EDITED BY:

MING WANG, MD, PHD

Clinical Associate Professor of Ophthalmology
University of Tennessee
Director, Wang Vision Institute
Nashville, Tennessee
International President and Co-Owner
Shanghai Aier Eye Hospital
Shanghai, China

CO-EDITOR:
TRACY S. SWARTZ, OD, MS, FAAO
Center Director, VisionAmerica
Huntsville, Alabama

Foreword by Daniel S. Durrie, MD

www.slackbooks.com

ISBN : 978-1-55642-913-2

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Library of Congress Cataloging-in-Publication Data

Keratoconus & keratoectasia : prevention, diagnosis, and treatment / edited by, Ming Wang ; co-editor, Tracy S. Swartz.
p. ; cm.
Includes bibliographical references and index.
ISBN 978-1-55642-913-2 (hardcover : alk. paper) 1. Keratoconus. I. Wang, Ming, MD. II. Swartz, Tracy Schroeder. III.
Title: Keratoconus and keratoectasia.
[DNLM: 1. Keratoconus--diagnosis. 2. Keratoconus--therapy. 3. Corneal Surgery, Laser. WW 220 K388 2009]
RE339.K47 2009
617.7’19--dc22
2009027425

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 DEDICATION
My dear friends Gene Angle and Wallace Rasmussen are no longer with us, but they have left a memorable and endur-
ing legacy with their dedication and important contributions to our 501c(3) charity, the Wang Foundation for Sight
Restoration. The foundation has helped patients from over 40 states in the US and 55 countries, with all sight restoration
surgeries performed free of charge.

Gene and Wallace, we miss you both very much!

 CONTENTS
Dedication . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . v
Acknowledgments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ix
About the Editors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . xi
Contributing Authors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . xiii
Preface . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . xv
Foreword by Daniel S. Durrie, MD . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . xvii

SECTION I: ANATOMICAL, PHYSICAL, AND PHYSIOLOGICAL CONSIDERATIONS OF THE CORNEA

Chapter 1. Anatomy, Physiology, and Molecular Biology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
Ashkan M. Abbey, MD and Sonia H. Yoo, MD

Chapter 2. Clinical Biomechanics and the Ocular Response Analyzer in Ectatic Disease. . . . . . . . . . . . . . . . . . . . . . . . 13
William J. Dupps Jr, MD, PhD; Marcella Q. Salomão, MD; and Renato Ambrósio Jr, MD, PhD

SECTION II: KERATOCONUS AND KERATOECTASIA

Chapter 3. Clinical Characteristics of Keratoconus . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 33
Stephen S. Khachikian, MD, and Michael W. Belin, MD, FACS

Chapter 4. Clinical Features of Keratoectasia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 43

J. Bradley Randleman, MD

Chapter 5. Keratoectasia: Preoperative Risk Factors and Medical and Legal Considerations . . . . . . . . . . . . . . . . . . . . . 51
J. Bradley Randleman, MD

SECTION III: DEVICES FOR THE DIAGNOSIS OF KERATOCONUS AND KERATOECTASIA

Chapter 6. Topography in the Diagnosis of Keratoconus and Keratoectasia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 61
Stephen D. Klyce, PhD

Chapter 7. Posterior Corneal Changes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 69

Dora Sztipanovits, MS, OD, and Ming Wang, MD, PhD

Chapter 8. Corneal Evaluation Using the Artemis VHF Digital Ultrasound Epithelial Thickness Profiles . . . . . . . . . 77
Dan Z. Reinstein, MD, MA(Cantab), FRCSC, FRCOphth; Timothy J. Archer, MA(Oxon), DipCompSci
(Cantab); and Marine Gobbe, MST(Optom), PhD

Chapter 9. Studies of Wavefront Aberrometry in Corneal Ectasia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 89

Thomas J. Dingle, MD; Jay S. Pepose, MD, PhD; Mujtaba A. Qazi, MD; and Geunyoung Yoon, PhD

Chapter 10. Infrared Photorefraction Screening . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 97

Ying-Ling Ann Chen, PhD; James W. L. Lewis, PhD; Lei Shi, MS; Ming Wang, MD, PhD;
and Tracy S. Swartz, OD, MS, FAAO

Chapter 11. Assessment of Visual Performance in Keratoconus . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 109

Konrad Pesudovs, OD, PhD

SECTION IV: TREATMENT OF KERATOCONUS AND KERATOECTASIA

Chapter 12. Non-Surgical Treatment of Keratoconus Using Contact Lenses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 119
Shawna L. Hill, OD, FAAO

Chapter 13. Penetrating and Lamellar Keratoplasty Techniques. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 135

Soosan Jacob, MS, FRCS, Dip NB; Gaurav Prakash, MD; Dhivya Ashok Kumar, MD; Athiya Agarwal, MD, DO;
Amar Agarwal, MS, FRCS, FRCOphth; Leopoldo Spadea, MD; and Charles Wm. Stewart, OD
viii CONTENTS

Chapter 14. Excimer Laser Photorefractive Keratectomy for Keratoconus . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 145

Arun C. Gulani, MD; Lee T. Nordan, MD; Noel Alpins, FRANZCO, FRCOphth, FACS;
and George Stamatelatos, BScOptom

Chapter 15. Topography-Guided Excimer Laser Treatment. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 153

Aleksandar Stojanovic, MD, and Xiangjun Chen, MD

Chapter 16. Intacs for the Treatment of Keratoconus and Keratoectasia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 161
George O. Waring IV, MD; Jason E. Stahl, MD; Brian Boxer Wachler, MD;
and William B. Trattler, MD

Chapter 17. Corneal Cross-Linking With Riboflavin and Ultraviolet Irradiation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 169
Ronald R. Krueger, MD, MSE; Karolinne Maia Rocha, MD, PhD; and Mirko R. Jankov II, MD, PhD

Chapter 18. New and Future Treatments: Excimer Laser Lamellar Keratoplasty and Advanced Cross-Linking . . . . . 177
Leopoldo Spadea, MD; Dale P. Devore, PhD; Richard A. Eiferman, MD, FACS; Bruce DeWoolfson, PhD;
Charles Wm. Stewart, OD; Tracy S. Swartz, OD, MS, FAAO; and Ming Wang, MD, PhD

Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 187
 ACKNOWLEDGMENTS
I would like to express my sincere appreciation to the co-editor and project manager of this book, Dr. Tracy Swartz,
for her hard work and dedication. Without Tracy, this book would not have been possible.
I would like to also thank the members of Wang Vision Institute: Drs. Helen Boerman, Shawna Hill, Tracy Winton,
and Dora Sztipanovits; staff members Leona Walthorn, Suzanne Gentry, and my personal assistant, Lisa Flores; and the
entire team at Wang Vision Institute. An honorable mention also belongs to the board members of our 501c(3) charity, the
Wang Foundation for Sight Restoration: Charles Grummon, Kim Campbell, Maclin Davis, Barry Doston, Mark Hilliard,
Monty Landford, and Shirley Zeitlin; our EyeBall 2008 co-chairs Ted Welch and Colleen Conway-Welch; past EyeBall
chair and board members Dr. Robert Frist, Priscilla Garcia, Polly Nichols, and Mary Beth Thomas; EyeBall event coordi-
nator Alanna Napier; and the former governor of Tennessee, Dr. Winfield Dunn and his wife, Betty Dunn.
I have had the fortuity of learning from many great teachers, and I am forever indebted to them: PhD thesis advisor
(physical chemistry and laser spectroscopy) Professor John Weiner; Harvard and MIT (MD, magna cum laude) thesis
advisor Professor George Church; professors at the Wills Eye Hospital, where I did my ophthalmology residency and
ocular genetics fellowship: Drs. Larry Donoso and William Tasman; professors at Bascom Palmer Eye Institute, where
I did my corneal, external disease, and refractive surgery fellowship: Drs. Richard Foster, William Culbertson, Scheffer
Tseng, Khallil Hann, Carol Karp, Stephen Pflugfelder, Andrew Huang, Eduardo Alfonso, and Lori Ventura; professors at
Vanderbilt University, where I started my career as a corneal and refractive surgery specialist: Drs. Dennis O’Day, James
Elliott, and Donald Gass; Dr. Harry Jacobson and the professors at the University of Tennessee, where I am presently
a faculty member: Drs. Barrett Haik, Peter Netland, Natalie Kerr, Thomas Gettelfinger, James Freeman, and Spencer
Thornton, and Ms. Linda Garceaus-Luis, Vice Chancellor of Development and Alumni Affairs.
I would like to thank my colleagues nationally and internationally, from whom I have learned so much about ophthal-
mology over the years: Drs. Aleksandar Stonjavic, Giuseppe D’lppolito, Steve Klyce, Peter Arrowsmith, Mark Bearman,
Steve Dell, David Chang, Marguerite McDonald, Dan Durrie, Doug Koch, Steve Brint, Steve Slade, George Waring, Doyle
Stulting, William Trattler, Eric Donnenfeld, Richard Lindstrom, Peter Hersh, Mitch Jackson, Lee Nordan, Ralph Chu,
John Vukich, Jack Holladay, John Doane, Terry Kim, Keith Walters, Karl Stonecipher, Brian Boxer Wachler, Terrence
O’Brien, Jay Pepose, Arun Gulani, Guy Guzarin, Deborah Distefano, Noel Alpins, and my local colleagues Drs. Stuart
Shofner, Daniel Weikert, Morgan Parker, James Conrad, Gates Wayburn, Michael Green, Gary Jerkins, Paul Harrell, Jeff
Horn, Sam Simon, Matt Drew, Allison Jones, Gary Radish, Bart Lynn, Scott Cranford, Anita Cranford, Michelle Sonsino,
David Brown, Jeff Kegerise, Susan Kegerise, Stuart Nieber, David Shen, Greg Coley, Ginger Coley, Ron Willliams, Terry
Hendrickson, Stan Dickerson, Rob Szeliga, and Chris Adams.
Often one learns as much from the fellows that he trains as from those who teach him, and I am fortunate to have a
great group of doctors who have been my fellows over the years: Drs. Shin Kang, Ilan Cohen, Uyen Tran, Walid Haddard,
Mouhab Aljajeh, Keming Yu, Yangzi Jiang, Ray-Ann Lin, Lav Panchal, Lisa Martén, and optometry residents Drs. David
Coward and Tracy Winton.
I have enjoyed the interaction with my colleagues in China over the years and especially over the course of the develop-
ment of this book: Drs. Michael Zhou, Baosung Liu, Wei-li Li, Zhu-guo Liu, Zhen-ping Zhang, Jun-wen Zhen, Shao-wei
Li, Xiao-bing Wang, Tong Sun, Hai-yan Li, Xiao-lu Wang, as well as Mr. Jay Hsu and Mr. Bang Chen.
Many friends have assisted with this book in various ways, including Carlos Gonzalez, Eliud Trevino, Aida Hughes,
Peng Liang, Xiao-dong Wang, John Wang, Vivien Wang, Rong Yang, Qiang Wu, David Lin, John Ma, Brandon Lin,
Darrell Denson, Todd Napier, Jakie Cook, Lili Shu, Lihui Marcin, Dr. John Dayani, Mrs. Libby Dayani, Dr. Leonard Madu,
Howard Gentry, and Sharon Gentry.
Finally, I want to thank my family for their unfailing support and love: my wife Ye-jia “JJ” Wang, my father Dr.
Zhen-sheng Wang, my mother Dr. A-lian Xu, my brother Dr. Ming-yu Wang, my son Dennis Wang, my godmother June
Rudolph, and my godfather Misha Bartnovsky.
 ABOUT THE EDITORS
Ming Wang, MD, PhD is a clinical associate professor of ophthalmology of the
University of Tennessee, co-owner and international president of Shanghai Aier Eye
Hospital, attending surgeon at Saint Thomas Hospital, and director of Wang Vision
Institute in Nashville, Tennessee. Dr. Wang received his BS from the University of Science
and Technology of China in Hefei, China; his PhD in laser spectroscopy and atomic colli-
sion dynamics from the University of Maryland in College Park, Maryland; his postdoc-
toral fellowship at the Massachusetts Institute of Technology in Boston, Massachusetts;
and his MD from Harvard Medical School and MIT in Boston, Massachusetts. He
graduated magna cum laude, received the best graduation thesis award, and the Harold
Lamport Biomedical Research Prize from Harvard and MIT. After completing both a
residency in ophthalmology and a fellowship in ocular genetics and molecular biology at
the Wills Eye Hospital in Philadelphia, Pennsylvania, he completed a clinical fellowship
in cornea, external disease and refractive surgery from the Bascom Palmer Eye Institute
at the University of Miami School of Medicine in Miami, Florida. In 1997, he became the
founding director of the Vanderbilt Laser Sight Center and a full-time faculty member
of the Department of Ophthalmology at the Vanderbilt University School of Medicine in
Nashville, Tennessee. He remained there until 2002, when he went into private practice and established the Wang Vision
Institute and Wang Foundation for Sight Restoration.
Dr. Wang started his research career as a laser physicist and physical chemist. From 1982 to 1987, as its first author,
he published a dozen original papers in the leading physics journal, Physical Review A, describing the development of a
novel experimental atomic physics technique that he developed with Professor John Weiner, a Doppler velocity-selected
associative ionization process between sodium atoms. In 1987, Dr. Wang enrolled in Harvard Medical School and MIT,
where he conducted molecular biology research and published a paper in the world-renowned journal Nature, in which
he described a novel molecular biology technique—a whole-genome approach to in vivo DAN-protein interaction and
gene-expression regulation—that he invented with Professor George Church. In 1991, after completing his MD, he began
research in the field of ophthalmology, specifically ophthalmic genetics and corneal wound healing, at Wills Eye Hospital
and Bascom Palmer Eye Institute. Dr. Wang made an original contribution to the field of corneal wound healing by co-
publishing with Professor Scheffer Tseng the first paper of its kind regarding laboratory success of the reduction of corneal
scarring and keratocyte apoptosis with amniotic membrane transplantation.
Dr. Wang is an inventor of several US patented technologies, including an amniotic membrane contact lens, of
which he successfully created the first prototype. He was a former panel consultant of the United States Food and Drug
Administration (FDA) Ophthalmic Device Panel, and was a primary FDA reviewer for the first US FDA LASIK PMA
approval in 1999. Dr. Wang conducted the first large-scale clinical study and was the principal investigator of the first
three-dimensional stereo corneal topographer, the AstraMax. He was the first surgeon from the United States to study
a new, high frequency excimer laser and treatment platform designed to treat post-LASIK complications. Dr. Wang
performed the first femtosecond laser-assisted artificial cornea implantation. He was also a LASIK surgeon for ABC’s
national reality TV show, Extreme Makeover.
Dr. Wang received an honored award from the American Academy of Ophthalmology in 2003. He was a co-principal
investigator of an NIH RO1 grant, a recipient of Fight For Sight Grant-in-aid, Lawrence Award of the Association for
Research in Vision and Ophthalmology (ARVO), and Faculty Investigator Award of Vanderbilt University. He has edited
several books, including Corneal Dystrophy and Degenerations—A Molecular Biology Approach, Corneal Topography in the
Wavefront Era (SLACK Incorporated, 2006), and Irregular Astigmatism: Diagnosis and Treatment (SLACK Incorporated,
2007). Dr. Wang is a reviewer of many journals including: Ophthalmology, American Journal of Ophthalmology, Cornea,
Journal of Cataract and Refractive Surgery, Journal of Refractive Surgery, Genome, and Investigative Ophthalmology and
Visual Sciences.
Dr. Wang introduced femtosecond-laser LASIK to China and performed the first all-laser LASIK in China in 2005.
He is a co-owner and medical director of refractive surgery of Aier Eye Hospitals, the largest private eye hospital group
in China, which holds 10% of China’s refractive surgery volume, with the majority of its medical equipment made in the
USA. In 2007, Dr. Wang founded the first Chinese chamber of commerce of the state of Tennessee, the Tennessee Chinese
Chamber of Commerce, and contributed to the effort that helped Tennessee to become number one in the United States
in the growth rate of export to China.
xii ABOUT THE EDITORS

In 2003, Dr. Wang founded a non-profit 501c(3) charity, the Wang Foundation for Sight Restoration, which assists
severely corneally injured patients in undergoing novel eye reconstructive surgeries that are performed free of charge by
Dr. Wang. Each year the foundation holds its major fund-raising gala, the EyeBall. To date, the foundation has helped
patients from over 40 states in the US and 55 countries worldwide.
Dr. Wang has diverse interests and hobbies. He is a reigning finalist in the world ballroom dance championships in
open pro-am international 10-dance, and was a former member of the US collegiate champion Harvard University ball-
room dance team. Dr. Wang performs with a Chinese violin (er-hu), and played it with country music legend Dolly Parton
on a song, “The Cruel War,” from her recent CD, Those Were The Days. Dr. Wang lives in Nashville, Tennessee with his
beautiful wife and artist Ye-jia “JJ” Wang.

Tracy Schroeder Swartz, OD, MS, FAAO currently serves as the Center Director of
VisionAmerica in Hunstville, Alabama, where she practices consultative optometry, special-
izing in ocular surface disease and dry eye. Originally from Wisconsin, Dr. Swartz attended
Indiana University School of Optometry, graduating in 1994.
After completing her doctorate, she pursued a master’s degree in Physiological Optics,
specializing in pediatrics. She served as faculty at the IU School of Optometry for 4 years, and
earned the Indiana Chapter of the American Academy of Optometry Gordon Heath Fellowship,
1996.
After completion of her master’s, she relocated to Metro DC, where she specialized in
comanagement of refractive and corneal surgery. She later joined Wang Vision Institute in
Nashville, Tennessee, where she served as Director of Clinical Operations, Residency Director
for the Optometric Residency Program, and adjunct faculty to Indiana University School of
Optometry. While there, she edited two textbooks with Ming Wang, MD, PhD: Corneal Topography in the Wavefront Era
and Irregular Astigmatism: Diagnosis and Treatment (both for SLACK Incorporated), as well as authoring numerous book
chapters on refractive surgery, topography, aberrometry, and anterior segment disease. She served as co-editor for the lit-
erature review column for Cataract and Refractive Surgery Today from 2003 to 2008, and currently serves on the editorial
board of Optometry Times. She is adjunct faculty for the School of Optometry at the University of Waterloo, and serves on
the board of the Optometric Council of Refractive Technology.
 CONTRIBUTING AUTHORS
Ashkan M. Abbey, MD (Chapter 1) William J. Dupps Jr, MD, PhD (Chapter 2)
Bascom Palmer Laser Vision Center Cole Eye Institute
Miami, FL The Cleveland Clinic Foundation
Cleveland, OH
Athiya Agarwal, MD, DO (Chapter 13)
Dr. Agarwal’s Eye Hospital Richard A. Eiferman, MD, FACS (Chapter 18)
Chennai, India University of Louisville
Louisville, KY
Amar Agarwal, MS, FRCS, FRCOphth (Chapter 13)
Dr. Agarwal’s Eye Hospital Marine Gobbe, MST(Optom), PhD (Chapter 8)
Chennai, India London Vision Clinic
London, United Kingdom
Noel Alpins, FRANZCO, FRCOphth, FACS (Chapter 14)
New Vision Clinics Arun C. Gulani, MD (Chapter 14)
Cheltenham, Australia Gulani Vision Institute
Jacksonville, FL
Renato Ambrósio Jr, MD, PhD (Chapter 2)
Pontific Catholic University Shawna L. Hill, OD, FAAO (Chapter 12)
Instituto de Olhos Wang Vision Institute
Corneal Tomography and Biomechanics Study Group Nashville, TN
Rio de Janeiro, Brazil
Soosan Jacob, MS, FRCS, Dip NB (Chapter 13)
Timothy J. Archer, MA(Oxon), DipCompSci(Cantab) Dr. Agarwal’s Eye Hospital
(Chapter 8) Chennai, India
London Vision Clinic
London, United Kingdom Mirko R. Jankov II, MD, PhD (Chapter 17)
Milos Eye Hospital
Michael W. Belin, MD, FACS (Chapter 3) Belgrade, Serbia and Montenegro
Cornea Consultants of Albany
Albany Medical College Stephen S. Khachikian, MD (Chapter 3)
Albany, NY Black Hills Regional Eye Institute,
Rapid City, SD
Brian Boxer Wachler, MD (Chapter 16) Albany Medical College
Boxler Wachler Vision Institute Albany NY
Los Angeles, CA
Stephen D. Klyce, PhD (Chapter 6)
Xiangjun Chen, MD (Chapter 15) Mount Sinai School of Medicine
SynsLaser Kirurgi Port Washington, NY
Oslo, Norway
Ronald R. Krueger, MD, MSE (Chapter 17)
Ying-Ling Ann Chen, PhD (Chapter 10) Cole Eye Institute
University of Tennessee Space Institute The Cleveland Clinic Foundation
Tullahoma, TN Cleveland, OH

Dale P. Devore, PhD (Chapter 18) Dhivya Ashok Kumar, MD (Chapter 13)
DV Consulting Dr. Agarwal’s Eye Hospital
Chelmsford, MA Chennai, India

Bruce DeWoolfson, PhD (Chapter 18) James W. L. Lewis, PhD (Chapter 10)
Euclid Systems Corporation University of Tennessee Space Institute
Herndon, VA Tullahoma, TN

Thomas J. Dingle, MD (Chapter 9) Lee T. Nordan, MD (Chapter 14)

Pepose Vision Institute Eye Care Center
Columbus, OH Carlsbad, CA
xiv CONTRIBUTING AUTHORS

Jay S. Pepose, MD, PhD (Chapter 9) George Stamatelatos, BScOptom (Chapter 14)
Pepose Vision Institute New Vision Clinics
Chesterfield, MO Cheltenham, Australia

Konrad Pesudovs, OD, PhD (Chapter 11) Charles Wm. Stewart, OD (Chapters 13 & 18)
Flinders Medical Centre EyeMedis
Bedford, South Australia La Quinta, CA

Gaurav Prakash, MD (Chapter 13) Aleksandar Stojanovic, MD (Chapter 15)

Dr. Agarwal’s Eye Hospital SynsLaser Kirurgi
Chennai, India Tromsø, Norway

Mujtaba A. Qazi, MD (Chapter 9) Dora Sztipanovits, MS, OD (Chapter 7)

Pepose Vision Institute Wang Vision Institute
Chesterfield, MO Nashville, TN

J. Bradley Randleman, MD (Chapters 4 & 5) William B. Trattler, MD (Chapter 16)

The Emory Eye Center Center For Excellence In Eye Care
Atlanta, GA Miami, FL

Dan Z. Reinstein, MD, MA(Cantab), FRCSC, FRCOphth George O. Waring IV, MD (Chapter 16)
(Chapter 8) Private Practice
London Vision Clinic Emory University School of Medicine
London, United Kingdom Atlanta, GA

Karolinne Maia Rocha, MD, PhD (Chapter 17) Sonia H. Yoo, MD (Chapter 1)
Cole Eye Institute University of Miami Miller School of Medicine
The Cleveland Clinic Foundation Bascom Palmer Laser Vision Center
Cleveland, OH Miami, FL

Marcella Q. Salomão, MD (Chapter 2) Geunyoung Yoon, PhD (Chapter 9)

Rio de Janeiro, Brazil University of Rochester
Rochester, NY
Lei Shi, MS (Chapter 10)
University of Tennessee Space Institute
Tullahoma, TN

Leopoldo Spadea, MD (Chapters 13 & 18)

Rome, Italy

Jason E. Stahl, MD (Chapter 16)

Durrie Vision, P.A.
Overland Park, KS
 PREFACE
The resurgence of interest in keratoconus and keratoectasia recently is mainly due to three factors:
1. The emergence of a new, non-genetic form of the corneal ecstatic disease, which is largely human-created in the era
of keratorefractive surgery
2. The emergence of more powerful and sensitive diagnostic imaging devices
3. The emergence of several new and promising treatments for keratoectasia, including Intacs ring segments and UV
cross-linking
This textbook, Keratoconus and Keratoectasia: Prevention, Diagnosis, and Treatment, represents the first attempt to
comprehensively review the progress that we have made in understanding etiology and pathophysiology of these two
diseases, and in the development of all currently available treatments. The goal of this new textbook is to provide oph-
thalmologists, optometrists, and researchers a comprehensive review of this increasingly important disease in ophthal-
mology today and to provide clinicians a desktop reference for prevention, diagnosis, and treatment of keratoconus and
keratoectasia.
We led a group of world-class experts in this field and produced this concise, comprehensive, and well-illustrated
textbook of basic pathophysiology and practical clinical guidelines. We feel that this excellent textbook makes it possible
for clinicians to find, in one book, all of the essential information about the current understanding of the disease and its
treatment and helps them keep abreast of all the major developments in this field in recent years. Ample clinical cases
are described, which provide useful examples and well-indexed reference points to the sources of literature for further
investigation and inquiry.
The book starts out by comprehensively reviewing the anatomical, physical, and physiological considerations of the
cornea. Corneal biomechanical changes are just beginning to be understood. The most important key concept in corneal
shape maintenance is overall corneal strength. The currently used parameter, corneal thickness (or pachymetry), is, in
fact, a poor approximation of corneal strength because it implicitly assumes that strength-per-unit corneal thickness is
the same for all individuals, which is not true. A key differentiating feature between the genetic form of the corneal ectasia
disease, keratoconus, and the non-genetic form of the disease, keratoectasia, is that the corneal strength-per-unit corneal
thickness is reduced in the former. In this section, important corneal biomechanical strength versus thickness parameters
(such as ORA) are presented, including clinical guidelines for application.
The genetic form of the disease, keratoconus, is extensively reviewed. We have presented historical perspectives, epide-
miological and clinical presentations of the genetic form of this disease, and our current understanding of the genetics of
keratoconus. Keratoconus and pellucid marginal degeneration are compared and contrasted, and clinical guidelines for
diagnosis and treatment are presented.
The non-genetic and acquired form of the disease, keratoectasia, is then broadly discussed. We used the setting of kera-
torefractive surgery to illustrate the key concepts for prevention, diagnosis, and treatment of keratoectasia. We further
explore informed consent and key medical and legal issues involved in managing keratoectasia in the era of keratorefrac-
tive surgery.
Significant progress has been made in recent years in the development of new and more powerful diagnostic imaging
devices for corneal ectasia. We first review the criteria for topographic diagnosis of corneal ectasia. We then focus on the
new diagnostic modality, the posterior cornea, to highlight all key issues related to posterior corneal changes in the era of
LASIK. All major new technologies for corneal imaging are presented including ultrasound biomicroscopy for epithelial
mapping, wavefront analysis including both whole-eye and corneal wavefront measurements, infra-red sensing and cor-
neal ectasia screening, and optical quality quantitative assessment.
The availability of new treatment modalities for corneal ectasia in recent years has given the clinician a whole host
of treatment options. We first discuss the traditional, non-surgical contact lens treatment. We then review lamellar and
penetrating keratoplasty techniques, including the use of the femtosecond laser. Excimer treatments are also reviewed.
Topographically guided treatments have significantly expanded the treatment indications and have improved the results.
The Intacs ring segment is then discussed, including a list of useful clinical pearls. Finally, Riboflavin UV-cross-linking
is extensively presented and key clinical important guidelines for application are reviewed. Future treatment approaches
for corneal ectasia are also presented.
It is our goal that Keratoconus and Keratoectasia: Prevention, Diagnosis, and Treatment becomes a “one-stop-shop”—a
comprehensive and indispensable desktop clinical reference textbook for all clinicians and researchers who are involved
in managing this increasingly important (and largely human-created) vision-threatening disease.
xvi PREFACE

FFKC Criteria 2009

The following criteria were developed based upon discussions that occurred during “Corneal Topography for Refractive
Surgeons,” a course conducted at both AAO and ASCRS from 2004-2006.
2 D Rule
> 2 D difference in superior and inferior K readings outside the central 3-mm
> 2 D difference in the corresponding inferior corneal locations between two eyes
Absolute value of K very high (more than 50 D) in one eye

3-Point Touch
Coinciding of location of pathology of anterior and posterior elevation, pachymetry, and anterior curvature
Displaced apex in all maps

Anterior and Posterior Float

“Ominous purple” in the posterior surface
Anterior 15 to 20 µm
Posterior 20 to 25 µm (post-LASIK: 40 to 50 µm)

Pachymetry
Bed 250 to 300 µm
Normal: 535 µm, SD=35 µm. No LASIK below 1 D (500 µm), no PRK below 2 D (465 µm)
KC: 430 µm, SD=70 µm
Thinnest area is more than 15 µm thinner than center
The difference between thinnest areas between two eyes is greater than 15 to 20 µm
Abrupt and more rapid “out-of-zone” pachy increase from thinnest point radially out

IA Orientation, Amount, Pattern

3 D or more dioptric curvature change, in central 3-mm circle
In central 3-mm circle, not regular (bow-tie) pattern; across the pupil 180 degrees
Change of astigmatism orientation and amount
Against-the-rule astigmatism plus inferior steepening, the “C” pattern, suggesting PMD

Topo-Based FFKC Statistical Packages

Tomey: positive KC score with either the KCI or KCS index
EyeSys: I-S > 1.3
Pentacam: ISV, IVA, KI, CKI, /Rmi, IHA, IHD, and ABR
Humphrey Atlas: Path-finder, in red zone

Ming Wang, MD, PhD

Nashville, Tennessee
 FOREWORD
I have been involved with treating keratoconus and the variants for 30 years, and we now understand, more than ever,
the physiology and biomechanics of the cornea and have access to a wide array of diagnostic equipment and new treat-
ment modalities for ectasia. As a profession, we are diagnosing and educating patients early in the disease process, in
addition to deciding which patients meet the criteria to take advantage of new treatments as they become available.
There are three groups of patients who fall in the category of corneal ectatic disease. The first is the naturally-occur-
ring keratoconus and pellucid marginal degeneration patients. This group will benefit tremendously from the increased
knowledge provided in this book.
The second group is patients who have the genetic tendency for ectatic disease, but who have undergone laser refrac-
tive surgery—either PRK or LASIK. They fall into a unique category that has been called post-LASIK ectasia. I prefer
this group be called “post-LASIK keratoconus,” since this better defines the underlying problem; either the diagnosis
was missed at the time of surgery or there were no true findings confirming the diagnosis, even with good preoperative
evaluation.
The third group, which is much smaller, is comprised of patients who have received excessive corneal surgery, and their
biomechanically-weakened corneas mimic ectatic disease, such as keratoconus. This is the only group for which I use the
term “post-LASIK ectasia.” We know that if we make a flap extremely deep in the cornea, such as was done with hyperopic
ALK back in the early 90s, we can cause the cornea to bulge forward. These deep flaps had to be made at least 400 µm in
the cornea to get effect, and even when these patients were followed long term, they were not seen to develop progressive
ectasia like the patients with genetic tendency toward keratoconus. There are also highly myopic patients in the –20.00
range who had very deep surgery with multiple enhancements that have caused the center cornea to bulge. These patients
are truly ectatic because of the corneal disease.
When I look at these last two groups—those with a genetic tendency and those whose surgery caused weakness —there
is a very small number who fall into the post-refractive surgery ectasia group. Most people feel that it is less than 1% to
2%.
I believe use of proper terminology, such as “post-LASIK keratoconus,” is extremely important, as patients are more
likely to understand the natural history and time course of the disease process. This book confirms that under the micro-
scope or with diagnostic equipment, there is no way to tell naturally-occurring keratoconus from that which occurs after
refractive surgery. Once patients are diagnosed with keratoconus or pellucid degeneration, it is relatively easy to find
materials on treatments and doctors who can treat them. With the confusion of calling it “post-LASIK ectasia,” patients
have a tendency to end up with lawyers as consultants instead of doctors, and I think we do our patients a disservice by
mis-classifying this important disease.
Paolo Vinciquerra has demonstrated that patients’ corneas can be thinned to 200 µm with PTK and be stable for years.
Further, several studies have shown that high myopic young people with thin corneas have been stable for over 10 years
with no evidence of ectasia. My overall feeling is that we don’t diagnose these patients any differently, we don’t treat them
any differently, the biomechanics are no different, and we are not seeing increased incidence over the normal popula-
tion.
The chapters in this important text cover a wide range of topics, giving the reader the most up to date view available on
corneal ectasia. This book does a fabulous job of putting together all the facts, and if we can use this information to help
better educate our patients and our colleagues, our treatment of these patients will be tremendously advanced.

