Optical Science of the University of Michigan glass laser in refractive surgery. J Refract Surg 2003;19:94-
to provide a femtosecond laser. 103.
3. Nordan LT, Slade SG, Baker RN, Suarez C, Juhasz T, Kurtz
R. Femtosecond laser flap creation for laser in situ
SUMMARY
keratomileusis. six-month follow-up of initial US clinical
series. J Refract Surg 2003;19:8-14.
Purpose: to determine the incident energy required 4. Sletten KR, Yen KG, Sayegh S, Loesel F, Eckhoff C,
to generate plasma within the cornea and the Horvath C, Meunier M, Juhasz T, Kurtz RM. An in vivo
diameter of the cavitation bubbles as a function of model of femtosecond laser intrastromal refractive
surgery. Ophthalmic Surg Lasers 1999;30:742-9.
the degree of hydration of the cornea. 5. Heisterkamp A, Mamom T, Kermani O, Drommer W,
Methods: We used a neodynium-glass femto- Welling H, Ertmer W, Lubatschowski H. Intrastromal
refractive surgery with ultrashort laser pulses. in vivo
second laser; the wavelength used was 1065 nm. The
study on the rabbit eye. Graefes Arch Clin Exp Ophthalmol
pulse frequency could be adjusted between 1 and 10 2003;241:511-7.
KHz, and the maximum energy per pulse was 6. Dhaliwal DK, Mather R. New developments in corneal
and external disease—LASIK. Ophthalmol Clin North
60 ± 3 μJ. The corneas were divided into two groups Am 2003;16:119-25.
on the basis of their pachymetric dimensions: group 7. Seitz B, Langenbucher A, Hofmann-Rummelt C,
1: 1000 ± 75 μm; group 2: 700 μ ± 53 μm. Silicone oxide Schlotzer-Schrehardt U, Naumann GO. Nonmechanical
posterior lamellar keratoplasty using the femtosecond
samples constituted the reference group. The laser (femto-plak) for corneal endothelial
detection and measurement of the diameter of the decompensation. Am J Ophthalmol 2003;136:769-72.
cavitation bubbles was carried out using the confocal 8. Stern D, Schoenlein RW, Puliafito CA, Dobi ET, Birngruber
R, Fujimoto JG. Corneal ablation by nanosecond,
microscope . picosecond, and femtosecond lasers at 532 and 625 nm.
Arch Ophthalmol 1989;107:587-92.
Results 9. Juhasz T, Kastis GA, Suarez C, Bor Z, Bron WE. Time-
resolved observations of shock waves and cavitation
The plasma threshold found at the surface of the bubbles generated by femtosecond laser pulses in corneal
tissue and water. Lasers Surg Med 1996;19:23-31.
samples was 5 J/cm² for all three groups. The
10. Ratkay-Traub I, Juhasz T, Horvath C, Suarez C, Kiss K,
minimum incident energy required to generate Ferincz I, Kurtz R. Ultra-short pulse (femtosecond) laser
plasma rose linearly by 10 J/cm² per 100 μm of cornea surgery. initial use in LASIK flap creation. Ophthalmol
Clin North Am 2001;14:347-55.
crossed in group 1 and by 5 J/cm²/100 μm in group 11. Lubatschowski H, Maatz G, Heisterkamp A, Hetzel U,
2. The diameter of the cavitation bubbles was 6 ± 7 μm Drommer W, Welling H, Ertmer W. Application of
in group 1 and 25 ± 1.7 μm in group 2. The incident ultrashort laser pulses for intrastromal refractive surgery.
Graefes Arch Clin Exp Ophthalmol 2000;238:33-9.
laser beam was attenuated by any edema of the 12. Kurtz RM, Horvath C, Liu HH, Krueger RR, Juhasz T.
cornea. Lamellar refractive surgery with scanned intrastromal
picosecond and femtosecond laser pulses in animal eyes.
J Refract Surg 1998;14:541-8.
CONCLUSION
13. Vogel A, Capon MR, Asiyo-Vogel MN, Birngruber R.
Intraocular photodisruption with picosecond and
To make it possible to carry out flap or transfixed nanosecond laser pulses. tissue effects in cornea, lens,
transplants using the femtosecond laser, the incident and retina. Invest Ophthalmol Vis Sci 1994;35:3032-44.
energy must be appropriate for the degree of 14. Van den Bergt T, Spekreijse H. Near infrared light
absorption in the human eye media. Vis. Res 1997; 37,
hydration of the cornea. 249-53.
15. Stern D, Lin WZ, Puliafito CA, Fujimoto JG. Femtosecond
REFERENCES optical ranging of corneal incision depth. Invest
Ophthalmol Vis Sci 1989;30:99-104.
1. Sacks ZS, Kurtz RM, Juhasz T, Spooner G, Mouroua GA. 16. Stern D, Schoenlein RW, Puliafito CA, Dobi ET, Birngruber
Subsurface photodisruption in human sclera. wavelength R, Fujimoto JG. Corneal ablation by nanosecond,
dependence. Ophthalmic Surg Lasers Imaging picosecond, and femtosecond lasers at 532 and 625 nm.
2003;34:104-13. Arch Ophthalmol 1989;107:587-92.
508 Mastering Advanced Surface Ablation Techniques
17. Ren Q, Simon G, Legeais JM, Parel JM, Culbertson W, 18. Hanna KD, Pouliquen YM, Waring GO, 3rd, Savoldelli M,
Shen J, et al. Ultraviolet solid-state laser (213-nm) Fantes F, Thompson KP. Corneal wound healing in
photorefractive keratectomy. In vivo study. monkeys after repeated excimer laser photorefractive
Ophthalmology 1994;101:883-9. keratectomy. Arch Ophthalmol 1992;110:1286-91.
 CHAPTER

60 Advanced Surface
Ablation (ASA)

Ahmad Salamat Rad, Neil Vice, Tarak Pujara

(Australia)

BACKGROUND induced high-order aberrations and keratectasia gave

surgeons enough reasons to return to surface ablation.
The development of excimer and solid state laser
In 1999, Camellin introduced laser-assisted sub-
ablation represented a breakthrough in the correction
epithelial keratectomy (LASEK) which decreases
of refractive errors in the past two decades. Excimer
visual recovery time as well as postoperative pain
or solid state laser has changed the face of refractive
and haze formation3.
surgery more than any other technology in the
Pallikaris and colleagues described the technique
history of refractive surgery. Trokel et al demons-
in which a microkeratome is used to create the
trated a new form of laser–tissue interaction, termed
epithelial flap, preserving the integrity of the basement
photoablation in 19831. Photorefractive keratectomy
membrane, and avoiding the use of alcohol and its
(PRK) employs a 193 nm argon fluoride excimer laser
consequent epithelial toxicity. 4,5 They named this
or 213 nm solid state laser to ablate the anterior
modified technique, epithelial LASIK (Epi-LASIK).
corneal stroma to a new radius of curvature to
Modified PRK and its more recent variants LASEK
decrease refractive error.
and epi-LASIK are collectively named advanced
McDonald and co-workers treated the first sighted
surface ablation6. The goal of modern surface ablation
human eye in 19882. In the early 1990s, PRK became a
techniques is to avoid the potential complications of
common technique worldwide for treating low to
lamellar surgery while minimizing the traditional
moderate myopia due to its high predictability and
disadvantages associated with PRK.
stable results. The popularity of PRK faded rapidly
when laser in situ keratomileusis (LASIK) was
TYPES OF REFRACTIVE LASERS
popularised in the late 1990s, primarily because LASIK
offered a faster visual recovery and less post- 190 to 220 nm is the wavelength range wherein photo-
operative discomfort. The problems with early PRK ablation of corneal tissue can occur with a high degree
made surgeons abandon this procedure in favor of of precision and minimal collateral and thermal
LASIK. These problems include pain, delayed visual damage.
recovery, prolonged use of steroids and loss of The two most common refractive lasers available
corneal transparency (haze). The increasing number in the market are:
of flap related complications such as button holes, 1. 193 nm ArF – Excimer Laser (Figure 60.1)
free flaps, striae, diffuse lamellar keratitis (DLK), 2. 213 nm Solid State Refractive Laser (Figure 60.2)
510 Mastering Advanced Surface Ablation Techniques

Figure 60.1: Creation of 193 nm

Figure 60.2: Creation of 213 nm

Excimer Lasers systems (atoms or molecules) do not form a strong

‘Excimer’ is a contraction of the term ‘excited dimer’. chemical bond when one of them is in an excited state,
Dimers are usually considered to be molecules made then the bound excited state is called an excimer.
up of two identical atoms, however the term ‘excimer’ Currently, ArF gas is used to generate 193 nm
has subsequently been extended to include other wavelength for corneal ablation for use in laser vision
excited molecules (though usually diatomic). If two correction.
 Advanced Surface Ablation (ASA) 511
Excimer lasers usually consist of a large, elongated
aluminum box. This box is filled with the appropriate
gas mixture. Running the full length of this box are
two metal electrodes spaced about 2-3 cm apart. At
one end of the box, aligned with the gap between the
electrodes, a mirror is mounted. At the opposite end
is a window. The window is usually an uncoated optic. Figure 60.3: Creation of 213 nm from 1064 nm
The small amount of reflection that normally occurs
from each surface is enough to provide laser action.
Outside the box there is usually a large bank of
capacitors and these are charged using a high voltage
power supply to several tens of kilovolts. A special
switch (thyraton) is used to dump the energy stored
in these capacitors across the electrodes inside the
box. The electrical discharge through the gas between
the electrodes ionizes the gas and allows the excimer
molecules to form. Lasing action usually occurs within
nanoseconds.

Solid State Lasers Figure 60.4: Relationship between refractive error and ablation depth
according to Munnerlyn formula ( Munnerlyn CR, Koons SJ, Marshall J.
The laser system is based on a quintupled Q-switched Photorefractive keratectomy: a technique for laser refractive surgery.
Nd:YAG laser. The 1064 nm Nd:Yag laser is flash J Cataract Ref Surg.1988; 14: 46-52)
lamp or diode pumped and frequency converted via
Ablation depth (μm) = [Optical zone diameter
a series of three non-linear optical (NLO) crystals
(mm)] ² × 1/3 power (D)
(Figure 60.3), which are used to facilitate harmonic
Refractive lasers operate through a process known
generation processes to produce the surgical beam
as photoablation. Photoablation occurs because the
with a wavelength of 213 nm.
cornea has an extremely high absorption coefficient
The first NLO crystal doubles the fundamental
at wavelength in the range 190 to 220 nm. The higher
1064 nm Nd: YAG infrared beam to green light at
the absorption of light of a given wavelength, the
532 nm. The second crystal doubles the green light
easier it is for that wavelength to destroy tissue.8 A
to ultraviolet light at 266 nm. The final crystal mixes
single photon in this range has sufficient energy to
the 266 nm ultraviolet beam with residual Nd: YAG
directly break the carbon–carbon and carbon–
infrared light to produce far ultraviolet light at
nitrogen bonds that form the peptide backbone of
213 nm. This wavelength, close on the spectral scale
the corneal collagen molecules. Consequently,
to the clinically well-accepted 193 nm ArF excimer
refractive laser radiation ruptures the collagen
laser beam, is used to perform the surgical treatment.
polymer into small fragments, and a discrete volume
INTERACTION OF REFRACTIVE LASERS AND of corneal tissue is expelled from the surface with
CORNEAL TISSUE each pulse of the laser.9,10
The penetration depth of laser light is lower when
Munnerlyn described that when using refractive lasers the absorption of the light is higher. Thermal damage
to reshape corneal curvature with a small optical zone, is least when the light penetrates minimally with total
less tissue removal was required to create the same absorption. The Argon Fluoride (ArF) excimer laser and
change in curvature as when using a larger zone.7 The neodymium: yittrium-aluminium-garnet (Nd:YAG)
relationship is simplified to (Figure 60.4). ultraviolet laser have very small penetration depths and
512 Mastering Advanced Surface Ablation Techniques
can perform corneal surgery with minimal thermal findings to the 193 nm excimer laser and claimed to
effect. The ArF laser with its wavelength of 193 nm deliver a number of potential benefits over the 193 nm
and solid state laser with 213 nm create a regular margin wavelength of traditional excimer lasers, including
of excision, with less damage to adjacent tissue than reduced dependence on tissue hydration, less thermal
other wavelengths do.11,12 Fluid on the cornea can result effect and more efficient tissue ablation.13,14
in a reduction of the ablation rate during refractive
surgery procedures with 193 nm laser pulses. This Corneal Wound Healing
reduction in ablation rate is evidenced by the high The reactions of the human cornea to refractive lasers
degree of absorption of 193 nm light in balanced salt have long interested ophthalmologists and have been
solution (BSS). Underlying tissue, therefore, is effectively the subject of several investigations in recent years.
masked from incident radiation. The 213 nm solid-state Refractive lasers alter the normal structure, cellu-
laser has shown a similar clinical course and histologic larity, and innervation of the cornea (Figure 60.5).