Daniel S. Durrie, MD
Overland Park, Kansas
 SECTI ON I

Anatomical, Physical,
and Physiological
Considerations of the
Cornea
 CHAP TER 1

Anatomy, Physiology,
and Molecular Biology

Ashkan M. Abbey, MD and Sonia H. Yoo, MD

B
ecause keratoconus and keratoectasia can cause sig- The thinning often involves the paracentral cornea, most
nificant anatomic and physiologic alterations to the commonly the temporal inferior region, producing corneal
cornea, an understanding of the normal anatomy protrusion (Figure 1-1) and a myopic shift.3 Keratoectasia
and physiology of the cornea is essential for their diagnosis after excimer laser keratorefractive surgery (laser-assisted
and management. in situ keratomileusis [LASIK] or photorefractive keratec-
tomy [PRK]) is similar to keratoconus in that it involves
progressive steepening and thinning that results in an
GROSS ANATOMY AND abnormal protuberance of the cornea.
PHYSIOLOGY Two types of cone morphology have been reported from
analysis of gross histopathologic specimens of keratoconic
The cornea is the transparent, avascular anterior por- corneal buttons. The more common round or “nipple-
tion of the eye that covers the iris, pupil, and anterior shaped” cone most often lies in the inferonasal quadrant
chamber. It comprises the external layer of the eye along closer to the center of the cornea. This cone has a limited
with the sclera, with which it is continuous. The transition diameter but may reach any degree of conicity. The oval or
area between the cornea and sclera is the limbus, a highly sagging cone is usually larger and lies in the inferotemporal
vascularized area of pluripotent stem cells. Fluid covers region, more towards the periphery of the cornea. More
both its anterior (tear film) and posterior (aqueous) sur- severe manifestations of the disease are often associated
faces. The average horizontal diameter of the oval-shaped with oval-shaped cones.4
cornea is 11.7 mm, while the vertical diameter is 10.6 mm, The curvature of the normal cornea progressively chang-
providing an overall area equivalent to one-sixth of the es with age. During infancy, the cornea is more spherical.
circumference of the eyeball.1 The cornea is thinnest at its During childhood and adolescence, with-the-rule astigma-
center and undergoes progressive thickening towards the tism develops. Middle age results in a more spherical cor-
periphery. On average, corneal thickness ranges from 0.5 nea, with progression toward against-the-rule astigmatism
mm centrally to 1 mm peripherally.2 The overall corneal in the elderly. Interestingly, keratoconus classically begins
thickness tends to increase with age. to develop during puberty and progresses into middle age
With respect to shape, the central one-third (optic zone) (third or fourth decade) before halting.
of the cornea is almost spherical, and asymmetric flat- The cornea serves 2 primary functions in the eye, vision
tening occurs with extension to the periphery. The nasal and protection. With respect to vision, the cornea acts
superior portion of the cornea displays more extensive as a transparent tissue to allow light to be transmitted to
flattening than the temporal inferior portion. Keratoconus the lens and the retina. Its transparency is dependent on
is a disease that involves non-inflammatory thinning of several factors, including regularity and smoothness of the
the corneal stroma that results in a conical corneal shape. epithelium, its avascularity, and the size and arrangement

Wang M, ed.
Keratoconus & Keratoectasia: Prevention, Diagnosis, and Treatment (pp.3–10) 3
© 2010 SLACK Incorporated
4 CHAPTER 1

Figure 1-1. Side profile photograph of keratoconic eye, demonstratinginferior

protrusion of the cornea. (Courtesy of Heidelberg Engineering, Heidelberg,
Germany.)

of extracellular and cellular components in the stroma,

which are dependent on the state of hydration, metabolism,
and nutrition of the stromal elements.5 Furthermore, the
cornea provides significant refractive power so that light
may be appropriately focused upon the retina. In fact, the
anterior surface of the cornea and its associated tear film
account for 44 of the total 64 D of refractive power in the
eye.6 With respect to protection, the cornea provides both Figure 1-2. Normal histology of the cornea. (Courtesy of Heidelberg
a barrier to fluid loss through tight junctions in apical Engineering, Heidelberg, Germany.)
epithelial cells and a barrier to pathogens through mem-
brane-spanning mucins at the apical surface.2 The cornea’s
rigidity and ability to quickly regenerate from mitotically
active basal epithelial cells make it well suited to act as a
natural physical shield against ocular trauma.

MICROSCOPIC ANATOMY AND

PHYSIOLOGY
The normal cornea consists of 5 layers, listed from Figure 1-3. Histologyof a keratoconiccornea with a rupture of Bowman’s layer.
anterior to posterior: the epithelium, Bowman’s layer, (Courtesyof Heidelberg Engineering, Heidelberg, Germany.)
stroma, Descemet’s membrane, and endothelium (Figure
1-2). Although its presentation can be variable, the classic
triad of histopathological findings for keratoconus includes thickness of 50 to 52 µm.7,8 It is a smooth, regular surface
thinning of the stromal layer, iron deposition in the basal to which the tear film adheres and plays an integral role as a
layers of the epithelium, and breaks in Bowman’s layer barrier to pathogens and fluid and solute loss. Keratoconic
(Figure 1-3). However, depending on the severity of the corneas often demonstrate thinning of the central epi-
disease, keratoconus can have manifestations in all layers thelium, which is significantly greater in the presence of
of the cornea. Post-excimer laser keratoectasia has findings breaks in the Bowman’s layer.9 The data in the literature
primarily in the epithelium, Bowman’s layer, and stroma of are controversial regarding the presence of epithelial thick-
the cornea (Figure 1-4). ening in keratoconus, and this may be further evidence of
the variable presentation of the disease.10 The epithelium
Epithelium may also show basal cell degeneration, epithelial breaks
accompanied by downgrowth of epithelium into Bowman’s
The corneal epithelium is composed of 5 to 7 layers layer, particles within a thickened subepithelial basement
of stratified, squamous epithelial cells and has an overall membrane-like layer and between basal epithelial cells, and
 ANATOMY, PHYSIOLOGY, AND MOLECULAR BIOLOGY 5

The corneal basement membrane is an extracellular

matrix that lies beneath the basal cell layer. Basal cells are
responsible for secreting its components, which include
Type IV collagen, laminin, and other glycoproteins. The
basement membrane separates the epithelium from the
stroma and provides a scaffold for the organization of the
epithelium.16
Chi and colleagues suggested that the earliest manifesta-
tions of keratoconus are degenerative changes in the basal
cell layer of the epithelium. Using histopathology, they
observed that, as the disease advances in severity, degenera-
tion of the basal cell layer progresses and can even disap-
pear. Thus, in the most severe cases of keratoconus, histo-
Figure 1-4. Light photomicrograph of human post-LASIKcorneal button with pathology demonstrates one or two abnormally appearing
ectasia. This image demonstrates epithelial hypoplasia (blackarrowhead) over superficial epithelial cell layers lying upon an abnormal
an ectatic region and peripheral epithelial hyperplasia (grey arrowheads). basement membrane, Bowman’s layer, or directly upon
Ectatic regions commonly display Bowman’s layer breaks (black asterisk) the anterior stroma.17 Confocal microscopy has confirmed
and larger-than-normal artifacteous interlamellar clefts (white arrowhead), these observations by demonstrating marked irregularity in
particularly in the posterior-most region of the residual stromal bed. The basal cell nuclei with more advanced cases of keratoconus.
insets show higher magnification views demonstrating epithelial hypopla- The keratoconic changes in these cells are similar to those
sia, Bowman’s layer breaks, and larger-than-normal artifacteous clefting. of the wing cells, including large and abnormally appear-
(Courtesyof Heidelberg Engineering, Heidelberg, Germany.) ing nuclei.18 More severe cases may also demonstrate faint
cell borders and a general hazy appearance.19 Furthermore,
accumulation of ferritin particles within and between basal brightly reflective deposits can be seen in the basal cells,
epithelial cells.11 In post-LASIK ectasia, the corneal epi- which most likely represent hemosiderin deposits.20
thelium may demonstrate focal areas of central epithelial
hypoplasia or hyperplasia.12 Bowman’s Layer
The corneal epithelium can be divided into three dis- Bowman’s layer is an acellular condensation of ran-
tinct sections based on cell type, and confocal microscopy domly oriented collagen fibrils and proteoglycans that does
has aided in defining specific changes to each of these sec- not regenerate after injury. It is attached anteriorly to the
tions in keratoconus. Flattened superficial epithelial cells basement membrane and blends into the more organized
(“squames”) compose the outer three to four layers of the anterior stroma. Its function remains unclear, but many
epithelium. Moderate keratoconus often does not demon- have hypothesized that it plays a role in the maintenance
strate any significant changes to these cells. In more severe of epithelial uniformity and structure and thereby helps
cases of keratoconus, confocal microscopy demonstrates to uphold the refractive power of the cornea. The his-
elongated or spindle-shaped irregular squames arranged topathologic features of keratoconus seen in Bowman’s
in a whorl-like fashion.13 Spindle-shaped cells are evidence layer include breaks filled by epithelial downgrowth or
of the wound-healing response and its associated cellular eruptions of underlying stromal collagen, periodic acid
migration.14 Schiff-positive nodules, and Z-shaped interruptions, pos-
Below the superficial epithelial cells are one to three sibly due to separation of collagen bundles and reticular
layers of wing cells, aptly named for their thin wing-like scarring.11 Confocal microscopy often does not show any
extensions that project laterally from the cell body. Like changes in this layer. However, superficial epithelial cell
superficial cells, moderately keratoconic corneas usually nuclei and keratocyte nuclei from the anterior stroma may
do not demonstrate changes in this cell layer with confo- be observed in the same plane as Bowman’s layer,14 likely
cal microscopy. In more severe cases, wing cells displayed confirming the presence of breaks in the layer with either
strikingly large and irregularly spaced nuclei.15 epithelial downgrowth or anterior stromal eruptions. Post-
The final layer is composed of basal cells, which are LASIK keratoectasia also demonstrates breaks in Bowman’s
the mitotically active cells of the epithelium. These cells layer in ectatic regions of the cornea.12
replicate and differentiate to form all layers of the corneal
epithelium. The basal cell layer is anchored to the base- Stroma
ment membrane and stroma through an anchoring com-
plex. In this complex, a hemidesmosome located on the The corneal stroma lies between Bowman’s layer and
cytoplasmic side of the basal cell membrane adheres to the Descemet’s membrane and comprises approximately 90%
basement membrane and is attached to the stroma through of the corneal thickness. It is primarily composed of
anchoring fibrils composed of Type VII collagen. flattened bundles of Type I collagen fibrils arranged in
6 CHAPTER 1

corneal stroma, which correspond to the degree of apical

scarring seen with the slit-lamp biomicroscope. Hyper-
reflective keratocyte nuclei are thought to indicate the
presence of fibroblastic cells, and the increased stromal
haze can be attributed to fibroblastic accumulation and
irregular collagen fibrils.15 Confocal microscopy has also
shown that keratocyte density is significantly lower in
keratoconic stroma, and the decline in keratocyte density
correlates with disease severity.25 Histopathological find-
ings observed in the stroma of keratoconic eyes include
compaction and loss of arrangement of collagen fibrils in
the anterior stroma, decrease in the number of collagen
Figure 1-5. Color contrast polarized light microscopy at the boundary of a lamellae, normal and degenerating fibroblasts in addi-
keratoconus epikeratoplasty. The normal (donor) human cornea is seen at the tion to keratocytes, and fine granular and microfibrillar
top, demonstrating the lamellar structure. The keratoconic host cornea is at material associated with the keratocytes.26 In post-LASIK
the bottom (magnification 100×). Notice the disorganization of the kerato- ectatic stroma, histopathological findings include thin-
conic lamellae. (Courtesyof Heidelberg Engineering, Heidelberg, Germany.) ning of the residual stromal bed and abnormally large
artifacteous interlamellar clefts, particularly in the deepest
layers of the residual stromal bed. Post-PRK ectatic stroma
parallel known as lamellae (Figure 1-5). These collagen demonstrates thinning of the hypercellular fibrotic stromal
fibrils are embedded within a matrix of glycoproteins and scar in addition to the findings seen in post-LASIK ectatic
proteoglycans that maintain adhesion between cells of the stroma.12
stroma and allow for transport of nutrients and oxygen.
In normal corneal stroma, collagen fibrils are arranged
Proteoglycans also play a significant role in the regulation
along the vertical and horizontal meridians, orthogonal
of spacing between collagen fibrils.
to one another.27-30 Furthermore, stromal collagen mass
The diameter of each collagen fibril ranges from 27 to progressively increases from the center of the cornea to
35 nm, and the distance between each fibril is between 41.4 the periphery.28,29 Both of these characteristics of the cor-
and 60 nm.21,22 The diameter of the collagen fibril is con- neal stroma are integral to the maintenance of appropriate
sidered too small to result in significant scattering of light.23 corneal shape. In keratoconus, collagen fibrils abandon
It has been proposed that stromal transparency will be the vertical and horizontal meridians and instead ori-
maintained if the following two conditions are met: (1) col- ent at approximately 20/160 degrees.27-29 The distribu-
lagen fibrils maintain a fairly uniform small size; (2) colla- tion of collagen fibrils may become highly irregular in
gen fibrils are not spaced apart greater than approximately keratoconic stroma, particularly in the apex of the cone.27
λ/2n, in which λ is the wavelength and n is the refractive Transmission electron microscopy of keratoconic corneas
index of the medium. Unlike the orientation of collagen revealed that the thickness of collagen lamellae is unal-
fibrils in other parts of the body, both the diameter of and tered.31 However, the number of lamellae in the stroma
the distance between each collagen fibril in the corneal is significantly reduced, indicating the progressive loss
lamellae are highly uniform. This regular arrangement is of lamellae in keratoconus. The apex of the cone shows
thought to play a significant role in the establishment of the the most dramatic irregularities in fibril orientation and
shape, strength, and transparency of the cornea. arrangement and the greatest reduction in corneal mass,
The primary cell type found within the corneal stroma while the corneal periphery often maintains its normal
is the keratocyte, which is a type of fibroblast, or special- orientation and mass.29
ized cell of connective tissue. The keratocyte is a flattened Proteoglycans in the corneal stroma are also affected by
cell that is interposed between lamellae, and its elongated keratoconus. X-ray diffraction studies have demonstrated
processes often attach through gap junctions to those of that the relative distribution of proteoglycan molecules in
other keratocytes. Keratocytes secrete and maintain the collagen fibrils is altered in keratoconic corneas.30 This
collagen and proteoglycans that form the majority of the may contribute to the decreased corneal strength observed
corneal stroma. They also produce enzymes that are able in the disease.
to degrade older collagen fibrils in need of replacement.
Furthermore, keratocytes migrate to areas of stromal
injury in order to assist with scar formation and collagen
Descemet’s Membrane
repair.24 Descemet’s membrane is the basement membrane of the
Keratoconus may cause alterations to the corneal stroma corneal endothelium. It is synthesized by endothelial cells
that significantly disturb the transparency, shape, and and assembled at the basal surface of the cell layer.31 This
strength of the cornea. Confocal microscopy shows vary- membrane is primarily composed of Type IV and VIII col-
ing amounts of haze and hyper-reflectivity in keratoconic lagen, and it does not regenerate after injury. Its primary
 ANATOMY, PHYSIOLOGY, AND MOLECULAR BIOLOGY 7

Figure 1-6. Hydrops in keratoconus. Notice the opacification of the corneal

stroma and injection of the conjunctiva. (Courtesyof Heidelberg Engineering,
Heidelberg, Germany.)

functions include filtering of solutes passing to and from

epithelial cell layers and serving as a substrate for the Figure 1-7. Ultrasound biomicroscopy demonstrating acute hydrops in kera-
induction of polarity and differentiation of the overlying toconus. Arupture of Descemet’s membrane and intrastromal clefts can be
epithelium.32 seen. (Courtesyof Heidelberg Engineering, Heidelberg, Germany.)
In keratoconus, Descemet’s membrane often appears
normal, except in cases of acute hydrops. In patients with hydrops. Furthermore, the separation between the stroma
advanced keratoconus, breaks in Descemet’s membrane and Descemet’s membrane caused by the clefts may delay
may occur, providing channels for the aqueous humor to the closure of Descemet’s membrane and therefore impede
pass into the stroma, resulting in marked corneal edema. the deturgescence of stromal edema.
This condition, known as acute hydrops, presents clinically
as a sudden onset of pain and loss of vision. It occurs in Endothelium
approximately 3% of keratoconic eyes.33 Slit-lamp biomi-
croscopy demonstrates diffuse opacification of the corneal The corneal endothelium is a single layer of hexagonal
stroma and injection of the conjunctiva (Figure 1-6). The cells adherent to the posterior aspect of Descemet’s mem-
opacification often resolves without intervention over the brane. Their abundant organelles demonstrate the high
course of 6 to 10 weeks, but scarring commonly occurs level of metabolic and synthesizing activity of these cells.
after deturgescence. Non-resolution of the opacification is Endothelial cells in an adult are arrested in the G1 phase
an indication for penetrating keratoplasty. of the mitotic cell cycle, meaning that they do not replicate
despite their capacity to do so.36 A major function of the
Histopathology of post-keratoplasty corneal buttons
endothelium is the maintenance of corneal transparency
4 months after the onset of hydrops demonstrated sig-
through the regulation of stromal hydration. The endothe-
nificant stromal edema.34 The rupture and detachment of
lial cells provide a “leaky barrier” to aqueous humor and
Descemet’s membrane resulted in the formation of ledges
contain numerous specialized ion transport systems to
or ridges. In the process of healing the detached areas, new
transfer excess water out of the cornea. These two functions
endothelium completely covered the exposed posterior
of the endothelium facilitate its regulation of the amount
stroma and the corresponding anterior aspect of the ledges.
of water within the corneal stroma. The endothelium gen-
The endothelium also regenerated considerable basement
erally remains unaffected in keratoconic corneas. Rarely,
membrane.
intracellular “dark structures,” nuclear pleomorphism, and
Ultrasound biomicroscopy of keratoconic eyes with
elongation of endothelial cells may be observed.11
acute hydrops reveals intrastromal clefts connected to the
anterior chamber, which separate the stroma from the
ruptured Descemet’s membrane (Figure 1-7).35 These clefts
Tear Film
may develop simultaneously or immediately after the rup- The tear film of the eye covers the anterior surface of the
ture of Descemet’s membrane. By augmenting the stromal cornea. It is composed of three separate layers, an anterior
surface area exposed to the anterior chamber, intrastromal lipid layer, a middle aqueous layer, and a posterior mucin
clefts may facilitate the development of stromal edema in layer. The average thickness of the tear film is approxi-
8 CHAPTER 1

mately 7 µm, the majority of which is the aqueous layer.37 in the corneal epithelium and the stroma.42 The damage
The tear film serves the following functions: lubricates the was particularly evident in the sub-basal nerve plexus.
anterior surface of the eye; acts as a smooth, transparent Confocal microscopy of the sub-basal nerve plexus in
refractive surface for the transmission of light; transfers keratoconic corneas reveals abnormal nerve architecture,43
nutrients and oxygen to the corneal epithelium; protects significantly reduced central sub-basal nerve density, and
against infection; and removes desquamated epithelial cells thickened, more prominent nerve fibers, often with exces-
from the surface of the eye.38 The lipid layer is produced by sive branching or curling.20 Similar findings have also been
meibomian glands as a means by which to increase surface noted in the stromal nerves.44
tension and therefore prevent evaporation of the aqueous
layer. The aqueous layer is secreted by the main lacrimal Molecular Biology
glands and the accessory lacrimal glands of Wolfring and
Although the pathophysiology of keratoconus remains
Krause and primarily serves to lubricate the corneal epithe-
poorly understood, recent studies in molecular biology
lium. The mucin layer is manufactured by the goblet cells
have elucidated possible contributing factors for the dis-
of the conjunctiva and serves to reduce the surface tension
ease. One hypothesis suggests that thinning of the corneal
of the aqueous tear layer so that it may adsorb to the epi-
stroma in keratoconus may be due to aberrant degradation
thelium and remain intact between blinks.38
processes in the cornea. Immunohistochemical staining
Keratoconic eyes demonstrate a significant reduction
and Western blot assays demonstrated a significant reduc-
in tear break-up time, and tear film instability progresses
tion in alpha 1-proteinase inhibitor and alpha 2-macro-
as keratoconus becomes more severe. Furthermore, kera-
globulin, two major proteinase inhibitors, in keratoconic
toconus results in prominent goblet cell loss, which can
epithelium and stroma.45 Similar studies found augmented
contribute to tear film instability. Significant squamous
levels of the several proteolytic enzymes, including acid
metaplasia is present in these eyes, which most likely is a
esterase, acid phosphatase, acid lipase, and cathepsins B
result of the drying effect produced by keratoconus.39
and G.46,47 These shifts in molecular concentrations create
a heightened degradative state in the cornea, which most
Corneal Innervation likely results in the stromal thinning seen in keratoconus.
The cornea has an extensive supply of sensory nerve Another area of great interest in the etiology of kerato-
fibers, making it one of the most highly innervated tis- conus and keratoectasia involves apoptosis, or programmed
sues in the body. Corneal sensory nerves are derived from cell death. Wilson and colleagues suggest that damage to
the ophthalmic division of the trigeminal nerve (Cranial epithelial cells causes a reduction in anterior stromal kera-
Nerve V). Nerve branches enter the anterior corneal stroma tocytes due to apoptosis.48 It is hypothesized that damaged
from an annular nerve plexus near the limbus. At this epithelial cells release pro-apoptotic cytokines, including
entry point, myelination of the nerve axons is lost, which interleukin-1 (IL-1) and Fas-ligand, that then initiate the
is essential for the maintenance of corneal transparency.40 apoptotic cascade in stromal keratocytes.48 Both molecular
The nerve fibers then proceed to run parallel to the epithe- testing and transmission electron microscopy were utilized
lium, forming a sub-basal nerve plexus. From this plexus, to confirm that keratoconic corneas exhibit significantly
axons without Schwann cells penetrate Bowman’s layer and increased numbers of anterior keratocytes with signs of
extend into the epithelium. The corneal nerves serve two apoptosis.49 Furthermore, in keratoconus, keratocytes have
main functions. First, they provide protection by serving as been shown to have four times as many IL-1 receptors as
the afferent portion of an aversion reflex in response to any those of normal eyes.50 These excess receptors may sensi-
contact with the corneal surface. Second, corneal nerves tize the keratocytes to IL-1, thereby reducing the threshold
secrete trophic factors for the preservation of corneal for apoptosis and progressive loss of keratocytes. This
health.40 If corneal nerves are damaged either by disease or hypothesis helps to explain the association of keratoconus
trauma, the lack of adequate production of trophic factors with eye rubbing, atopy, and contact lens wear. All three
could lead to neurotrophic keratitis, which is characterized of these risk factors result in epithelial damage that could
by epithelial sloughing and impaired healing.2 potentially trigger the release of IL-1 and Fas-ligand from
Corneal sensitivity was shown to be significantly dimin- epithelial cells.51
ished in keratoconic eyes, implicating the negative effects
of keratoconus on corneal nerve function.41 Dogru and
colleagues found that corneal sensitivity was significantly CONCLUSION
lower in patients with severe keratoconus compared with
patients with mild or moderate disease.39 Transmission The cornea is a complex, intricate component of the eye
electron microscopy of keratoconic corneal buttons dem- that is integral to vision. Keratoconus and keratoectasia are
onstrated mitochondrial degeneration, liquefaction of neu- diseases that result in significant abnormalities of the anat-
rofibrils, and breaks in the membranes of nerve fibers omy and physiology of the cornea, often resulting in sub-
 ANATOMY, PHYSIOLOGY, AND MOLECULAR BIOLOGY 9

stantial visual disturbances. The following chapters provide 22. Krachmer JH, Mannis MJ, Holland EJ. Cornea. 2nd ed. Vol
a guide for the diagnosis, management, and prevention of I Fundamentals, Diagnosis and Management. London: Elsevier-
Mosby; 2005.
keratoconus and keratoectasia in ophthalmologic practice. 23. Farrell RA, McCally RL. Corneal transparency. In: Albert DM,
Jakobiec FA, eds. Principles and Practice of Ophthalmology.
Philadelphia: WB Saunders; 2000:629-643.
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1. Duke-Elder S, Wybar KC. Cornea. System of ophthalmology, vol. 2: 25. Ku JY, Niederer RL, Patel DV, Sherwin T, McGhee CN. Laser scan-
the anatomy of the visual system. Henry Kimpton. 1961:95-131. ning in vivo confocal analysis of keratocyte density in keratoconus.
2. Gipson IK, Joyce NC, Zieske JD. The anatomy and cell biology of Ophthalmology. 2008;115:845-850.
the human cornea, limbus, conjunctiva, and adnexa. In: Smolin 26. Krachmer JH, Feder RS, Belin MW. Keratoconus and related non-
G, Foster CS, Thoft RA, Azar DT, Dohlman CH, eds. Smolin and inflammatory corneal thinning disorders. Surv Ophthalmol. 1984;
Thoft’s the Cornea: Scientific Foundations & Clinical Practice. 28:293-322.
Philadelphia: Lippincott Williams & Wilkins; 2005:1-17. 27. Meek KM, Boote C. The organization of collagen in the corneal
3. Krachmer HJ, Feder RS, Belin MW. Keratoconus and related non- stroma. Exp Eye Res. 2004;78:503-512.
inflammatory corneal thinning disorders. Surv Ophthalmol. 1984; 28. Daxer A, Fratzel P. Collagen fibril orientation in the human corneal
28:293-322. stroma and its implications in keratoconus. Inv Ophthal Vis Sci.
4. Perry HD, Buxton JN, Fine BS. Round and oval cones in keratoco- 1997;38:121-129.
nus. Ophthalmology. 1980;87:905-909. 29. Meek KM, Tuft SJ, Huang Y, et al. Changes in collagen orientation
5. McMenamin PG, Steele C, McGhee CNJ. Cornea: anatomy, physiol- and distribution in keratoconus corneas. Inv Ophthal Vis Sci. 2005;
ogy, and healing. In: McGhee CNJ, Taylor HR, Gartry DS, Trokel 46:1948-1956.
SL, eds. Excimer Lasers in Ophthalmology: Principles and Practice. 30. Hayes S, Boote C, Tift SL, Quantock AJ, Meek KM. A study of
London: Martin Dunitz; 1997:41-45. corneal thickness, shape and collagen organization in keratoconus
6. Davson H. Physiology of the Eye. 5th ed. New York: Pergamon Press; using videokeratography and X-ray scattering techniques. Exp Eye
1990. Res. 2007;84:423-434.
7. Maurice DM. The Cornea and the Sclera. London: Academic Press, 31. Takahashi A, Nakayasu K, Okisaka S, Kanai A. Quantitative analy-
1985. sis of collagen fiber in keratoconus. Nippon Ganka Gakkai Zasshi.
8. Warwick R. Eugene Wolff ’s Anatomy of the Eye And Orbit. 8th ed. 1990;94:1068-1073.
London: Chapman & Hall Medical; 1997:235. 32. Fullwood NJ, Tuft SJ, Malik NS, Meek KM, Ridgway AE, Harrison
9. Scroggs MW, Proia AD. Histopathological variation in keratoconic RJ. Synchrotron x-ray diffraction studies of keratoconus corneal
corneas. Cornea. 1992;11:553-559. stroma. Invest Ophthalmol Vis Sci. 1992;33:1734-1741.
10. Sherwin T, Brookes NH. Morphological changes in keratoconus: 33. Tuft SJ, Gregory WM, Buckley RJ. Acute corneal hydrops in kerato-
pathology or pathogenesis. Clin Experiment Ophthalmol. 2004; conus. Ophthalmology. 1994;101:1738-1744.
32:211-217. 34. Stone DL, Kenyon KR, Stark WJ. Ultrastructure of keratoconus
11. Rabinowitz YS. Keratoconus. Surv Ophthalmol. 1998;42:297-319. with healed hydrops. Am J Ophthalmol. 1976;82:450-458.
12. Dawson DG, Randleman JB, Grossniklaus HE, et al. Corneal ectasia 35. Nakagawa T, Maeda N, Okazaki N, Hori Y, Nishida K, Tano
after excimer laser keratorefractive surgery: histopathology, ultra- Y. Ultrasound biomicroscopic examination of acute hydrops in
structure, and pathophysiology. Ophthalmology. 2008;115(12):2181- patients with keratoconus. Am J Ophthalmol. 2006;141:1134-1136.
2191. 36. Joyce NC, Meklir B, Joyce SJ, Zieske JD. Cell cycle protein
13. Somodi S, Hahnel C, Slowik C, Richter A, Weiss DG, Guthoff expression and proliferative status in human corneal cells. Invest
R. Confocal in vivo microscopy and confocal laser-scanning Ophthalmol Vis Sci. 1996;37:645-655.
fluorescence microscopy in keratoconus. Ger J Ophthalmol. 1996; 37. Holly FJ, Lemp MA. Tear physiology and dry eyes. Surv Ophthalmol.
5:518-525. 1977;22:69-87.
14. Tsubota K. In vivo observation of the corneal epithelium. Scanning. 38. Stein HA, Slatt BJ, Stein RM, Freeman, MI. Fitting Guide for Rigid
1994;16:295-299. and Soft Contact Lenses: A Practical Approach. Philadelphia: Mosby;
15. Efron N, Hollingsworth JG. New perspectives on keratoconus as 2002:3-12.
revealed by corneal confocal microscopy. Clin Exp Optom. 2008; 39. Dogru M, Karakaya H, Ozçetin H, et al. Tear function and ocular
91:34-55. surface changes in keratoconus. Ophthalmology. 2003;110:1110-
16. Vracko R, Benditt EP. Basal lamina: the scaffold for orderly cell 1118.
replacement. Observations on regeneration of injured skeletal 40. Müller LJ, Marfurt CF, Kruse F, Tervo TM. Corneal nerves: struc-
muscle fibers and capillaries. J Cell Biol. 1972;55(2):406-419. ture, contents, and function. Exp Eye Res. 2003;76:521-542.
17. Chi HH, Katzin HM, Teng CC. Histopathology of keratoconus. Am 41. Zabala M, Archila EA. Corneal sensitivity and topogometry in
J Ophthalmol. 1956;42:847-860. keratoconus. CLAO J. 1988;14:210-212.
18. Hollingsworth JG, Bonshek RE, Efron N. Correlation of the appear- 42. Teng CC. Electron microscope study of the pathology of keratoco-
ance of the keratoconic cornea in vivo by confocal microscopy and nus: part I. Am J Ophthalmol. 1963;55:18-47.
in vitro by light microscopy. Cornea. 2005;24: 397-405. 43. Patel DV, McGhee CN. Mapping of the normal human corneal sub-
19. Efron N, Perez-Gomez I, Mutalib HA, Hollingsworth J. Confocal basal nerve plexus by in vivo laser scanning confocal microscopy.
microscopy of the normal human cornea. Contact Lens Ant Eye. Invest Ophthalmol Vis Sci. 2005;46:4485-4488.
2001;24:16-24. 44. Simo Mannion L, Tromans C, O’Donnell C. An evaluation of
20. Uçakhan OO, Kanpolat A, Ylmaz N, Özkan M. In vivo confocal corneal nerve morphology and function in moderate keratoconus.
microscopy findings in keratoconus. Eye Contact Lens. 2006;32: Contact Lens Ant Eye. 2005;28:185-192.
183-191. 45. Sawaguchi S, Twining SS, Yue BY, et al. Alpha 2-macroglobulin lev-
21. Hogan MJ, Alvarado JA, Wedell JE. Histology of the Human Eye. els in normal human and keratoconus corneas. Invest Ophthalmol
Philadelphia: WB Saunders; 1971. Vis Sci. 1994;35:4008-4014.
10 CHAPTER 1

46. Sawaguchi S, Yue BYJT, Sugar J, Gilboy JE. Lysosomal enzyme 49. Kim WJ, Rabinowitz YS, Meisler DM, Wilson SE. Keratocyte apop-
abnormalities in keratoconus. Arch Ophthalmol. 1989;107:1507- tosis associated with keratoconus. Exp Eye Res. 1999;69:475-481.
1510. 50. Fabre EJ, Bureau J, Pouliquen Y, Lorans G. Binding sites for human
47. Zhou L, Sawaguchi S, Twining SS, et al. Expression of degradative interleukin 1 alpha, gamma interferon and tumor necrosis factor
enzymes and protease inhibitors in corneas with keratoconus. on cultured fibroblasts of normal cornea and keratoconus. Curr Eye
Invest Ophthalmol Vis Sci. 1998;39:1117-1124. Res. 1991;10:585-592.
48. Wilson SE, He YG, Weng J, et al. Epithelial injury induces kerato- 51. Bron AJ, Rabinowitz YS. Corneal dystrophies and keratoconus.
cyte apoptosis: hypothesized role for the interleukin-1 system in the Curr Opin Ophthalmol. 1996;7:71-82.
modulation of corneal tissue organization and wound healing. Exp
Eye Res. 1996;62:325-327.
 CHAP TER 2

Clinical Biomechanics and the

Ocular Response Analyzer in
Ectatic Disease
William J. Dupps Jr, MD, PhD; Marcella Q. Salomão, MD;
and Renato Ambrósio Jr, MD, PhD

T
he cornea is a complex biomechanical composite ly more oblique branching and interweaving is noted.3
whose behavior depends on its structural subcom- Interlamellar branching is also more extensive in the
ponents and their organizational motifs (Figure corneal periphery than in its center.7,8 Interweaving of col-
2-1). Bowman’s layer and the stroma are the only collag- lagen bundles between neighboring lamellae provides an
enous layers of the cornea and thus provide the major- important structural mechanism for shear (sliding) resis-
ity of the cornea’s tensile strength. The epithelium has a tance9 and sharing of tensile loads between lamellae.10,11
minimal role in this tensile strength, and its removal causes In addition, x-ray diffraction studies provide evidence of
little or no change in the anterior corneal curvature.1 The a predominantly circumferential fibril orientation in the
extensibility and low stiffness of Descemet’s membrane corneal periphery12 that may favor conservation of lim-
ensure its laxity over a broad range of intraocular pres- bal circumferential dimensions even in ectatic disease.13
sures (IOPs)2 and may serve as a high-compliance buffer to Proteoglycans play a critical role in collagen fibril assembly
protect the endothelium from the effects of high stromal and spacing,14 and their mechanical importance may be
stresses. The role of Bowman’s layer, an 8- to 12-µm thick greater than currently recognized.
acellular condensation of stroma with more randomly ori-
ented collagen fibrils,3 has been a subject of controversy.4,5
Although some have proposed a structural role distinct CORNEAL MATERIAL
from that of the stroma, extensiometry studies in normal PROPERTIES
corneas suggest that removal of Bowman’s layer does not
measurably alter the bulk mechanical properties of the cor- The mechanical properties of the cornea and its con-
nea.5 However, such measurements may not be sufficiently stituent materials link the cornea’s morphology to its
sensitive to detect the contribution of Bowman’s layer mechanical behavior under the stresses of surgery or
in a full-thickness corneal sample, and the biomechani- disease. In the terminology of material science, the cor-
cal effects of histologically confirmed fragmentation of nea is a complex anisotropic composite with non-linear
Bowman’s layer in much thinner keratoconic tissues have elastic and viscoelastic properties. It is a composite because
yet to be characterized. its properties are determined by the interaction of dis-
The mechanical response of the cornea to injury is parate materials like collagen and a polyanionic ground
dominated by the stroma. On a weight basis, the stroma substance, and anisotropic because its properties are not
is approximately 78% water, 15% collagen, and 7% non- directionally uniform. The cornea is also highly hetero-
collagenous proteins, proteoglycans, and salts.6 A total of geneous in the central to peripheral, anterior to posterior,
300 to 500 lamellae run from limbus to limbus stacked and rotational dimensions. A generalized solution of the
with angular offsets. This orientation becomes increas- three-dimensional equations describing such a complex
ingly random in the anterior stroma where significant- system is untenable, and reduction of the problem to the

Wang M, ed.
Keratoconus & Keratoectasia: Prevention, Diagnosis, and Treatment (pp.13–28) 13
© 2010 SLACK Incorporated
14 CHAPTER 2

Figure 2-1. The cornea is a complexbiomechanical composite whose

behavior depends on its structural subcomponents and their organi-
zational motifs.

Figure 2-2. An example of non-linear

elastic (A) and viscoelastic (B) behavior A B
in a donor cornea specimen.

linear, isotropic case is required to arrive at the more tissue with an extensiometer that measures force gen-
familiar definitions of Young’s modulus and other proper- eration during steady axial elongations of the sample.
ties described below. The slope of stress (force per unit area, N/m 2) over strain
Friedenwald defined the ocular rigidity coefficient and (a dimensionless quantity defined by the current length
performed some of the earliest characterizations of ocular divided by the starting length) is calculated for a represen-
biomechanical properties.15 A pressure–volume curve is tative portion of the curve. A high modulus indicates a stiff
recorded during a volumetric distention experiment and or low-compliance material. While most biological soft
provides a measure of whole-globe stiffness. This relation- tissues approximate linear elastic behavior when a small
ship is characterized by the slope of the pressure–volume range of stresses is considered, their overall elastic behavior
curve (mmHg/µL). It is non-linearly dependent on IOP is non-linear. A linear approximation can be obtained from
and has been shown to increase with age.16 Its utility in the instantaneous slope of the stress–strain curve (tangent
refractive surgery remains to be demonstrated and may be modulus) or as a chord between two points on the curve
limited to the extent that corneal contributions to rigidity (secant modulus).18
are inseparable from scleral and uveal components. In Figure 2-2, an example of non-linear elastic behavior
The elastic (or Young’s) modulus may be one of the most in a donor cornea specimen is presented. Non-linearity
critical material properties in understanding the corneal arises from an initially slow uptake of load as the collagen
response to refractive surgery17 and provides an indicator takes up slack, followed by stiffening as maximal fibril
of stiffness. An elastic material regains its original geom- recruitment is approached. Plastic responses such as yield
etry when an imposed stress is removed and does so in a and failure occur when a permanent strain is incurred and
reversible manner along the same stress–strain pathway. the material does not recover its original configuration
The elastic modulus is traditionally measured in excised upon unloading.
 CLINICAL BIOMECHANICS AND THE OCULAR RESPONSE ANALYZER IN ECTATIC DISEASE 15

The range of reported values for the elastic modulus of

the human cornea spans orders of magnitude.19 Although
CLINICAL MEASUREMENT OF
some biological variability is expected, this variability also CORNEAL BIOMECHANICAL
reflects the challenges of obtaining representative data
with a range of tissue hydrations, loading conditions, and
PROPERTIES
experimental techniques in ex vivo tissue. It should also be
Traditional extensiometry, despite its limitations, has
clear from the above discussion that a non-linear function
revealed deficits in elastic tensile strength in keratoconus25
does not allow definition of a single modulus value but,
and suggests a diagnostic role for elastic modulus deter-
instead, requires its definition as a function of load or as
mination in the clinical setting. The obvious unsuitability
a mean value over a specified loading interval. Membrane
of destructive techniques for in vivo testing, however, has
inflation experiments in normohydrated donor globes pro-
led to accelerated efforts to develop non-destructive, non-
vide a more physiological alternative to extensiometry20
invasive tools for clinical biomechanical property measure-
but do not abrogate the ultimate need for in vivo measure-
ment.
ment techniques.
Ultrasonic shear wave propagation velocity has been
Poisson’s ratio is a conversion for relating strain in one
investigated as a method for measuring the elastic modu-
direction to secondary strain in the transverse direction. A lus without need for tissue destruction.26,27 Experiments
stromal lamella under tensile stress will thin or narrow to with a prototype handheld device (Sonic Eye, PriaVision,
some degree in its other dimensions. An out-of-plane/in- Inc, Menlo Park, CA) have demonstrated the ability to
plane strain ratio of 0.49 is typically assumed because it measure directional and regional stiffness differences in
approximates the cornea’s fluid-filled, near-incompressible porcine27 and human donor globes,28 corneal stiffness
status. In reality, Poisson’s ratio is a true physical property changes with keratotomy, and marked increases in stiffness
of the tissue and not a constant; as such, its role as a variable with stromal collagen cross-linking, which also produce
in elastic, plastic, and viscoelastic thinning of the residual artifactual increases in applanation pressures.27 Young’s
stromal bed (RSB) after LASIK and in keratoconic tissue modulus is related to the product of corneal density and
may be important. the square of the wave velocity measured between the two
Viscoelastic properties arise from the time-dependent transducer tips, which are positioned along the anterior
nature of biomechanical responses and are a feature of all corneal arc. Stiffness is measured in the plane of the lamel-
biological soft tissues. These properties are represented by lae, similar to traditional extensiometry, and thus may be
the phenomena of hysteresis, stress relaxation, and creep. As more comparable to published elastic modulus values than
opposed to the symmetric loading and unloading behavior properties elicited from out-of-plane perturbations. Signal
of purely elastic materials, viscoelastic materials return to attenuation in the presence of the precorneal tear film
their pre-stress configuration via different stress–strain is the primary challenge to clinical implementation, and
pathways that depend on loading rates. This discordance developmental efforts are ongoing.
between loading and unloading behavior can be partially The commercially available Ocular Response Analyzer
characterized by hysteresis. Viscoelastic creep is a time- (ORA, Reichert Inc, Depew, NY) utilizes a high-speed
dependent elongation that occurs under a sustained stress air-puff to quantify the dynamics of corneal deformation
(such as IOP) and may be an important contributor to the and recovery as an indicator of corneal hysteresis (CH).29
mechanics of ectasia.21 Finally, Figure 2-2B illustrates a Figure 2-3 illustrates a typical response waveform. In- and
viscoelastic stress relaxation experiment in which strain is outgoing applanation events are indicated by the two
increased then held constant while a slow time-dependent peak intensities of a 3-mm infrared beam reflected off the
relaxation of the load is observed. central cornea, and the air pressures intersecting these
Shear strength describes stromal resistance to sublayer two applanation events are recorded as P1 (ingoing) and
sliding. The shear resistance provided by collagen inter- P2 (outgoing). Corneal hysteresis is simply the difference
weaving and other matrix forces may be related to metrics between the in- and outgoing applanation pressures (P1−
such as the interlamellar cohesive strength.8,21 Corneal P2). A higher CH indicates a greater capacity for absorption
shear strength is low relative to its tensile strength 22 but of kinetic energy (a viscoelastic property). Eyes with more
provides a mechanism for load transfer between lamellae mechanical “momentum” produce a higher CH due in
that may contribute to hyperopic shift after photoabla- part to a delay in deformation (and therefore applanation)
tion according to the model presented in Figure 2-1 and relative to the onset and decay of the pressure stimulus. As
discussed below.11 Abnormalities of bending strength and illustrated in Figure 2-3, this viscous delay shifts the appla-
lamellar sliding have potential relevance in the pathogen- nation peaks to the right, resulting in a rise in P1, a decrease
esis of ectasia.13,23,24 in P2, and an increased CH.
16 CHAPTER 2

material would rebound immediately, without the slowly

fading imprint of a stressor that is no longer present.
During an air puff, this capacity to absorb energy may
manifest in the cornea as similar delays in the indenta-
tion and recovery responses relative to the air pressure. In
Figure 2-3, the result would be a shift of both applanation
events to the right, leading to an increase in P1, a decrease
in P2, and thus a higher corneal hysteresis (P1–P2). The
complex interaction of elastic and viscoelastic behaviors,
even in the span of a 20 to 30 millisecond air puff, has
been modelled recently by Glass et al,30 and reinforces the
importance of careful nomenclature, a point made at the
conclusion of this chapter.
Figure 2-3. Atypical response waveform. In- and outgoing applanation events The ORA is currently being investigated in glaucoma,
are indicated by the two peak intensities of a 3-mm infrared beam reflected keratoconic, and refractive surgery patients. Both CH and
off the central cornea, and the air pressures intersecting these two applana- CRF are lower after LASIK29,31 and in eyes affected by
tion events are recorded as P1 (ingoing) and P2 (outgoing). Corneal hysteresis keratoconus.29 Lower CH has also been associated with a
is simply the difference between the in- and outgoing applanation pressures higher risk of visual field progression in a cross-sectional
(P1–P2). study of glaucoma patients.32 The role of these measure-
ments in screening refractive surgery candidates for ectasia
risk or evaluating the risk of optic neuropathy in glaucoma
The corneal resistance factor (CRF) is derived from suspects is a rapidly evolving area of research, and the ORA
the same dual-applanation signal and is proposed to be a clearly provides novel information about biomechanical
measure of the elastic resistance of the cornea. The formula risk for which CCT is an incomplete proxy.
for the CRF is similar to CH but incorporates an empiri-
cal adjustment (k CRF) to P2 (CRF=P1−k CRFP2) designed to
reflect a greater dependence on central corneal thickness
THE OCULAR RESPONSE
(CCT) and IOP. The ORA also reports two IOP values: the ANALYZER IN KERATOECTASIA
Goldmann-correlated IOP (IOPG) derived from the mean
of P1 and P2 and the cornea-compensated IOP (IOPCC). Understanding the pathophysiology of keratoco-
The IOPCC was designed to be less sensitive to corneal nus requires better knowledge of corneal biomechanics.
properties than traditional applanation tonometry and Accordingly, studies in this field have increased incredibly
was calibrated empirically to be relatively unaffected by in recent years. In addition, reports of keratoectasia after
LASIK. laser in situ keratomileusis (LASIK) with no identifiable
Hysteresis is not observed in purely elastic materials preoperative risk factors33 have awakened the interest of
like springs, in which the stress-deformation relationship refractive surgeons to better understand corneal behavior
is completely reversable and insensitive to whether the after surgical procedures. This section reviews recent pub-
stress is being applied or removed. Hysteresis is a property lications regarding corneal biomechanical assessments in
of materials that cannot be characterized by their stiffness keratoconic as well as post-refractive surgery eyes.
alone. These “viscoelastic” materials can be conceptualized Increased distensibility is one significant feature in the
as a combination of two mechanical elements: a spring development of keratoectasia,34 and keratoconic eyes are
to incorporate elastic behavior and a dashpot (or shock- less rigid and more elastic than normal eyes.35 In 2005,
absorber) to account for viscous behavior. The dashpot Luce29 first described the biomechanical properties of the
introduces a dissipative or damping capacity to a tissue—in cornea employing the ORA. The author pointed out that
other words, it provides a certain standing resistance or low corneal hysteresis (CH) values might be a predictive
momentum that must be overcome to move the tissue, indicator of a “pre-ectatic” state and also suggested that
and introduces a temporal delay in the response to and CH values might be predictors of outcomes of refractive
recovery from the stressor. Readers who sleep on certain surgery.
viscoelastic mattresses have access to an excellent model for In a study involving 207 normal and 93 keratoconic eyes,
this behavior: push your open hand into the mattress then Shah et al compared corneal hysteresis and mean central
hold, noting the initially high resistance followed by the corneal thickness (CCT) between these two groups.35 The
palpable creep and relaxation of the material under your analysis revealed that both CH and CCT were significantly
hand. Then, rapidly remove your hand and note the slow higher in normal compared to keratoconic eyes. Moreover,
restoration of the material’s initial geometry. An elastic it also demonstrated CH values to decrease with the sever-
 CLINICAL BIOMECHANICS AND THE OCULAR RESPONSE ANALYZER IN ECTATIC DISEASE 17

ity of the disorder, suggesting that this measurement can deeper layers of the corneal stroma with material proper-
potentially be useful to assess progression of the disease. ties that are different from anterior stroma.17 Gatinel et al
The authors also suggest that CH measurements may show suggest that flap creation has a critical role in the reduction
abnormalities even before topographic or clinical changes of CH values as well, so that the decrease of biomechani-
become apparent. cal parameters after LASIK is in fact a combination of flap
In another study, Kirwan et al evaluated patients clini- creation and corneal thinning.40 Thus, creating thin LASIK
cally diagnosed with early forms of ectasia (forme fruste flaps became an interesting alternative to refractive sur-
keratoconus [FFKC]) and compared them with normal geons when trying to preserve the biomechanical integrity
and keratoconus patients. The purpose of the study was to of the cornea. In a study comparing CH between LASIK and
search for early abnormalities of biomechanical measure- laser-assisted subepithelial keratectomy (LASEK), Kirwan
ments, trying to identify preclinical signs of the disease. and O’Keefe found similar reductions of CH values follow-
They found no difference in CH and corneal resistance fac- ing both procedures, indicating that a thin LASIK flap (120
tor (CRF) between normal and FFKC eyes, although they µm) did not induce any additional biomechanical compro-
could find significant differences when comparing those mise as measured by the ORA.41 Similar findings were pre-
measurements between these 2 groups and the keratoconus sented by Slade when assessing the biomechanical effects of
group.36 PRK and sub-Bowman keratomileusis (SBK), as the results
Recently, there has been an increasing awareness of the suggest that PRK offered no biomechanical advantage over
importance of variables other than CH and CRF values, SBK.42 It should be clearly stated that such studies do not
derived from the ORA response waveform. Hallahan et necessarily prove a lack of biomechanical effect since the
al derived several alternative measures of biomechanical sensitivity of CH and CRF to detect clinically significant
behavior from the ORA response signal and compared alterations in properties is not yet clear. The introduction
their performance in distinguishing normal and kerato- of the femtosecond laser in refractive surgery has allowed
conic eyes. Several new derived variables showed statisti- the creation of thinner and more geometrically predictable
cally significant differences between keratoconus and flaps,43 representing an advance in the attempt to reduce
normal patients, and one, the hysteresis loop area (HLA), the biomechanical impact of flap creation on the cornea.
was more sensitive and specific than either CH or CRF. Corneal biomechanics remains not completely under-
These and other derived variables may provide important stood, especially regarding the actual cause of post-LASIK
new information when trying to differentiate early cases of corneal ectasia. Kerautret et al have published a case of uni-
keratoconus.37 lateral corneal ectasia after bilateral LASIK. The study was
CH and CRF have also been shown to decrease after designed to evaluate biomechanical differences between
refractive surgery, especially after LASIK.29 Thus, a num- normal corneas after LASIK and corneas that developed
ber of studies were performed so as to provide a reference ectasia. They found analogous results of CH and CRF
and establish typical values of biomechanical param- between both eyes. Nevertheless, the ORA signal shape
eters for each condition. A recent study by Ortiz and co- showed multiple oscillations and diminished spikes in the
authors compared biomechanical properties measured ectatic eye, advocating that details of the waveform could
with the ORA between normal, keratoconus, and post- provide more information to differentiate an ectatic and a
LASIK patients. According to their results, the keratoconus stable cornea postoperatively.44
group presented significantly lower values of CH and CRF
compared to normal eyes and post-LASIK eyes, although a
significant decrease in these parameters were observed in CASE STUDIES
the LASIK group 1 month after surgery.38
In another report, Touboul and co-workers not only
found lower CH and CRF values in both keratoconus and Case 1: Keratoconus-Like Topo-
post-excimer laser patients compared to normal patients,
but they also suggest a new parameter (CH–CRF) as a
graphic Patterns Without Ectasia
possible new signature of corneal weakness, which might A 35-year-old man presents with anterior axial (sagittal)
be attractive in FFKC screening.39 CRF tended to be lower curvature maps demonstrating keratoconus-like patterns
than CH in keratoconus patients. using both Placido and Scheimpflug (Figures 2-4, 2-5, and
Concerns regarding the increasing incidence of kerato- 2-6) topographers. In the right eye, an asymmetric bowtie
ectasia after LASIK have resulted in a tendency of many with skewed radial axis and inferior steepening was found
surgeons to return to surface ablation. Therefore, diverse within the central 5-mm in diameter. In the left eye, a ver-
studies have been performed to compare the biomechanical tical D shape is observed with 3 D of horizontal asymme-
effects of different modalities of refractive surgery. LASIK try. Maximal K is 46.3 D in both eyes. Ultrasound central
might induce a higher risk of viscoelastic failure then pho- corneal thickness (50 MHz) is 502 and 504 µm in OD and
torefractive keratectomy (PRK) since it is performed in OS, respectively.
18 CHAPTER 2

Figure 2-4. Case 1: PentacamAnterior Sagittal (or Axial) fromboth eyes usingAbsolute Klyce-Smolek Scale. Asymmetric bowtie pattern, suggestingkeratoconus.

Figure 2-5. Case 1: Stable corneal topography (Placido, Axial) from 2002 to Figure 2-6. Case 1: Stable corneal topography (Placido, Axial) from 2002 to
2008 in OD. 2008 in OS.

The topographic findings, along with a thin cornea, nus. This case illustrates the opportunity for enhanced
represent characteristics of subclinical forms (or forme specificity of the screening process taking into consider-
fruste) of keratoconus45,46 and are seen in less than 1% in ation the biomechanical and tomographic data based on
normal eyes.47 However, based on uncorrected visual acu- thickness profiles. ORA exam was first performed when
ity (UCVA) of 20/15, normal ocular health upon examina- the subject was 33, and results are listed in Table 2-1. ORA
tion, and documented topographic stability since 2002 (see normal signal demonstrates nice peak amplitudes without
Figures 2-5 and 2-6), this patient does not have keratoco- a second hump after P2 in any exam (Figure 2-7).
 CLINICAL BIOMECHANICS AND THE OCULAR RESPONSE ANALYZER IN ECTATIC DISEASE 19

TAB LE 2 -1

O RA FINDING S FO R CASE 1
O RA FINDING OD OS
CH 12.1 m m Hg 10.2 m m Hg
C RF 11.4 m m Hg 10.1 m m Hg
IO Pg 14.2 m m Hg 13.1 m m Hg
IO Pc c 14.9 m m Hg 15.6 m m Hg

Figure 2-7. Case 1: ORAreadings are normal.

Figure 2-8. Case 1: Pentacam corneal thickness distribu-

tion is within normal limits in both eyes.

Similar values were obtained from repeated exams in

2007 and 2008. Interestingly, corneal thickness spatial pro-
Case 2: Natural Ectasia Development
file (CTSP) and percentage of thickness increase (PTI) 48 From “Innocent” Topography
graphs from Pentacam (Oculus, Wetzlar, Germany) also A 16-year-old man presented for a general eye exam in
demonstrate a normal pattern, similar to the mean of the 2004 complaining of ocular itching and poor vision. UCVA
values for the thickness distribution in the normal popula- was 20/200 in both eyes. Best spectacle corrected visual
tion in both eyes (Figure 2-8). Considering the data from acuity (BSCVA) was 20/20+ in both eyes with –1.75 –0.50
biomechanical and tomographic approaches, this case x 156° OD and –2.00 –0.50 x 9° OS. Patient had a history
represents a thin cornea with normal biomechanical prop- of atopic disease, and clinical exam demonstrates symp-
erties. There is no ectasia despite the abnormal curvature toms of eye rubbing. Clinical signs included mild papillae
findings. indicating allergic conjunctivitis. Corneal topography was
performed (Figures 2-9 and 2-10), demonstrating normal
corneal asphericity and mild with-the-rule corneal astig-
matism with regular bowtie in both eyes. Ultrasound cen-
20 CHAPTER 2

Figure 2-9. Case 2: Placido (Axial) topography in 2004 and 2008. Normal Figure 2-10. Case 2: Unstable corneal topography (Placido, Axial) from 2004
corneal asphericityand mild with-the-rule corneal astigmatismwith a regular to 2008 in OS.
bowtie pattern.

in each eye (see Table 2-2). Subclinical keratoconus was

tral corneal thickness (50 MHz) was 520 and 513 µm in OD diagnosed, and the patient was counseled about the risk of
and OS, respectively. Glasses were prescribed along with eye rubbing for the progression of the disease. Therapy to
anti-allergic medications, which resolved the symptoms improve control of allergic conjunctivitis was also initiated.
within 6 weeks. If the patient had been evaluated for elective surgical
Patient returned for follow-up in 2006, when placido correction in 2006, this patient would have qualified as a
topography, Pentacam and ORA exams were performed. proper candidate for LASIK based on age, level of myopia,
Anterior axial curvature maps from corneal topography low variation in refraction, central corneal thickness, and
demonstrate normal patterns using both placido and surface curvature topographic maps. The Randleman score
Scheimpflug imaging. In both eyes, less than 1 D of simu- for keratoectasia would have been 3 in both eyes (due to
lated keratometric astigmatism is noted, and less than 1 age).49 Interestingly, in the exam from 2006, ORA bio-
D of superior/inferior asymmetry is identified. Maximal mechanical data already revealed a suspicious pattern for
K is 45.6 and 45.8 D in OD and OS, respectively (Figure ectasia in both eyes based on signal analysis and relatively
2-11). ORA exam was first performed at this visit when low CRF. These data, along with the average progression of
the patient was 18, and results are listed in Table 2-2. ORA thickness index of 1.2, a borderline PTI graph, a more than
signal demonstrates relatively low peak amplitudes with a 10-µm difference from the thinnest point, and the central
second hump after P2 in all exams taken (Figure 2-12). cornea with more than 1 mm of distance between these
Central corneal thickness (50MHz) was 514 and 513 µm points, lead us to recognize ectasia susceptibility in the
in OD and OS, respectively. Interestingly, corneal thickness left eye. This is a good example of the enhanced sensitivity
spatial profile (CTSP) and percentage of thickness increase based on biomechanical and tomographic approaches for
(PTI) graphs from Pentacam demonstrate a suspicious screening for ectasia. The need for such sensitivity is well
pattern of thickness distribution in the left eye (Figure 2- argued in the literature, considering the cases with “unex-
13). BSCVA was 20/20+ in both eyes with manifest refrac- plained” ectasia following LASIK.50,51
tion of –2.25 –0.50 x 156° OD and –2.25 –0.50 x 179° OS.
Adjustments in prescription for glasses were taken, and soft Case 3: Asymmetric Keratoconus
contact lens fit was performed for both eyes.
In 2008, patient returned for follow-up at age 20. He com-
(Not “Unilateral”)
plained of worsening of vision and contact lens intolerance A 20-year-old man presented for a second opinion regard-
due to symptoms related to allergic conjunctivitis. Manifest ing a diagnosis of ectasia. The patient complained of severe
refraction evidenced myopic progression to –3.00 –0.50 x eye itching and poor vision in both eyes. UCVA was 20/80
162° OD and –3.50 –0.75 x 179° OS. Placido corneal topogra- OD, and corrected to 20/20-1 using +0.25 –3.25 x 79°. UCVA
phy along with tomography revealed a progressive pattern of was 20/200 OS, which improved to 20/15 when corrected
ectasia in both eyes, greater in the left eye. Subtraction axial with –1.00 –0.50 x 126°. Slit-lamp corneal exam revealed
topography map demonstrated increased inferior steepening prominent corneal nerves in the mid-stroma in both eyes.
between 2004 and 2008 in OS (see Figure 2-10). Placido corneal topography findings were similar to
ORA was repeated, and a slight reduction was found those found using Pentacam corneal tomography (Figure
 CLINICAL BIOMECHANICS AND THE OCULAR RESPONSE ANALYZER IN ECTATIC DISEASE 21

Figure 2-11. Case 2: PentacamAnterior Sagittal (or Axial) fromboth eyes using Absolute Klyce-Smolek Scale. Normal corneal asphericityin 2006.

TAB LE 2 -2

SERIAL O RA FINDING S FO R CASE 2

O RA FINDING :
AG E 18 OD OS
CH 10.0 m m Hg 9.0 m m Hg
C RF 8.9 m m Hg 8.0 m m Hg

O RA FINDING :
AG E 20 OD OS
CH 9.4 m m Hg 8.8 m m Hg
C RF 8.7 m m Hg 7.7 m m Hg

2-14). Asymmetry was noted between the two eyes, with

greater inferior steepening OD. While OD had typical
findings of keratoconus, the corneal surface curvature map
from OS was within normal limits with normal prolate
asphericity and mild with-the-rule regular astigmatism.
ORA findings are listed in Table 2-3. ORA signal dem-
onstrates low peak amplitudes with a second hump after P2
in all exams taken (Figure 2-15). Figure 2-12. ORAsignal demonstrates relatively lowpeak amplitudes with a
second hump after P2 in all exams.
22 CHAPTER 2

Figure 2-13. Case 2: Pentacam Corneal Thickness distri-

bution demonstrating abnormal profile OSin 2006.

Figure 2-14. Case 3: PentacamAnterior Sagittal (or Axial) fromboth eyes using Absolute Klyce-Smolek Scale. Asymmetric (“unilateral”) keratoconus .

Ultrasound central corneal thickness (50 MHz) was 511 mean of a normal population, these findings demonstrate
and 533 µm in OD and OS, respectively. Average progres- abnormal thickness distribution in both eyes.
sion of thickness index was 1.4 OD, 1.3 OS falling outside Keratoconus is, by definition, a bilateral progressive
the 95% CI limits in both eyes for the CTSP and PTI. Also, disease, characterized by corneal thinning and anterior
a distance greater than 1 mm existed between the thin- bulging due to abnormal corneal structure.45 Corneal
nest point and apex in both eyes (Figure 2-16). Despite the topography was typical of keratoconus in the right eye,
central thickness within one standard deviation from the suggesting that curvature mapping enables early diagno-
 CLINICAL BIOMECHANICS AND THE OCULAR RESPONSE ANALYZER IN ECTATIC DISEASE 23

TAB LE 2 -3

O RA FINDING S FO R CASE 3
O RA FINDING :
AG E 18 OD OS
CH 8.9 m m Hg 8.8 m m Hg
C RF 7.5 m m Hg 7.6 m m Hg
IO Pg 10.6 m m Hg 10.2 m m Hg
IO Pc c 13.0 m m Hg 13.5 m m Hg

Figure 2-15. Case 3: ORAsignal demonstrates low peak amplitudes with a

second hump after P2 in all exams.