Figure 60.5: Confocal section of a normal cornea.( A) The surface epithelial cells. Dark and light cells are visible with dark nuclei. (B) Parallel
and vertical orientation of the central subbasal nerve fiber bundles presenting as long branching linear structures located at the basal aspect
of the epithelial cell layer. (C) Small, numerous anterior keratocyte nuclei with a characteristic multiangulated border. (D) The cell nuclei of
midstroma keratocytes have a round to oval shape and are the predominant type throughout most of the stroma.(E) A nerve fiber bundle, which
is highly reflective, is seen located parallel to the tissue layer. (F) The endothelial monolayer (Erie JC, Corneal wound healing after photorefractive
keratectomy: a 3-year Confocal microscopy study. Trans Am Ophthalmol Soc. 2003; 101: 293–333)
 Advanced Surface Ablation (ASA) 513
Biologic variability in the subsequent wound healing apoptotic loss begin to undergo proliferation to
response is thought to be a major factor limiting the repopulate the wound area. Proliferation occurs 24
predictability of the outcome of laser refractive to 48 hours after wounding and as part of this phase
procedures.15,16 these proliferating cells activate or transform into
wound repair keratocyte-derived cells or repair-
Epithelial Healing fibrocytes (Figure 60.6).
The epithelial covering of the ablated corneal surface
after laser surgery is an early and important step in
wound healing. Corneal epithelial wound repair is a
multifaceted process that can be divided into three
overlapping phases.
In the first phase, which lasts about 8 hours, the
epithelial cells synthesise structural proteins and the
hemidesmosomal attachments between the basal cells
and the basement membrane disappear from the
wound edge.
The second phase begins with the migration of
epithelial cells onto the wound surface. The
reepithelialization of the cornea is usually accom-
plished in 2 to 4 days.
In the final phase, hemidesmosomes are
permanently reformed and reassembly occurs; a
process that takes weeks following operation.17,18
In several studies, the central epithelium was
shown to return to preoperative thickness by 1 month
following PRK. The regenerated central epithelium
Figure 60.6: Confocal microscopy images of anterior keratocytes at
continued to thicken progressively in the first year 5 days post-PRK. (A) The most anterior keratocyte layer demonstrates
following PRK. At 12 months after PRK, the central decreased cell density compared with (B) the keratocyte layer at 8%
stromal depth (Erie JC, Corneal wound healing after photorefractive
epithelium was 21% thicker than preoperatively, keratectomy: a 3-year Confocal microscopy study. Trans Am Ophthalmol
presumably because of epithelial hyperplasia. The Soc. 2003; 101: 293–333)
clinical advantage of epithelial thickening after PRK The final phase involves contraction of the wound
is unclear.19 and appearance of a new cell type: the myofibroblast.
After PRK the myofibroblast cells eventually dis-
Stromal Healing
appear in weeks to months with minimal scarring22.
Stromal wound healing after PRK also occurs in three Erie and colleagues23 demonstrated a gradual loss
phases and depends on a coordinated interaction of keratocytes from the anterior stroma after PRK
between epithelial cells and keratocytes.20 and from the stromal flap and the stroma immediately
In the first phase, superficial keratocytes disappear posterior to the ablation interface after LASIK. By
in the area adjacent to the epithelial debridement. In 5 years after both procedures, keratocyte loss was
1996, Wilson and colleagues first reported that this also significant in the posterior stroma. In the normal
disappearance of keratocytes was mediated by cornea, keratocyte density is highest in the anterior
apoptosis.21 5 to 10% of the stroma — approximately 40% higher
In the second phase of stromal wound repair, the than cell density in the middle and posterior stroma.
remaining keratocytes surrounding the area of During PRK, this keratocyte-rich anterior stroma is
514 Mastering Advanced Surface Ablation Techniques
removed by photoablation. Although keratocytes are inflammatory drugs (NSAIDs) and mitomycine-C
able to divide and migrate after wounding, their provide surgeons with new opportunities in
study showed that keratocytes do not repopulate the controlling the results and managing the
post-PRK anterior stroma to the densities in this layer complications of refractive surgery.
before PRK for at least 5 years. The clinical
significance of a reduced keratocyte population after Regeneration of Corneal Nerves
PRK and LASIK and its effect on the long-term health The human central cornea is densely innervated by
of the cornea is unknown. nerve fibres of the ophthalmic division of the
trigeminal nerve. PRK ablates and destroys the nerves
Growth Factors and Wound Healing of the subbasal plexus and the anterior stroma.
Growth factors involved in wound healing are Regenerating fine sub-basal nerve fibers were found
ubiquitous throughout the body tissues and have a 1 week post PRK and reinnervation would complete
variety of actions including extracellular matrix at 8 to 12 months after PRK.
degradation and production, chemotaxis, proliferation, Stromal nerve fibre bundles in the normal human
autocrine cytokine production, and angiogenesis.24 cornea have been quantified and found to be limited
Several studies have suggested that injury-induced to the anterior 60% of the stroma. Researchers
keratocyte apoptosis is mediated by the release of described a persistent abnormal morphology of
proapoptotic cytokines from the injured epithelium. regenerated anterior stromal nerves after PRK in
Cytokines that have been implicated in keratocytes humans and inferred a lower density up to 34 months
apoptosis include interleukin (IL)-1, Fas ligand, and postoperative28 (Figure 60.7).
tumor necrosis factor (TNF). These cytokines bind to
Summary
receptors on keratocytes immediately beneath the
wounded epithelium and set in motion a complex Erie28 performed a sequential quantitative analysis
cascade of epithelial and stromal wound healing of corneal wound healing after surface ablation by
events. The proliferation and migration of repair- using confocal microscopy in vivo and presented
fibrocytes in the second phase of stromal healing is several interesting results.
probably mediated by platelet-derived growth factor The central corneal epithelium thickens 21% in the
(PDGF) released from the epithelium. Cytokines first year after PRK. The increased epithelial thickness
produced by underlying repair-fibrocytes, in part, stabilises by 1 year after PRK but does not return to
regulate the proliferation, migration, and diffe- pre-PRK thickness by 3 years. The central corneal
rentiation of the healing epithelium.25 stromal thickness remains stable after PRK and does
Much of the synthetic activity of the repair- not significantly change between 1 and 36 months
fibrocyte is involved with the production of the repair after PRK. The dense keratocyte population found in
extracellular matrix (ECM). IL-1 and other cytokines the preoperative anterior stroma is partially or
also stimulate repair-fibrocytes to produce metallo- completely removed during PRK photoablation. This
proteinases, collagenases, and other enzymes that high keratocytes density is not reconstituted in the
turn on new synthesis of enzymes that can degrade anterior 10% of the post-PRK stroma and results in a
repair ECM.26 new uniform distribution of keratocytes throughout
the anterior to posterior post-PRK stroma.
Transforming growth factor Beta (TGF-β) is
another growth factor that is secreted by both corneal
CORNEAL BIOMECHANICS
epithelium and keratocytes and may induce epithelial
wound closure and keratocyte proliferation and Corneal biomechanical properties influence the
migration after refractive laser ablation.27 Modulating results and outcomes of ocular measurements and
these factors by steroids, non-steroidal anti- procedures. Understanding the biomechanical
 Advanced Surface Ablation (ASA) 515

Figure 60.7: Confocal images of central sub-basal nerve fiber bundles before PRK (A) at 3 months,
(B) 6 months, (C) 12 months, (D) post-PRK. Nerve bundles at all post-PRK examinations were subjectively
thinner compared with preoperative (Erie JC, Corneal wound healing after photorefractive keratectomy: a
3-year confocal microscopy study. Trans Am Ophthalmol Soc. 2003;101:293–333)

behavior of the cornea is essential for predicting the 0.87 mmHg IOP readings, however, this is dependant
results of any keratorefractive surgery. Ocular on biomechanical properties; especially stress/strain
measurements such as intraocular pressure (IOP) ratio.
readings, IOL power calculation and outcomes of The Young’s modulus or modulus of elasticity is
many refractive surgeries may be influenced by three defined as the ratio of stress (load per unit area) and
main corneal characteristics: thickness, curvature and the strain (displacement per unit length). According
biomechanical properties. Ablative corneal refractive to the model proposed by Liu and Roberts,29 when
surgeries, either surface or lamellar, can change all Young’s modulus is 0.19 MPa, a 10% difference in
these characteristics. corneal thickness would result in a 0.87 mmHg
These procedures decrease corneal thickness, difference in IOP measurements; with a Young’s
modify radius of curvature of both anterior (direct) modulus of 0.58 MPa, a 2.63 mmHg difference in IOP
and posterior (indirect) faces of the cornea and change from the same amount of difference in corneal
the biomedical properties such as stress/strain ratio.29 thickness would be measured. How can surgeons take
Goldmann predicted that applanation tonometry into account the aforementioned variables in
would be affected by differences in central corneal evaluating patients? Pascal dynamic contour
thickness (CCT) but believed that there would only tonometer [DCT (Ziemer AG)] and ocular response
rarely be significant variations in CCT from the mean analyzer [ORA (Reichert ophthalmic instruments)] are
of 500 μm. 30 It has been observed that IOP two devices which provide ophthalmologists with
measurements tend to be lower after ablative corneal new measuring options in pre- and postoperative
refractive surgeries.31,32 Within the range of normal evaluation of patients. Surgeons can measure IOP
eyes, a 10% decrease in corneal thickness results in independent of central corneal thickness using DCT
516 Mastering Advanced Surface Ablation Techniques
and evaluate corneal biomechanics and its ratio of
stress and strain by ORA.
Roberts and Dupps 33 criticised the ‘shape-
subtraction’ model of Munnerlyn and clearly
demonstrated that:
1. Myopic laser ablative surgery may give rise to
unexpected increases in elevation, pachymetry and
curvature well beyond the ablation zone.
2. There are considerable differences between
predicted and measured postoperative topo-
graphic maps, which cannot simply be attributed
to known ablation profiles.
3. The changes in the elevation map outside the
Figure 60.8: Peripheral corneal thickening following PRK. (Lewis JR,
ablation zone are linked to central curvature Roberts CJ; Corneal biomechanics in surface ablation and LASIK, in
changes. They proposed the “biomechanical Vinciguerra P, Camesasca FI, Refractive surface ablation 2007:41-
theory” and hypothesised that during laser 57)

ablative surgeries, central ablation causes an diseases is associated with unstable/unreliable