Figure 2-16. Case 3: Pentacamcorneal thickness distribu-

tion with abnormal profile in both eyes, demonstrating
that in OS, despite a normal surface curvature map,
ecasia pattern is present. Average progression of thick-
ness index: 1.4 OD, 1.3 OS, and the PTI curves fall outside
the 95% CI limits in both eyes. More than 1 mm of
distance existed between the thinnest point and apex
in both eyes.

sis of the disease before corneal biomicroscopic changes hydrops about 6 months prior to examination. UCVA was
and reduction in BSCVA.52 Using the ORA and thickness counting fingers at 2 meters in both eyes. Thinning of both
profiles, subtle signs were found OS that exhibited normal corneas and a central scar was noted upon biomicroscopy.
topography. The low biomechanical parameters, along with Placido surface topography was not possible due to very
the abnormal thickness distribution in the left eye, make severe irregularity and scarring compromising the corneal
this a good example of the enhanced sensitivity to detect reflex, but Pentacam tomography was possible due to the
ectasia by the corneal biomechanics and tomography. Scheimpflug slit projection photography. More than 70 D
of curvature was noted in both eyes with more than 7 D of
Case 4: Advanced Keratoconus delta simulated keratometry (Figure 2-17). Corneal thick-
ness profiles were typical of severe thinning in both eyes
A 21-year-old man was referred for corneal surgery due (Figure 2-18), and Scheimpflug image also demonstrated
to advanced keratoconus in both eyes. The patient was the same (Figure 2-19).
diagnosed at age 12 and reported contact lens intolerance ORA results are listed in Table 2-4. Exam demonstrated
that was greater in the left eye after an episode of corneal very low peak amplitudes OD (Figure 2-20) and low peak
24 CHAPTER 2

Figure 2-17. Case 4: PentacamAnterior Sagittal (or Axial) fromboth eyes using Absolute Klyce-Smolek Scale. Advanced keratoconus.

Figure 2-18. Case 4: Thickness profiles in advanced keratoconus.

 CLINICAL BIOMECHANICS AND THE OCULAR RESPONSE ANALYZER IN ECTATIC DISEASE 25

Figure 2-20. Case 4: ORAresults in advanced keratoconus, OD.

Figure 2-19. Case 4: Thickness profiles in advanced keratoconus.

TAB LE 2 - 4

O RA FINDING S FO R CASE 4
O RA FINDING :
AG E 18 OD OS
CH 4.3 m m Hg 9.0 m m Hg
C RF 3.1 m m Hg 8.4 m m Hg Figure 2-21. Case 4: ORAresults in advanced keratoconus, OS.
IO Pg 7.6 m m Hg 12.2 m m Hg
IO Pc c 14.2 m m Hg 15.3 m m Hg
ments without considering 1) how the measurements are
obtained, 2) how the measurements may or may not relate
to classical biomechanical constructs like elasticity, and 3)
amplitudes OS (Figure 2-21). The second hump after P2 was what variables may affect the measurement.
noted in the majority of the exams taken. Corneal trans- Based on this understanding, terms such as “viscous
plant was scheduled for the left eye, which was performed damping” or “stress damping capacity” are perhaps more
with success. accurate descriptors of what CH measures than “stiffness,
Despite the higher CH and CRF OS, the analysis of sig- elasticity, or rigidity.” Elasticity and stiffness are reciprocol
nal amplitudes demonstrated a pattern of advanced kera- expressions of the elastic modulus, a property very dif-
toconus. Objective analysis of the signal is an important ferent from hysteresis that does not account for viscous
development for such technology. The effect of scarring behavior as described earlier in this chapter. A high elastic
associated with corneal hydrops upon corneal biomechani- modulus indicates a steep stress versus strain relation-
cal properties and resulting ORA exam are not well under- ship characteristic of stiff materials; a low modulus has a
stood and require further investigation. smaller slope and represents a more extensible material.
Although the ORA does provide a measurable stress and
indicates the temporal point of applanation relative to this
CLINICAL INTERPRETATION pressure function, the lack of a direct measure of strain
OF THE OCULAR RESPONSE complicates the calculation of a traditional modulus of
elasticity. Alternatively, the word rigidity invokes specific
ANALYZER definitions of ocular compliance in the biomechanics lit-
erature15 and should be avoided as a substitute term for
Efforts to express the output of the ORA in standard corneal hysteresis. The use of expressions such as “more
parlance with terms like “rigidity,” “stiffness,” or “elastic- viscoelastic” for high CH and “less viscoelastic” for low CH
ity” have led to some confusion regarding what is measured are not meaningful. The word viscoelastic describes a con-
and how to describe what is measured. A posture of caution tinuum of mixed viscous and elastic properties, not a single
is appropriate when extrapolating the ORA’s measure- property that can be characterized as high or low.
26 CHAPTER 2

differences in the global ocular biomechanics of glaucoma-

TAB LE 2 -5
tous eyes. In other applications, it is not clear whether axial
RISK FAC TO RS FO R EC TASIA IN bending behavior is the most relevant variable of interest;
even so, signficant differences between keratoconic and
REFRAC TIVE SURG ERY CANDIDATES
normal eyes have been demonstrated,35 and CH values are
• Pre o p e ra tive c e n tra l c o rn e a l th ic kn e ss: signficantly lower after keratorefractive surgery.31
<500 µm One of the major challenges in using the ORA as a diag-
nostic aid in refractive surgery screening is the considerable
• Re sid u a l stro m a l th ic kn e ss: <250
overlap of CH values in normal patients and patients with
• Ag e : <25 clinically evident keratoconus. Binder has performed a ret-
• Atte m p te d c o rre c tio n : > –8 D rospective analysis of presumed ectasia risk in 9,700 myo-
pic LASIK patients.56 Although several hundred patients
• Me a n ke ra to m e try: >47 D were identified with one risk factor for ectasia and another
• Re fra c tive a stig m a tism a g a in st-th e -ru le o r 7 with multiple risk factors (Table 2-5), only 3 patients
o b liq u e : >2 D developed ectasia, and none were in the at-risk group. The
study underscores our need for more sensitive and specific
Ad a p te d fro m Bin d e r PS. An a lysis o f e c ta sia a fte r la se r in indicators of ectasia risk. While there is great hope that
situ ke ra to m ile u sis: risk fa c to rs. J C a ta ra c t Re fra c t Su rg . 20 07; measures of intrinsic biomechanical properties will ulti-
33(9):1530 -1538.
mately fill this need, particularly in subclinical cases, CH
has not proven to be superior to central corneal thickness
as a predictor of keratoconus in one study.35
Awareness of test conditions that affect the measurement It is possible that hysteresis as measured by the ORA’s
of P1 and P2 are important in interpreting corneal hyster- axial stressor is not consistently lower in clinically evident
esis. Because the applanation endpoint relies on a specular keratoconus and that other perturbations could be more
reflection from the central cornea, severe tear film distur- informative of frank and preclinical disease. The waveform
bances might affect the quality, magnitude, or repeatability may carry more robust information related to ectasia risk
of the applanation signal.53 Hysteresis is dependent upon that has yet to be mined through signal analysis. Finally, it
the type, time course, and magnitude of the perturbation, is possible that the ORA’s central corneal analysis reduces
and the impact of variable air pressure is being investi- its sensitivity to the heterogenous and often eccentric
gated both as a source of error and as a means of eliciting manifestations of keratoconus. Under-representation of
additional biomechanical information from the ORA.54 abnormalities outside the central cornea might also explain
Indicators like CH that are derived from more complex the disturbing overlap of hysteresis values of keratoconic
signals are essential for practical clinical use, yet important and non-ectatic post-LASIK eyes: here, the insult of myopic
qualitative characteristics of the signal can be overlooked. LASIK is predominantly central and perhaps more fully
The value of exploring other features of the ORA signal has represented than the biomechanical abnormalities of eyes
been recognized, and active efforts to derive more informa- with paracentral or peripheral cones. These are exciting
tion at the signal analysis level are underway. challenges that would not exist without a clinical method
Ultimately, the success of corneal hysteresis and other for biomechanical property measurement, and their solu-
biomechanical variables depends on evidence of their util- tions are increasingly within our reach.
ity for detecting disease and guiding clinical management.
Several groups are pursuing such questions in earnest.
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28 CHAPTER 2

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mechanical parameters as a function of peak applied pressure in factors. J Cataract Refract Surg. 2007;33(9):1530-1538.
the Reichert Ocular Response Analyzer. Invest Ophthalmol Vis Sci.
2007:ARVO E-abstract 1247. Financial Disclosure: Dr. Dupps is a NIH grant recipient from Research to
Prevent Blindness.
 SECTI ON I I

Keratoconus
and Keratoectasia
 CHAP TER 3

Clinical Characteristics of
Keratoconus

Stephen S. Khachikian, MD, and Michael W. Belin, MD, FACS

K
eratoconus is a non-inflammatory thinning disor- agent and pressure patching was also employed to hasten
der in which the cornea assumes a conical shape.1,2 healing, further flatten the cornea, and sharpen images.
Earliest references to the disorder are attributed to In 1888, a less invasive approach to treatment was intro-
the Benedict Duddell in 1729, when he described a patient duced by Eugene Kalt, a French physician.7 Kalt fabricated
with protruding conical corneas and associated poor a glass scleral shell to be used as a contact lens in patients
vision. The German anatomist and surgeon, Burchard with keratoconus. This early contact lens improved vision
Mauchart, provided a slightly more detailed account of the by flattening the cornea and reducing astigmatism. These
condition in 1748.3 Mauchart presented an early descrip- lenses were a vast improvement over glasses and the
tion of a case of likely keratoconus, which he called staphy- stenopeic slit, which only marginally improved vision in
loma diaphanum. advanced disease.
The disorder was described in much greater detail by Early gross descriptions of keratoconus were limit-
British physician John Nottingham in 1854 in his book ed in their ability to effectively classify the condition.
Practical Observations on Conical Cornea: And On the Keratoconus was initially broadly defined based on the
Short Sight, and Other Defects of Vision Connected With It.4 shape and location of the cone. These included round, or
Nottingham provided a meticulous account of the clinical nipple cones, with a central conical protrusion, and oval
signs of a conical cornea with thinning, protrusion, and cones, often with inferior sagging and projection. Amsler’s
weakness. This was the first time that the condition (later studies in the early 20th century contributed greatly to the
termed keratoconus) was described as a single entity unique clinical detection of the disease. Amsler used a Placido’s
from other ectatic diseases with similar findings. In 1859, disk to classify early keratoconus into keratoconus fruste
Sir William Bowman, an English surgeon, expanded on and mild keratoconus (Figure 3-1).2,8 These classifications
the condition when he described the use of the retinoscope were based on the deviation of horizontal axis symmetry
and the retinoscopic reflex to further classify keratoconus.5 from the normal. A 1- to 4-degree deviation was labeled
Bowman’s work described the technique of pulling the iris keratoconus fruste and a 4- to 8-degree deviation was
into a slit configuration (stenopeic slit) to improve vision in early or mild keratoconus. In 1980, Perry further classi-
patients with keratoconus. fied advanced cones using histopathological evaluation.
The disorder received its current name “keratoconus” He noted that nipple-shaped cones are typically limited in
when Johann Horner wrote a thesis entitled “Treatment of diameter and have a center mostly in the lower nasal quad-
Keratoconus.”6 The accepted management of keratoconus at rant, while oval or sagging cones are larger and more com-
that time was one ascribed to a fellow German ophthalmolo- monly in the inferotemporal quadrant close to the periph-
gist, Albrecht von Graefe. This treatment technique used ery.9 Perry found that the oval cone is usually associated
silver nitrate to scar the cornea, changing the shape to reduce with a higher incidence of corneal hydrops, with increased
corneal steepening and thereby improve vision. A miotic scarring and greater difficulty in fitting contact lenses.

Wang M, ed.
Keratoconus & Keratoectasia: Prevention, Diagnosis, and Treatment (pp.33–41) 33
© 2010 SLACK Incorporated
34 CHAPTER 3

Figure 3-2. Videokeratoscopic anterior curvature image of a keratoectasia in

a patient who underwent LASIKfor high myopia, followed byan enhancement
for what was thought to be regression. (Courtesyof TracySwartz, OD, MS.)
Figure 3-1. Placido disk. By evaluating the reflection of the Placido rings on
the cornea, the examiner can assess topographic abnormalities and deter-
mine the amount of astigmatism.
EPIDEMIOLOGY
While using the Placido disk to define keratoconus was
As the detection of keratoconus has been enhanced over
a major advancement, there were limitations to this tech-
the past 20 years by computer imaging, the incidence and
nique. One issue encountered is that in order to produce
prevalence have also been affected. The current reports on
an obviously distorted image on Placido topography, the
prevalence of keratoconus vary greatly between 50 and 203
cornea must be quite distorted itself. If the irregularity is
per 100,000 people in the general population.1,2,19-22 The
only minor, while it may have a drastic effect on a patient’s
vision, it is not likely to be visible by gross inspection of the incidence is about 50 per 100,000, although this is equally
reflected image. It is generally accepted that astigmatism variable. This variation is likely largely dependent on the
of at least 3 diopters (D) must be present to be detected by criteria used to establish the diagnosis. Keratoconus is
traditional keratoscopy.10 More recently, the descriptions diagnosed in all ethnicities, and it is generally accepted that
of keratoconic patterns are dependent on Placido-based males and females are equally affected. It should be noted,
videokeratography and the use of various indices to define however, that 2 major cohort studies suggest that there may
the severity of the disease process, including those by be a slight preponderance of the condition in males.23-25
Rabinowitz and colleagues and Madea and colleagues.11,12 The onset of keratoconus typically begins at puberty and
The union of computer analysis and digital video by undergoes variable progression until the third or fourth
Klyce in 1984 transformed the gross examination of the decade. Many people, however, only develop refractive error
cornea by incorporating computer imaging.13 The first early in the disease course, and so, in the absence of other signs
color-coded map of corneal curvature (Figure 3-2) was or symptoms, the diagnosis of keratoconus is often delayed. It
published in 1987 and led to multiple commercially avail- may not be until the late second or early third decade that a
able computerized videokeratoscopes.14 Computerized change in the examination or vision prompts further evalua-
videokeratoscopes are capable of digitizing information tion. Often, the patient can no longer be refracted to 20/20, or
from thousands of points on the corneal surface to produce clinically detectable anatomic signs suggestive of keratoconus
detailed color-coded maps depicting corneal curvature. develop. Rarely, slowed disease progression may delay the
Videokeratoscopy has become an essential clinical tool for diagnosis even further. Fewer than 10% of patients are diag-
assessing corneal anatomy and has allowed the identifica- nosed after 40 years of age, and progression of the disease will
tion of more subtle changes in corneal curvature. often slow by the fourth decade.25-27
More recently, elevation-based topographic devices have Keratoconus is considered a bilateral condition although
been used to characterize the condition and have been useful asymmetry is very common. A patient may have clinical
in detecting false-positive curvature findings and detect- signs of the disease and reduced best spectacle-corrected
ing early disease.15-17 These devices have the advantage of visual acuity (BSCVA) in one eye, with only limited topo-
assessing both the anterior and posterior changes on the cor- graphic evidence of keratoconus in the fellow eye (Figure
neal surface and providing a pachymetric map (Figure 3-3). 3-4). The reason for this asymmetry is poorly understood.
Because progressive corneal thinning is the main pathogenic The use of videokeratography has enhanced our ability
mechanism of ectatic conditions, elevation topography may to detect subtle disease, however, this has also led to an
provide greater sensitivity in the detection of the disease and increasing number of patients with only subtle changes in
allow a more detailed classification of keratoconus.18 one eye and no topographic findings in the other.28,29 The
 CLINICAL CHARACTERISTICS OF KERATOCONUS 35

Figure 3-3. PentacamScheimpflug topographydisplayof a patient with keratoconus showing anterior curvature, anterior and posterior elevation and pachym-
etrymaps.

A B

Figure 3-4. Four-viewcomposite maps of a patient with asymmetric keratoconus. Mild inferior steepening in the right eye demonstrates early keratoconus (A)
while more severe disease is seen in the opposite eye (B).

findings make the diagnosis of true keratoconus difficult. error undergo topographic analysis, and irregularities are
Marked asymmetry in the disease process appears to be noted on curvature or elevation maps.
more common because of the increase in refractive surgery Although keratoconus has been documented in patients
screening where “normal” patients with simple refractive in conjunction with numerous ocular and systemic dis-
36 CHAPTER 3

Figure 3-5. Slit-lamp photograph of a patient with keratoconus showing cor- Figure 3-6. Slit-lamp photograph of a patient with hydrops. Note the corneal
neal thinning and an anterior stromal scar. edema and large epithelial bulla resulting froma sudden break in Descemet’s
membrane. This condition often presents with acute pain and decreased
vision.
eases, there are few accepted associations. These include
eye rubbing, atopy, Down syndrome, Leber’s congenital
striations in Descemet’s membrane and the deep stroma.
amaurosis, retinitis pigmentosa, Marfan Syndrome, and
These are known as Vogt’s striae and are corneal stress lines
mitral valve prolapse.30 Certain aspects of these conditions
that parallel the axis of the cone.1,2,31,32 These lines are
do overlap, with eye rubbing being associated with Down
induced by the corneal protrusion in the area of the cone
syndrome and atopy, and connective tissue defects linking
and can temporarily resolve with gentle limbal pressure.
keratoconus with Marfan syndrome and mitral valve pro-
Also associated with keratoconus are prominent, more vis-
lapse. Overwhelmingly, however, keratoconus is found as a
ible corneal nerves. While Fleisher’s ring, Vogt’s striae, and
sporadic condition without any other associated process.
prominent corneal nerves are common slit-lamp findings,
there may be findings suggestive of early keratoconus on
CLINICAL PRESENTATION ophthalmoscopy or retinoscopy as well. Ophthalmoscopy
can show the outline of the early cone as an oil droplet
against the background red reflex of the fundus. This is
The symptoms of keratoconus are highly variable, rang- known as the Charleaux “oil droplet” sign. Retinoscopy on
ing from refractive error due to moderate astigmatism, to a patient with early keratoconus may show scissoring of the
severely distorted vision and reduced BSCVA. Monocular reflex as the light passes over the pupil.
polyopia, or multiple ghost images, are a common com- As patients develop more moderate keratoconus, they are
plaint. Other symptoms such as subjective blurred vision, often found to have central scars (Figure 3-5). Anterior stro-
despite 20/20 Snellen acuity, and unexplained light sen- mal scars developing independently or secondary to rigid
sitivity have also been documented.23 Often, frequent contact lens wear can be seen. In advanced disease, an acute
changes in refractive error or inability to adequately fit presentation of corneal hydrops (Figure 3-6) is also not
contact lenses leads to topographic testing, which reveals uncommon. In these cases, patients with severe keratoconus
the diagnosis. Many times, the patient has been treated present with an acute episode of pain, blurred vision, and
for “high astigmatism” and subjectively reduced vision light sensitivity. On exam, there is diffuse corneal haze due
because early in the disease process the clinical signs were to edema in the area of the cone. This is caused by breaks in
not readily apparent. Descemet’s membrane leading to the profound edema along
The most frequently noted slit-lamp sign of keratoco- with epithelial disruption. Treatment with topical hyper-
nus is a Fleischer’s ring.23 First described in 1906, this is tonic saline and aqueous suppressants can often control the
epithelial deposition of the iron oxide hemosiderin in a condition, and, over time, the cornea will scar.
line or circle surrounding the cone and is thought to occur Also commonly noted in advanced cases of keratoconus
because of an irregular tear film over the cornea in this is Munson’s sign.33 In patients with Munson’s sign, when
area.31 The ring can be seen even if the corneal thinning the keratoconic eye is in down gaze, there is a change in the
and conical shape are not readily apparent. The use of the normal arc of the lower lid. Rather than seeing a smooth
cobalt blue filter can also highlight the finding. Another arc of the lid over the corneal surface, the lid is peaked in
common slit-lamp sign is the appearance of fine vertical a V-shaped pattern as it passes over the cone of the cornea.
 CLINICAL CHARACTERISTICS OF KERATOCONUS 37

Rizzuti’s sign, also in advanced keratoconus, is seen when genes known to code for collagen have been evaluated.
a conical reflection is created on the nasal cornea when a Collagen gene COL6A1 has been excluded as the gene caus-
penlight is shone from the temporal side.34 ing keratoconus in one family with multiple generations of
As keratoconus is progressive, bilateral, and asymmet- the disease. Subsequent work has excluded multiple other
ric, a patient with the disease may have all or none of these collagen genes as a cause of keratoconus in a single fam-
findings in either eye. This is, in part, due to the hetero- ily.42 Mutations in genes COL8A1 and COL8A2, which
geneous nature of the keratoconus corneas and the likely code for the alpha 1 and alpha 2 chains of type 8 collagen,
multifactorial nature of the disease. were also investigated because they have been shown, in
animal models, to cause structural changes in the anterior
Family Studies segment of the eye. These genes are associated with corneal
protrusion similar to that of keratoglobus in mice. When
While the most common presentation for keratoconus these genes were screened in multiple human patients with
is sporadic, a positive family history has been documented keratoconus and keratoglobus, however, no pathogenic
in 8% to 11% of patients.1,2 Dominant genetic heredity mutations were found.43
was first noted in 1969 when transmission of keratoconus More recent reports looking at target genes and an
was found to occur over 2 generations.35 Current literature analysis of mutations leading to keratoconus led to the
suggests an autosomal dominant form of the disorder, investigation of a visual system homeobox 1 gene (VSX1).
with variable phenotypic expression.2,35 Other heritance This is a known genetic marker for posterior polymor-
patterns, including autosomal recessive and sex-linked phous dystrophy and may also be linked to keratoconus.
transmission have been reported.36 There is no exact heri- Investigations to this point suggest that the VSX1 gene
tance pattern ascribed to the different cone morphologies, mutations are not pathogenic mutations leading to kera-
rates of progression, or severity of symptoms in the disease. toconus.44 It is encouraging, however, that gene linkage
Improved sensitivity of videokeratoscopy for detecting analysis on pedigrees with familial keratoconus have iden-
form fruste keratoconus patterns may increase the per- tified multiple loci for susceptible genes warranting further
centage of those with a positive family history. Still, many investigation.45-49
patients and family members who are asymptomatic with Twin studies in keratoconus are limited; however, there
the condition may go undetected, and those with only high are reports of monozygotic twins discordant for kerato-
astigmatism are difficult to classify in terms of heritabil- conus.49 Many of these reports either lack modern video-
ity and penetrance. In familial studies, when assessing the keratoscopy or report patients who may still develop kera-
topography of family members of patients with keratoco- toconus given their young age at the time of presentation.
nus, up to 50% of family members have been shown to have There is evidence, however, that videokeratoscopy in the
some level of topographic abnormality.37 Additional stud- twin without clinical evidence of keratoconus will show
ies looking at parents of those with keratoconus showed topographic changes consistent with the disease.50 In addi-
that in 58% of parents, abnormalities in topographic tion, studies evaluating the genetic identity and process of
indices for keratoconus can be found.38 Reports of kerato- twinning suggest that even though there are monozygotic
conus occurring in multiple generations of family members twins with discordance for keratoconus, this does not limit
have also been described.1,35-37 While this provides strong the possibility of a predominantly genetic component.49
evidence to the heritability component of keratoconus,
environmental effects have not been accounted for in these
and other studies. RECURRENCE IN THE GRAFT
Although keratoconus has associations with certain
genetic conditions such as Down Syndrome (chromosome While the definitive treatment for keratoconus is pen-
21) and Leber’s congenital amaurosis (chromosome 17), the etrating keratoplasty (PKP), keratoconus has been reported
inciting genetic abnormality that leads to keratoconus has to occur after PKP in many studies. First reported by
yet to be determined. Along those lines, studies have been Abelson in 1980, examination of the cornea with recurrent
done to assess abnormalities on chromosome 21 in patients keratoconus revealed histopathological evidence of the
with keratoconus. While a gene locus thought to be linked disease including apical thinning and breaks in Bowman’s
to keratoconus was identified on chromosome 21, no major layer.51 The cause for this recurrence remains unknown and
genes are currently known at that site.39,40 Similar inves- may be due to host factors, donor factors, or both. Whether
tigations have been made looking into chromosome 17 in environmental, mechanical, metabolic, or genetic, the fac-
patients with LCA but no pathogenic mutations leading to tors leading to keratoconus in the host are unlikely to be
keratoconus have been detected.41 altered by corneal grafting. The host tissue will repopulate
As keratoconus has been associated with other dis- the donor cornea over time, and any genetic or biochemi-
orders of collagen such as mitral valve prolapse, Ehlers- cal predisposition that the host has for keratoconus may be
Danlos and osteogenesis imperfecta, abnormalities on transferred to the donor graft. Atopy, eye rubbing, or envi-
38 CHAPTER 3

A B

Figure 3-7. (A) Slit-lamp photograph of a patient with pellucid marginal degen-
eration. Note the inferior band of corneal thinning and the superior corneal
flattening. (B) Four-viewcomposite map of a patient with keratoconus. Despite
the “crab claw” curvature map, the thinnest portion of the cornea is clearly
central rather than peripheral, and the anterior and posterior elevation maps
show a central island of elevation consistent with keratoconus. (C) Four-view C
composite map of a patient with pellucid marginal degeneration. The curvature
map shows the traditional vertical flattening, the thinnest portion of the cornea
is peripheral, and the anterior and posterior elevation maps showa steepening
of the inferior cornea as it falls belowthe best fit sphere.

ronmental influences affecting the host may not change toconus at the time of surgery. Fewer studies suggest this
significantly after transplantation. mechanism of recurrence, but cases where fellow eyes of a
Post-keratoplasty, the topography of the host may donor are grafted into hosts without keratoconus, and the
remain irregular even years after corneal transplant. This latter develop keratoconus make this theory more plausible.
makes identification of corneal changes indicative of Unal et al showed that fellow corneal buttons of a donor
recurrent keratoconus difficult. Disease recurrence can without keratoconus went on to manifest the disease in
easily go unrecognized on topography until an advanced the hosts after grafting.52 Krivoy et al had a similar report
stage, and there is some question as to whether grafting of keratoconus developing in a non-keratoconus patient
alone contributes to the topographic appearance over time. after grafting.53 As noted, it must also be considered that
Nevertheless, histopathologic examination of the donor performing a corneal graft alone may incite structural
button manifesting the recurrent disease has confirmed changes that lead to the development of a corneal ectasia.
the diagnosis of recurrent keratoconus.51 Additionally, a poorly centered host button that bisects the
Another possibility for recurrence of keratoconus in the host cone will leave behind cornea with a propensity for
corneal graft is previously undiagnosed keratoconus in the ectasia. This residual area on the host may go unnoticed
donor. Early keratoconus can be difficult to identify, and until many years after grafting, but would slowly become
grafted corneas from younger donors may have had kera- more ectatic over time, falsely suggesting recurrence.
 CLINICAL CHARACTERISTICS OF KERATOCONUS 39

While recurrent “secondary” keratoconus is a rare dis- clarify questionable cases.56 Careful attention to the axes of
order, there are many published and likely many unpub- vertical flattening may help distinguish the disorders.
lished reports of its occurrence. The etiology has yet to When using elevation-based topography to evaluate the
be clarified, and the treatment is the same as for primary PMD, cross-sectional anterior segment images, anterior
keratoconus. and posterior corneal topography, and corneal pachymetry
maps are generated. Accurate images of the peripheral
cornea (up to 12.0 mm) are also obtained. The peripheral
KERATOCONUS VS PELLUCID corneal steepening and thinning seen in the Scheimpflug
MARGINAL DEGENERATION images in these cases can be clearly identified. This con-
figuration, with superior corneal protrusion over inferior
Another bilateral thinning disorder of the cornea, pel- thinning located adjacent to the limbus, can be seen as
lucid marginal degeneration (PMD) is often confused with separate and unique from keratoconus.5
keratoconus. PMD is a relatively rare disorder that in its
pure form presents with a distinct clinical picture sepa-
rate from keratoconus.54,55 Classically, PMD is a bilateral, UNILATERAL KERATOCONUS
progressive, ectatic, non-inflammatory corneal disorder
involving thinning of the inferior cornea in a cresenteric Keratoconus is believed to be a bilateral condition;
pattern (Figure 3-7A).54,55 Characteristically, this thinning however, its highly variable phenotypic expression has led
occurs 1 to 3 mm from the limbus in the 4- to 8-o’clock to many cases of seemingly unilateral disease. Current
position.2 This configuration causes the cornea superior to reports, however, suggest that the frequency of unilateral
the ectasia to protrude, causing a “beer belly” configura- keratoconus is only as high as 4%.59 Improved diagnostic
tion producing a flat vertical meridian above the thinning technologies and indices have enabled us to identify sub-
with high against-the-rule astigmatism.54 Clinically, this is clinical changes in patients with clinical signs of kerato-
distinctly different from keratoconus, where the thinning conus in only one eye. Longitudinal studies by Rabinowitz
and area of conical protrusion coincide (Figures 3-7B and have shown that in those patients with clinically unilateral
C). In moderate to advanced cases of PMD, the location keratoconus, 50% will develop keratoconus in the fellow eye
of the thinning near the limbus can be differentiated on over a period of 17 years, and most of those patients (83%)
slit-lamp evaluation.56 In early cases, the clinical distinc- will develop it within 6 years.59 A great deal of research
tion between PMD and keratoconus is more difficult as the has also been done, evaluating the fellow normal eye in
cornea may appear relatively normal. Videokeratoscopy, patients with unilateral keratoconus to identify changes
Scheimpflug photography, and pachymetric mapping can that will indicate disease progression. Recently, the use of
help in these situations.57 combined elevation and pachymetry data has been used to
Similar to keratoconus, PMD patients may retain good better assess the “normal” eyes in cases of unilateral kera-
BSCVA early in the disease process and diagnosis may be toconus.60 Assessment of the posterior corneal surface and
delayed. Compared to the onset of keratoconus, the onset the change in pachymetry from the thinnest point to the
of PMD is thought to be much later in life, beginning in the periphery has been shown to reveal abnormalities in the
late second and into third decade. As PMD progresses, the “normal” fellow eyes of patients with keratoconus (Figure
corneal protrusion becomes more obvious. Unlike kera- 3-8). While there are many patients who truly appear to
toconus, however, PMD does not have associated scarring have unilateral keratoconus, it is possible that many of
(although hydrops has been reported), and striae and iron these patients have corneal topographic abnormalities that
deposition are less common.1,2 can be seen only on the posterior surface or with thorough
In advanced disease, PMD is often confused with inferior pachymetric evaluation.
keratoconus. This idea may be entrenched in attempts at
differentiating these diseases with limited diagnostic tech-
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30. Grünauer-Kloevekorn C, Duncker GI. Keratoconus: epidemi- lies. Invest Ophthalmol Vis Sci. 2002;43:3160-3164.
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626. 48. McMahon TT, Shin JA, Newlin A, Edrington TB, Sugar J, Zadnik
32. Zadnik K, Barr JT, Gordon MO, Edrington TB. Biomicroscopic K. Discordance for keratoconus in two pairs of monozygotic twins.
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965.
 CHAP TER 4

Clinical Features of Keratoectasia

J. Bradley Randleman, MD

K
eratoectasia remains a rare but feared complication an end-stage manifestation of corneal warpage that likely
of usually uneventful corneal refractive surgery. arises from a variety of causes, including patients already
Since the first reports by Seiler and colleagues in destined to develop keratoconus in their lifetime, preop-
1998,1,2 numerous authors have reported multiple patients eratively weak corneas that may not have developed kerato-
developing keratoectasia cases in case reports or small conus but have decompensated after surgical intervention,
case series.3-48 From these reports a variety of concepts and otherwise normal corneas that have been excessively
have emerged regarding the clinical, anatomical, and bio- weakened postoperatively from residual stromal bed too
mechanical corneal properties that predispose patients to thin to maintain structural integrity.
postoperative corneal weakening and warpage, and the
optical alterations induced by keratoectasia have been
evaluated. EPIDEMIOLOGY OF
KERATOECTASIA
DEFINITION
There are currently approximately 200 keratoectasia
Keratoectasia is a progressive steepening and thinning cases in the English literature. There have been incidence
of the cornea after excimer laser corneal refractive surgery estimates ranging from 0.04%29 to 0.2%36 to 0.6%17;
that reduces uncorrected visual acuity (UCVA) and often however, the actual incidence remains undetermined.
best spectacle-corrected visual acuity (BSCVA).29 This Keratoectasia has likely been under-reported recently due
steepening usually occurs inferiorly, and in eyes with pre- to the lack of novelty of repeated case reports, thus pro-
operative topographic abnormalities usually correspond- hibiting publication of each case. A 2004 survey of the
ing to the specific area of preoperative steepening. International Society of Refractive Surgery (ISRS) indicated
A variety of terms have been used to signify the develop- that up to 50% of responding members had at least one case
ment of ectatic change after excimer laser corneal refractive of ectasia in their practices.49 Further complicating accu-
surgery, including corneal ectasia, keratectasia, keratoecta- rate incidence estimations is the fact that keratoectasia can
sia, iatrogenic ectasia, keratoconus after LASIK, progressive develop many years after uneventful LASIK.50 However,
post-LASIK ectasia, and postoperative corneal ectasia. For both literature reported cases and those presenting to a
consistency throughout this chapter and book, we will use single referral institution have decreased significantly over
keratoectasia. the past 5 years,51 which may be an indication that the
Rather than representing a specific disease entity, kera- utilization of improved preoperative screening modalities
toectasia, like naturally occurring ectatic diseases such as are excluding high-risk candidates and thereby reducing
keratoconus or pellucid marginal corneal degeneration, is keratoectasia development.

Wang M, ed.
Keratoconus & Keratoectasia: Prevention, Diagnosis, and Treatment (pp.43–48) 43
© 2010 SLACK Incorporated
44 CHAPTER 4

TAB LE 4 -1

SUMMARY O F KERATO EC TASIA PATIENT DEMO G RAPHIC S

DEMO G RAPHIC AVERAG E RANG E
Ag e (ye a rs) 35 18 to 62
Se x (% m a le ) 60 %
Ma n ife st Re fra c tio n (D) -8 +5 to –24
C o rn e a l Th ic kn e ss (µm ) 520 406 to 597
Re sid u a l Stro m a l Be d (µm ) 260 170 to 419
Ab n o rm a l Pre o p e ra tive To p o g ra p h y 45%

Patient Demographics
There is great variability in the preoperative presenta-
tion of patients who develop keratoectasia (Table 4-1).
Keratoectasia patients tend to be younger, more myopic, have
thinner corneas preoperatively, lower postoperative residual
stromal bed thickness, and more frequently have abnormal
preoperative topographies as compared to patients who do
not develop ectasia.51,52 There is also a slight preponderance
of males developing keratoectasia. The significance of this
finding remains undetermined. However, there is no single
criterion that definitively predicts the development of kera-
toectasia, and cases have presented from wide ranges of the
aforementioned parameters.

Clinical Presentation
The earliest clinical manifestations of keratoectasia
can be subtle and require a high index of suspicion for
diagnosis. Most patients experience increasing myopia and
astigmatism that can be misinterpreted as simple refrac- Figure 4-1. Slit-lamp features of keratoectasia. Note the signifi-
tive regression. In these stages, topographic changes may cant corneal thinning (inferior white arrows) that has developed
also be quite subtle. Posterior float and elevation maps are after LASIK in comparison to the region with normal corneal
inherently unreliable postoperatively to determine absolute thickness (upper white arrows).
differences compared to preoperative maps; however, sig-
nificant increases in elevations noted on serial topography
after surgery may indicate early ectatic changes. Anatomy and Biomechanical
Advanced keratoectasia is clinically indistinguishable
from other corneal ectatic disease processes such as kera-
Considerations
toconus or pellucid marginal corneal degeneration. There There is still much to learn about corneal biomechani-
is usually an area of significant thinning and protrusion cal processes as they relate to the development of ectatic
that can be seen with slit-lamp biomicroscopy (Figure 4- corneal disease. Recent studies have begun to shed light
1) with corresponding topographic alterations, including on the biomechanical effects of flap creation and excimer
increasing corneal steepening and irregular astigmatism laser ablation in the normal and abnormal cornea and the
(Figure 4-2). biomechanical alterations that occur when corneas become
The onset of presentation is also highly variable. ectatic.
Approximately 25% of cases have presented by 3 months, Excimer laser ablation reduces both keratocyte density
50% by 12 months, and 80% by 2 years postoperatively;51 and corneal tensile strength.53-55 LASIK reduces overall ten-
however, cases have presented as early as 1 week and as late sile strength more than equivalent surface ablation because
as 5 years after LASIK and more than 10 years after PRK. the LASIK flap contributes minimally to postoperative
 A C B
D
CLINICAL FEATURES OF KERATOECTASIA

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46 CHAPTER 4

tensile strength.56,57 While in the unoperated cornea physi-

ologic stresses are distributed uniformly throughout the
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2004;30(12):2623-2628. Corneal Surg. 1992;8(2):139-142.
39. Seo KY, Lee JH, Kim MJ, Park JW, Chung ES, Lee YS, Kim EK. 62. Smolek MK, McCarey BE. Interlamellar adhesive strength in human
Effect of suturing on latrogenic keratectasia after laser in situ ker- eyebank corneas. Invest Ophthalmol Vis Sci. 1990;31(6):1087-1095.
atomileusis. J Refract Surg. 2004;20(1):40-45. 63. Dawson DG, Grossniklaus HE, McCarey BE, Edelhauser HF.
40. Chung SH, Im CY, Lee ES, Choi SY, Kwon YA, Kim EK. Clinical Biomechanical and wound healing characteristics of corneas after
manifestation and pathologic finding of unilateral acute hydrops excimer laser keratorefractive surgery: is there a difference between
after bilateral laser in situ keratomileusis. J Cataract Refract Surg. advanced surface ablation and sub-Bowman’s keratomileusis? J
2005;31(6):1244-1248. Refract Surg. 2008;24(1):S90-96.
41. Hiatt JA, Wachler BS, Grant C. Reversal of laser in situ keratomileu- 64. Condon PI, O’Keefe M, Binder PS. Long-term results of laser in situ
sis-induced ectasia with intraocular pressure reduction. J Cataract keratomileusis for high myopia: risk for ectasia. J Cataract Refract
Refract Surg. 2005;31(8):1652-1655. Surg. 2007;33(4):583-590.
42. Lifshitz T, Levy J, Klemperer I, Levinger S. Late bilateral keratec- 65. Rajan MS, Jaycock P, O’Brart D, Nystrom HH, Marshall J. A long-
tasia after LASIK in a low myopic patient. J Refract Surg. 2005; term study of photorefractive keratectomy; 12-year follow-up.
21(5):494-496. Ophthalmology. 2004;111(10):1813-1824.
43. Spirn MJ, Dawson DG, Rubinfeld RS, et al. Histopathological 66. Bron AJ. Keratoconus. Cornea. 1988;7(3):163-169.
analysis of post-laser-assisted in situ keratomileusis corneal ecta-
sia with intrastromal corneal ring segments. Arch Ophthalmol.
2005;123(11):1604-1607.
48 CHAPTER 4

67. Bron AJ. The architecture of the corneal stroma. Br J Ophthalmol. 71. Woodward MA, Randleman JB, Russell B, Lynn MJ, Ward MA,
2001;85(4):379-381. Stulting RD. Visual rehabilitation and outcomes for ectasia after
68. Dawson DG, Randleman JB, Grossniklaus HE, et al. Corneal ectasia corneal refractive surgery. J Cataract Refract Surg. 2008;34(3):383-
after excimer laser keratorefractive surgery: Histopathology, ultra- 388.
structure, and pathophysiology. Ophthalmology. 2008;115:2181– 72. Wollensak G. Crosslinking treatment of progressive keratoconus:
2191. new hope. Curr Opin Ophthalmol. 2006;17(4):356-360.
69. Daxer A, Fratzl P. Collagen fibril orientation in the human corneal 73. Wittig-Silva C, Whiting M, Lamoureux E, et al. A randomized con-
stroma and its implication in keratoconus. Invest Ophthalmol Vis trolled trial of corneal collagen cross-linking in progressive kerato-
Sci. 1997;38(1):121-129. conus: preliminary results. J Refract Surg. 2008;24(7):S720-S725.
70. Patey A, Savoldelli M, Pouliquen Y. Keratoconus and normal cor-
nea: a comparative study of the collagenous fibers of the corneal
stroma by image analysis. Cornea. 1984;3(2):119-124.
 CHAP TER 5

Keratoectasia
Preoperative Risk Factors and Medical and Legal Considerations

J. Bradley Randleman, MD

K
eratoectasia has been the source of much discus- further refined screening criteria,8,15-18 and epidemiologic
sion and great debate over the past few years1-7 studies evaluated topographic patterns in unilateral/asym-
due to its infrequent and often unpredictable metric keratoconus19 and established a normative database
occurrence, the possibility for delayed presentation after for placido-based topographic patterns.10 Using this infor-
seemingly uneventful corneal refractive surgery, and its mation, placido-based topographic patterns were estab-
potentially devastating visual consequences. As with most lished for screening with the Ectasia Risk Score System 14
extremely rare surgical complications such as endophthal- and were classified as follows:
mitis after cataract extraction, it is difficult to establish 1. Normal/symmetrical (includes round, oval, or sym-
definitive mechanisms for the development of keratoec- metric bowtie patterns)
tasia. Therefore, it is challenging to establish firm risk
2. Suspicious (includes the following asymmetric bowtie
factors and screening criteria for avoidance. Nevertheless,
patterns):
significant progress has been made recently in establishing
and validating certain risk factors for keratoectasia and Asymmetric bowtie
dispelling others. This chapter will delineate established a. Asymmetric steepening in any direction less
and purported risk factors for keratoectasia, including an than 1.0 diopter (D)
in-depth analysis of topographic screening criteria, and b. No skewed radial axis
provide case examples to illustrate the current state of
Inferior steep/skewed radial axis
refractive surgical screening.
a. Significant skewed radial axis with or with-
out inferior steepening
TOPOGRAPHIC EVALUATION b. 1.0 D or more of inferior steepening in some
FOR KERATOECTASIA RISK area but an I-S value of less than 1.4.
3. Abnormal (includes keratoconus, pellucid marginal
Placido-based imaging remains the mainstay of preop- corneal degeneration, or forme fruste keratoconus
erative screening, as these topographic patterns have been with an I-S value of 1.4 or greater)
well described, documented, evaluated, and validated.8-14 In addition to these placido-based patterns, there are a
Placido-based topographic features of forme fruste kera- variety of slit-beam based and Scheimpflug image-based
toconus and pellucid marginal corneal degeneration were criteria that have been purported to improve ectasia
described by Rabinowitz and McDonnell9 and Maguire screening, but these remain unvalidated in large popula-
and colleagues11 in the late 1980s. Subsequent studies tion studies.

Wang M, ed.
Keratoconus & Keratoectasia: Prevention, Diagnosis, and Treatment (pp.51–57) 51
© 2009 SLACK Incorporated
52 CHAPTER 5

TAB LE 5 -1

PURPO RTED BUT NO T VALIDATED RISK FAC TO RS FO R KERATO EC TASIA

PARAMETER VALUE

C e n tra l C o rn e a l Th ic kn e ss Ab so lu te va lu e (ie , < 500 µm )

Re sid u a l Stro m a l Be d Th ic kn e ss Ab so lu te va lu e (ie , < 250 µm )

O rb sc a n II In d ic e s Po ste rio r Flo a t Ele va tio n , a b so lu te va lu e

Po ste rio r Flo a t Ele va tio n , lo c a tio n
Irre g u la rity Zo n e va lu e s
Th in n e st p o in t/ c e n tra l c o rn e a l th ic kn e ss c o m p a riso n
Pe rip h e ra l/ c e n tra l c o rn e a l th ic kn e ss c o m p a riso n
“No rm a l Ba n d ” sc a le m e a su re m e n ts

Pe n ta c a m In d ic e s An te rio r Flo a t Ele va tio n s

Po ste rio r Flo a t Ele va tio n s

Wa ve fro n t An a lyse s

PURPORTED RISK FACTORS most significant variable; however, a large proportion of

ectasia cases had normal or only mildly asymmetric bow-
FOR KERATOECTASIA tie patterns. Thus, topographic pattern is insufficient as a
singular indicator of risk.
A variety of factors and screening modalities have been Low residual stromal bed thickness has long been con-
reported and devised to discriminate normal from at-risk sidered a risk factor for keratoectasia, and this has been
eyes (Table 5-1); however, the majority of these recom- validated through recent studies. However, keratoectasia
mendations have come from anecdotal experiences and has occurred in eyes with a wide range of RSB values,
not from well-constructed case-control studies. Some pre- signifying that reduced residual stromal bed thickness rep-
viously advocated high-risk criteria, such as preoperative resents a continuum of risk for keratoectasia, that a firm
corneal thickness less than 500 µm or residual stromal bed safety threshold does not exist, and that accurate RSB mea-
thickness less than 250 µm, have been refuted by statistical surements are critical. A residual stromal bed thickness of
analysis of reported keratoectasia cases.12-14 Many papers 250 µm has commonly been recommended as the minimal
have reported differences in a variety of slit-beam based requirement for the safe performance of LASIK; however,
and wavefront indices that may distinguish keratoconic recent analyses have concluded that this specific number
corneas from normal corneas20-23; however, the clinical has little value as a cut-off point.7,12-14
relevance of these strategies to identify abnormal corneas Young patient age was a significant factor in every recent
without clear anterior topographic abnormalities remains analysis and was the only significant differentiating charac-
undetermined. teristic between ectasia cases with and without topographic
abnormalities.14 The reason for the association between
IDENTIFIED RISK FACTORS age and keratoectasia risk is likely primarily related to the
natural incidence of keratoconus presentation and disease
FOR KERATOECTASIA progression. Although keratoconus usually manifests rela-
tively early in life, a significant proportion of individuals
Statistical analysis of 2 case-control population stud- first manifest symptoms after age 40. Because keratoconus
ies13,14 has elicited several risk factors, listed in Table 5-2 is a progressive disease, it stands to reason that some young
in order of importance. In 2 case-control analyses, more patients with initially normal topographies will eventually
than 40% of ectasia cases with available topographies had develop keratoconus at a later date, regardless of whether or
abnormal preoperative patterns, making this the single not they have refractive corneal surgery repeated.
 KERATOECTASIA: PREOPERATIVE RISK FACTORS AND MEDICAL AND LEGAL CONSIDERATIONS 53

TAB LE 5 -2
A
VALIDATED RISK FAC TO RS FO R
KERATO EC TASIA
• Ab n o rm a l p re o p e ra tive to p o g ra p h y
• Lo w re sid u a l stro m a l b e d th ic kn e ss
• Yo u n g p a tie n t a g e
• Lo w p re o p e ra tive c o rn e a l th ic kn e ss
• Hig h m yo p ia

The influence of preoperative corneal thickness on kera-

toectasia risk is a topic of great debate. In every case-con- B
trol analysis, keratoectasia cases had significantly thinner
corneas preoperatively than did controls, with an average
corneal thickness at least one standard deviation below
the average corneal thickness of the control population.
Keratoconic corneas are generally thinner than normal
corneas; therefore, low preoperative corneal thickness
could be indicative of an abnormal cornea that is destined
to develop keratoconus. Alternatively, thinner corneas
could be at higher risk for ectasia because there is a higher
probability that a thicker than expected corneal flap will
result in an extremely low RSB that does not provide suf-
ficient structural integrity to prevent ectasia.
Preoperative corneal thickness, myopia, and residual Figure 5-1. Preoperative topographic images fromCase 1.
stromal bed are somewhat inter-related variables. Eyes that
developed ectasia have been significantly more myopic than
controls in previous studies,12,14 and there are many reports multiple risk factors that have had uneventful postopera-
of ectasia developing after treatment for extreme myopia tive courses indefinitely,12,39 including a recent case report
(>–12 D).24-27 However, Condon recently reported long- of a patient with frank keratoconus that has remained
term follow-up with good stability and the absence of ectasia stable 7 years after LASIK.40 Thus, the development of
in highly myopic eyes,28 and ectasia has been reported in keratoectasia screening strategies remains a work in prog-
many patients with low myopia29-31 and hyperopia.32 Thus, ress, and while the incidence should significantly decrease,
the level of myopia may in itself be a poor predictor for ecta- keratoectasia will likely still rarely occur even when the
sia as long as surgeons avoid treating extreme myopia. most thorough screening strategies are utilized.

KERATOECTASIA RISK ANALYSIS KERATOECTASIA

Through multivariate analysis of these factors, a weight-
CASE EXAMPLES
ed risk score system, the Ectasia Risk Score System, was
developed.14 This system correctly identified more than
90% of ectasia cases as high risk and less than 5% of con-
Case 1
trols as high risk and represents a significant improvement A 32-year-old man presented for refractive surgical evalu-
over previous systems.12,14,33 However, this system is still ation. Best spectacle-corrected visual acuity (BSCVA) was
far from ideal because it cannot absolutely and completely 20/20 in both eyes with manifest refractions of –3.75 +2.75
discriminate between keratoectasia cases and controls. x 180 OD and –5.25 +5.00 x 180 OS. Preoperative corneal
Further, while our biomechanical understand- thickness was 510 µm OD and 520 µm OS. Preoperative
ing of keratoectasia has improved,34,35 there are still topographies are shown in Figure 5-1 and demonstrate
keratoectasia cases reported without any identified risk significant inferior steepening in both eyes with a “crab-
factors.13,14,30-32,36-38 There are also reports of cases with claw” topographic pattern consistent with pellucid marginal
54 CHAPTER 5

A
A

B B

Figure 5-3. Preoperative topographic images fromCase 2.

Figure 5-2. Postoperative topographic images fromCase 1.

corneal degeneration. Ablation depths and residual stromal

bed thickness were not available. The patient underwent
uneventful LASIK but subsequently developed keratoectasia
(Figure 5-2). This patient’s topographic pattern is indicative
of pellucid marginal corneal degeneration and represents
a clear contraindication to LASIK based on our current
knowledge. In patients with definitive topographic abnor-
malities, LASIK should be avoided. The safety and risk of
surface ablation in these patients has not been established.

Case 2
A 28-year-old woman presented for refractive surgical Figure 5-4. Postoperative topographic images fromCase 2.
evaluation. BSCVA was 20/20 in both eyes with manifest
refractions of –2.50 +0.50 x 005 OD and –2.75 +0.50 x 030
OS. Preoperative corneal thickness was 490 µm OD and 510 ablation depths of 64 µm OD and 70 µm OS, leaving a cal-
µm OS. Preoperative topographies are shown in Figure 5-3 culated residual stromal bed thickness of 286 µm OD and
and demonstrate an inferior steepening pattern in the right 300 µm OS. The patient underwent uneventful LASIK but
eye and forme fruste keratoconus in the left eye. Surgery subsequently developed keratoectasia (Figure 5-4). While
was performed with a 140 µm microkeratome head with the topographic abnormality is less dramatic than Case 1,
 KERATOECTASIA: PREOPERATIVE RISK FACTORS AND MEDICAL AND LEGAL CONSIDERATIONS 55

A A

B B

Figure 5-5. Preoperative topographic images fromCase 3. Figure 5-6. Postoperative topographic images fromCase 3.

this patient’s topographic pattern is also a contraindica- pattern, corneal thickness was above 500 µm, predicted
tion for LASIK and keratoectasia developed despite a low RSB was greater than 250 µm, and the manifest refraction
myopic correction. was moderate. However, there are a variety of findings that,
in aggregate, preclude her from being a good LASIK candi-
Case 3 date, including young age, low predicted residual stromal
bed thickness, borderline preoperative corneal thickness,
A 21-year-old woman presented for refractive surgical
high astigmatism, and BSCVA <20/20. Based on the Ectasia
evaluation. The patient had been diagnosed with amblyo-
Risk Score System, this patient would be considered “high
pia in the left eye by her primary eye care provider. BSCVA
risk” with a score of 5 OD and 4 OS. This case demonstrates
was 20/25 in the right eye and 20/30 in the left eye with
the utility of considering a variety of factors in a combined,
manifest refractions of –6.25 +3.50 x 090 OD and –7.75
weighted fashion when screening patients for LASIK.
+5.50 x 090 OS. Preoperative corneal thickness was 530 µm
OD and 510 µm OS. Preoperative topographies are shown
in Figure 5-5 and demonstrate symmetric bowtie patterns
in both eyes. Surgery was performed with a 160-µm micro-
MEDICAL AND LEGAL
keratome head with ablation depths of 160 µm OD and 101 CONSIDERATIONS
µm OS, leaving a calculated residual stromal bed thickness
of 269 µm OD and 285 µm OS. The patient underwent Keratoectasia has become a major focus of medico-legal
uneventful LASIK but subsequently developed keratoec- proceedings over the past few years. This focus prompted a
tasia (Figure 5-6). This patient had no single definitive consensus opinion report from a committee formed from
abnormality that precluded her from LASIK. Notably, the members of the American Academy of Ophthalmology,
patient’s preoperative topography was a symmetric bowtie the International Society of Refractive Surgery, and the
56 CHAPTER 5

American Society of Cataract and Refractive Surgery.1 5. Seiler T. Iatrogenic keratectasia: academic anxiety or serious risk? J
Among the many conclusions from this group, the consen- Cataract Refract Surg. 1999;25(10):1307-1308.
6. Rosen ES. Ectasia. J Cataract Refract Surg. 2007;33(6):931-932.
sus opinion was that there is a spectrum between clearly 7. Salz JJ, Binder PS. Is there a “magic number” to reduce the risk of
normal and clearly ectatic corneas, no specific test or mea- ectasia after laser in situ keratomileusis and photorefractive kera-
surement is diagnostic for corneal ectatic disease, kerato- tectomy? Am J Ophthalmol. 2007;144(2):284-285.
ectasia is a known complication of laser vision correction, 8. Rabinowitz YS. Videokeratographic indices to aid in screening for
and ectatic corneal disease can progress even in the absence keratoconus. J Refract Surg. 1995;11(5):371-379.
9. Rabinowitz YS, McDonnell PJ. Computer-assisted corneal topogra-
of corneal refractive surgery. Thus, the development of
phy in keratoconus. Refract Corneal Surg. 1989;5(6):400-408.
keratoectasia does not specifically mean that LASIK was 10. Rabinowitz YS, Yang H, Brickman Y, et al. Videokeratography data-
causative or contributory to the ectatic process, nor does base of normal human corneas. Br J Ophthalmol. 1996;80(7):610-
the development of keratoectasia necessarily imply that 616.
malpractice has occurred. 11. Maguire LJ, Klyce SD, McDonald MB, Kaufman HE. Corneal
topography of pellucid marginal degeneration. Ophthalmology.
As stated above, even with the most comprehensive 1987;94(5):519-524.
screening modalities currently available, there are reports 12. Randleman JB, Russell B, Ward MA, Thompson KP, Stulting
of keratoectasia developing after uneventful surgery in eyes RD. Risk factors and prognosis for corneal ectasia after LASIK.
without any risk factors.30,31,36,37 Ophthalmology. 2003;110(2):267-275.
13. Randleman JB, Trattler WB, Stulting RD. Validation of the Ectasia
Risk Score System for preoperative laser in situ keratomileusis

CONCLUSIONS 14.
screening. Am J Ophthalmol. 2008;145(5):813-818.
Randleman JB, Woodward M, Lynn MJ, Stulting RD. Risk assess-
ment for ectasia after corneal refractive surgery. Ophthalmology.
Keratoectasia is a rare but known risk of excimer laser 2008;115(1):37-50.
surgery. Currently identified risk factors include topo- 15. Klyce SD, Smolek MK, Maeda N. Keratoconus detection with the
KISA% method-another view. J Cataract Refract Surg. 2000;26(4):
graphic abnormalities, low residual stromal bed, low pre-
472-474.
operative corneal thickness, young age, and high myopia. 16. Maeda N, Klyce SD, Smolek MK. Comparison of methods for
Other factors, such as a history of eye rubbing, unstable detecting keratoconus using videokeratography. Arch Ophthalmol.
refractions, a family history of ectatic corneal disease, 1995;113(7):870-874.
and an underlying increase in corneal elasticity may also 17. Maeda N, Klyce SD, Smolek MK, Thompson HW. Automated
keratoconus screening with corneal topography analysis. Invest
be relevant to consider during refractive surgical patient
Ophthalmol Vis Sci. 1994;35(6):2749-2757.
screening. However, no single characteristic identifies 18. Smolek MK, Klyce SD, Hovis JK. The Universal Standard Scale:
all at-risk patients. Considering a variety of factors in a proposed improvements to the American National Standards
weighted fashion appears to be the most effective screen- Institute (ANSI) scale for corneal topography. Ophthalmology.
ing strategy currently available. For all patients, special 2002;109(2):361-369.
emphasis should be placed on topographic pattern analysis, 19. Rabinowitz YS, Nesburn AB, McDonnell PJ. Videokeratography
of the fellow eye in unilateral keratoconus. Ophthalmology. 1993;
and factors in addition to I-S values or computer-generated 100(2):181-186.
indices should be considered in the screening assessment. 20. Schlegel Z, Hoang-Xuan T, Gatinel D. Comparison of and cor-
For younger patients, heightened scrutiny is warranted. relation between anterior and posterior corneal elevation maps in
Further advances in our understanding of fundamen- normal eyes and keratoconus-suspect eyes. J Cataract Refract Surg.
2008;34(5):789-795.
tal corneal biomechanical and biochemical processes,
21. Nilforoushan MR, Speaker M, Marmor M, et al. Comparative eval-
especially in the development of ectatic corneal disease, uation of refractive surgery candidates with Placido topography,
advanced topographic interpretation, and routine mea- Orbscan II, Pentacam, and wavefront analysis. J Cataract Refract
surement of intraoperative residual bed thickness, should Surg. 2008;34(4):623-631.
decrease the incidence of ectasia and make LASIK an even 22. Kaya V, Utine CA, Altunsoy M, Oral D, Yilmaz OF. Evaluation
safer procedure. of corneal topography with Orbscan II in first-degree relatives of
patients with keratoconus. Cornea. 2008;27(5):531-534.
23. Sonmez B, Doan MP, Hamilton DR. Identification of scanning slit-
beam topographic parameters important in distinguishing normal
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1. Binder PS, Lindstrom RL, Stulting RD, et al. Keratoconus and cor- 24. Pallikaris IG, Kymionis GD, Astyrakakis NI. Corneal ectasia
neal ectasia after LASIK. J Cataract Refract Surg. 2005;31(11):2035- induced by laser in situ keratomileusis. J Cataract Refract Surg.
2038. 2001;27(11):1796-1802.
2. Comaish IF, Lawless MA. Progressive post-LASIK keratectasia: bio- 25. Rad AS, Jabbarvand M, Saifi N. Progressive keratectasia after laser
mechanical instability or chronic disease process? J Cataract Refract in situ keratomileusis. J Refract Surg. 2004;20(5 Suppl):S718-722.
Surg. 2002;28(12):2206-2213. 26. Seiler T, Koufala K, Richter G. Iatrogenic keratectasia after laser in
3. Koch DD. The riddle of iatrogenic keratectasia. J Cataract Refract situ keratomileusis. J Refract Surg. 1998;14(3):312-317.
Surg. 1999;25(4):453-454. 27. Spadea L, Palmieri G, Mosca L, Fasciani R, Balestrazzi E. Iatrogenic
4. Kohnen T. Iatrogenic keratectasia: current knowledge, current keratectasia following laser in situ keratomileusis. J Refract Surg.
measurements. J Cataract Refract Surg. 2002;28(12):2065-2066. 2002;18(4):475-480.
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28. Condon PI, O’Keefe M, Binder PS. Long-term results of laser in situ 35. Dawson DG, O’Brien TP, Dubovy SR, et al. Post-LASIK Ectasia:
keratomileusis for high myopia: risk for ectasia. J Cataract Refract Histopathology, Ultrastructure, and Corneal Physiology from
Surg. 2007;33(4):583-590. Human Corneal Buttons and Eye Bank Donors Presented at the
29. Amoils P. Corneal ectasia after photorefractive keratectomy. J AAO Annual Meeting, Las Vegas NV, 2006.
Cataract Refract Surg. 2007;33(6):941-942; author reply 2. 36. Tuli SS, Iyer S. Delayed ectasia following LASIK with no risk fac-
30. Klein SR, Epstein RJ, Randleman JB, Stulting RD. Corneal ectasia tors: is a 300-microm stromal bed enough? J Refract Surg. 2007;
after laser in situ keratomileusis in patients without apparent pre- 23(6):620-622.
operative risk factors. Cornea. 2006;25(4):388-403. 37. Mohammadpour M. Corneal ectasia after LASIK in one eye and
31. Lifshitz T, Levy J, Klemperer I, Levinger S. Late bilateral keratec- uneventful PRK in the fellow eye. J Cataract Refract Surg. 2007;
tasia after LASIK in a low myopic patient. J Refract Surg. 2005; 33(10):1677; author reply 1678.
21(5):494-496. 38. Amoils SP, Deist MB, Gous P, Amoils PM. Iatrogenic keratectasia
32. Randleman JB, Banning CS, Stulting RD. Corneal ectasia after after laser in situ keratomileusis for less than -4.0 to -7.0 diopters of
hyperopic LASIK. J Refract Surg. 2007;23(1):98-102. myopia. J Cataract Refract Surg. 2000;26(7):967-977.
33. Tabbara KF, Kotb AA. Risk factors for corneal ectasia after LASIK. 39. Binder PS. Analysis of ectasia after laser in situ keratomileusis: risk
Ophthalmology. 2006;113(9):1618-1622. factors. J Cataract Refract Surg. 2007;33(9):1530-1538.
34. Dawson DG, Grossniklaus HE, McCarey BE, Edelhauser HF. 40. Jampaulo M, Maloney RK. Lack of progression of ectasia seven
Biomechanical and wound healing characteristics of corneas after years after LASIK in a highly myopic keratoconic eye. J Refract Surg.
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Refract Surg. 2008;24(1):S90-96.
 SECTI ON I I I