immediate circumferential severing of corneal refraction and unpredictable results as well as risk
lamellae under tension, with a subsequent of progression of ectasia.
relaxation of peripheral lamellar segments and an 2. Ocular surface disease (dry eye, blepharitis, exposure
increase in stromal thickness outside the ablation keratopathy): These diseases may alter wound
zone. The outward expansive force in the healing and give rise to haze formation. The risk
periphery causes the central cornea to flatten of infection is shown to be higher in blepharitis
independent of ablation profile (Figure 60.8). cases.
At the present time, it is not precisely known how 3. Previous herpes infection (simplex or zoster): Several
much of the corneal shape is due to ablation profile, studies have shown that PRK and LASEK may
wound healing and biomechanical response res- induce recurrences of HSV.
pectively. Subsequent investigations will help 4. Monocularity: Patients who are functionally or
surgeons in modulating and fine tuning the results anatomically one eyed should be discouraged from
of refractive surgery. elective refractive surgery. Although the risks are
low, they are not nonexistent.
PREOPERATIVE EVALUATION 5. Advanced diabetes mellitus: Diabetes mellitus delays
the tissue repair response and promotes the onset
When a patient is considering refractive surgery, of infections.
several issues must be evaluated preoperatively. 6. Autoimmune/collagen vascular diseases: These diseases
First, it is important to determine pre-existing ocular are considered contraindications to PRK due to
or systemic conditions that could interfere with unpredictable corneal wound healing and the
healing or the predictability of the procedure. In potential for corneal melting.
addition, the patient’s refractive status, including 7. Pregnancy and breast feeding: Pregnant patients and
stability, degree of refractive error and astigmatism, those who are breast feeding are at higher risk of
must be determined. Finally, and perhaps most being over- or under-corrected due to increased
importantly, the patient’s goals and expectations must levels of various hormones which can affect the
be evaluated. Contraindications (absolute/relative) healing process and stability of refraction.
to surface ablation include:34-37 8. Medications: Chemotherapeutic agents (unpredic-
1. Corneal ectasias (keratoconus, pellucid marginal table wound healing, risk of infection), systemic
degeneration, and keratoglobus): This spectrum of steroids (risk of infection, dry eye, delayed
 Advanced Surface Ablation (ASA) 517
wound healing), isotretinoin (dry eye), rotary brush (Figure 60.9A). After the laser ablation
sumatriptan (delayed wound healing), oral (Figure 60.9B), the stroma is irrigated with chilled
contraceptives (dry eye). BSS and a contact lens placed on the eye (Figure
60.9C). The bandage contact lens is left in situ for 3
Ophthalmic Examination to 5 days. Often, at the time of lens removal, the
The preoperative ophthalmic examination consists of epithelium will be disturbed causing discomfort and
uncorrected visual acuity (UCVA), best corrected a transient drop in vision.
visual acuity (BCVA), evaluation of extra ocular
muscles and lids, determination of ocular dominance, LASEK
pupil size measurement in photopic and mesopic LASEK seeks to preserve the epithelium as a sheet
conditions, manifest and cycloplegic refraction, slit that is replaced at the end of surgery.
lamp examination, IOP measurement, tear break-up A dilute alcohol solution is applied to facilitate
time (BUT), funduscopy, topography and pachymetry separation of the epithelium from the Bowman’s
(Orbscan/ultrasound). membrane at the level of the hemidesmosomes.
Camellin introduced laser assisted sub-epithelial
INDICATIONS
keratectomy (LASEK) which decreases visual
Despite the popularity of LASIK, surface ablation has recovery time as well as postoperative pain and haze
been well accepted by both surgeons and patients formation3.
around the world because of its higher level of safety, The eye is draped and prepared. Local anesthetic
lower rate of complications and good visual results. drops are instilled and a lid speculum positioned.
Myopia of –1.0 to –8.0, astigmatism of –1.0 to –4.0 and The epithelium is treated with 20% alcohol for
hyperopia of +1.0 to +4.0 are reported to be correc- 20 seconds, using a special trephine (Figure 60.10A).
ted by surface ablation methods quite well.36–38 The pre-cut margin is lifted with a hockey spatula
and epithelium is gently detached and folded up at
SURGICAL TECHNIQUES the 12 o’clock position.
After the laser ablation (Figure 60.10B), the stroma
PRK
is irrigated with chilled BSS. The epithelial flap is
PRK is a surface corneal-based refractive surgical procedure repositioned onto a relatively dry stromal bed
that is approved by the Food and Drug Administration (Figure 60.10C) and a contact lens placed on the eye
(FDA) to treat myopia, hyperopia and astigmatism. (Figure 60.10D). The bandage contact lens is left in
The eye is draped and prepared. Local anesthetic situ for 3 to 5 days. Often, at the time of lens removal,
drops are instilled and a lid speculum positioned. the epithelium will be disturbed causing discomfort
Epithelium is debrided by a hockey knife or Amoils and a transient drop in vision.

Figures 60.9A to C: PRK Procedure (Courtesy of Connecticut Eye Care Center, CT)
518 Mastering Advanced Surface Ablation Techniques

Figures 60.10A to D: LASEK Procedure (Courtesy of University of Florida Laser Center)

Epi-LASIK used for LASIK and visual blackout may occur along
with pupil dilation. Balanced salt solution (BSS) is
Epi-LASIK was developed as a procedure to create a
applied to the epithelium and the epithelial separator
viable epithelial flap that would remain on the cornea
advanced across the cornea to create the flap
after laser ablation. Pallikaris and colleagues 4,5
(Figure 60.11A). The vacuum is released and the epi-
described the technique in which a microkeratome is
LASIK unit removed from the eye. An epithelial flap
used to create the epithelial flap, preserving the
is soft and distensible. Experienced LASIK surgeons
integrity of the basement membrane and avoiding the
will need to revisit flap-handling techniques to avoid
use of alcohol and its consequent epithelial toxicity.
stretching and tearing epi-LASIK flaps. After the
Epi-LASIK aims to preserve the basement membrane
excimer ablation (Figure 60.11B), the stroma is
of the corneal epithelium (in contrast with LASEK,
immediately irrigated with chilled BSS. The epithelial
where the basement membrane is divided at the level
flap is repositioned onto a relatively dry stromal bed
of the lamina lucida). An intact basement membrane
(Figure 60.11C) and a contact lens placed on the eye
may provide a barrier function preventing the
(Figure 60.11D). The bandage contact lens is left
penetration of inflammatory cytokines into the corneal
in situ for 3 to 5 days. Often, at the time of lens
stroma, thus modulating the wound healing response.
removal, the epithelium will be disturbed causing
The intact basement membrane also increases the
discomfort and a transient drop in vision.
chance of survival of the basal epithelial cells.
The eye is draped and prepared. Local anesthetic
Phototherapeutic Keratectomy (PTK)
drops are instilled and a lid speculum positioned.
The epi-LASIK suction ring is positioned on the eye Phototherapeutic keratectomy (PTK) involves the use
and a vacuum applied. The vacuum is similar to that of the refractive laser to treat visual impairment or
 Advanced Surface Ablation (ASA) 519

Figures 60.11A to D: Epi-LASIK procedure (Courtesy of mid peninsula Ophthalmology, CA)

irritative symptoms relating to diseases of the anterior adhesion. Moreover, superficial corneal disorders
cornea by sequentially ablating uniformly thin layers which, in some cases, would otherwise require
of corneal tissue. Phototherapeutic keratectomy may corneal transplant may be amenable to treatment
be performed in a routine surgery setting using with the PTK procedure.
topical anesthesia.
Depth Offset
Indications for PTK
This feature of the CustomVis Pulzar Z1 refractive
PTK may be considered medically necessary for
laser allows for PTK treatments to be combined with
treatment of the following conditions:
refractive treatments as well as other potential
• Corneal scarring and opacities
benefits:
• Anterior corneal dystrophy
• Allows PTK treatments to be performed either at
• Recurrent corneal erosion (RCE) refractory to
the same time as a refractive procedure, or
conservative treatment with patching, cyclo-
independently by entering zero subjective
plegia, topical antibiotics and lubricants
• RCE when refractory to mechanical surgical correction.
treatment such as, corneal micropuncture or • Allows the maximum depth of the plan to be
epithelial curettage. reduced by entering a negative offset, providing
While some of these conditions, therefore, could a means of saving tissue that is particularly useful
be treated by mechanical superficial keratectomy in highly irregular cornea requiring custom
techniques, PTK may minimize tissue removal and treatment.
surgical trauma. The smoother stromal surface • Allows the surgeon to save tissue or ablate
achieved by the refractive laser procedure may additional tissue if the need arises, e.g. in PTK
improve surface smoothness of the cornea, improve treatments.
postoperative corneal clarity and decrease post- The depth offset feature is available for standard
operative scarring, and facilitate subsequent epithelial and customized surgeries with the Pulzar Z1.
520 Mastering Advanced Surface Ablation Techniques
Custom Surface Ablation (CSA) coupled with a limbal-based eye tracker due to the
potential for the pupil centre to shift.
In order to treat non-standard refractive errors or
With the detailed information that a topography
to correct errors induced by previous surgery, a
exam provides about the preoperative corneal surface,
treatment plan custom-generated for the patient is
any and all irregularities in the cornea can be
required based on topography and/or wavefront
corrected for, including irregular shapes caused by
examinations.
injury or previous surgery, resulting in an ideal
A topography exam provides a relatively accurate
postoperative corneal surface as indicated by the
depiction of the pre-operative shape of the cornea.
patient’s refraction.
From this data an astigmatic pre-operative kerato-
The determination of what the ideal postoperative
metry measurement can be calculated that has the
corneal surface for an individual patient is can be
potential to be more accurate than an APK (Average
enhanced through the use of a wavefront exam. As a
Pre-operative Keratometry) measured using tradi-
wavefront examination produces a map of the optical
tional means. In this way, topography data can be
power of the eye it can entirely replace a topography
useful as input to standard treatments by allowing
exam when generating a custom surgery plan. However,
treatment planning software to algorithmically
there are some disadvantages to this approach.
determine parameters from the topography exam that
A wavefront exam provides no keratometry
would otherwise be estimated and entered by the
measurement so a separate reading needs to be taken.
user.
As has already been discussed, a topography exam
In addition, the calculation of preoperative
is an excellent source of keratometry information. In
keratometry from topography data can incorporate
addition, as a wavefront exam analyses the entire
advanced techniques such as accounting for corneal visual system, care must be taken when basing a plan
asphericity. As even an ideal cornea is not spherical, on a wavefront exam to ensure that aberrations not
corneal asphericity will have a subtle effect on due to the corneal shape are not corrected.
keratometry measurements resulting in inaccuracies As such, an approach that combines both
in determining the true optical power of the cornea topography and wavefront data may be preferable.
if mean radii are used. In this case the wavefront exam can be used to
In the same way preoperative asphericity can be determine certain ideal postoperative parameters
measured from a topography exam. This provides a such as asphericity, corneal vertex position for
means of generating a treatment plan designed to correction of coma and refractive correction, while
maintain preoperative asphericity thereby reducing the topography exam is used to determine the
the induction of spherical aberrations. This technique preoperative keratometry and to correct for irregu-
can be used both for topography-based treatments larities. This is the approach taken by CustomVis
and aspheric standard treatments. When treating- ZCAD™ treatment planning software.
based on wavefront data the wavefront exam can
be used to determine the optimal postoperative IMPORTANT FEATURES OF REFRACTIVE LASERS
asphericity.
If a photograph is taken along with the topography Eye Tracking
exam, the position of the pupil and limbus with To accurately perform an ablation it is essential to
respect to the corneal vertex can be automatically account for any lateral movement of the subject and
determined using image processing techniques. This adjust the beam position accordingly. For this
has the advantage that the treatment can then be purpose, it is common to track the motion of the pupil
automatically appropriately positioned on the eye in a live video image.
without the need for manual selection of a treatment The use of the pupil as a tracking target has some
centre by the user. This is particularly effective when drawbacks however. There can be very little contrast
 Advanced Surface Ablation (ASA) 521
between the pupil and iris in patients with dark eyes with many possible solutions, which could potentially
and this is further obscured by the optical properties also be impacted by the flap in LASIK treatments.
of the cornea once the epithelium is removed making
the pupil difficult to distinguish. Furthermore, the Cyclorotation Correction
pupil centre and dimensions are not necessarily fixed When performing astigmatic or custom treatments
causing changes in the pupil to be incorrectly the rotational orientation of the treatment becomes
interpreted as shifts in the cornea (Figure 60.12). significant. As there can be significant rotation of the
eye between the preoperative examinations and the
time of treatment this needs to be measured and
corrected for to achieve the desired treatment
outcome (Figure 60.13).

Figure 60.12: Limbus vs. Pupil Eye Tracker—Limbus easily

visible; Pupil not at all visible

As the contrast between the iris and sclera is

higher in the average case and the position of the iris
relative to the cornea is fixed, the limbus may make
a better target for lateral eye-tracking.
Currently, the CustomVis Pulzar Z1 solid state Figure 60.13: Cyclorotation
laser is the only laser that tracks the limbus in real-
time. Some other devices are performing one–off If a photograph is taken at the time of the pre-
measurements of the pupil position relative to the operative examinations then this can be compared to
limbus but then track the pupil. a photograph taken by the laser at the time of surgery
Something that needs to be considered when and the rotational difference between the two
implementing limbal, eye-tracking when performing calculated using image processing techniques. In this
LASIK surgery is how the flap may obscure the way the plan can be adjusted to the patient’s
limbus. Given this, it can be easier to implement orientation immediately prior to treatment.
higher-performance eye-tracking for surface
Bandage Contact Lenses (BCL)
treatments.
Another factor to consider is variation in the The main goals of surgeons in ASA are avoiding
patient’s gaze. Ideally, the patient would remain epithelial problems, haze and regression and
consistently fixated however this can by no means minimizing pain and discomfort. Surgeons need to
guaranteed. As such, a means of measuring deviations select bandage contact lenses (BCL) that not only
in the patient’s gaze could serve to alleviate errors relieve pain but also enhance the healing process. By
due to a lack of fixation. This poses a unique problem preventing contact between exposed corneal nerves
522 Mastering Advanced Surface Ablation Techniques
and overlying eyelids, pain is relieved. BCLs splint
the epithelium and serve as a protective barrier during
the repair process. As such, they provide protected
migration and replication and secure attachment of
epithelial cells during basement membrane repair.
BCLs also provide a smooth optical surface in the
presence of an irregular corneal surface, improving
vision (Figure 60.14). Patients with a 6.5 mm epithelial
defect may need a BCL for 2 to 3 days; those with
8.5-9.0 mm defects may need 4 to 5 days.39
Oxygen requirements are greater when the corneal
regeneration process is taking place. Allowing more
oxygen to the cornea may improve epithelial cell
Figure 60.14: Bandage contact lens
reproduction and wound healing and could alleviate
hypoxia related complications. To provide enough
oxygen to a healing cornea, surgeons have two
options: (1) high water content hydrogels or (2) high
DK/T, low water content silicon hydrogels. The
former group has long been used as BCLs and
includes lenses with water content from 58 to79
percent. The silicon hydrogels may reduce the
dependence of lenses on tears, are less prone to
dehydration and result in faster corneal reepi-
thelialization and less patient discomfort.40,41