Devices for the

Diagnosis of
Keratoconus and
Keratoectasia
 CHAP TER 6

Topography in the Diagnosis of

Keratoconus and Keratoectasia

Stephen D. Klyce, PhD

I
t may be said that the single most important diagnostic toconus. This is because corneal topography with unusual
instrument to permit the current success of refractive inferior steepening, for example, may be due to other fac-
surgery was the development of computerized corneal tors such as contact lens warpage1 rather than a form of
topography analysis. The integration of pachymetry mea- keratoconus. However, there is clear evidence that corneas
surements into some of the modern corneal topographers designated as keratoconus suspect can progress to clinical
has extended the clinical information available for screen- keratoconus.2 While multiple signs signal the presence of
ing patient for refractive surgery candidacy and to evaluate clinical keratoconus and are used to make its diagnosis,
the postoperative results. In this chapter, we review the the only clinical evidence currently available to designate
effective use of these clinical diagnostic tools in the detec- keratoconus suspect is that provided by corneal topog-
tion and tracking of corneal keratoectasia in its pathologic raphy. Other than a faint scissoring of the light reflex on
and iatrogenic forms. retinoscopy, there are no other currently available measur-
able signs. The presumptive initial corneal thinning with
suspect keratoconus is below the current resolution that
SCREENING REFRACTIVE pachymetry can detect.
SURGERY PATIENTS USING There are essential guidelines in the use of corneal
topography to differentiate between normals and abnor-
CORNEAL TOPOGRAPHY mals using the color-coded contour map of corneal power.3
A challenge is provided in discerning abnormality in cor-
Keratoconus and signs of keratoconus, including the neal topography because there is a large variation in topo-
related non-inflammatory thinning disorder pellucid mar- graphic patterns among the general population; individual
ginal degeneration, are contraindications to refractive topographies are similar to fingerprints with patterns that
surgery. This is stated in the labeling of excimer lasers used are unique.4 While efforts have been made to classify the
for this purpose. These diseases are slowly progressive, shapes of normal corneas between those that are radially
and one of the biggest challenges for the diagnostician is symmetrical and those that show ovality in topographic
to differentiate between normal corneas and corneas that contours, for example, in reality, there is a continuous pro-
have subtle topographic characteristics that may be the gression of topographic shapes among these classifications
first diagnostic clues of keratoconus. When the diagnosis of in normals.5
keratoconus is uncertain, commonly the condition is called Generally, these variations among normals are not
forme fruste keratoconus (FFKC). Because the dictionary known to detract from excellent visual acuity. This knowl-
definition of forme fruste is “an incomplete, abortive, or edge helped to create a fixed standard scale for display-
unusual form of a syndrome or disease” we prefer to use ing corneal power distributions, one that would hide
the term keratoconus suspect rather than forme fruste kera- the normal variations in corneal power that were not of

Wang M, ed.
Keratoconus & Keratoectasia: Prevention, Diagnosis, and Treatment (pp.61–67) 61
© 2010 SLACK Incorporated
62 CHAPTER 6

consequence to either vision or to the detection of corneal

pathology. This scale3 underwent minor revision,6,7 with
DEVELOPMENT OF INDICES
the details being published.7 The scales were included in AND SCREENING SOFTWARE TO
the American National Standards Institute standard on
corneal topography, and the scale is now available on a
DETECT KERATOCONUS
number of corneal topographers. The scale is referred to
While the development of the color-coded map of cor-
as the Universal Standard Scale7 and has a 1.5 D interval
neal curvature remains a major clinical standard for the
between power contours and a range of 30.0 to 65.5 D. This
detection of corneal pathology, it was the development of
scale has been shown to be adequate for routine clinical use
topographic indices that made the corneal topographer a
in distinguishing between normal corneas and those that
diagnostic instrument. Corneal topographic indices were
have abnormal aberrations.8
originally developed to emulate keratometry (SimK values),
to assess the optical quality of the corneal surface, and for
THE SEVERAL FACES OF IOL calculations.15-19 Quickly, corneal topography indi-
ces were developed to detect pathology. Rabinowitz and
KERATOCONUS McDonnell20 showed in their classic paper that a vertical
dioptric gradient (the so-called I-S Index) greater than 1.4
Classically, keratoconus appears as steepening in the D could discriminate suspect keratoconus from the asym-
inferior cornea and is often more advanced in one eye metry often seen in normal corneas. They also proposed
than the other (Figure 6-1A). However, there are several that corneas with a vertical gradient greater than 1.9 D were
variations that can be seen with corneal topography exami- consistent with corneas that had definite or clinical kerato-
nation. The apex of the cone can be central or even supe- conus, a characteristic abnormality in corneal topography
rior.9 Keratoconus can also appear to be unilateral,10 but, accompanied by traditional signs such as corneal thinning.
recalling that this pathology has genetic underpinnings, Today, the I-S Index remains a tool that can be esti-
unilateral keratoconus likely reflects lack of current expres- mated with all of the corneal topographers available today.
sion in the unaffected cornea. A common presentation of The precise method for calculating I-S is shown in Figure
keratoconus is a “lazy 8” or sagging bowtie as shown in 6-2. Note, however, I-S can be estimated quickly by mea-
Figure 6-1B. This form is detected with the variable SRAX suring the inferior and superior corneal surface powers by
(skewing of the radial axes) introduced by Szczotka and moving the cursor to positions 3 mm out in the topography
colleagues.11 Another characteristic form that keratoconus map. The approximate readings are subtracted to have an
takes is a symmetrical central bowtie that is truncated, estimate of corneal asymmetry. It is recommended that this
but without skew (Figure 6-1C). Finally, keratoconus can be done along the steep axis of astigmatism for the great-
sometimes present with a “claw” or “C shape” topogra- est sensitivity. If the estimated I-S reaches the values stated
phy—the hallmarks of the topography of pellucid marginal above, the corneal topography is not normal.
degeneration (Figure 6-1D).12-14 Both keratoconus and The above considerations and findings formed the basis
pellucid marginal degeneration involve non-inflamma- for the further development in the automatic detection
tory thinning. The differential diagnosis must rely on the of keratoconus with corneal topography. The use of 2 or
nature of corneal thinning. Typically, keratoconus involves 3 indices is not sufficient to detect all the variations in
a central or paracentral localized thinning as it progresses corneal topography. It will be seen that extensions of the
whereas pellucid marginal degeneration is identified by corneal topography index strategy can be used to detect
its perilimbal arcuate shape. When there is the claw or and to track keratoectasia automatically.
“C shape” seen on corneal topography, in the absence of Using corneal topography indices developed to specifi-
definitive pachymetric data or slit-lamp observation, the cally capture additional characteristics of keratoconus, a set
interpretation should be topographic pellucid marginal of 8 indices were used as the input to an expert system classi-
degeneration. These cases are generally differentiated using fier.21 The system was trained with examinations of clinical
slit-lamp examination. Both conditions should disqualify a keratoconus (a mixture of mild, moderate, and advanced
candidate from traditional refractive surgery because of the stages) and non-keratoconus corneas (normals, regular
risk for iatrogenic ectasia. The various corneal topography astigmatism, keratoplasty, epikeratoplasty, photorefractive
patterns need to be recognized and a final diagnosis con- keratectomy, radial keratotomy, contact lens–induced warp-
firmed with pachymetry and slit-lamp observation. age, astigmatic keratotomy, scarred corneas, post-retinal
 TOPOGRAPHY IN THE DIAGNOSIS OF KERATOCONUS AND KERATOECTASIA 63

Figure 6-1. Corneal topography of

A keratoconus. (A) The topographic
appearance in these corneas is
typical of keratoconus. Inferior
steepening in the left eye is more
advanced than the right. This also
is an extreme example of the
asymmetrical bowtie. (B) This is an
example of the lazy eight bowtie
keratoconus caused by skewing of
the radial axes. (C) Keratoconus
also occurs centrally in the form of
a truncated bowtie, seen here in
the right eye of this patient. Note
the relatively normal appearing
corneal topography OS. It is impor-
B tant to always examine both cor-
neas. (D) Keratoconus sometimes
presents with the “claw” shape
characteristic of pellucid marginal
degeneration. However, this case
did not have perilimbal thinning
by slit lamp examination and was
diagnosed as keratoconus.

D
64 CHAPTER 6

explored to characterize the corneal surface in keratoconus

and penetrating keratoplasty.27
In a move away from using corneal surface power
for characterizing corneal shape, Schwiegerling and
Greivenkamp28 proposed the use of Zernike polynomials
to fit actual three-dimensional height data to detect kerato-
conus. Although the method showed some merit, it did not
appear to be as sensitive or specific to detect keratoconus
as the discriminant analysis approach mentioned earlier.
The use of height data, however, to characterize or detect
keratoconus continues to be a research interest,29 although
the bulk of published data indicates important shortcom-
ings to the approach.30
Important lessons have been learned from the schemes
that have been developed to detect keratoconus. Significantly,
Figure 6-2. Calculation of I-Svalue. If I-S>1.4, the topography is consistent no method will be 100% specific, sensitive, and accurate.
with suspect keratoconus. If I-S>1.9, the topographyis consistent with clinical Like all clinical tests, the information from corneal topog-
keratoconus. raphy screening programs must be considered within the
spectrum of additional clinical information available. With
keratoconus detection, zonal pachymetry ranks highest on
detachment surgery, post-cataract surgery, and keratomileu-
the list of adjunct information for consideration. While
sis). The purpose of including the abnormal corneas in the
abnormal topography is the highest risk factor for the devel-
non-keratoconus group was to permit the detection system
opment of iatrogenic ectasia after refractive surgery, others
to discriminate these from clinical keratoconus. Analysis
that have been identified include high myopia, reduced
yielded the keratoconus prediction index (KPI), which, in
preoperative corneal thickness, reduced residual stromal
turn, was introduced to a binary decision tree to differenti-
bed after refractive surgery, and age.31 Equally important,
ate between central and peripheral keratoconus. Validation
of this approach was done with a second set of independent we have learned that screening tests that have been devel-
topographic examinations consisting of keratoconus corneas oped to discriminate only between clinical keratoconus
and normal and abnormal nonkeratoconus corneas. and normals are of limited use; they will not detect suspect
keratoconus and cannot discriminate among the several
Since that initial work, other methods using neural
other common aberrations seen in the clinic.
networks have been employed to extend discrimination
to include suspect keratoconus.22,23 In addition, more
elaborate approaches have been developed that are able
to discriminate among several classifications of corneal
TRACKING KERATOCONUS
topography. Specifically, a system has been developed that PROGRESSION
is able to discriminate between normals, astigmats, sus-
pect keratoconus, clinical keratoconus, pellucid marginal Keratoconus begins with mild asymmetries in corneal
degeneration, penetrating keratoplasty, myopic refractive topography so slight that only Placido topographers can
surgery, hyperopic refractive surgery, and an unclassifi- detect it. As noted above, with no other clinical signs, this
able group called “other” (Figure 6-3).24 Importantly, this stage is deemed suspect keratoconus. When this stage pro-
corneal topographer classifier system was developed to gresses to a true diagnosis of clinical keratoconus, thinning
be system independent using a technique that unifies the can start to be detected in the vicinity of the cone apex. This
characteristics of input Placido corneal topography maps stage is often referred to as mild keratoconus. The last two
whether they arise from a wide mire or a fine mire cor- stages are moderate and severe or advanced keratoconus. It
neal topographer.24 A different approach has been taken by is important to note that not all eyes with keratoconus will
Mahmoud and colleagues to simulate corneal topographic require corneal transplantation. Keratoconus progresses
indices across different platforms.25 most rapidly in the teenage years, and then slows or even
The index-based methods described above have used halts with time. Some experts claim that 75% to 85% of
semi-empirical indices derived from the corneal topogra- all keratoconus eyes will halt progression and not require
pher surface power values. Other more global techniques surgery.
have been attempted as well. Wavelet analysis of corneal Progression of keratoconus can be tracked with the
topography has been attempted with some success with Keratoconus Severity Index (KSI) developed by Smolek
the idea that eyes could be screened for prior refractive and Klyce (see Figure 6-3).32 Mamoud et al have developed
surgery,26 and the use of wavelet analysis has also been an alternate method with to track the position and magni-
 TOPOGRAPHY IN THE DIAGNOSIS OF KERATOCONUS AND KERATOECTASIA 65

Figure 6-3. The corneal topography classification systemon the Nidek Magellan (Fremont, CA). Note the multiple classifications of topography that are deter-
mined bya trained neural network operating on the statistical indices listed in the lower right.

tude of the cone, the Cone Magnitude and Location Index the correction of myopia, the central cornea is flattened so
(CMLI).33 These indices can be very useful clinically. With that the lowest powers on the corneal surface are now cen-
these, the progression in a given patient can be tracked over tral instead of being peripheral. With an adaptable scale, the
the years, aiding prognosis for treatment. central portion of the color map will be assigned the blue
and green colors while the periphery will now be assigned
the warmer yellow and red colors. With the normalized
DETECTING AND TRACKING scale, the corneal periphery appears ectatic. Using a fixed
IATROGENIC ECTASIA AND ITS standard scale will avoid this mistaken interpretation.
Perhaps the most certain way to determine whether a
TREATMENT cornea is becoming ectatic following refractive surgery is
to use differential analysis. Corneal topography difference
The focus of this chapter has been on the detection and maps are available on most corneal topographers. These
tracking of keratoconus. As noted above, there are a num- can be used to compare changes in corneal topography
ber of risk factors for ectasia as a complication to refractive with time. This is a retrospective analysis that requires
surgery. Iatrogenic ectasia can be misdiagnosed by using the clinician to maintain the original corneal topography
normalized or adaptable scales. After refractive surgery for examination data on the instrument hard drive. To make
66 CHAPTER 6

A B

Figure 6-4. (A) Documentingectasia with the difference map. (A) Three months postoperative, there is no sign of ectasia. (B) At 18 months, ectasia is significant
using the difference map. This patient eventuallyunderwent bilateral penetrating keratoplasty.

Figure 6-5. Ectasia can be tracked with the difference map. This patient underwent cross-linking with riboflavin/ UVtreatment. Typically, at
1 month, there is a small amount of steepening (upper row), but at 6 months a significant flattening occurs (lower row). MaxKis defined as
the highest power measured on the ectatic area accompanied by its location within the corneal topography map. MaxK’s are indicated by
the white diamond and power value on these topographymaps.

a comparison of corneal topography, two examinations of using the difference map approach to determine whether
the same cornea from different visits are selected. The cor- a cornea is undergoing ectasia after LASIK is shown in
neal topographer automatically subtracts the two exami- Figure 6-4. An example of a cornea with keratoconus that
nations, creating a map of the difference. Ordinarily, the has undergone the stabilizing riboflavin/UV cross-linking
difference map shows no change as a green color and varia- procedure is shown in Figure 6-5.
tions toward the blue or red ends of the palette. It should be Note that the difference map cannot only detect the
noted that fixation nystagmus will produce maps that are occurrence of ectasia, but also will show the actual charac-
slightly out of registration, so a small amount of “noise” is teristics of the ablation produced. Ordinarily, pre-existing
expected and not taken as a sign of trouble. An example irregularities in corneal topography will be preserved in
 TOPOGRAPHY IN THE DIAGNOSIS OF KERATOCONUS AND KERATOECTASIA 67

conventional laser treatments, and these should not be 9. Wilson SE, Lin DT, Klyce SD. The corneal topography of keratoco-
mistaken in the postoperative period as irregular astig- nus. Cornea. 1991;10:2-8.
10. Kennedy RH, Bourne WM, Dyer JA. A 48-year clinical and epide-
matism induced by the laser. This can be verified with the miologic study of keratoconus. Am J Ophthalmol. 1986;101:267-273.
difference map. 11. Szczotka LB, Rabinowitz YS, Yang H. Influence of contact lens wear
If ectasia is suspected or detected with the difference on the corneal topography of keratoconus. CLAO J. 1996;22:270-
map, it should be tracked rigorously using sequential visits. 273.
12. Maguire LJ, Klyce SD, McDonald MB, Kaufman HE. Corneal
One technique to track ectasia that is appropriate for rou-
topography of pellucid marginal degeneration. Ophthalmology.
tine use has been called “MaxK.” MaxK is defined as the 1987;94:519-524.
highest power measured on the ectatic area accompanied 13. Ambrósio JR, Klyce SD, Smolek MK, Wilson SE. Pellucid marginal
by its location within the corneal topography map. This corneal degeneration. J Refract Surg. 2002;18:86.
has been used in clinical trials and is shown in the differ- 14. Lee BW, Jurkunas UV, Harissi-Dagher M, et al. Ectatic disorders
associated with a claw-shaped pattern on corneal topography. Am J
ence maps of Figure 6-5. This metric is direct and can be Ophthalmol. 2007;144:154-156.
graphed against time for trend analysis and prognosis. It 15. Dingeldein SA, Klyce SD, Wilson SE. Quantitative descriptors of
should be valuable for tracking both keratoconus severity corneal shape derived from computer-assisted analysis of photoker-
as well as iatrogenic ectasia. atographs. Refract Corneal Surg. 1989;5:372-378.
16. Wilson SE, Klyce SD. Quantitative descriptors of corneal topogra-
phy. A clinical study. Arch Ophthalmol. 1991;109:349-353.

CONCLUSIONS 17. Alimisi S, Miltsakakis D, Klyce S. Corneal topography for intraocu-

lar lens power calculations. J Refract Surg. 1996;12:S309-S311.
18. Holladay JT. Corneal topography using the Holladay Diagnostic
Corneal topography examinations have become the Summary. J Cataract Refract Surg. 1997;23:209-221.
19. Hovanesian JA, Shah SS, Onclinx T, Maloney RK. Quantitative
standard of care for anterior segment specialists. A thor-
topographic irregularity as a predictor of spectacle-corrected visual
ough understanding of how to interpret corneal topog- acuity after refractive surgery. Am J Ophthalmol. 2000;129:752-
raphy displays is especially critical for the refractive sur- 758.
geon in the process of screening candidates. The ability 20. Rabinowitz YS, McDonnell PJ. Computer-assisted corneal topogra-
to differentiate between the topographic variations that phy in keratoconus. Refract Corneal Surg. 1989;5:400-408.
21. Maeda N, Klyce SD, Smolek MK, Thompson HW. Automated
occur in normal corneas from pathology is improved
keratoconus screening with corneal topography analysis. Invest
using the Universal Standard Scale. Additional assistance Ophthalmol Vis Sci. 1994;35:2749-2757.
can be derived from topographic indices and automatic 22. Maeda N, Klyce SD, Smolek MK. Application of neural networks to
topographic classifiers along with a consideration of all the classification of corneal topography: preliminary demonstra-
the ancillary traditional clinical observations (pachymetric tion. Invest Ophthalmol Vis Sci. 1995;36:1327-1335.
23. Maeda N, Klyce SD, Smolek MK. Comparison of methods for
data, slit-lamp findings, etc). But with all the technology
detecting keratoconus using videokeratography. Arch Ophthalmol.
available today, it is the clinician’s diagnostic acumen that 1995;113:870-874.
will determine the proper course of action in the manage- 24. Klyce SD, Karon MD, Smolek MK. Screening patients with the cor-
ment of patient care. neal navigator. J Refractive Surg. 2005;21:S617-S622.
25. Mahmoud AM, Roberts C, Lembach R, Herderick EE, McMahon TT.
The Clek Study Group. Simulation of machine-specific topographic

REFERENCES 26.
indices for use across platforms. Optom Vis Sci. 2006;83:682-693.
Smolek MK, Klyce SD. Screening of prior refractive surgery by a
wavelet-based neural network. J Cataract Refract Surg. 2001;27:1926-
1. Wilson SE, Lin DTC, Klyce SD, Reidy JJ, Insler MS. Rigid contact 1931.
lens decentration—a risk factor for corneal warpage. CLAO J. 27. Langenbucher A, Sauer T, Seitz B. Wavelet analysis for corneal top-
1990;16:177-182. ographic surface characterization. Curr Eye Res. 2002;24:409-421.
2. Maguire LJ, Lowry JC. Identifying progression of subclinical 28. Schwiegerling J, Greivenkamp JE. Keratoconus detection based on
keratoconus by serial topography analysis. Am J Ophthalmol. 1991; videokeratoscopic height data. Optom Vis Sci. 1996;73:721-728.
112:41-45. 29. Schlegel Z, Hoang-Xuan T, Gatinel D. Comparison of and cor-
3. Maguire LJ, Singer DE, Klyce SD. Graphic presentation of com- relation between anterior and posterior corneal elevation maps in
puter-analyzed keratoscope photographs. Arch Ophthalmol. 1987; normal eyes and keratoconus-suspect eyes. J Cataract Refract Surg.
105:223-230. 2008;34:789-795.
4. Dingeldein SA, Klyce SD. The topography of normal corneas. Arch 30. Cairns G, McGhee CN. Orbscan computerized topography: attri-
Ophthalmol. 1989;107:512. butes, applications, and limitations. J Cataract Refract Surg. 2005;
5. Bogan SJ, Waring GO 3rd, Ibrahim O, Drews C, Curtis L. 31:205-220.
Classification of normal corneal topography based on computer- 31. Randleman JB. Ectatic disorders associated with a claw-shaped pat-
assisted videokeratography. Arch Ophthalmol. 1990;108:945-949. tern on corneal topography. Am J Ophthalmol. 2007;144:977-978.
6. Wilson SE, Klyce SD, Husseini ZM. Standardized color coded maps 32. Smolek MK, Klyce SD. Current keratoconus detection methods
for corneal topography. Ophthalmology. 1993;100:1723. compared with a neural network approach. Invest Ophthalmol Vis
7. Smolek MK, Klyce SD, Hovis JK. The Universal Standard Scale: Sci. 1997;38:2290-2299.
proposed improvements to the American National Standards 33. Mahmoud AM, Roberts CJ, Lembach RG, et al. CLEK Study Group.
Institute (ANSI) scale for corneal topography. Ophthalmology. CLMI: the cone location and magnitude index. Cornea. 2008;
2002;109:361-369. 27:480-487.
8. Wilson SE, Klyce SD. Screening for corneal topographic abnormali-
ties prior to refractive surgery. Ophthalmology. 1994;101:147-152. Financial Disclosure: Dr. Klyce is a consultant to Nidek.
 CHAP TER 7

Posterior Corneal Changes

Dora Sztipanovits, MS, OD, and Ming Wang, MD, PhD

P
osterior corneal analysis is important for two rea- effect of refractive surgery on a surface we were previously
sons: its role in the diagnosis of ectasia and for unable to evaluate. Since the Orbscan, the development of
its contribution to the variability in cataract sur- Scheimpflug imaging has further enhanced the arsenal of
gery outcome in eyes following keratorefractive surgery. tools clinicians can use to evaluate the posterior cornea.
Posterior elevation mapping may indicate non-candi- Changes in posterior surface elevation, including signifi-
dacy for laser in-situ keratomileusis (LASIK). Following cant keratoectasia, may occur after ablative procedures.5-9
keratorefractive surgery, attention to posterior elevation is It has been suggested that the overall decrease in corneal
important for patients with visual complaints or increas- thickness,10 the residual bed thickness,11,12 and/or higher
ing myopia, making them keratoectasia suspects. Even in intraocular pressure13 may be responsible for increased
patients without ectasia following keratorefractive surgery, elevation. An increase in posterior corneal elevation may
posterior corneal changes may contribute to inaccuracies be more common in eyes with multiple treatments.14 These
in intraocular lens implantation. Conventional methods changes may resolve over time, and edema immediately
of keratometric measurements underestimate refractive after surgery may play a role in the increased incidence of
power change due to a discrepancy in refraction and keratoectasia noted in the early postoperative course.15
keratometric power that results after refractive surgery.1-4
This is important because as millions of patients who have
undergone LASIK continue to age, becoming cataract POSTERIOR CORNEAL CHANGES
patients, they subsequently require improved methods for IN KERATOCONUS
determination of intraocular lens (IOL) implant power to
achieve a satisfactory outcome after cataract surgery. In keratoconus, an inherently weakened cornea loses its
LASIK directly affects the anterior surface of the cor- structural integrity and begins to deform, resulting in ecta-
nea, changing its shape to neutralize the refractive error. sia, irregular astigmatism, and eventually a reduction of
For myopic patients, the keratometric readings are flat- visual acuity. In the initial stages of the disease, the earliest
ter, the total corneal power is lower, and the anterior tomographic sign of ectasia is often noticed on the poste-
elevation is decreased. Historically, the power of the cornea rior surface of the cornea. As the area of posterior elevation
was measured using a manual keratometer. This method progresses, a corresponding area of anterior elevation is
yields measurements using a mathematical calculation that noted. In more advanced presentations of keratoectasia, the
assumes several variables remain unchanged, including posterior elevation change is larger in magnitude than the
the posterior surface of the cornea and the index of refrac- anterior elevation change (Figure 7-1).
tion. The Orbscan (Bausch and Lomb, Rochester, NY) was In order to accurately diagnose a patient that has steep-
the first device to measure both the anterior and poste- ening on an anterior curvature map as indeed ectatic in
rior surfaces of the cornea, allowing investigation into the nature, you should look for a corresponding area of poste-

Wang M, ed.
Keratoconus & Keratoectasia: Prevention, Diagnosis, and Treatment (pp.69–75) 69
© 2010 SLACK Incorporated
70 CHAPTER 7

A B C

Figure 7-1. Summaryof posterior corneal relative to anterior corneal change in

the progression of keratoconus. On tomography, posterior surface is affected
first, followed bythe anterior surface. Figure 7-2. (A) Scenarios that can mimic keratoconus based on anterior curva-
ture maps include inferior tissue addition such as in Salzmann’s degeneration.
(B) Superior corneal thinning such as in Terrien’s marginal degeneration can
rior elevation on an elevation map. Various corneal diseases result in relative inferior steepening. (C) Central anterior surface flattening
generate anterior maps that masquerade as ectatic disease. from surface subtraction in myopic refractive surgery can result in relative
For example, tissue addition inferiorly which creates relative inferior steepening on topography.
steepening inferiorly compared with the normal corneal
surface elsewhere. Superior thinning generating steepening
on anterior maps is another example. Eyes with a history of amount of refractive correction appears to indicate the
keratorefractive surgery may result in suspicious anterior magnitude of increase in posterior power contribution.
curvature maps due to increased relative inferior steepening This change is more pronounced centrally versus pericen-
due to central surgical flattening. Figure 7-2 illustrates these trally suggesting an asymmetric “bowing” of the posterior
scenarios. In these cases, it is useful to analyze the posterior cornea centrally, possibly due to mechanical factors affect-
surface to rule out corneal ectasia as the etiology. ing the thinned cornea. Therefore, total corneal power
calculated using posterior power appears to be a more
accurate measure of corneal power changes after LASIK.
STUDY EXAMINING The relationship between keratometric changes and
POSTERIOR CORNEAL POWER refractive changes are highly correlated and keratometric
CONTRIBUTION S/P LASIK measurement changes by a factor of 0.7 to 0.8 times the
refractive change in myopic treatment. Because traditional
keratometric readings are based on estimates derived from
Seventeen eyes were treated using a VISX Excimer S2
anterior corneal curvature, and because the anterior sur-
Laser (AMO, Abbott Park, IL) for a primary LASIK proce-
face of the cornea is the only aspect that is intentionally
dure for myopia. These eyes were retrospectively analyzed
modified, it seems intuitive that changes in keratometric
and followed up 3 months postoperatively. Changes in
keratometric (K), total (T), anterior (A), and posterior (P) measurements should account for changes in observed
corneal power from preop to 3-months post-LASIK were refraction. However, keratometry fails to accurately esti-
compared and correlated with changes in refraction (R). mate the change.16,17 Therefore, there must be another
Within this study, a statistically significant increase in mechanism accounting for the difference.
the ratio of mean posterior corneal power to mean total In a healthy, untreated eye, the anterior surface of the
corneal power (P/T) after LASIK was noted. Additionally, cornea accounts for approximately 88% of the refractive
there was a significant correlation between the amount of power of the cornea, while the posterior surface accounts
refractive correction (ΔR) and the magnitude of change in for about 12%. While it was not apparent to surgeons early
posterior power contribution to total power (Δ[P/T]). The on, it was quickly found that cataract surgery on eyes with a
increase in posterior power centrally was greater than the history of myopic ablation resulted in hyperopic surprises.
pericentral 3-mm zone (statistical significance, p<0.001) As was found by Seitz et al and confirmed in this study,
and central total corneal power change correlated sig- the curvature of the posterior surface of the cornea does in
nificantly with refractive correction, with a ratio of 1.08 ± fact change after surgery.18 In fact, the contribution of the
0.26. Change in central keratometric power also correlated posterior surface to the total refractive power of the cornea
highly with refractive correction, but with a lower ratio increases significantly after surgery, as was shown in this
of 0.80 ± 0.27, a difference that is statistically significant study and reported by Langenbucher.17 This increase is
(p<0.001). partially due to the expected increase in posterior contri-
The contribution of posterior power to total corneal bution secondary to surgical flattening. This increase is
power increased significantly after myopic LASIK. The compounded by an increased posterior power contribu-
 POSTERIOR CORNEAL CHANGES 71

A B

Figure 7-4. Atypical keratoconic cornea with corresponding areas of anterior

Figure 7-3. This is an example of a cornea before surgery (a) and after (b). and posterior elevation. Notice that the posterior surface elevation is greater
Notice howpower (P) changes in both the anterior corneal surface and the than the anterior elevation, and corresponds to the area of thinning.
posterior surface. The posterior power contribution (PPC) doubles after
anterior tissue ablation.
elevation. Notice that the area of elevation of the posterior
surface is greater than the elevation of the anterior surface
tion due to a physical change in the posterior surface. The and also corresponds to the area of thinnest cornea.
change in posterior power in the paracentral region is not
as pronounced as the change centrally. This suggests that Case 2
there is a greater mechanical weakening centrally, resulting A 32-year-old Hispanic man presented complaining of
in an asymmetric bowing of the posterior cornea. progressively decreasing vision in the left eye with ghosting
Figure 7-3 is a model of an untouched cornea. If, for and distortion. His BCVA with spectacles is 20/20 OD and
example, the anterior surface power is +48 D and the poste- 20/200 OS. This patient was subsequently diagnosed with
rior surface power is –6 D, then the posterior contribution pellucid marginal degeneration. Looking at the maps of the
to total power is 1/8 (or 12.5%). If we were to then surgically left eye (Figure 7-5), significant posterior elevation is seen
flatten the anterior surface and generate a new anterior with corresponding anterior elevation and increased front
surface power of +40 D for myopic treatment, the posterior surface curvature diagnostic of pellucid marginal degen-
corneal surface will bulge forward by approximately –4 D, eration. Interestingly, the right eye topography maps (see
thereby changing the posterior power to -10 D. This means Figure 7-5) illustrate an earlier point in the disease with
that after anterior corneal flattening, the posterior surface a noticeable posterior surface change. There is significant
power now contributes twice as much to the total refractive change of the posterior surface relative to the anterior.
power of the cornea, from 1/8 (12.5%) to 1/4 (25%). What is unique about this case is that these are scans of
Given the importance of the posterior surface, interpre- different eyes in the same patient. Keratoconus is a bilateral
tation of topographic findings is crucial for success both but often asymmetric condition.
in surgery and managing patients who have undergone
keratorefractive procedures. Case 3
A 51-year-old Caucasian man presented seeking LASIK
CLINICAL CASES to correct his vision to 20/20 without glasses. BCVA with
spectacles is 20/20 OD and 20/30 OS. Analyzing his topog-
raphy in the right eye (Figure 7-6), posterior elevation is
Case 1 seen with no corresponding anterior elevation. These may
be early signs of posterior corneal change in a patient with
A 39-year-old African American woman diagnosed
forme fruste keratoconus (FFKC). This patient should be
with keratoconus 8 years ago presented to see if anything
monitored for progression rather than undergo LASIK.
can be done to improve her vision. Best-corrected visual
acuity (BCVA) with spectacles is 20/30 OD and 20/50
OS. Topographical slit imaging with Pentacam (Oculus,
Case 4
Wetzlar, Germany) (Figure 7-4) in the left eye shows an area A 52-year-old Caucasian woman came in with a chief
of posterior elevation with a corresponding area of anterior complaint of decreased vision and dryness. Her manifest
72 CHAPTER 7

Figure 7-6. Acase of normal anterior surface with early posterior elevation.
B This is an indication of forme fruste keratoconus.