COMPLICATIONS

The major postoperative complications of surface

ablation are corneal haze, dry eye, epithelial
Figure 60.15: A case of severe haze following PRK
complications, under- and over-correction, and
infection. Most histological studies from animals and
humans treated with PRK have demonstrated an
Corneal Haze and Opacification increase in the number and activity of stromal
Corneal haze is a significant problem after PRK. Sub- keratocytes, which suggests that increased keratocyte
epithelial corneal haze typically appears several weeks activity may be the source of the extracellular
after PRK, peaks in intensity at 1–2 months, and deposits.42, 43 Although the majority of cases resolve
gradually disappears during the next 6–12 months. and cause no visual sequelae, the possibility of
Several histological animal and human studies have regression and loss of BSCVA makes haze a great
shown that the subepithelial corneal haze resulting concern for refractive surgeons. The grading of haze
from PRK is most likely due to abnormal gly- has been standardized in the literature.44
cosaminoglycans, no-lamellar type III collagen and
hyaluronic acid deposited in the anterior stroma as a Grades of Corneal Haze
consequence of the epithelial-stromal wound healing The most important predisposing factor for haze
process (Figure 60.15). formation is the amount of myopic correction that
 Advanced Surface Ablation (ASA) 523
determined the depth of ablation. Braunstein et al44 colleagues52 performed a prospective study on 28
found that ablations with depths greater than 80 μm myopic patients with spherical equivalent of ≥ –5.0
produced higher levels of haze with decreased visual dioptres and found it both safe and effective in
acuity than ablations less than 80 μm. Corneal sub- preventing haze.
epithelial haze is more severe in patients who have Stojanovic and colleagues recently suggested that
been treated with smaller-diameter ablation45 (Figure oral ascorbic acid supplementation may have a
60.16). prophylactic effect against haze development after
Grade Description
PRK53. Although its safety and efficacy has not yet
been shown by randomized and prospective trials.
0 Clear, no haze
0.5+ Barely detectable or trace
1+ Mild, not affecting refraction Dry Eye
1.5+ Mildly affecting refraction
2+ Moderate, refraction possible but difficult Dry eye may occur after PRK as a result of the
3+ Opacity prevents refraction, anterior chamber easily ablation of corneal nerve fibers. This is similar to
visualized conditions after LASIK, but generally with PRK the
4+ View of anterior chamber difficult
5+ Unable to view anterior chamber
results are less severe and of shorter duration (Figure
60.17).
Figure 60.16: Grades of corneal haze

Pharmacological Modulation of Wound Healing

Many studies have been performed to elucidate and
control wound healing and many drugs or protective
substances have been used to modulate corneal the
wound healing process.
Topical corticosteroids have been used to inhibit
haze formation after PRK. The main mechanism
through which corticosteroids may prevent haze is
inhibition of collagenase synthesis.46,47
Among topical drugs evaluated to prevent or treat
corneal haze, mitomycin-C (MMC) has recently
gained the interest of refractive surgeons. MMC is
an antibiotic, antineoplastic agent that selectively
inhibits the synthesis of DNA, RNA, and proteins.
The logic behind using MMC is that the topical
application of the drug on the cornea can inhibit sub-
epithelial fibrosis through preventing the
proliferation of stromal keratocytes, while the main
causes of regression and haze are overactivity and
proliferation of stromal keratocytes following laser
ablation.48
The effects of mitomycin-C 0.02% in preventing
haze has been shown by Talamo et al49, and Xu et al50
in experimental models. Majmudar et al51 reported
a successful series of 30 eyes treated using a 0.02%
MMC solution to prevent recurrent haze after PRK
and radial keratotomy. More recently Hashemi and Figure 60.17: Dry eye
524 Mastering Advanced Surface Ablation Techniques
Ozdamar and colleagues54 evaluated Schirmer’s Infectious Keratitis
test and tear break-up time of treated eyes compared Any breach of the barrier function of the corneal
with contralateral untreated eyes. They found a epithelium predisposes the patient to infectious
significant decrease in both Schirmer’s and break-up keratitis. Thus, bacterial keratitis should be a
time in the treated eyes at 6 weeks and related this significant problem facing all refractive surgeons.
to a decreased corneal sensitivity. It is unclear Etiologic agents include Pseudomonas aeruginosa,
whether this phenomenon persists beyond the Staphylococcus epidermidis, Streptococcus pneumoniae,
6 weeks because of the restoration of corneal and Mycobacterium chelonae. All patients with this
sensation during the first 6 to 8 months.55 Meticulous complication had typical keratitis symptoms, pain,
patient selection and preoperative evaluation is the photophobia, and redness.59,60 Infectious keratitis
key to avoid this serious complication. may result in scarring and decreased vision.
Appropriate culture and aggressive treatment with
Epithelial Complications broad spectrum antibiotics should be used.
The epithelial defect created during PRK usually heals Keratitis after PRK is not always infectious. Sterile
within 3 to 4 days with the aid of a BSCL or pressure keratitis can present as sub-epithelial infiltrates that
patch. In some cases, especially older patients, this are associated with the use of topical NSAIDs or
period may be prolonged. A frequent cause of antibiotics. 61 If topical NSAIDs are used without
delayed re-epithelialization is dry eye, which may appropriate coverage of steroids, leukocyte migration
be treated with increased lubrication and temporary into the cornea may occur, causing inflammatory
punctal occlusion. Patients with undiagnosed auto- infiltrates.35
immune connective tissue disease or diabetes mellitus
COMPARISON OF 193 NM AND 213 NM WAVE-
may also have poor epithelial healing.34
LENGTHS
Recurrent erosions may occur in areas outside of
the ablation zone or more rarely in the treated zone. Importance of Corneal Hydration during Ablation
Phototherapeutic keratectomy appears to be an
There are two types of refractive lasers available on
effective treatment for this complication.35
the market. Solid state refractive lasers with a
213 nm wavelength have a special characteristic. As
Under- and Over-correction a 213 nm pulse is delivered to the corneal bed it
Under-corrections occur after PRK most often when produces a fluid over the corneal surface. Traditional
a significant myopic regression occurs. The incidence 193 nm wavelength lasers (excimer lasers) behave in
and amount of myopic regression depend on the the opposite way by drying out the cornea.
degree of correction that is attempted.56 In addition, In addition, 213 nm is less affected by the corneal
regression is markedly increased with optical zones hydration or fluid on the cornea. As such, there is no
less than 6.0 mm in diameter.57 need to continuously wipe accumulated fluid. Fluid
Over-correction may occur if substantial stromal over the cornea will allow the patient to have a more
dehydration develops before the laser treatment is clear view of the fixation target than a dry cornea
initiated because more stromal tissue will be ablated resulting from a 193 nm ablation would have. It will
per pulse.34 Sensitivity to corneal dehydration is signi- allow the patient to fixate very well during the whole
ficantly reduced when using a laser based on 213 nm treatment, reducing the chance of decentred
technology. Over-correction tends to occur more treatments and increasing the comfort for the patient
often in older individuals (35-45 years old) as a result and surgeon. Figure 60.18 clearly shows the
of inadequate wound healing in the postoperative production of fluid over the corneal bed as a 213 nm
period.58 laser fires.
 Advanced Surface Ablation (ASA) 525

Figure 60.18: Corneal hydration during 213 nm ablation

Tissue Hydration Study on Surface Treatments depth of 193 nm in BSS is 72 μm and 123 μm in 0.9%
Absorption coefficients were obtained for sodium sodium chloride, while penetration depth of 213 nm
chloride solution (saline) and balanced salt solution in BSS is 1450 μm (almost 20 times higher than
at 193 nm and 213 nm laser wavelengths. This was 193 nm) and in 0.9% sodium chloride is 2 × 105 μm
achieved by measuring laser pulse transmission (over 1000 times higher than 193 nm) (Figures 60.20
through both solutions. Results were used to obtain and 60.21).
an overall absorption coefficient and penetration During refractive surgery, fluid placed on the
depth for balanced salt solution and 0.9% sodium surface of the cornea proved to be a barrier to
chloride (Figure 60.19). ablation for the 193 nm wavelength. The increased
Absorption coefficients in balanced salt solution penetration depth through sodium chloride and
for the 193 nm and 213 nm wavelengths were found balanced salt solution for the longer 213 nm laser
to be 140 and 6.9 cm–1, respectively. In 0.9% sodium wavelength proves to be very good for laser vision
chloride solution, the absorption coefficient was correction as the significance of hydration is greatly
81 cm–1 at 193 nm and 0.05 cm-1 at 213 nm. Penetration reduced.
526 Mastering Advanced Surface Ablation Techniques
Absorption coefficients and penetration depths of various fluids state laser. The subtle effects of these conditions upon
193 nm 213nm excimer laser performance are the primary reason
Absorption Penetration Absorption Penetration most refractive surgeons have personalized nomo-
Solution coefficient depth coefficient depth
grams. This allows us to compensate as best we can
BSS 140 72 6.9 1450
for hydration issues related to surgeon technique (e.g.
0.9% Sodium 8 1 123 0.05 2.0 × 105
chloride wet vs. dry technique, duration of bed exposure) and
localized climatic conditions. By eliminating these
Figure 60.19: Absorption coefficients and penetration depths of
193 nm and 213 nm variables, the outcome of solid state procedures
should be more predictable.

Treatment Times/Ablation Rates

When performing surface ablations, the difference in
ablation rates between the stroma and Bowman’s
membrane must be considered to ablate an accurate
depth of corneal tissue. Due to the lower ablation rate
of the Bowman’s membrane when compared to the
stroma, surgery times will be slightly longer for surface
treatments than for equivalent LASIK treatments.
Because of the relative thinness of the Bowman’s layer
this is effectively a small fixed overhead.
Because the treatment time of surface treatments
are a little higher than for intra-stromal ablations,
fluid can have a major impact on the outcome of
Figure 60.20: Transmission through 0.9% NaCl
surgeries. The 213 nm wavelength has increased
penetration depth through sodium chloride and
balanced salt solution, alleviating concerns over fluid
build-up in surface treatments. This also reduces
reliance on a surgeon’s technique related to corneal
hydration. These advantages become more significant
with higher corrections.
While 193 nm excimer laser results depend on
corneal hydration or environmental humidity,
requiring personalized nomograms for each surgeon
or even surgical technique, e.g. surface treatments.

HISTOPATHOLOGICAL COMPARISON OF PRK IN

RABBITS

Introduction
The cornea is commonly re-shaped by photorefractive
Figure 60.21: Transmission through BSS
keratectomy (PRK), which ablates the cornea by
This feature of 213 nm has an important clinical removing micron-thick layers of tissue from the
advantage. Fluctuations in corneal hydration or Bowman’s layer and anterior stroma. PRK is typically
environmental humidity are unlikely to have a performed using a 193 nm excimer laser. However,
significant effect upon the performance of the solid there are concerns about the practicality and safety
 Advanced Surface Ablation (ASA) 527
of the excimer (193 nm) laser for corneal surgery. To Analysis
address these concerns, a solid state 213 nm (5th Photographs of the sections were taken with a
Harmonic) Nd:YAG laser has been developed. fluorescence microscope. Six photographs of each
Programmed cell death, or apoptosis, is parti- section were taken, two inside the crater, two at the
cularly important to measure as it is a precursor for edges of the crater within the transition zone and
post-operative corneal opacification or haze. Other two from the non-lasered portions of the cornea
important contributors to haze are cell proliferation, outside of the ablation zone.
migration and morphological changes.
Discussion
A study was performed to examine the short-term
time course of live cells (keratocytes) and apoptosis There was no difference in the amount of apoptosis
in the cornea of adult rabbits following PRK treatment induced by both lasers.
The increased number of live cells (keratocytes)
using a 193 nm or 213 nm laser (Figures 60.22 and
in the crater of the 193 nm lasered corneas suggests
60.23).
cell proliferation and/or migration. It also suggests
that 193 nm lasered cornea has more inflammation
Methods
than 213 nm lasered cornea.
New Zealand White rabbits underwent PRK (–5 In conclusion these results demonstrate that the
dioptres, 6.5 mm optical zone, 7 mm transition zone) 213 nm solid state laser has similar cell death inducing
laser surgery with the 213 nm solid state laser and a properties, but causes less cell proliferation/migra-
193 nm excimer laser. Corneas were evaluated after tion (inflammation) compared to the 193 nm excimer
3 days. laser.