Figure 7-5. (A) Early keratoconic change of the right eye in the same patient
as (B). (B) Moderate keratoconus in the left eye of the same patient in (A).
Notice the asymmetric disease.

B
refraction is OD -3.25 +1.50 x 140 and OS –3.25 +1.75 x
020 yielding BCVA of 20/25 in each eye. Upon slit-lamp
evaluation, a decreased tear lake was seen with noticeable
lagophthalmos, greater in the left eye. There was peripheral
corneal neovascularization inferiorly in the right eye, and
inferior elevation and scarring in the left eye extending
about 3 mm into the cornea. The corneal findings were
diagnosed as Salzmann’s degeneration, as seen in Figure
7-7A.
Notice that there is an area of inferior elevation on the
front elevation map that mimics the topography classi-
cally seen in pellucid marginal degeneration. This cor-
responds to the area affected by Salzmann’s degeneration. Figure 7-7. (A) Apatient with inferior tissue addition secondaryto Salzmann’s
The keratoconus screening profile categorizes this cornea degeneration. Notice the anterior curvature map mimics pellucid marginal
as possible keratoconus (Figure 7-7B). However, there is degeneration. However, there is no corresponding area of posterior change
no corresponding posterior elevation in the area. If our and therefore no ectatic disease. (B) Apatient with inferior tissue addition
patient had PMD, there would be elevation both anteriorly secondary to Salzmann’s degeneration. The keratoconic screening profile
and posteriorly in the same area of the cornea. This illus- gives a possible keratoconus result due to the irregular astigmatismand aber-
trates the value of posterior corneal analysis in a case where rometryproduced bythe nodules.
anterior topography is misleading due to tissue addition
inferiorly on a normal cornea.
 POSTERIOR CORNEAL CHANGES 73

Figure 7-9. A case of relative increased inferior corneal curvature on

B Humphrey Atlas in a patient who has undergone myopic LASIK. Note the flat
central cornea and the relative steepening inferiorly.

we have an area of superior thinning, which, in turn,

results in relative inferior steepening, giving a map that
mimics anterior corneal changes as seen in ectasia.

Case 6
In a patient with central anterior flattening second-
ary to myopic refractive surgical treatment, we often see
increased inferior curvature due to relative steepening of
Figure 7-8. (A) Acase of superior corneal thinning secondary to Terrien’s the inferior cornea compared with the surgically flattened
marginal degeneration. Notice the keratoconic anterior curvature map area. A suspicious anterior curvature map is commonly
resembles early keratoconus. (B) Acase of superior corneal thinning second- generated. Not taking into account the surgical history of
aryto Terrien’s marginal degeneration resultingin a false positive keratoconic a patient such as this, it is useful to analyze the posterior
screening. Again, we see no corresponding area of posterior change, thereby curvature in order to rule out inferior steepening second-
ruling out keratoconus. ary to ectasia as posterior curvature would be increased in
the same area in a diseased cornea. Figure 7-9 illustrates
this; notice the relative increased inferior curvature in this
patient who has undergone myopic LASIK treatment.
Case 5
A 38-year-old Caucasian man presented with decreasing Case 7
vision OS over the past month. He denied pain, photo- A 26-year-old Caucasian man presented with a chief
phobia, foreign body sensation, or redness. His manifest complaint of decreasing vision in the right eye over the
refraction was OD –5.50 +0.50 x 101 (20/30) and OS –3.75 past few years wanting to know if LASIK could improve
+1.00 x 143 (20/50). Slit-lamp examination revealed ante- his vision. His manifest refraction was OD –6.00 +3.25 x
rior basement membrane dystrophy with superior corneal 120 (20/50) and OS –1.75 +0.50 x 180 (20/20). Slit-lamp
degeneration resulting in thinning, possibly a variant of examination revealed a posterior corneal reflection (Figure
Terrien’s Marginal Degeneration. 7-10A) with Vogt’s striae OD and clear cornea OS (Figure
Looking at the corneal topography maps of the left eye 7-10B). Pachymetry was 315 OD and 530 OS, significantly
(Figure 7-8A), we notice inferior steepening that is classi- thinner in the right eye.
fied by the keratoconus screening profile (Figure 7-8B) as Looking at the topography of his right eye, we see nor-
probable keratoconus (KK 1-2). The anterior map alone mal anterior corneal topography but an area of significant
does indeed show characteristic keratoconic changes. Once posterior elevation (Figure 7-11A), explaining the cause of
again, by looking at the posterior topography, we can rule the distorted vision in his right eye. As we can see, his left
out ectasia as the cause of steepening because there is no eye is unaffected (Figure 7-11B). This is a case of posterior
corresponding area of posterior elevation. In this patient, keratoconus that has not traveled to the anterior surface
74 CHAPTER 7

A A

B
B

Figure 7-11. (A) Tomographic data of the eye from Figure 7-10A. In this case,
keratoconus has only affected the posterior cornea, anterior cornea unaf-
Figure 7-10. (A) Adigital image of the right eye with posterior keratoconus. fected. This would be easy to miss in anterior corneal analysis alone. (B)
The arrowis pointing at the deflection image of the posterior surface (B) A Tomographic data of the eye fromFigure 7-10B. This eye is unaffected in the
digital image of the normal left eye, for comparison. same patient with posterior keratoconus.

and would most likely be missed on anterior corneal

analysis alone (Figure 7-12). It highlights the importance of
REFERENCES
posterior cornea in the identification of keratoconus. 1. Waring GO, Lynn MJ, Culbertson W, et al. Three year results of
the prospective evaluation of radial keratotomy (PERK) study.
Ophthalmology. 1987;94:1339-1354.
CONCLUSION 2. Hugger P, Kohnen T, La Rosa FA, Holladay JT, Koch DD. Comparison
of changes in manifest refraction and corneal power after photore-
fractive keratectomy. Am J Ophthalmol. 2000;129(1):68-75.
We often see normal anterior surfaces in the presence 3. Smith RJ, Chan WK, Maloney RK. The prediction of surgi-
of posterior ectasia; however, we seldom see abnormal cally induced refractive change from corneal topography. Am J
anterior surfaces without accompanying posterior change Ophthalmol. 1998;125(1):44-53.
in cases of ectasia. The magnitude of posterior eleva- 4. Trocme SD, Mack KA, Gill KS, Gold DH, Milstein BA. Corneal
topography after excimer laser photorefractive keratectomy for
tion change tends to be larger than anterior elevation in myopia. J Am Optom Assoc. 1997;68(7):448-451.
advanced cases of ectasia. These indicate the potential 5. Seiler T, Koufala K, Richter G. Iatrogenic keratectasia after laser in
predictive value of tomographic posterior corneal analysis situ keratomileusis. J Refract Surg. 1998;14:312-317.
in the determination of keratoconic disease. Variation of 6. Seiler T, Quurke AW. Iatrogenic keratectasia after LASJK in a case
of forme fruste keratoconus. J Cataract Refract Surg. 1998;24:1007-
elevation change between the anterior and posterior sur- 1009.
faces may indicate early disease and make intraocular lens 7. Geggel HS, Talley AR. Delayed onset keratectasia following laser in
calculation problematic. situ keratomileusis. J Cataract Refract Surg. 1999;25:582-586.
 POSTERIOR CORNEAL CHANGES 75

11. Wang Z, Chen J, Yang B. Posterior corneal surface topographic

changes after laser in situ keratomileusis are related to residual
corneal bed thickness. Ophthalmology. 1999;106:406-409; discus-
sion 409-410.
12. Kamiya K, Oshika T, Amano S, et al. Influence of excimer laser
photorefractive keratectomy on the posterior corneal surface. J
Cataract Refract Surg. 2000;26(6):867-871.
13. Price FW Jr, Koller DL, Price MO. Central corneal pachymetry in
patients undergoing laser in situ keratomileusis. Ophthalmology.
1999;106(11):2216-2220.
14. Rani A. Balasubramanya RM, et al. Posterior corneal topographic
changes after retreatment LASIK. Ophthalmology. 2002;109:1991-
1995.
15. Patel S, Alio JL, Perez-Santonja JJ. A model to explain the dif-
ference between changes in refraction and central ocular surface
power after laser in situ keratomileusis. J Refract Surg. 2000;
16(3):330-335.
16. Rosa N, Cennamo G, Rinaldi M. Correlation between refractive
and corneal topographic changes after photorefractive keratectomy
for myopia. J Refract Surg. 2001;17:129-133.
Figure 7-12. Aprofile image depicting posterior keratoconus. 17. Langenbucher A, Torres F, Behrens A, Suarez E, Haigis W, Seitz B.
Consideration of the posterior corneal curvature for assessment of
corneal power after myopic LASIK. Acta Ophthalmol Scand. 2004;
82(3 Pt 1):264-269.
8. Speicher L, Gottinger W. Progressive keratektasie nach laser-in- 18. Seitz B, Torres F, Langenbucher A, Behrens A, Suarez E. Posterior
situ-Keratomileusis (LASLK). Klin Monatsbl Augen heilkd. 1998; corneal curvature changes after myopic laser in situ keratomileusis.
213:247-251. Ophthalmology. 2001;108(4):666-672.
9. Shimmura S, Yang HY, Bissen-Miyajima H, et al. Posterior corneal
protrusion after PRK. Cornea. 1997;16:686-688.
10. Naroo SA, Charman WN. Changes in posterior corneal curvature
after photorefractive keratectomy. J Cataract Refract Surg. 2000;
26(6):872-878.
 CHAP TER 8

Corneal Evaluation Using the

Artemis VHF Digital Ultrasound
Epithelial Thickness Profiles
Dan Z. Reinstein, MD, MA(Cantab), FRCSC, FRCOphth;
Timothy J. Archer, MA(Oxon), DipCompSci(Cantab);
and Marine Gobbe, MST(Optom), PhD

K
eratoconus is a non-inflammatory corneal disease between normal eyes with unusual topography and early
characterized by a cone-like shaped protrusion of keratoconus was more difficult and so efforts to improve
the cornea associated with thinning of the stroma. the detection of keratoconus were undertaken.
Prior to the use of advanced imaging techniques, kerato- In 1989, Rabinowitz et al analyzed and compared the
conus was diagnosed clinically by high against-the-rule topographic findings of keratoconic eyes with normal eyes.
astigmatism, a history of refractive progression, scissoring They described the pattern of inferior steepening and asym-
effect on retinoscopy, microscopic signs visible on slit- metric bowtie, but also derived three quantitative param-
lamp examination, and progressive corneal thinning, often eters from the topography data that were statistically sig-
resulting in impaired quality of vision. The introduction of nificantly different between normal eyes and keratoconus
color-coded maps derived from computerized front surface eyes including central corneal power, difference in corneal
placido topography by Klyce in 19841 has made the diag- power between fellow eyes in the same patients, and steep-
nosis of keratoconus easier, as patterns including inferior ening of the inferior cornea compared with the superior
steepening, asymmetric bowtie, and skew bowtie typical cornea.3 Since then, many different indices derived from
of keratoconus can be seen early in the progression of the front surface corneal topography have been suggested by
disease.2,3 Rabinowitz et al and Klyce et al to provide physicians with
The detection of keratoconus took on a greater impor- an automated detection of keratoconus to complement the
tance following the introduction and burgeoning popu- subjective interpretation of the topographic pattern.3-12
larity of corneal refractive surgery. It did not take long Rabinowitz et al also published a concise topography clas-
before it was realized that excimer laser surgery in frank sification summary to describe the differing pattern types
keratoconic eyes could accelerate the progression of the seen on topography and the related association with cor-
disease. However, it was not known whether PRK or LASIK neal abnormalities.2
could be safely performed in eyes with mild keratoconus, In 1995, the Orbscan tomographer (Bausch & Lomb,
although it seemed likely that these eyes would be at Rochester, NY) was introduced as the first commercially
higher risk of developing ectasia. Mild keratoconus is often available instrument capable of obtaining corneal posterior
described as forme fruste keratoconus (FFKC), which we surface elevation data. In keratoconus, the front and back
will define here as an eye with demonstrable topographic surface of the stroma are yoked together, so the forward
abnormalities consistent with keratoconus in the absence of bulge associated with the cone is evident on both the front
clinical evidence of keratoconus. With computerized front surface and the back surface of the stroma. Therefore, a
surface topography, keratoconus could be easily picked up topographic eccentric cone on the anterior elevation best-
from earlier stages of the disease; however, differentiating fit sphere (BFS) coincident with a topographic cone on the

Wang M, ed.
Keratoconus & Keratoectasia: Prevention, Diagnosis, and Treatment (pp.77–86) 77
© 2010 SLACK Incorporated
78 CHAPTER 8

posterior elevation BFS would be expected in a keratoconic In eyes with FFKC, it has been suggested that LASIK
eye. Such posterior elevation BFS information promised to should be avoided but PRK might be suitable34,35; however,
improve the sensitivity of keratoconus screening. However, corneal ectasia after PRK in eyes with FFKC has also been
the corneal epithelium has the ability to alter its thickness described.26,29,31,36,37 Combining this fact with the number
profile to re-establish a smooth, symmetrical, optical outer of procedures that have been performed, in the context of
corneal surface and either partially or totally mask the low usage of posterior elevation BFS and inadequate diag-
presence of an irregular stromal surface from front surface nosis of front surface topography, this suggests that PRK or
topography.13 This phenomenon is known clinically as LASIK has probably been performed on many thousands of
extreme steepening leads to epithelial breakdown. Epithelial eyes with FFKC (as defined by front surface topography).
thinning over the cone has been demonstrated using histo- However, ectasia continues to be a relatively rare occurrence,
pathologic analysis of keratoconic corneas by Scroggs and which raises the question as to whether FFKC may only in
Proia14 and later using custom software and a Humphrey- some cases be true keratoconus. Inferior steepening on front
Zeiss OCT system (Humphrey Systems, Dublin, CA) by surface topography might indicate a diagnosis of FFKC, but
Haque et al.15 Therefore, it might be expected that epithelial there can be other causes of inferior steepening aside from
compensation by thinning over the cone in keratoconus keratoconus. For the remainder of this chapter, we will refer
would also be seen to a lesser degree in early keratoconus. to such eyes as suspect keratoconus rather than FFKC.
Taking this idea further, epithelial thinning could be suf- If absolutely all eyes with inferior steepening, asymmet-
ficient in early keratoconus to compensate completely for a ric bowtie or skew bowtie on front surface topography were
small stromal front surface cone and cause the front surface excluded from surgery, then most eyes with keratoconus
corneal topography to appear normal. This would also sig- would probably be identified, thus operative sensitivity
nify that posterior elevation BFS might be a more sensitive would be high. However, not all eyes with inferior steepen-
method of screening for keratoconus, as posterior elevation ing, asymmetric bowtie or skew bowtie have keratoconus,
BFS changes would be evident before front surface topog- so a number of suitable patients would be rejected for sur-
raphy changes occur. Corneal posterior elevation BFS and gery. Similarly, if all eyes with an eccentric posterior eleva-
indices obtained from tomographers such as Orbscan 16,17 tion BFS apex were also excluded from surgery, then the
and Pentacam 18 (Oculus, Wetzlar, Germany) have certainly sensitivity would be increased further and perhaps virtual-
improved the sensitivity of keratoconus screening over ly all eyes with keratoconus would be identified. However,
using front surface topography alone. However, posterior this would exclude even more patients who might actually
elevation BFS alone does not provide the complete solution be suitable candidates. In this scenario, the screening sensi-
as many eyes with an eccentric posterior elevation BFS apex tivity would be high, but the specificity would be very low.
will be normal variants in corneal anatomy in the popula- The low specificity appears to be the root of the problem
tion. with current methods of screening for keratoconus. In
Despite such improvements in keratoconus screening, practice, modern surgeons determine suitability for sur-
performing LASIK on undiagnosed keratoconus is prob- gery in equivocal cases using clinical judgment taking into
ably the leading cause of corneal ectasia.19-31 In many of account all the other recognized indicators for keratoconus
the reported cases, a diagnosis of keratoconus could have as well as front surface topography and posterior elevation
been made from the available preoperative topography BFS. For example, consider an eye with 1.25 D of superior/
maps. In a study of 50 cases of ectasia, Randleman et al20 inferior curvature difference on front surface topography,
identified risk factors for ectasia and found that more than but a normal posterior elevation BFS, an average keratom-
40% of these cases had abnormal preoperative patterns etry of 42 D, no cylinder, no coma, a minimum corneal
including keratoconus, pellucid marginal degeneration, thickness of 520 µm, and best spectacle-corrected visual
and FFKC, with an additional 24.5% of cases that had sus- acuity (BSCVA) of 20/16. If the front surface topography
picious topographic patterns. This suggests that the most was taken in isolation, the patient would likely be rejected
up-to-date keratoconus screening methods or criteria are for surgery. But if the front surface topography is taken
not always employed. For example, the American Society in context with the other information, the surgeon might
of Cataract and Refractive Surgery (ASCRS) annual survey decide against a diagnosis of keratoconus and to proceed
found that only 12% of ASCRS members performing laser with surgery. This means that even the most conscientious
refractive surgery owned an Orbscan in 2000,32 while this surgeon may eventually operate on an eye with keratoconus
has increased to just 45% using either an Orbscan or a at some point. As the popularity of laser refractive surgery
Pentacam in 2007.33 Therefore, 55% of ASCRS members continues to increase with about 3.7 million procedures
still do not consider posterior elevation BFS and rely only performed globally in 2007,38 improving screening for
on front surface topography for preoperative screening. keratoconus has become a critical issue.
It seems likely that even fewer cases of ectasia would be What is needed is a diagnostic technique that would
reported if posterior elevation BFS was used by all sur- render a definitive diagnosis of keratoconus, ideally with
geons. 100% specificity and 100% sensitivity. If keratoconus was
 CORNEAL EVALUATION USING THE ARTEMIS VHF DIGITAL ULTRASOUND 79

present, corneal refractive surgery would not be performed, highlighted. The most commonly used reference surface
whereas if keratoconus was excluded, either PRK or LASIK is the best-fit-sphere. Belin and Ambrosio have suggested
could be performed safely. If the diagnostic test was not using an enhanced reference surface based on the geometry
sensitive enough, some keratoconic eyes would be wrongly of the individual’s own cornea after excluding any conical
classified as normal. This might occur, for example, for or ectatic region. This has the advantage of better defining
some early cases of keratoconus, which might not show the ectatic regions of the cornea and may assist in the iden-
any changes on front surface corneal topography. These tification of early keratoconus.54
eyes are at greater risk of developing ectasia after corneal
refractive surgery. On the other hand, if the diagnostic test
is not specific enough, some normal eyes will be wrongly EPITHELIAL THICKNESS
diagnosed as keratoconus, and, therefore, perfectly good
candidates would be denied the benefits of corneal refrac-
PROFILES
tive surgery.
A new area of interest suggested by our group and the
Recently, a number of other instruments and sugges-
tions have been made as additional methods of screening subject of this chapter is the use of epithelial thickness pro-
for keratoconus. Corneal height data obtained with a files, given that there is epithelial thinning over the cone in
commercial videokeratoscope, decomposed into the set of keratoconus. We first suggested using epithelial thickness
orthogonal Zernike polynomials, have been investigated.39 profiles as a screening tool for keratoconus in January 2003
Corneal wavefront aberrations have been studied and ver- while assessing the suitability of a patient for laser refrac-
tical coma identified as the most useful parameter for dif- tive surgery who had an eccentric posterior elevation BFS
ferentiating normal and suspect keratoconus eyes.40,41 The apex, but front surface topography and anterior elevation
Ocular Response Analyser (Reichert, Depew, NY) intro- BFS were normal (personal communication, DZ Reinstein).
duced two new parameters, corneal hysteresis and corneal The patient also did not have against-the-rule astigmatism,
resistance factor, which provide an indication of corneal steep keratometry, elevated coma, decreased BSCVA, nor
biomechanical properties. However, because of significant low contrast sensitivity. The only suspicious parameter
overlap between normal and keratoconic populations, the was the eccentric posterior elevation BFS apex making a
sensitivity of corneal hysteresis and corneal resistance fac- confident diagnosis of keratoconus difficult; this patient
tor is relatively low. Several new variables derived from sig- could easily have been operated on had posterior elevation
nal analysis of the response waveform have been proposed, BFS been unavailable. In an attempt to make a definitive
and the value of these variables in discriminating between diagnosis, we considered the possibility that the epithelium
normal and suspect keratoconus is currently being inves- might be masking the cone on the stromal front surface
tigated.42,43 that was apparent on the posterior elevation BFS. To do
Indices based on corneal thickness profile44 have also this, we obtained a map of the epithelial thickness pro-
been suggested. Knowledge of the corneal thickness profile file using the Artemis very high-frequency (VHF) digital
in keratoconus is certainly of interest as progressive cor- ultrasound scanner (ArcScan Inc, Morrison, CO), which
neal thinning is a well-known indicator of the evolution of showed a localized area of thin epithelium coincident with
keratoconus. Some studies have provided corneal thickness the (x,y) location of the posterior elevation BFS apex. This
measurements in the peripheral cornea as well as the cen- led us to the conclusion that the eye had a mild form of
tral cornea and have suggested that the difference between keratoconus and was therefore rejected for surgery.
central and peripheral thickness could be used as an index A similar example of an eye where epithelial changes
to detect keratoconus.45-50 More recently, the progression have completely masked a posterior elevation BFS apex
of pachymetric values from the thinnest point to a 10-mm from the front surface topography is shown in Figure 8-1
diameter44,51,52 has been suggested as a useful parameter (column 5). Following this case, we decided to formally
for the evaluation and screening of keratoconus. investigate epithelial thickness profiles in suspect kerato-
Work is also being done in the area of genetics to try to conus eyes to find out whether the conclusion we had come
identify genes associated with keratoconic patients.53 For to in this example was correct.
example, Rabinowitz et al found that there was a suppres- To formally distinguish abnormal from normal epi-
sion of transcripts for aquaporin 5, which is an important thelial thickness profiles, we set out to study a population
water channel protein, in keratoconic corneas. of normal eyes to define the normal epithelial thickness
Using the Pentacam, Belin and Ambrosio suggested profile. In parallel, we also set out to study the epithelial
a new display to enhance the ability to screen for cor- thickness profile in a population of keratoconic eyes to
neal abnormalities. Elevation maps are typically viewed by describe epithelial changes with keratoconus. Knowing the
comparing the elevation data to some standard reference epithelial thickness profile in each population, we aimed to
surface. By subtracting a known shape from the raw eleva- qualitatively assess the differences to be able to discrimi-
tion data, the elevation differences or abnormalities are nate between the two populations. Any departure from
80 CHAPTER 8

a normal epithelial thickness profile might be used as a

very sensitive indicator of stromal surface irregularity and
Epithelial Thickness Profile
therefore as a tool to detect early keratoconus. in Normal Eyes
The Artemis VHF digital ultrasound system has been We set out to characterize the in vivo epithelial thick-
previously described in detail.55-57 Briefly, Artemis VHF ness profile in a population of normal eyes with no ocular
digital ultrasound is carried out using an ultrasonic stand- pathology other than refractive error. We obtained the
off medium. The patient sits and positions the chin and epithelial thickness profile across the central 10 mm diam-
forehead into a headrest while placing the eye in a soft eter of the cornea for 110 normal eyes of 56 patients and
rimmed eye-cup. Warm sterile normal saline (33°C) is averaged the data in the population. Epithelial thickness
filled into the darkened scanning chamber. The patient values for left eyes were reflected in the vertical axis and
fixates on a narrowly focused aiming beam, which is coax- superimposed onto the right eye values so that nasal/tem-
ial with the infra-red camera, the corneal vertex, and the poral characteristics could be combined.57
center of rotation of the scanning system. The technician
The average epithelial thickness map revealed that the
adjusts the center of rotation of the system until it is coaxial
epithelium was not a layer of homogeneous thickness as
with the corneal vertex. In this manner, the position of
had previously been thought, but followed a very distinct
each scan plane is maintained about a single point on the
pattern (Figure 8-1A). The epithelium was 5.7 µm thicker
cornea, and corneal mapping is therefore centered on the
inferiorly than superiorly and 1.2 µm thicker temporally
corneal vertex. The Artemis VHF digital ultrasound uses
than nasally. The pattern of thicker epithelium inferiorly
a broadband 50 MHz VHF ultrasound transducer (band-
than superiorly and thicker epithelium nasally than tempo-
width approximately 10 to 60 MHz), which is swept by a
rally was consistent across a majority of eyes in the popula-
reverse arc high-precision mechanism to acquire B-scans as
tion sampled. The average central epithelial thickness was
arcs that follow the surface contour of anterior or posterior
53.4 µm, and the standard deviation was only 4.6 µm.57
segment structures of interest. Performing a three-dimen-
This indicated that there was little variation in central epi-
sional scan set with the Artemis 1 takes approximately 2 to
3 minutes per each eye. thelial thickness in the population. The thinnest epithelial
point within the central 5 mm of the cornea was displaced
Using VHF digital ultrasound, interfaces between tis-
0.33 mm (±1.08) temporally and 0.90 mm (±0.96) supe-
sues are detected at the location of the maximum change
riorly with reference to the corneal vertex (Figure 8-2).
in acoustic impedance (the product of the density and
Figure 8-3A shows a B-scan of a normal cornea where the
the speed of sound). It was first demonstrated in 1993
epithelium appears regular in thickness.
that acoustic interfaces being detected in the cornea
were located spatially at the epithelial surface and at the Figure 8-4, Column 1 shows the keratometry, Atlas 995
interface between epithelial cells and the anterior surface (Carl Zeiss Meditec, Jena, Germany) corneal topography
of Bowman’s layer.58 This indicated that stromal thick- map and PathFinder corneal analysis, Orbscan II (software
ness measurement with VHF digital ultrasound includes version 3.00) anterior elevation BFS, Orbscan II posterior
Bowman’s layer. The posterior boundary of the stroma elevation BFS, and Artemis epithelial thickness profile of
with VHF digital ultrasound is located at the interface a normal eye.
between the endothelium and the aqueous as this is the
location of the maximum change in acoustic impedance. Epithelial Thickness Profile
This indicated that stromal thickness measurement with in Keratoconic Eyes
VHF digital ultrasound includes Descemet’s and the endo-
thelium. We have characterized the in vivo epithelial thickness
profile in a population of keratoconic eyes. The subjects
Three-Dimensional Epithelial included for the study had previously been diagnosed with
keratoconus, and the diagnosis was confirmed by clinical
Pachymetric Topography signs of keratoconus such as microscopic signs at the slit-
For three-dimensional scan sets, the scan sequence con- lamp, corneal topographic changes, high refractive astig-
sisted of four meridional B-scans at 45-degree intervals. matism, reduced best-corrected visual acuity (BCVA) and
Each scan sweep takes about 0.25 seconds and consisted contrast sensitivity, and significant levels of higher-order
of 128 scan lines or pulse echo vectors. Ultrasound data aberrations, in particular vertical coma. We measured the
are digitized and stored. The digitized ultrasound data are epithelial thickness profile across the central 10-mm diam-
then transformed using patented Cornell University digital eter of the cornea for 20 keratoconic eyes of 13 patients and
signal processing technology, which includes auto-cor- averaged the data in the population. Epithelial thickness
relation of back surface curvatures to center and align the values for left eyes were reflected in the vertical axis and
meridional scans. A speed of sound constant of 1640 m/s superimposed onto the right eye values so that nasal/tem-
was used. poral characteristics could be combined.
 CORNEAL EVALUATION USING THE ARTEMIS VHF DIGITAL ULTRASOUND 81

B Figure 8-2. Plot showing the mean location of the thinnest epithelium in a
population of 110 normal eyes and 20 keratoconic eyes. The blue dot repre-
sents the mean location of the thinnest point for the normal population, and
the dotted blue line represents one standard deviation. The red dot repre-
sents the mean location of the thinnest point for the normal population, and
the dotted red line represents one standard deviation.