Figure 60.22: TUNEL staining of rabbit cornea following PRK62

528 Mastering Advanced Surface Ablation Techniques
5. Pallikaris IG, Naoumidi II, Kalyvianaki MI, Katsanevaki
VJ. Epi-LASIK: Comparative histological evaluation of
mechanical and alcohol-assisted epithelial separation. J
Cataract Refract Surg 2003; 29:1496-1501.
6. Proceedings of the First International LASEK Congress
Houston, TX, 2001.
7. Munnerlyn CR, koons SJ, Marshall J. Photorefractive
keratectomy: a technique for laser refractive surgery. J
Cataract Ref Surg 1988;14:46-52.
8. Puliafito CA, Steinert RF, Deutsch TF, et al. Excimer laser
photoablation of the cornea and lens. Experimental
studies, Ophthalmology 1985;92:741-8.
9. Puliafito CA, Wong K, Steinert RF. Quantitative and
ultrastructural studies of excimer laser ablation of the
cornea at 193 and 248 nanometers. Lasers Surg Med
1987;7:155-9.
10. Srinivasan R, Sutcliffe E. Dynamics of the ultraviolet laser
ablation of corneal tissue. Am J Ophthalmol 1987;103:
470-1.
11. Krueger RR, Trokel S, ShubertH. Interaction of UV light
with the cornea. Invest Ophthalmol Vis Sci 1985; 26: 1455-
64.
12. Marshall J, Trokel S, Rothery S, et al. Photoablative
reprofiling of the cornea using an excimer laser:
photorefractive keratectomy. Lasers Ophthalmol.1986;1:
21-48.
13. Ren Q, Simon G, Legeais JM, Parel JM, et al. Ultraviolet
solid-state laser (213-nm) photorefractive keratectomy.
Ophthalmology 1994;101(5):883-9.
Figure 60.23: Total live cells and apoptotic cells in crater on day 3
14. Vukich, JA, Solid State Lasers May Shape Future of
Custom Ablation. Refractive Eye Care For Ophthalmo-
logists 2003;8:16-7.
CONCLUSION
15. Steinert RF. Wound healing anomalies after excimer laser
photorefractive keratectomy: correlation of clinical
These studies demonstrate that the solid state 213 nm outcomes, corneal topography, and confocal microscopy.
laser produces a similar clinical and histological course Trans Am Ophthalmol Soc 1997;95:629-714.
to the excimer 193 nm laser. Given its reduced 16. Tuft SJ, Gartry DS, Rawe IM, et al. Photorefractive
keratectomy: implications of corneal wound healing. Br J
dependence on corneal hydration and reduced cell
Ophthalmol 1993; 77:243-7.
proliferation/migration when compared to 193 nm, 17. Zieske JD, Gipson IK. Agents that affect corneal wound
the 213 nm wavelength may prove to be a potentially healing: modulation of structure and function. In: Albert
superior tool for refractive surgery, particularly for DM, Jacobiec FA, (Eds). Principles and Practice of
Ophthalmology. (2nd edn). Philadelphia: WB Saunders;
surface treatments.62,63 2000:364-72.
18. Gipson IK, Kiorpes TC. Epithelial sheet movement: pro-
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27. Strissel KJ, Rinehart WB, Fini ME. Regulation of paracrine keratectomy. Acta Ophthalmol 1994;72:229–33.
cytokine balance controlling collagenase synthesis by 45. Braunstein RE, Jain S, McCally RL, et al. Objective
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Release of TGF-beta1 and VEGF in tears following 46. Corbett MC, Verma S, O’Brart DPS, et al. The effect of
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Clinical Ophthalmology 2006; Vol.6: chapter 48. corneal surgery. Ophthalmology 2000;107:89-94.
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surface ablation 2007:41-57. 55. özdamar A, Aras C, Karakas N, et al. Changes in tear
39. Chen CC, AzarDT. LASEK vs PRK, in Krieglstein GK, flow and tear film stability after photorefractive
Weinerb RN, Essentials in ophthalmology 2005: 215-6. keratectomy. Cornea 1999;18:437–9.
40. Jackson WB, Casson F, Hodge WG, et al. Laser vision 56. Kauffman T, Bodanowitz S, Hesse L, et al. Corneal
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Discussion 1737-38. videomicroscopy. Ger J Ophthalmol 1996;5:508-12.
530 Mastering Advanced Surface Ablation Techniques
57. Kim JH, Sah WJ, Park CK, et al. Myopic regression after 62. Teal P, Breslin C, Arshinoff S, Edmison D. Corneal
photorefractive keratectomy. Ophthalmic Surg Lasers subepithelial infiltrates following excimer laser
1996;27:S:435-9. photorefractive keratectomy. J Cat Refract Surg
58. O’Brart DP, Corbett MC, Verma S, et al. Effects of ablation
1995;21:516-8.
diameter, depth, and edge contour on the outcome of
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59. Loewenstein A, Lipshitz I, Levanon D, et al. Influence of Saarloos. School of Animal Biology. The University of
patient age on photorefractive keratectomy for myopia. Western Australia, Corneal Refarctive Surgery using the
J Refract Surg 1997;13:23-22. solid state 213 nm laser causes less apoptosis than the
60. Amayem A, Ali AT, Waring GO III, Ibrahim O. Bacterial excimer 193 nm laser.
keratitis after photorefractive keratectomy. J Refract Surg 64. Histological Changes and Unscheduled DNA Synthesis
1996;12:642-4.
61. Brancato R, Carones F, Venturi E, et al. Mycobacterium in the Rabbit Cornea Following 193-nm, 213-nm, and
chelonae keratitis after excimer laser photorefractive 266-nm Irradiation Paul P. Van Saarloos, PhD; Jennifer
keratectomy. Arch Ophthalmol 1997;115:1316-8. Rodger, PhD Journal of Refractive Surgery, 2007;23:5.
 CHAPTER Advances in
61 CorneoplastiqueTM:
Art of Laser Vision Surgery

Arun C Gulani, Lee T Nordan (USA)

INTRODUCTION Corneoplastique™ includes all forms of Laser

Vision Surgery itself. LASIK and various variants of
The individual or combined use of Amniotic Laser Vision Surgery are performed on the Cornea .
membranes, Glue, Lamellar cornea, Synthetics, i.e. It is important that refractive surgeons recognize the
INTACS, etc and finally the excimer laser as a importance of the ART of Laser Vision Surgeries by
sculpting tool towards an effort to perfect vision is understanding the cornea and the whole spectrum
what I wish to introduce as a new trend and possibly of corneal surgery.
a super-specialty in eye care- Corneoplastique™. I remind LASIK surgeons that besides Technique
Simply put, the ocular surface inclusive of the and Technology, the third “T” is of equal, if not more
importance and that is “Tissue” (in this case; Cornea).
cornea (irrespective of the causative incident, i.e.
Corneal surgical experience and knowledge will
LASIK complications/infection/trauma/previous
in all probability enhance the ability of a laser vision
surgery) is prepared by any one or a combination of surgeon to better select the candidacy of their
the above techniques in single or multiple stages to patients, prevent complications and also prepare them
prepare for the final fine tuning using the excimer to react in an efficient manner towards any inade-
laser towards a visual goal where early rehabilitation quate/unforeseen outcomes.
and aesthetic outcomes are a welcome association Similarly, these advanced corneal techniques can
with promising uncorrected visual acuity (Gulani be used to even prepare patients who have had
AC Corneoplastique™ Advanced Corneal corneal problems like, corneal scars, pterygiums,
Surgery Course. SASCRS-Durban, South Africa; Aug previous surgeries like cataract surgery/corneal
transplants/radial keratotomy, etc. to make them
2005).
suitable for laser vision surgery in a therapeutic mode
This is in contrast to the more extensive standard
towards a visual goal.
surgical techniques like penetrating keratoplasties, This ART of blending the full spectrum of ocular
etc. where in most cases the final unaided visual surface and corneal surgery in a therapeutic approach
outcome despite a long rehabilitation period is less either before (to prepare the cornea) or after laser
than optimal. Synergistically though, these standard vision surgery (to repair the cornea) is the core function
surgeries, due to their proven track record can always of this possible new super-specialty.
serve as a back-up plan in selection of any of the above This ability to Prepare the cornea for laser vision
mentioned techniques. surgery and to Repair the cornea from laser vision
532 Mastering Advanced Surface Ablation Techniques
surgery using these techniques will raise the Using my recently introduced 5S system (Gulani
confidence of refractive surgeons and patients alike. AC. 5S Classification System: ASCRS, California
March 2006) we can devise a plan to heal/repair the
INDICATIONS OF CORNEOPLASTIQUE TM cornea appropriately and finally fine tune using the
Indications for Corneoplastique™ would be the Excimer Laser (VISX Star S4 Santa Clara, CA). My
following: goal all the time is unaided 20/20. The 5 Ss stand for
1. Corneal Scars (from previous surgeries / trauma / Shape, Sight, Scar, Site and Strength.
healed corneal ulcers / infections) This 5S system is an expansion of a three-level
2. Pterygiums (advanced/ recurrent) corneal classification system I devised several years
3. Previous surgeries (cataract surgery / corneal ago1 (Table 61.1). The three-level system was based
transplants / radial keratotomy, etc.) on the tissue components involved in the LASIK
4. LASIK and laser vision surgery complications surgery, and I assigned LASIK corneal complications
5. Corneal degenerations / dystrophies to Level I (corneal section), Level II (interface) or
The art of blending the whole spectrum of surface Level III (ablation bed). This helped identify and treat
ocular and corneal surgery using these topical, brief, a range of corneal problems.
aesthetic, and visually promising techniques either Similarly, the 5S system addresses questions about
singly or in combinations shall raise the bar on making the cornea’s state in order to customize a treatment
all surface surgeries visually focused. plan. It does not give importance to the technology
used or the causative pathology itself.2
CORNEOPLASTIQUE™ IN ACTION
Here are its components:
What I want more surgeons to do is use less 1. Sight. Is the patient correctable to 20/20 with
terminology and more logic. “When I look at a glasses and/or hard contact lenses?
complication it does not matter to me what surgery 2. Site. Is the involvement central or peripheral?
was done or what Laser was used. I look at it as, 3. Scar. Is the cornea clear or scarred
here’s a cornea; what does it have? Does it have a 4. Strenght. Is the cornea thin/ectatic (Keratoconus)
scar, irregular astigmatism, is it thin, de-centered or thick (Epikeratophakia/Bullous keratopathy)
ablation, etc.? and approach that problem 5. Shape. Is the cornea myopic (Steep), Hyperopic
accordingly”. (Flat) or Astigmatic (Regular /Irregular)

Table 61.1: Gulani ‘SS’ classification system

 Advances in CorneoplastiqueTM: Art of Laser Vision Surgery 533
This 5S system allows you to understand, allocate New technology corneal surgical Lasers, i.e.
and plan a corrective approach in addition to your Intralase, Da Vinci, Femtec and Carl Zeiss are moving
knowledge of not only LASIK but lamellar corneal in this direction and I see them as an integral part of
surgery in general (LASIK is lamellar surgery, hence my corneoplastique™ concept.
any preparation or repair of the cornea for LASIK I could be planning a posterior lamellar transplant
shall usually involve a lamellar approach). Surgeons – DLEK/DSAEK (My technique is called Key Hole
must be familiar with the wide spectrum of advanced Transplant) ReStor IOL, INTACS, Wavefront LASIK,
surgical options available to provide the most Amniotic resurfacing, etc. it does not matter as long
appropriate way to deal with a problem (Gulani AC. as the sequence and stages of surgery make sense
Corneoplastique™: Art of Vision Surgery (Abstract). for a final outcome-unaided emmetropia.
ISOPT, Berlin, Germany March 2006). The knowledge Also, at any stage we can always fall back on any
of optics, anatomy, physiology and the combination of the traditional surgeries which will always be a
of these unchanged concepts can only be strengthened back up for these patients ie PKP, etc.
with advancing technology. What we realize with the above examples and
For an example on how this concept works, let’s many more (Figures 61.1 to 61.7) is that we need to
take two cases and make a surgical plan: plan each stage with preparation for the next; also if
1. Patient with LASIK ectasia: the patient is already very happy at any intermediary
Here the patient’s cornea basically has a problem stage- Stop. The patient and their satisfaction is what
with 3 of the 5Ss, i.e. Strength, Shape and Sight. we are addressing not a topography chart.
Stage I: Sutureless Lamellar Keratoplasty (Provides In summary, practically any ocular situation
the Strength)- Remember to use a donor cap that (status postcataract surgery, glaucoma surgery,
is THICKER (Two reasons: remember the fact that retinal surgery, corneal transplant, trauma, chemical
the donor will deturgese and also that you will burns, etc.) provided it has visual potential and no
have more cornea to sculpt with the Excimer Laser ongoing or uncontrolled visually debilitating
at a later stage) pathology can be addressed to achieve its best
Stage II: Excimer Laser ASA (provides Shape and unaided visual capacity.
therewith Sight) It is also very important to note here that the 20/
2. Now lets take a patient with an opposite problem. 20 we aim for in such cases is not the same as in
Aphakic Epikeratophakia with decentered, scarred a virgin LASIK case where we are not pleased with
epi-lenticle. 20/20 and constantly strive to achieve 20/15 and
Here the cornea has a problem with all 5 Ss (It is 20/10. The 20/20 in these cases is qualitatively low
thicker (Strength), Scarred, central Site affected (Gulani AC. Ginsberg A. Quality of Vision and Optec
with poor Shape and Sight) 5000- March 2006). These are patients with poor/
Stage I: Remove the Epi-lenticle (Scar and Strength distorted vision and becoming functional even with
are addressed) 20/40 (as refractive surgeons we must always talk in
Stage II: Secondary IOL (Sight is addressed) terms of unaided vision) is an ecstatic, life-changing
If needed further Stage III. Excimer Laser to fine outcome. Especially if you consider that these
tune the Shape and further improve Sight techniques are all brief/topical/aesthetically pleasing
Having personal experience with the full spectrum and therefore a fond memory for the patients.
of vision corrective surgeries including presbyopic As long as there is no intraocular pathology or
multiocal lenses like ReStor, Phakic Implants like the disease, i.e. retinal/neurological/uncontrolled
anterior, posterior and iris-supported IOLs, INTACS, glaucoma, etc. there is no reason why we cannot stage
etc. we can use these concepts universally to plan towards a perfected visual outcome. The ability to
through the anterior chamber and cornea for final help patients with refractive surgical complications/
unaided vision. previous surgeries/chemical burns/trauma, etc.
534 Mastering Advanced Surface Ablation Techniques

Figure 61.1: Pictures of Radial Keratotomy, Astigmatic Keratotomy, Hexagonal Keratotomy and previous
Corneal Transplant. In all of these cases the S factor affected was Shape so the only treatment needed
was Excimer Laser Vision Surgery for unaided emmetropia

Figure 61.2: In cases of Keratoconus, besides Shape the factor affected could also be Strength. When
the corneal thickness is still above 350 microns we can put synthetic inserts like INTACS. Assymetric,
On-Axis INTACS for Keratoconus and PMD
 Advances in CorneoplastiqueTM: Art of Laser Vision Surgery 535

Figure 61.3: Pictures of conditions wherein the Amniotic graft was used to correct ocular surface
problems and also extended to heal the corneal defects associated with them (i.e. Extensive pterygium
with central corneal involvement). Thus correcting the Site, Sight, Strenght and Scar. This was
followed by Excimer Laser Ablation for achieving the desired Shape for unaided emmetropia

Figure 61.4: These are cases of anterior supra-Bowman scars. The Sight and Strenght being good,
we can peel these Scars under the Excimer laser followed by simultaneous refractive ablation leading
to correction of Scar (Unclear Cornea), Shape (Ammetropia) and Site (Central).
536 Mastering Advanced Surface Ablation Techniques

Figure 61.5: Patient who had Aphakic decentered Epikeratophakia nearly two decades ago
with best corrected 20/200 vision.
Stage I: Removal of her Epi-Lenticle (Correction of Site, Scar, Shape and Strenght).
This was followed by placement of secondary IOL (Sight) to uncorrected vision 20/25

Figure 61.6: Posteior Corneal Transplant (DSEK, DSAEK , KeyHole) for a case of Pseudophakic Bullous
keratopathy. We have thus corrected the Site, Scar, Strenght and Sight.
This was followed by Excimer laser surgery to correct the Shape
 Advances in CorneoplastiqueTM: Art of Laser Vision Surgery 537

Figure 61.7: Various forms of Lamellar Corneal repairs to build the cornea in preparation for the final S (Shape)
with the Excimer Laser.
These repairs could be anterior lamellar (Sutureless or sutured) or Posterior (Sutureless-KeyHole) transplants

towards 20/20 vision is no longer out of reach in through the waters of innovation as our
aspirations or outcomes. understanding and demands have surely increased
I use the Pentacam in my practice routinely (Gulani and so have patient expectations.
AC. Pentacam in Full Spectrum Refractive Surgery:
Advanced Corneal Topography Course-AAO, Las REFERENCES
Vegas 2006) and find it to be an essential tool towards
1. Gulani AC. ‘LASIK Corneal Complications: A New
a synergistic planned approach towards achieving Stratified Classification’. Ophthalmology 1999; 106:
emmetropia. This coupled with imaging techniques 1457-8.
(ReSeevit Software and CSO imaging systems) 2. Gulani AC. ‘A New Concept for Refractive Surgery:
Corneoplastique’ Ophthalmology Management 2006;
provides intricate details for surgical planning.
57-63.
With numerous refractive surgical modalities 3. Gulani AC, Wang M. Future of Corneal Topography.
available today3,4 and also the new combinations of Textbook of Corneal Topography in the Wavefront Era.
surgeries that we are seeing in their infancy (Cataract Slack Inc. 2006;26:303-4.
4. Gulani AC, L Probst. ‘CONS of PRESBYOPIC LASIK’ In:
surgery post LASIK, etc.) I believe diagnostic LASIK: Advances, Controversies and Custom. Slack Inc
technologies will need surgeons to guide them (2004). 32B; 367-9.
538 Mastering Advanced Surface Ablation Techniques

CHAPTER
Corneal Biomechanical
62 Properties

Jorge L Alió, Mohamed H Shabayek (Spain)

INTRODUCTION first introduced into scientific vocabulary in 1890 by

the Scottish physicist, Sir James Alfred Ewing.
Corneal refractive surgery advanced rapidly during
Hysteresis is a property of physical systems that do
the past two decades, due to the encouraging,
not instantly follow the forces applied to them, but
predictable and stable results of corneal remodelling
react slowly, or do not return completely and
by photoablation using excimer lasers. A result of
instantaneously to their original state.
such advancement a new frontier of diagnostic
equipments and tools became accessible to ophthalmic
Corneal Resistance Factor
surgeon such as; corneal topographer, wavefront
sensors, very high frequency optical coherence The static resistance component of the cornea which
tomography (VHF OCT), and confocal microscopy. indicates the overall corneal resistance or simply the
This technology aided in analysing not only the optical pressures “force” needed to applanate “deform” the
but also the structural properties of the cornea. cornea, this deformation is proportional to applied
Recently the biomechanical properties of the force and is expressed in mmHg (Figure 62.1).
cornea have been introduced as a new parameter in
corneal refractive surgery, parameter that evaluates
corneal characteristics form the biomechanical
perspective; such as the corneal resistance factor, and
corneal hysteresis. These parameters can be helpful
for diagnosing certain corneal pathologies especially
corneal ectatic diseases, were the biomechanical
corneal characteristics are different form normal
corneas.

TERMINOLOGY Figure 62.1: Corneal resistance factor which is the amount of

pressure needed to flatten the anterior corneal surface.
Corneal Hysteresis
The term “Hysteresis” is derived from an ancient However, measuring the biomechanical properties
Greek word which means “coming behind”. It was in vivo is a challenging task, and has been approached
 Corneal Biomechanical Properties 539
by several methods,1-8 whether invasive as anterior
Chamber saline injection and measuring ocular
rigidity or noninvasive as dynamic corneal imaging
with central indentation and dynamic bidirectional
air applanation. Pallikaris et al6 measured the ocular
rigidity in living human eyes increasing the intraocular
pressure by injecting a saline solution into the anterior
chamber; while, Grabner et al7 used the dynamic
corneal imaging method by central indentation to
assess the individual elastic properties of eyes. Where
as, Luce8 determined the biomechanical properties
of the cornea using the Reichert ocular response
analyzer (ORA), based on a dynamic bidirectional Figure 62.3: The infrared light intensity is maximally detected when
the anterior corneal surface is applanated
applanation process.
CORNEAL BIOMECHANICAL PROPERTIES IN
OCULAR RESPONSE ANALYZER ORA
NORMAL, KERATOCONIC EYES AND POST-LASIK
The Ocular Response Analyzer, (ORA Reichert EYES
Ophthalmic Instruments, Depew NY) (Figure 62.2)
In Prospective, conventional, comparative,
measures the corneal biomechanical properties by
interventional study, 9 that reported the corneal
using a dynamic bidirectional air applanation process
biomechanical properties in normal non complaining
(non invasive method). It is composed of an air pump
individual and keratoconic eyes using the Ocular
which applies a force on the anterior corneal surface
Response Analyzer ORA. The study included a total
(specific point) through a pressure transducer while
of 250 eyes divided into three groups: 164 normal
an infrared light emitter is focused on the same point
eyes, 21 keratoconic eyes and 65 eyes that had
and the reflection of this infrared beam is monitored
undergone a corneal refractive surgery procedure to
by a light intensity detector. This system records two
evaluate the effect of LASIK on the corneal
applanation pressure measurements; one while the
biomechanical properties.
cornea is moving inward, and the other as the cornea
The author’s inclusion criteria were: for normal
returns. Due to its biomechanical properties, the
and post-refractive surgery groups, patients with any
cornea resists the dynamic air puff causing delays in
irregular patterns of corneal topography or history
the inward and outward applanation events,
of ocular disease were not included; and for
resulting in two different pressure values (Figures
keratoconus group, only eyes with keratoconus with
62.3 and 62.4).
at least one clinical sign that was confirmed by corneal
topography.
Results of this study, demonstrated that in the
normal group, a decrease in the corneal biomechanical
properties was observed in elder patients. This
implies a loss of the elastic properties of the cornea
with age, which coincides with the increase of ocular
rigidity found by Pallikaris et al.6
As for the post LASIK surgery group, or the effect
of excimer laser photoablation on the corneal
biomechanical properties, a significant decrease in the
Figure 62.2: Ocular response analyzer (ORA) biomechanical properties was found after the surgery.
540 Mastering Advanced Surface Ablation Techniques

Figure 62.4: ORA graph showing the difference in pressure between the In signal peek and the Out
signal peek which evaluates the viscoelastic property of the cornea (corneal hysteresis)

This result coincides with other studies 1,7,10 and 3. Vaughan JM, Randall JT. Brillouin scattering, density and
elastic properties of the lens and cornea of the eye. Nature
implies that the creation of the flap and the corneal
1980; 284:489-91.
thinning by ablation weaken the cornea and decreases 4. Kasprzak H, Forster W, von BG. Measurement of elastic
its elastic properties. This could lead later to corneal modulus of the bovine cornea by means of holographic
ectasia after refractive surgery.11,12 This can be an interferometry. Part 1. Method and experiment. Optom
Vis Sci 1993; 70:535-44.
indicator for the importance of evaluating corneal 5. Wang H, Prendiville PL, McDonnell PJ, Chang WV. An
biomechanical properties precisely the corneal ultrasonic technique for the measurement of the elastic
hysteresis and resistance factor in screening refractive moduli of human cornea. J Biomech 1996;29:1633-6.
6. Pallikaris IG, Kymionis GD, Ginis HS, et al. Ocular rigidity
surgery candidates. in living human eyes. Invest Ophthalmol Vis Sci 2005;
In keratoconic eyes, the corneal hysteresis (CH) 46:409-14.
and the corneal resistance factor (CRF) were 7. Grabner G, Eilmsteiner R, Steindl C, et al. Dynamic corneal
imaging. J Cataract Refract Surg 2005;31:163-74.
significantly lower than in normal eyes and post
8. Luce DA. Determining in vivo biomechanical properties
LASIK surgery corneas. Low values of CH imply that of the cornea with an ocular response analyzer. J Cataract
the cornea is less capable of absorbing the energy of Refract Surg 2005;31:156-62.
the air pulse, where as, low values of CRF, indicates 9. Ortiz D, Piñero D, Shabayek MH, et al. Corneal
biomechanical properties in normal, post-laser in situ
the cornea rigidity is lower than normal. keratomileusis, and keratoconic eyes. J Cataract Refract
Surg 2007;33:1371–5.
REFERENCES 10. Kamiya K, Miyata K, Tokunaga T, et al. Structural analysis
of the cornea using scanning-slit corneal topography in
1. Jaycock PD, Lobo L, Ibrahim J, et al. Interferometric eyes undergoing excimer laser refractive surgery. Cornea
technique to measure biomechanical changes in the 2004; 23:S59-S64.
cornea induced by refractive surgery. J Cataract Refract 11. Dupps WJ, Jr. Biomechanical modeling of corneal ectasia.
Surg 2005;31:175-84. J Refract Surg 2005;21:186-90.
2. Mamelok AE, Posner A. Measurements of corneal 12. Guirao A. Theoretical elastic response of the cornea to
elasticity in relation to disease, using the Wiegersma refractive surgery: risk factors for keratectasia. J Refract
elastometer. Am J Ophthalmol 1955;39:817-21. Surg 2005; 21:176-85.
 CHAPTER
Surface Ablation after Laser
63 in situ Keratomileusis;
Retreatment on the Flap

Jeroen JG Beerthuizen (Netherland)

INTRODUCTION approach. Microstriae in the flap tend to smoothen

out after surface ablation,9 which might improve
The most common complication of laser in situ quality of vision. Patients in need of a hyperopic
keratomileusis (LASIK) is postoperative over- retreatment with a small flap can be treated without
correction or undercorrection. Such residual the need of recutting a larger flap. Furthermore,
ametropia can be bothersome to a patient and laser wavefront-guided treatment of flap-induced higher-
retreatment can be considered. There are different order aberrations is more logical when the flap is
ways to retreat a post-LASIK cornea. The flap can be left in place. Finally, patients with a history of post-
relifted, even years after the original LASIK LASIK dry-eye syndrome are better off without a
procedure, although this might be challenging at relift.
times. It is also possible to recut a new flap, although The biggest disadvantage of surface ablation
this is less safe1 and effective2 than a relift. In both retreatment is the chance of developing haze (Figure
procedures, the underlying stromal bed is being 63.1). Carones et al10 found severe haze in 14 of 17
treated and the amount of residual stroma should be eyes after PRK retreatment for regressed myopic
sufficient to prevent ectasia. Disadvantages regarding LASIK. The average amount of corrected myopia in
safety include an increased chance of epithelial that study was –2.48 ± –0.74 D (range –1.50 to –3.75).
ingrowth after a relift 3,4 and the risk for diffuse The wound reaction was much more aggressive than
lamellar keratitis and flap striae. expected and seemed to be related to the lamellar
To avoid problems with residual stromal cut. It is hypothesized that applying laser energy to
thickness, ablation can also be performed on the a stromal area with previously actived keratocytes,
underside of the flap5,6 or on the surface of the flap. which can be found around the flap interface, leads
Surface ablation options include intraepithelial7,8 or to an exaggerated wound-healing response.10,11 This
subepithelial photorefractive keratectomy (PRK) and would imply that the combination of flap thickness
laser-assisted subepithelial keratectomy (LASEK). and amount of ablated flap stroma relates to the
Subepithelial PRK/LASEK will be discussed in this chance of developing haze.
chapter. Problems with severe haze have not been seen
Surface ablation has additional advantages. after PRK treatment of patients with LASIK flap
Superficial abnormalities such as map-dot-fingerprint complications12 and PRK retreatment after compli-
lesions are likely to benefit from a superficial cated LASIK.13 In more recent studies,9,11 good results
542 Mastering Advanced Surface Ablation Techniques
TECHNIQUE

The epithelium is trephined with the LASEK flap

hinge opposite to the LASIK flap hinge. Application
of 20% ethanol for 20 to 30 seconds is advisable to
sufficiently loosen up the epithelium. After rinsing
away the ethanol, a LASEK flap can be created by
moving epithelium away from the LASIK flap hinge.
By moving in that direction, changes of accidentally
dislocating the LASIK flap are extremely low. When
the epithelium is removed and Bowman’s membrane
dried, the appearance of microstriae is very common,
also in eyes that did not show microstriae
preoperatively at the slitlamp. Laser ablation can be
performed in the usual manner. After the ablation,
Figure 63.1: Severe haze after PRK on the flap the cornea is rinsed with chilled balanced salt solution
regarding safety and efficacy were found for (BSS) and the epithelial flap is either repositioned or
removed. A bandage contact lens is placed on the
correcting low amounts, less than –1.50 D and –2.00
eye. Postoperative medications and follow-up visits
D respectively, of residual ametropia (Figure 63.2).
are the same as for a regular surface ablation.
Caution should be taken with hyperopic corrections.9
In both studies, no Mitomycin-C (MMC) was used.
REFERENCES
The use of MMC might be considered in treating
higher amounts of residual ametropia if surface 1. Rubinfeld RS, Hardten DR, Donnenfeld ED, et al. To lift
or recut: changing trends in LASIK enhancement.
ablation is still preferred.
J Cataract Refract Surg 2003; 29:2306-17.
2. Davis EA, Hardten DR, Lindstrom M, et al. LASIK
enhancements; a comparison of lifting to recutting a flap.
Ophthalmology 2002; 109:2308-2313; discussion by RS
Rubinfeld, 2313-4.
3. Pérez-Santonja JJ, Ayala MJ, Sakla HF, et al. Retreatment
after laser in situ keratomileusis. Ophthalmology 1999;
106:21-28; discussion by ME Whitten, 28.
4. Brahma A, McGhee CNJ, Craig JP, et al. Safety and
predictability of laser in situ keratomileusis enhancement
by flap reelevation in high myopia. J Cataract Refract
Surg 2001; 27:593-603.
5. Versace P, Watson SL. Cornea-sparing laser in situ
keratomileusis: ablation on the flap. J Cataract Refract
Surg 2005; 31:88-96.
6. Grim M, Sheard J, Martin L. LASIK enhancement using
excimer laser ablation on the back of the flap. J Refract
Surg 2005; 21:S610-S613.
7. Lohmann CP, Güell JL. Regression after LASIK for the
treatment of myopia: the role of the corneal epithelium.
Semin Ophthalmol 1998; 13:79-82.
8. Güell JL, Lohmann CP, Malecaze FA, et al. Intraepithelial
photorefractive keratectomy for regression after laser in
situ keratomileusis. J Cataract Refract Surg 1999; 25:670-74.
9. Beerthuizen JJG, Siebelt E. Surface ablation after laser in
Figure 63.2: Attempted versus achieved correction in surface situ keratomileusis: retreatment on the flap. J Cataract
ablation after LASIK9 Refract Surg 2007;33:1376-80.
 Surface Ablation after Laser in situ Keratomileusis; Retreatment on the Flap 543
10. Carones F, Vigo L, Carones AV, Brancato R. Evaluation 12. Weisenthal RW, Salz J, Sugar A, et al. Photorefractive
of photorefractive keratectomy retreatments after re- keratectomy for treatment of flap complications in laser
gressed myopic laser in situ keratomileusis. Ophthal- in situ keratomileusis. Cornea 2003; 22:399-404.
mology 2001;108:1732-37. 13. Shaikh NM, Wee CE, Kaufman SC. The safety and efficacy
11. Cagil N, Aydin B, Ozturk S, Hasiripi H. Effectiveness of of photorefractive keratectomy after laser in situ
laser-assisted subepithelial keratectomy to treat residual keratomileusis. J Refract. Surg 2005; 21:353-8.
refractive errors after laser in situ keratomileusis. J
Cataract Refract Surg 2007;33:642-7.
544 Mastering Advanced Surface Ablation Techniques

CHAPTER
Surface Retreatments for
64 Residual Myopic Refractive
Errors after LASIK

Bahri Aydin, Narullah Cagil (Turkey)

RATIONALE visible. There is no need to correct this kind of striae.

In addition to standard antibiotic and artificial tear
Residual refractive errors such as overcorrection, drops, topical steroids should be administrated to
undercorrection, and residual or induced astigmatism prevent haze development. Additional preventive
commonly occur after LASIK. The retreatment measures such as protective eyeglasses may also be
options for residual myopic errors are divided into helpful against haze development.
two major group: 1-Flap lifting (flap relift and flap
recutting) 2-Surface retreatments (PRK and LASEK OUTCOMES AND COMPLICATIONS
retreatments). Flap relift is standard therapy in the
majority of the cases. However, if the residual stromal Severe haze formation is known to be the major
bed thickness is less than 250 to 300 μm after primary limitation of surface retreatment for residual
LASIK, there is risks of inducing iatrogenic ectasia refractive errors after LASIK. There are controversial
with flap relift. In those cases, surface retreatments reports regarding role of PRK for residual refractive
(especially LASEK) are very useful. Significant haze errors after LASIK. Corones et al reported dense haze
with myopic regression develops with a spheric formation with myopic regression and BCVA loss
equivalent above –2.0 diopters. So, LASEK after PRK retreatment.1 In contrast Shaikh et al have
retreatments could be only applied to myopic residual achieved good results without significant haze
refractive errors less than –2.0 D spheric equivalent. development by performing PRK after LASIK.2
Studies evaluating role of LASEK retreatment for
LASEK RETREATMENT TECHNIQUE residual refractive errors after LASIK have given
encouraging results. Li et al have found that LASEK
A standard LASEK procedure could be applied. It is retreatments in eyes with myopic regression after
preferable that size of epithelial flap is below the LASIK results in an improvement in uncorrected
LASIK flap. A 7.5-mm trephine may be ideal for visual acuity without any significant postoperative
alcohol application and epithelial flap preparation. and intraoperative complication.3 In the study by
20% alcohol can be applied for 25 seconds. Spherical Cagil et al, 87.5% of the eyes achieved 20/40 or better
and cylindrical ablation is performed according to and 62.5% of the eyes achieved 20/25, or better
manifest refraction. After the epithelial flap is lifted, UCVA after retreatment with LASEK.4 These results
unrecognized LASIK flap striae usually become are comparable to results of LASIK retreatment with
 Surface Retreatments for Residual Myopic Refractive Errors after LASIK 545
flap relift. However, significant postoperative haze flap in LASEK retreatment seems to have a partial
developed in eyes with SE of attempted correction protective effect against haze formation.
equal to or above –2.0 diopters (Figure 64.1). In some For the eyes with a stromal bed less than 250 to
of these cases, haze formation also led to myopic 300 μm and requiring retreatment for SE bigger than
regression and BCVA loss. –2.0 D, LASEK with mitomycin C may be employed.
However a recent report about the role of mitomycin
C in LASEK retreatment for post LASIK myopic
regression have shown that 75% of the eyes treated
with LASEK using MMC developed unacceptable
overcorrection.5 This group of the eyes seems to be
risky to treat to date.

REFERENCES
1. Carones F, Vigo L, Corones AV, Brancato R. Evaluation
of photorefractive keratectomy retreatments after
regressed myopic laser in situ keratomileusis.
Ophthalmology 2001;108:1732-7.
2. Shaikh NM, Wee CE, Kaufman SC. The safety and efficacy
of photorefractive keratectomy after laser in situ
keratomileusis. J Refract Surg. 2005;21(4):353-8.
3. Li Y, Li JH, Zhou F. LASEK for the correction of residual
Figure 64.1: Severe haze development unresponsive to medical myopia and astigmatism after LASIK. Zhonghua Yan Ke
treatment after LASEK retreatment. BCVA decreased in that eye
Za Zhi 2005; 41:981-5.
4. Cagil N, Aydin B, Ozturk S, Hasiripi H. Effectiveness of
Lamellar corneal cut and excimer laser application laser-assisted subepithelial keratectomy to treat residual
both lead to keratocyte apoptosis and keratocyte refractive errors after laser in situ keratomileusis. J
Cataract Refract Surg. 2007;33:642-7.
activation. Potentially, with a deep ablation (bigger
5. Teus MA, de Benito-Llopis L. Laser-assisted subepithelial
than –2.0 D SE), two effect may combine producing keratectomy with MMC to treat post-LASIK myopic
an exaggerated wound healing response. Epithelial regression. J Cataract Refract Surg. 2007;33:1674-5.
 Index

A Anterior chamber depth 102 Corneal scars 160, 246

Anterior corneal aberrations 73 Corneal shape and asphericity 216
AA-PRK 49 causes 73 Corneal wound healing 250
complications 51 comparison of aberrations between both Corneoplastique 531, 532
indications 49 eyes 74 Crystalscan 498
results 50 limitations of measurements 76 cTEN 457
surgical technique 50 previous studies of heritability on Custom surface ablation 113, 520
Aberration rate calibration 68 refraction 75 Customized corneal reshaping 71
Ablation algorithms 69 twin study 73 Cyclotorsion control 329
Actual corneal curvature 92 Artificial recentration 330
Advanced surface ablations 4, 190, 278, 509 Aspheric surface 266
Asphericity comparison 478
D
complications
corneal haze 522 Astigmatism 160, 219
Decentration of left eye 329
dry eye 523 Automated lamellar keratoplasty 38
Defocus curve 319
epithelial complications 524 Axial eye length 91
Diffraction 223
infectious keratitis 524 Direct Q value adjustment 317
opacification 522 B Disruption and healing of corneal nerve
pharmacological modulation 523 fibers 381
under and over-correction 524 Band keratopathy 168 difference between epi-LASIK and
corneal biomechanics 514 Bandage contact lens 339, 470, 521 LASEK 384
indications 5, 517 Beeline epikeratome 390 disruption pattern 382
interaction of refractive lasers and corneal Benzalkonium chloride 254 distribution of corneal nerves 381
tissue 511 Bifocal (presby-LASIK) 478 healing process 382
corneal wound healing 512 Bilateral near vision 320 after epi-LASIK or LASEK 382
epithelial healing 513 Blurred vision 355 after LASIK 382
growth factors and wound healing Buttonholing 355 Distant vision in central cornea 318
514 Dry eye 430, 523
regeneration of corneal nerves 514
stromal healing 513 C
methods for epithelial removal 5 E
193 nm and 213 nm wavelengths 524 Cavitation bubbles 504
tissue hydration study 525 CIPTA 456 Ectasia 398
treatment times/ablation rates 526 CLAT 457 Effective lens position 88, 102
pearls for the care in surface ablation Cold vs. hot lasers 11 Energy delivery 8
patients 5 Collagen shield 470 Epi-keratome 121, 122
preoperative evaluation 516 Compound astigmatism 219 Epikeratophakia 39
ophthalmic examination 517 Conductive keratoplasty 40 Epikeratoplasty 39
surgical techniques 517 Confocal microscopy 19, 22, 26, 179 Epi-LASIK 45, 48, 112, 116, 119, 289, 313,
epi-LASIK 518 Constant slope transition zone 457 322, 334, 341, 400, 518
LASEK 517 Contact lens 36 clinical deductions 345
PRK 517 Contrast sensitivity 236 clinical results 324
types of refractive lasers 509 Contrast sensitivity function 236 early postoperative course 324
Amadeus II for LASIK 295 Contrast visual acuity 428 histological findings 323, 341
Amadeus II microkeratome 292 Corneal asphericity 70, 78 indications 289
benefits 293 Corneal biomechanical properties 539 intraoperative course 344
designed with flexibility in mind 295 Corneal collagen networks 450 market development 399
device description 293 Corneal dystrophies 164 postoperative treatment 324
indications 293 Corneal epithelium 451 principle 342
predictable result 293 after surface ablation 194 procedure 323, 342
technical data 293 Corneal haze 135, 257, 356, 522 resurgence of surface ablations 341
Anatomy of the cornea 36, 249 Corneal multifocality 315 technique 290
Angle kappa management 327 Corneal power after keratorefractive clinical results 291
measure and compensate angle kappa surgery 78 corneal sensitivity rehabilitation 292
330 Corneal power correcting factor 92 epi-LASIK and LASEK-PRK 291
patients and methods 327 Corneal radius 91 histological studies 292
Anisometropia 155 Corneal refractive surgery 190 Epi-LASIK and LASEK 436, 473
Anterior and posterior corneal surfaces 80 Corneal resistance factor 538 methods 436
548 Mastering Advanced Surface Ablation Techniques
comparison of the different techniques data analysis 272 Keratorefractive surgeries 22
437 patients and methods 271 investigation of FTC 23
data analysis 439 results 272 technology of LASIK procedure 22
epi-LASIK surgery procedure 436 surgery procedure LASEK 272 technology of PRK operation 23
examination 436 Harmonic generation 12
patients 436 Haze 375, 397,402, 542
surgery procedure LASEK 437 formation 292
L
surgery procedures 436 Heritability 75
Lachrymal fluid 21
phases of healing 474 High order aberration after myopia LASIK
Lamellar keratoplasty 39
results 485
LASEK 112, 354, 391
efficiency 439 age-dependence 487
advantages 404
predictability 440 data analysis 486
complication 133, 391
safety 440 methods 486
disadvantages 355, 404
therapeutic medications 473 results 486
haze and pain management 402
topical anesthesia 473 whole-eye-spherical aberration 487
indications 133
Epithelial cell viability 399 H-LASEK 371
LASEK with mitomycin C 355
Epithelial cleavage 399 Horizon epi-keratome 120
management 392
Epithelial hyperplasia after surface ablation Hysteresis 538
operation done 391
194
other surface ablation modalities 401
Epithelial irregular astigmatism 241 I relation to PRK and epi-LASIK 356
Epithelium-rhexis ASA technique 446
surgical considerations 354
Excimer laser 306, 491, 510 Iatrogenic keratectasia 205 techniques 394
basic concepts 491 Ideal pupil 455 haze and pain management 397
corrosiveness and toxicity of fluorine Image blur 223 optical issues 395
gas 491 Incisional refractive surgery 95 LASEK flap loss 404
early replacement of special switch Infectious keratitis 524 LASEK retreatment technique 544
491 Intraocular lens power calculation 89, 104 Laser ablative refractive surgery 95
high cost for proper storage 492 aphakic intraoperative refraction Laser assisted subepithelial keratectomy 39
high voltage requirement 491 techniques 94 Laser assisted subepithelial keratomileusis
hydration dependence of 193 nm 492 clinical history methods 89 44, 47, 388
recurrent expenses of excimer contact lens method 90 Laser epithelial keratomileusis 149, 364, 371,
gases 492 empirical method 89 398
subepithelial ablation 349 refraction-derived method 93 corneal aberrations 376
advantages 352 the Camellin-Calossi formula 94 disturbances of corneal transparency 375
clinical results 351 topographic data 90 operative considerations 377
disadvantages 352 when prior data is available 104 potential complications 373
postoperative medication 351 back calculated IOL power 106 preoperative assessment and counseling
surgical instruments 351 corrected keratometry 106 376
surgical procedure 349 corrected refractive index method 107 refractive and visual outcomes 371
Eye tracking 520 DBR method 105 refractive stability 373
Eyedrops 339 double K method 105 Laser 490
history method 104 common properties 491
F modified keratometry method 106 media 490
nomogram based adjustment 107 parameters 9
FDA approved PRK 115 theoretical formula 2004 106 phacoemulsification 14
Femtosecond laser system 503 using corneal topography 105 phacoemulsification 54
Flap removal 401 when prior data is not available photodisruption 15
Fluorophotometry 366 corneal topography 107 pulse width 8
Fluoroquinolones 254 Gaussian optics formula 109 pumps 490
Freeze myopic keratomileusis 37 hard contact lens method 108 spots 114
Frequency conversion 12 intraoperative retinoscopy 108 wavelength 8
Functional tear complex 20 regression derived clinical method 108 Laser thermal keratoplasty 40
theoretical variable refractive index Laser-matter interaction 14
method 109 Laser-tissue interaction 10
G IRES 459 LASIK 38, 43, 119, 400
ablation nomograms
Gatifloxacin 254 K aspherical surface 480
Gaussian beam spot 497 asphericity control 481
Glaucoma lasers 55 spherical surface 480
Keratoconus 155, 449
Gullstrand’s schematic eye 84 ablation rate 477
Keratocyte population 195
Keratometric refractive index 85 accuracy 64
H Keratomileusis in situ 37 optimal parameters for procedure
Keratophakia 39 time 66
H. Eye. Tech B and L and Mel 80 Zeiss 271 Keratorefractive operations 16 optimal scanning parameters 65
 Index 549
nomogram 296 P equipment used in clinic 415
procedure time 476 pre-and postoperative procedures
surgery 204 Pachymetry 157 416
Light microscopy 179 Pain reduction 334 step by step procedure 416
Light scatter 223 Painless epi-LASIK 337 techniques 407
Light-matter interaction 9 advantages of rotational epikeratome 338 automated lamellar keratoplasty 408
postoperative management 339 laser 407
surgery procedure 337 laser assisted epithelium
M keratomileusis 408
epi-LASIK technique
epi-trephine assisted LASEK laser assisted in situ keratomileusis
Maxifloxacin 254
technique 337 408
Microkeratome 121
Pallikaris and epi-LASIK 290 photorefractive keratectomy 408
Minimal corneal thickness 207
Pascal tonometer 425, 429 point spread function 408
Mitomycin C 187, 259, 264, 300, 341, 355,
Patching 470 surface ablation 408
358
Penetration depth 8 Placido topographer 103
adverse effects on the cornea 193
Permeability of the cornea 369 pMetrics dynamic pupillometer 455
endothelium 197
Photo refractive keratectomy 43, 46 Posterior corneal curvature 90
epithelium 194
Photochemical cross-linking 450 Post-LASK ectasia 205
stroma 195
Photodynamic therapy 54 Precision-high definition corneal and anterior
dose and exposure time 192 Photorefractive excimer laser astigmatic chamber tomography 453
interaction with the corneal wound correction 220 Predictive nomogram 123
healing mechanisms Photorefractive keratectomy 3, 38, 111, 132, Presby-LASIK 312, 315
healing after surface ablation 188 139, 263, 469 bifocal 478
histopathologic effect on the cornea ascorbate prophylaxis after PRK 264 PRK after RK 258
188 clinical results 139 PRK and LASIK 421
use of mitomycin C in corneal complications 147 biomechanical evidence 422
refractive surgery 190 epithelial defect closure 470 evolution 421
use of mitomycin C in ocular surface modulation of refractive and visual SBK vs. PRK study 424
neoplasias 189 results 471 measurement of results 425
use of mitomycin C in pterygium and corneal haze 471 OCT anterior segment imaging 425
glaucoma surgeries 189 corneal wound healing 471 patient demographics 424
mechanisms of action 187 post PRK management 471 surgical techniques for SBK and PRK
preparation and application 193 postprocedure therapeutic management
424
Mixed astigmatism 479 470
significance of results 433
Modulation transfer function 233 preoperative ocular therapeutics 469
study results 426
Myopic photorefractive keratectomy 172 PRK in the treatment of presbyopia 267
biomechanical results 429
clinical results 177 PRK with MMC 263
corneal sensitivity results 430
experimental corneal histology 178 haze after PRK 263
mitomycin C side effects 264 dry eye and corneal sensitivity results
confocal microscopy analysis 179
mitomycin C use as prophylaxis 264 430
lasers principles of function 172
surgical technique of PRK with MMC flap thickness results 426
achieving the fifth harmonic 174
264 patient complaints 433
customVis pulzar Z1 solid state laser
PRK with solid state lasers 267 subjective results 430
174
Q factor customized PRK 266 visual results 426
recent update in post PRK medications PRK in rabbits 496, 526
N 472 PRK patient evaluation 127
topical anesthesia 469 additional testing 129
Near vision in central cornea 317, 319 topography-guided PRK 265 corneal topography
Neurotrophic epitheliopathy 17 wavefront-guided PRK 265 pachymetry 131
Nomogram adjustment 498 Phototherapeutic keratectomy 240, 518 wavefront analysis 131
epithelial healing after PTK 240 examination 128
indications 240 dilated fundus evaluation 129
O laser vs. mechanical corrections 240 intraocular pressure 129
preoperative evaluation 241 orbital anatomy evaluation 128
Ocular aberration 224 surgical technique 243 pupillary, ocular motility,
Ocular gelling minitablets 365 techniques to treat surface irregularities confrontation field 128
Ocular response analyzer 425, 539 241 slit lamp evaluation 129
One-shot epithelium-rhexis 444 Pitfalls in advanced surface ablations 406 visual acuity and refraction 128
Ophthalmic lasers 53 bottom line 407 history 127
OPO 13 corneal topography and the tear film 408 medical history 128
Optical aberrations 73, 224 glaucoma and refractive surgery 414 ocular history 128
Optical quality 223, 224 IOP and refractive surgery 411 social history 127
analysis system 426 surgical processes and procedures 415 informed consent 131
Optimized transition zone 70 additional post-operative instructions patient expectations 127
Orthokeratology 37 417 Pterygium 168
550 Mastering Advanced Surface Ablation Techniques
R generation of UV-213 nm 59 V
Spherical aberration 103, 217, 312
Radial keratotomy 40, 257 free IOL 314 Value asphericity 312
Raman shift 13 Steeper eyes 122 Visual acuity 205
Real eye 85 Sub-Bowman keratomileusis 112 VISX B 2020 153
Refraction power 475 Supra-Bowman scars 246
Refractive error 475 Surface ablation 305, 393, 541 W
residual 544 with mitomycin C 196
Refractive lasers 57 Surface laser ablation 229, 234 Wavefront aberration 224, 225, 229
Refractive surgery 236 measurement 227
Retinal image quality 427 Wavefront aberrometry 428
Riboflavin 451 T Wavefront guided photorefractive
Rotational epikeratome 390 keratectomy 182, 265
T-CAT 320 clinical results 183
Tear film break-up time 20 custom wavefront PRK 183
S
Technologies for vision corrections 56 limitations 185
Theoretical variable keratometric refractive wavefront technology 182
Scanning LASIK system 58
index 91 Wavefront technology 182
Schirmer test 20
Solid state laser 493, 511 Thermal model of laser ablation 67 optimization 215, 217
technical advantages 494 Tissue hydration study 495 Wavefront-guided laser vision correction 220
Solid state technology 494 Topolink with small pupil 331
Solid-state 213-NM lasik system Transepithelial PRK 112 Z
ablation rates 59 Transmission electron microscopy 179
advantages of 213 nm laser 60 Traumatic scars 160 Zernike aberration 226