A B

Figure 8-1. Mean epithelial thickness profile for a population of 110 normal
eyes and a population of 20 keratoconic eyes. The epithelial thickness profiles
for all eyes in each population were averaged using mirrored left eye sym-
metry. The color scale represents epithelial thickness in microns. ACartesian
1-mm grid is superimposed with the origin at the corneal vertex. (Figure
Figure 8-3. (A) Horizontal non-geometrically corrected B-scan of a normal
8-1Ais reproduced with permission from Reinstein DZ, Archer TJ, Gobbe M,
cornea obtained using the Artemis very high-frequency digital ultrasound
Silverman RH, Coleman DJ. Epithelial thickness in the normal cornea: three-
arc-scanner. The epithelium appears uniform in thickness across the 10-mm
dimensional display with Artemis very high-frequency digital ultrasound. J
diameter of the scan. (B) Vertical non-geometricallycorrected B-scan of a ker-
Refract Surg. 2008;24:571-581.)
atoconic cornea obtained using the Artemis very high-frequency digital ultra-
sound arc-scanner. The epithelium appears very thin centrally coincident with
The average epithelial thickness profile in keratoconus a visible cone on the back surface. The epitheliumis clearly thicker on either
revealed that the epithelium was significantly more irregu- side of the cone. The central epithelium is much thinner, and the peripheral
lar in thickness. The epithelium was thinnest at the apex of epitheliumis much thicker compared to that seen in the normal eye.
the cone, and this thin epithelial zone was surrounded by
an annulus of thickened epithelium (Figure 8-1B). While
all eyes exhibited the same epithelial doughnut pattern, thinnest point and the thickest point as well as the differ-
characterized by a central thin zone surrounded by an ence in thickness between the thinnest and the thickest
annulus of thicker epithelium, the thickness values of the epithelium varied greatly between eyes. There was a sig-
82 CHAPTER 8

Figure 8-4. Central keratometry, Atlas corneal topography and PathFinder corneal analysis, Orbscan anterior and posterior elevation BFS, and Artemis
epithelial thickness profile for one normal eye, one keratoconic eye, and three example eyes where the diagnosis of keratoconus might be misleading
fromtopography. The final diagnosis based on the epithelial thickness profile is shown at the bottomof each example. (Reproduced with permission from
Reinstein DZ, Archer TJ, Gobbe M. Improved diagnosis in keratoconus screening bythe additional consideration of the epithelial thickness profile. JRefract
Surg. 2009;25:604-610.)

nificant correlation between the thinnest epithelium and the thickness of the thinnest epithelium and the difference
the steepest keratometry (D), indicating that as the cornea in thickness between the thinnest and the thickest epithe-
became steeper, the epithelial thickness became thinner. lium. This indicated that, as the epithelium thinned, there
In addition, there was a significant correlation between was an increase in the irregularity of the epithelial thick-
 CORNEAL EVALUATION USING THE ARTEMIS VHF DIGITAL ULTRASOUND 83

ness profile. The location of the thinnest epithelium within front surface topography. In other words, in the presence of
the central 5 mm of the cornea was displaced 0.49 mm (± normal front surface topography, thinning of the epithelium
0.58 mm) temporally and 0.46 mm (±0.49 mm) inferiorly coincident with the location of the posterior elevation BFS
with reference to the corneal vertex (see Figure 8-2). The apex would represent total masking or compensation for a
mean epithelial thickness for all eyes was 44.2 ± 6.0 µm at subsurface stromal cone and herald posterior elevation BFS
the corneal vertex and 36.4 ± 5.0 µm at the thinnest point. changes that do represent keratoconus. Conversely, finding
Figure 8-3B shows a B-scan for a keratoconic cornea, which thicker epithelium over an area of topographic steepening or
demonstrates the lack of homogeneity in epithelial thick- an eccentric posterior elevation BFS apex would imply that
ness as well as central corneal thinning. There is epithelial the steepening is not due to a keratoconic subsurface stromal
thinning over the cone and relative epithelial thickening cone, but more likely due to localized epithelial thickening.
adjacent to the stromal surface cone. Figure 8-4, Column Localized compensatory changes in epithelial thickness
2 shows the keratometry, Atlas 995 corneal topography profiles can be detected by Artemis VHF digital ultrasound
map and PathFinder corneal analysis, Orbscan II ante- once they exceed 1 to 2 µm. In a way, examination of epithe-
rior elevation BFS, Orbscan II posterior elevation BFS, and lial thickness profile irregularities provides a very sensitive
Artemis epithelial thickness profile of a keratoconic eye. As method of examining stromal surface topography-by-proxy.
expected, the front surface topography shows inferotem- Therefore, this technique provides increased sensitivity and
poral steepening with steep average keratometry and high specificity to a diagnosis of keratoconus well in advance of
astigmatism; the anterior and posterior elevation BFS maps any detectable corneal front surface topographic change.
demonstrate that the apex of the cone is located infero-
temporally; the epithelial thickness profile shows epithelial
thinning at the apex of the cone surrounded by an annulus CASE EXAMPLES
of thicker epithelium. The steepest cornea coincides with
the apex of the anterior and posterior elevation BFS as well Figure 8-4 shows three selected examples where epithelial
as with the location of the thinnest epithelium. thickness profiles helped to interpret and diagnose anterior
and posterior elevation BFS abnormalities. In each case, the
Diagnosing Early Keratoconus Using epithelial thickness profile appears to be able to differentiate
Epithelial Thickness Profiles cases where the diagnosis of keratoconus is uncertain, from
normal.59 Case 1 (OS) represents a 25-year-old man with
Mapping of the epithelial thickness profile reveals a very a manifest refraction of –1.00 –0.50 x 150 and a best spec-
distinct thickness profile in keratoconus compared to that tacle-corrected visual acuity (BSCVA) of 20/16. Atlas corneal
of normal corneas. Clearly, the epithelial thickness profile topography demonstrated inferior steepening, which would
will change as the keratoconus itself evolves. Therefore, traditionally indicate keratoconus. The keratometry was
epithelial thickness profiles can be used to confirm or 45.25/43.25 D x 76, and PathFinder corneal analysis classi-
exclude a diagnosis of keratoconus in eyes suggestive but fied the topography as normal. Orbscan II posterior eleva-
not conclusive of a diagnosis of keratoconus on topography tion BFS showed that the posterior elevation BFS apex was
at a very early stage in the expression of the disease. decentered infero-temporally. Corneal pachymetry mini-
The epithelial thickness profile in normal eyes demon- mum by handheld ultrasound was 479 µm. Contrast sensi-
strates that the epithelium is on average thicker inferiorly tivity was slightly below the normal range measured using
than superiorly and slightly thicker nasally than temporally. the CSV-1000 (Vector Vision Inc, Greenville, Ohio). There
There is very little variation in epithelial thickness within was –0.30 µm (OSA notation) of vertical coma on WASCA
both the inferior hemi-cornea and the superior hemi-cor- aberrometry. Corneal hysteresis was 7.5 mmHg, and corneal
nea. In contrast, in keratoconic eyes, the epithelial thick- resistance factor was 7.1 mmHg, which are low, but these
ness profile is doughnut shaped with localized thinning could be affected by the low corneal thickness. The combi-
inferotemporally overlying the stromal cone, surrounded nation of inferior steepening, an eccentric posterior eleva-
by an annulus of thicker epithelium. In early keratoconus, tion BFS apex, and thin cornea raised the suspicion of kera-
we would expect to see the pattern of epithelial thinning toconus although there was no suggestion of keratoconus
surrounded by an annulus of thicker epithelium coincident by refraction, keratometry, or PathFinder corneal analysis.
with a suspected cone on posterior elevation BFS. Therefore, Artemis epithelial thickness profile showed a pattern typical
epithelial thickness profiles might be used to confirm or of keratoconus with a region of epithelial thinning displaced
exclude a diagnosis of keratoconus in eyes suggestive but inferotemporally over the eccentric posterior elevation BFS
not conclusive of a diagnosis of keratoconus on front surface apex, surrounded by an annulus of epithelial thickening.
topography. The coincidence of epithelial thinning together The coincidence of an area of epithelial thinning with the
with an eccentric posterior elevation BFS apex may reveal apex of the posterior elevation BFS, as well as the increased
whether or not to ascribe significance to an eccentric poste- irregularity of the epithelium, confirmed the diagnosis of
rior elevation BFS apex occurring concurrently with a normal early keratoconus.
84 CHAPTER 8

Case 2 (OD) represents a 31-year-old woman, with topography and the normality of nearly all other screening
a manifest refraction of –2.25 –0.50 x 88 and a BSCVA parameters, it is feasible that this patient could have been
of 20/16. Atlas corneal topography demonstrated a very deemed suitable for corneal refractive surgery and subse-
similar pattern to case 1 of inferior steepening, therefore quently developed ectasia. As we were able to also consider
suggesting that the eye could also be keratoconic. The kera- the epithelial thickness profile, this patient was rejected for
tometry was 44.12/44.75 D x 148, and PathFinder corneal corneal refractive surgery. This kind of case may explain
analysis classified the topography as suspect subclinical some reported cases of ectasia “without a cause.”60
keratoconus. Orbscan II posterior elevation BFS showed
that the apex was slightly decentered nasally. Corneal
pachymetry minimum by handheld ultrasound was 538 CONCLUSION
µm. Contrast sensitivity was in the normal range. There
was 0.32 µm (OSA notation) of vertical coma on WASCA We have demonstrated that the epithelial thickness
aberrometry. Corneal hysteresis was 10.1 mmHg, and cor- profile was significantly different between normal eyes and
neal resistance factor was 9.8 mmHg, which are well within keratoconic eyes. Whereas the epithelium in normal eyes
normal range. The combination of inferior steepening, was relatively homogeneous in thickness with a pattern
against-the-rule astigmatism and high degree of vertical of slightly thicker epithelium inferiorly than superiorly,
coma raised the suspicion of keratoconus, which was also the epithelium in keratoconic eyes was irregular showing
noted by PathFinder corneal analysis. Artemis epithelial a epithelial doughnut pattern and a marked difference in
thickness profile showed a typical normal pattern with thickness between the thin epithelium at the center of the
thicker epithelium inferiorly and thinner epithelium supe- doughnut and the surrounding annulus of thick epithe-
riorly. Thicker epithelium inferiorly over the suspected lium. We have shown that the epithelial thickness profile
cone (inferior steepening on topography) was inconsistent progresses along with the evolution of keratoconus. More
with an underlying stromal surface cone, and, therefore, advanced keratoconus produces more irregularity in the
the diagnosis of keratoconus was excluded. This patient epithelial thickness profile. We have found that the distinc-
would have been rejected for surgery given a documented tive epithelial doughnut pattern associated with keratoco-
PathFinder corneal analysis warning of suspect subclinical nus can be used to confirm or exclude the presence of an
keratoconus, but given the epithelial thickness profile, this underlying stromal surface cone in cases with normal or
patient was deemed a suitable candidate for LASIK. suspect front surface topography as well as being a “quali-
The anterior corneal topography in case 3 (OD) bears no fier” for the finding of an eccentric posterior elevation BFS
features related to keratoconus. The patient is a 35-year-old apex.
woman with a manifest refraction of –4.25 –0.50 x 4 and Knowledge of the differences in epithelial thickness
a BSCVA of 20/16. The refraction had been stable for at profile between the normal population and the keratoconic
least 10 years, and the contrast sensitivity was within nor- population allowed us to identify several features of the
mal limits. The keratometry was 43.62/42.62 D x 74, and epithelial thickness profile that might help to discriminate
PathFinder analysis classified the topography as normal. between normal eyes and suspect keratoconus eyes. We are
Orbscan II posterior elevation BFS showed that the apex currently developing a scoring system based on these fea-
was slightly decentered inferotemporally, but the anterior tures to quantify the deviation from the normal epithelial
elevation BFS apex was well centered. Corneal pachymetry thickness profile.
minimum by handheld ultrasound was 484 µm. Pentacam Randleman, in his paper assessing risk factors for ectasia,
(Oculus, Wetzlar, Germany) keratoconus screening indices reported that ectasia might still occur after uncomplicated
were normal. WASCA ocular higher-order aberrations surgery in appropriately screened candidates.20 Mapping of
were low (RMS=0.19 µm) as well as the level of vertical epithelial thickness profiles might provide an explanation
coma (coma=0.066 µm). Corneal hysteresis was 8.9 mmHg, for these cases; it could be that a stromal surface cone was
and corneal resistance factor was 8.8 mmHg, both within masked by epithelial compensation and the front surface
normal limits. In this case, only the slightly eccentric topography appeared normal. Mapping of the epithelial
posterior elevation BFS apex and the low–normal corneal thickness profile may increase sensitivity and specificity
thickness were suspicious for keratoconus, while all other of screening for keratoconus compared to current conven-
screening methods gave no indication of keratoconus. tional corneal topographic screening alone and may be use-
However, the epithelial thickness profile showed an epithe- ful in clinical practice in two very important ways.
lial doughnut pattern coincident with the eccentric poste- First, epithelial thickness mapping can exclude the
rior elevation BFS apex, indicating the probable presence of appropriate patients by detecting keratoconus earlier or
keratoconus. In this case, it seems that the epithelium had confirming keratoconus in cases where topographic chang-
fully compensated for the stromal surface irregularity so es may be clinically judged as being “within normal limits.”
that the anterior surface topography of the cornea appeared Epithelial information allows an earlier diagnosis of kera-
perfectly regular. Given the regularity of the front surface toconus as epithelial changes will occur before changes on
 CORNEAL EVALUATION USING THE ARTEMIS VHF DIGITAL ULTRASOUND 85

the front surface of the cornea become apparent. Epithelial 9. Nesburn AB, Bahri S, Salz J, et al. Keratoconus detected by vid-
thinning coincident with an eccentric posterior elevation eokeratography in candidates for photorefractive keratectomy. J
Refract Surg. 1995; 11:194-201.
BFS apex, and, in particular, if surrounded by an annu-
10. Chastang PJ, Borderie VM, Carvajal-Gonzalez S, Rostene W,
lus of thicker epithelium, is consistent with keratoconus. Laroche L. Automated keratoconus detection using the EyeSys vid-
Excluding early keratoconic patients from laser refractive eokeratoscope. J Cataract Refract Surg. 2000;26:675-683.
surgery will reduce and potentially eliminate the risk of 11. Maeda N, Klyce SD, Smolek MK, Thompson HW. Automated
iatrogenic ectasia of this etiology and therefore increase the keratoconus screening with corneal topography analysis. Invest
safety of laser refractive surgery. From our data, 136 eyes Ophthalmol Vis Sci. 1994;35:2749-2757.
12. Kalin NS, Maeda N, Klyce SD, Hargrave S, Wilson SE. Automated
out of 1,532 consecutive myopic eyes screened for refrac-
topographic screening for keratoconus in refractive surgery candi-
tive surgery demonstrated abnormal topography suspect of dates. Clao J. 1996;22:164-167.
keratoconus. All 136 eyes were screened with Artemis VHF 13. Reinstein DZ, Archer T. Combined Artemis very high-frequency
digital ultrasound arc-scanning, and individual epithelial digital ultrasound-assisted transepithelial phototherapeutic kera-
thickness profiles were mapped. Out of 136 eyes with sus- tectomy and wavefront-guided treatment following multiple cor-
pect keratoconus, only 22 eyes (16%) were confirmed as neal refractive procedures. J Cataract Refract Surg. 2006;32:1870-
1876.
keratoconus.61
14. Scroggs MW, Proia AD. Histopathological variation in keratoco-
Secondly, epithelial thickness profiles may be useful nus. Cornea. 1992;11:553-559.
in excluding a diagnosis of keratoconus despite suspect 15. Haque S, Simpson T, Jones L. Corneal and epithelial thickness in
topography. Epithelial thickening over an area of topo- keratoconus: a comparison of ultrasonic pachymetry, Orbscan II,
graphic steepening implies that the steepening is not due and optical coherence tomography. J Refract Surg. 2006;22:486-
493.
to an underlying ectatic surface. In such cases, excluding
16. Auffarth GU, Wang L, Volcker HE. Keratoconus evaluation using
keratoconus using epithelial thickness profiles appears the Orbscan Topography System. J Cataract Refract Surg. 2000;26:
to allow patients who otherwise would have been denied 222-228.
treatment due to suspect topography to be deemed suit- 17. Rao SN, Raviv T, Majmudar PA, Epstein RJ. Role of Orbscan II in
able for surgery. From our data, out of the 136 eyes with screening keratoconus suspects before refractive corneal surgery.
suspect keratoconus screened with Artemis VHF digital Ophthalmology. 2002;109:1642-1646.
18. de Sanctis U, Loiacono C, Richiardi L, Turco D, Mutani B, Grignolo
ultrasound arc-scanning, 114 eyes (84%) showed normal
FM. Sensitivity and specificity of posterior corneal elevation
epithelial thickness profile and were diagnosed as non- measured by Pentacam in discriminating keratoconus/subclinical
keratoconic and deemed suitable for corneal refractive keratoconus. Ophthalmology. 2008;115:1534-1539.
surgery. Preliminary 1 year post-LASIK follow-up data on 19. Randleman JB, Trattler WB, Stulting RD. Validation of the Ectasia
these demonstrated equal stability and refractive outcomes Risk Score System for preoperative laser in situ keratomileusis
as matched control eyes.61 screening. Am J Ophthalmol. 2008;145:813-818.
20. Randleman JB, Woodward M, Lynn MJ, Stulting RD. Risk assess-
In summary, epithelial thickness mapping appears to be ment for ectasia after corneal refractive surgery. Ophthalmology.
a new and useful tool for aiding in the diagnosis of kerato- 2008;115:37-50.
conus when topographical changes are equivocal. 21. Seiler T, Quurke AW. Iatrogenic keratectasia after LASIK in a case
of forme fruste keratoconus. J Cataract Refract Surg. 1998;24:1007-
1009.
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6. Rabinowitz YS, Rasheed K. KISA% index: a quantitative video- torefractive keratectomy. Ophthalmology. 2000;107:640-652.
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30. Randleman JB, Russell B, Ward MA, Thompson KP, Stulting 48. Avitabile T, Marano F, Castiglione F, Reibaldi A. Keratoconus stag-
RD. Risk factors and prognosis for corneal ectasia after LASIK. ing with ultrasound biomicroscopy. Ophthalmologica. 1998;212
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Graefes Arch Clin Exp Ophthalmol. 2007;245:869-875. thickenss as a diagnostic test. Arch Ophthalmol. 1969;82:182-188.
32. Leaming D. 2000 Survey of US ASCRS Members, 2000. 50. Avitabile T, Franco L, Ortisi E, et al. Keratoconus staging: a com-
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35. Bahar I, Levinger S, Kremer I. Wavefront-supported photorefrac- tem. J Cataract Refract Surg. 2007;33:1708-1712.
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myopic astigmatism and suspected keratoconus. J Refract Surg. progression from the thinnest point to the limbus: study based on
2006;22:533-538. a normal and a keratoconus population to create reference values.
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ectasia after photorefractive keratectomy. J Cataract Refract Surg. 53. Rabinowitz YS, Dong L, Wistow G. Gene expression profile stud-
2006;32:1395-1398. ies of human keratoconus cornea for NEIBank: a novel cornea-
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keratectomy. J Refract Surg. 2002;18:535-541. 54. Belin MW, Ambrosio R. Keratoconus/ectasia detection with
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videokeratoscopic height data. Optom Vis Sci. 1996;73:721-728. pachymetric topography. Ophthalmology. 1994;101:432-438.
40. Buhren J, Kuhne C, Kohnen T. [Wavefront analysis for the diagno- 56. Reinstein DZ, Silverman RH, Raevsky T, et al. Arc-scanning very
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41. Gobbe M, Guillon M. Corneal wavefront aberration measurements the corneal epithelium and stroma in laser in situ keratomileusis. J
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42. Fry KL, Luce D, Hersh PS. Integrated Ocular Response Analyzer Epithelial thickness in the normal cornea: three-dimensional dis-
waveform score as a biomechanical index of keratoconus disease play with Artemis very high-frequency digital ultrasound. J Refract
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derived Ocular Response Analyzer (ORA) biomechanical measures sound measurement of the thickness of the corneal epithelium.
in keratoconus. Presented at ARVO; 2008; Ft. Lauderdale, FL. Refract Corneal Surg. 1993;9:385-387.
44. Ambrosio R Jr, Alonso RS, Luz A, Coca Velarde LG. Corneal-thick- 59. Reinstein DZ, Archer TJ, Gobbe M. Improved diagnosis in kera-
ness spatial profile and corneal-volume distribution: tomographic toconus screening by the additional consideration of the epithelial
indices to detect keratoconus. J Cataract Refract Surg. 2006; 32:1851- thickness profile. J Refract Surg. 2009;25:604-610.
1859. 60. Klein SR, Epstein RJ, Randleman JB, Stulting RD. Corneal ectasia
45. Gromacki SJ, Barr JT. Central and peripheral corneal thickness after laser in situ keratomileusis in patients without apparent pre-
in keratoconus and normal patient groups. Optom Vis Sci. 1994; operative risk factors. Cornea. 2006;25:388-403.
71:437-441. 61. Reinstein DZ, Archer TJ, Gobbe M. Stability of LASIK in topo-
46. Owens H, Watters GA. An evaluation of the keratoconic cornea graphically suspect keratoconus confirmed non-keratoconic by
using computerised corneal mapping and ultrasonic measurements Artemis VHF digital ultrasound epithelial thickness mapping: 1-
of corneal thickness. Ophthalmic Physiol Opt. 1996;16:115-123. year follow-up. J Refract Surg. 2009;25:569-577
47. Watters GA, Owens H. Evaluation of mild, moderate, and advanced
keratoconus using ultrasound pachometry and the EyeSys video- Financial Disclosure: Dr. Reinstein has a proprietary interest in Artemis
keratoscope. Optom Vis Sci. 1998;75:640-646. Technology, is an author of patents related to VHF digital ultrasound, and
acts as a consultant to Carl Zeiss Meditec.
 CHAP TER 9

Studies of Wavefront
Aberrometry in Corneal Ectasia

Thomas J. Dingle, MD; Jay S. Pepose, MD, PhD;

Mujtaba A. Qazi, MD; and Geunyoung Yoon, PhD

W
avefront aberrometers quantify whole eye opti- lenses,8 phase plates,9 large stroke adaptive optics,10 cus-
cal errors compared to an unaberrated refer- tomized laser vision correction following corneal collagen
ence wavefront. As first applied to the eye by cross-linking).
Howland and Howland in 1977,1 the shape of the eye’s Multiple authors have reported the specific, characteris-
wavefront error can be quantitatively described using a tic wavefront features of cohorts with keratoconus, forme
polynomial expansion. This methodology deconstructs fruste keratoconus (FFKC), and pellucid marginal degen-
the wavefront into unique Zernike components, calculat- eration, as described further herein. Furthermore, the
ing both lower- and progressively higher-order aberrations integration of wavefront technology as a diagnostic device
following the Zernike pyramid (Figure 9-1). in keratorefractive surgery screening may be another use-
Higher-order aberrations (HOAs) include third-order ful tool in identifying patients with FFKC who may have
and advancing higher Zernike modes, such as coma, trefoil, unanticipated and paradoxical responses to laser vision
spherical aberration, quadrafoil, among others. In normal correction. This information could help minimize the risk
human eyes, the predominant ocular aberrations are the of these elective keratorefractive surgery candidates who
second-order errors,2,3 accounting for 93% of the wave- may develop postoperative frank corneal ectasia.
front error in one study by Porter et al.2 The composite of
individual Zernike aberrations differs for each individual,
while in aggregate as a population they average zero except STUDIES OF WHOLE EYE
for spherical aberration. WAVE ABERRATIONS
In regard to the overall impact on image quality, the
specific Zernike aberrations interact and may be additive In 2002, Maeda et al11 published one of the first
or offset each other.4 However, in general, high levels of reports on wavefront aberrations in keratoconic eyes using
HOAs have a detrimental effect on retinal image quality Shack-Hartmann aberrometry. They found a statistically
that is pupil size dependent. This visual degradation occurs significant increase in total HOAs in 35 keratoconic eyes
in normal and, even more so, in highly aberrated diseased compared to 38 normal eyes, with the predominant HOA
eyes,5,6 such as those with keratoconus (characterized by increase being coma-like and spherical-like aberrations.
high negative vertical coma), pellucid marginal degenera- The characteristic finding of elevated negative vertical
tion (characterized by high trefoil), or corneal transplants. coma has been confirmed using multiple Shack-Hartmann
Up to ninth order Zernike modes may be required to aberrometers, including the Bausch & Lomb Zywave
accurately describe the simulated wavefront of these highly (Rochester, NY),12 the Alcon LADARwave (Fort Worth,
aberrated eyes.7 These latter groups of patients would TX),13 and AMO VISX Wavescan (Abbott Park, IL).14 The
thereby benefit the most from optical correction of higher- dynamic skiascopy-based Nidek-OPD scan (Fremont, CA)15
order aberrations by some means (eg, customized contact also measured a predominance of coma-like aberrations

Wang M, ed.
Keratoconus & Keratoectasia: Prevention, Diagnosis, and Treatment (pp.89–95) 89
© 2010 SLACK Incorporated
90 CHAPTER 9

Figure 9-2. Higher-order aberrations of eyes with mild (left), moderate

(middle), and advanced (right) keratoconus.

Figure 9-1. Lower-order (row 2) and higher-order (rows 3 to 5) wavefront STUDIES OF CORNEAL
aberrations, including third order central coma terms (Z3-1, Z31) and periph- WAVEFRONT ABERRATIONS
eral trefoil terms (Z3-3, Z33).
As opposed to the whole eye wavefront calculated using
aberrometers, the corneal wavefront is derived from video-
in keratoconic eyes. The negative sign of the vertical coma
keratographic measurements of anterior corneal elevation.
is attributed to an inferior shift of the cone’s apex causing
While reviewing the literature of first surface corneal wave-
a relative phase advance of the wavefront in the superior
front aberrations, one should be aware that most of these
cornea.16 Figure 9-2 demonstrates the whole eye wavefront
studies report data relative to the vertex normal, rather
aberrations in mild, moderate, and advanced keratoconus.
than the line of sight (ie, the axis joining the fovea with the
Kosaki et al17 utilized Shack-Hartmann aberrometry natural pupil center without pharmacologic manipulation),
and Zernike vector analysis to describe the magnitude and which is the conventional reference of wavefront aber-
orientation of the higher-order aberrations in keratoconic rometers. The current recommendation of the American
patients. As shown in other studies, the magnitude of total National Standards Institute (ANSI) is to represent all
HOA, vertical coma, trefoil, tetrafoil, and secondary astig- wavefront aberrations with reference to the line of sight.18
matism were significantly higher than in control eyes. In One study of normal eyes indicated that when the value of
addition, this group found that the orientation of the coma angle lambda (the angle between the line of sight and the
and trefoil aberrations differed significantly in keratoconus pupillary axis) is larger than 2 to 3 degrees, the misalign-
and normals. Coma in control eyes showed a superior slow ment, if ignored, can lead to incorrect estimates of cor-
pattern, with a mean axis of 253.7 degrees. However, the neal and internal aberrations as well as the corneal/internal
vertical coma aberrations in keratoconus showed an infe- aberration balance.19
rior slow pattern, as the aberrated wavefront was delayed
Alio et al20 used corneal videokeratography (CSO,
inferiorly (axis at 82.5 degrees for keratoconus and axis at
Florence, Italy) to measure first surface corneal wavefront
91.0 degrees for keratoconus suspects). Trefoil aberrations
aberrations in 40 normal eyes and 40 keratoconic eyes. As
in control eyes showed a fast triangular pattern, with an
with whole eye wavefront studies, there was a significant
axis of 35.4 degrees. In contrast, keratoconic and kerato-
increase in total corneal wavefront HOAs at a 6-mm optical
conus suspect eyes had a slow triangular pattern, with axes
zone in keratoconic eyes compared to normal eyes (RMS
around 90 degrees.
3.14 µm compared to 0.52 µm, respectively), with the larg-
One of the limitations of standard Shack-Hartmann est individual increase in Zernike values seen with coma-
wavefront aberrometry in measuring keratoconic eyes is like (RMS 2.90 µm to 0.35 µm, respectively) and spherical
the limited dynamic range of commercially available sen- aberrations (RMS 1.06 µm to 0.38 µm, respectively).
sors. Pantanelli et al16 recorded measurements in kerato-
Corneal videokeratography has also been used to mea-
conic eyes using a large dynamic range Shack-Hartmann
sure the aberrations in eyes with early or subclinical
wavefront device. They reported that the total HOAs
keratoconus. Buhren et al21 used scanning-slit videoker-
was 5.5 times higher in the keratoconic eyes (RMS 2.24
atography (Orbscan IIz, Bausch & Lomb, Rochester, New
µm) than in the control eyes (RMS 0.41 µm) over a 6.0-
York, USA) to measure 10 fellow eyes in subjects diagnosed
mm pupil. Vertical coma accounted for 53 ± 32% of the
with keratoconus in the contralateral eye. The fellow eye
higher-order variance. Higher-order Zernike modes that
had only minor topographic asymmetry, but no slit-lamp
were statistically different from zero included vertical and
pathology sufficient to independently establish a diagnosis
horizontal coma, secondary astigmatism, and secondary
of keratoconus. In this comparison to 127 normal eyes,
vertical coma.
seventh order Zernike decomposition of the corneal first
surface showed that vertical coma was statistically higher
 STUDIES OF WAVEFRONT ABERROMETRY IN CORNEAL ECTASIA 91

Figure 9-3. Comparison of the posterior

corneal higher-order aberrations in kera-
toconus and normal eyes.

deteriorate retinal image quality, and this may explain why

some studies have shown that the visual performance of
keratoconic eyes with a RGP lens that neutralizes only the
anterior cornea surface irregularity is poorer than that of
normal eyes.24,25
Alternatively, the posterior corneal aberrations may also
have a compensatory effect on the anterior corneal aber-
rations. This subject has been investigated in both normal
Figure 9-4. Wavefront aberrometrymaps showingthe compensatoryeffects of and keratoconic eyes.26 Although the magnitude of the
the posterior corneal aberrations in keratoconus. posterior corneal aberration in mild keratoconus did not
differ from normals, a significantly larger magnitude of
the aberration was measured in moderate and advanced
in the lesser involved eye of patients diagnosed with kera- keratoconus (Figure 9-3). Assuming both anterior and
toconus, suggesting that this is the earliest manifestation posterior corneal surfaces have a similar profile, the sign
of keratoconus. Gobbe et al22 also showed that the corneal- of the aberration induced from the surfaces is opposite to
derived wavefront error of vertical coma is the best detector each other due to the fact that the refractive index differ-
to differentiate between suspected keratoconus and normal ences are opposite in sign. This indicates the compensatory
corneas. In more advanced forms of keratoconus, there is mechanism between the corneal surfaces. While this effect
a toric component of astigmatism in addition to the domi- is negligibly small in normal eyes, 22% and 24% of the
nant odd, coma-like aberrations.21,23 anterior corneal coma were compensated for by the poste-
Several studies have been conducted to investigate the rior corneal coma in advanced and moderate keratoconus,
optical effect of the posterior corneal surface in ectatic dis- respectively. This results in a reduced amount of the total
eases. In normal eyes, the impact of the posterior surface corneal aberration compared to the anterior corneal aber-
on the corneal wavefront is significantly less compared to ration as illustrated in Figure 9-4.
the anterior surface because the difference in refractive Both whole eye wavefront-based studies and the corneal
index between air and cornea is much greater than between topography-based studies arrive at similar conclusions: 1)
the cornea and aqueous humor. However, in these ectatic HOAs in keratoconic eyes are significantly higher than in
eyes with both corneal surfaces highly and non-uniformly normal eyes; and 2) the coma-like aberrations are predomi-
aberrated, the posterior surface can still play a significant nant HOA in keratoconic eyes. However, it is important
role. This was demonstrated in a study using customized to consider the limitations of each technique. Whole eye
back-surface contact lenses, which neutralized the irregular wavefront aberrometry techniques have the advantage
anterior corneal surface but had no effect on the posterior of measuring the aberrations throughout the entire eye,
corneal surface8; significant residual aberrations, mainly including the anterior cornea (air-tear interface), the pos-
derived from the posterior cornea, were measured in some terior cornea, and the lens. In highly aberrated keratoconic
cases even after customized contact lens placement. These eyes, however, individual asymmetric aberrations may
uncorrected posterior corneal aberrations can significantly exceed the dynamic range of the instrument. Most corneal
92 CHAPTER 9

Figure 9-5. The correlation of the ocular higher-order aberrations (right) with
corneal topography (anterior elevation, left) in advanced keratoconus, both at
a 6-mmoptical zone.

Figure 9-6. Mean power maps (top) of

a patient with keratoconus (A) and a
patient with pellucid marginal degen-
eration (B). The area of ectasia is more
central in keratoconus and more periph-
eral in pellucid marginal degeneration.
The steepest region of the mean power
map corresponds to the highest elevation
points above the anterior and poste-
rior best fit spheres and the thinnest
pachymetry area on the Orbscan quad
map (bottom).

topographers and videokeratographers only measure the

anterior corneal surface. A few videokeratography systems
COMPARISON OF CORNEAL
are available that measure the posterior corneal surface; AND WHOLE EYE WAVEFRONTS
however, the accuracy of the posterior analysis has been
suspect.27
IN KERATOCONUS VERSUS
One advantage of topography-based calculations of PELLUCID MARGINAL
corneal first surface versus whole eye wavefront aberra- DEGENERATION
tions is that the diameter of measurement and analysis is
not limited by the pupil or the spacing and focal length of Videokeratographic analysis can demonstrate that the
the lenslet array. Therefore, generally, a far greater number location of the thinnest point on the ectatic cornea is
of data points can be analyzed to derive corneal wavefront significantly different between keratoconus and pellucid
aberrations compared to whole eye wavefront aberrometry. marginal degeneration, the latter having a more peripheral
However, not all topography systems have been validated location. Tang et al23 used a placido-based corneal topog-
to provide the source of reliable and repeatable wavefront rapher to show that the mean curvature data could be
corneal measurements, particularly in keratoconus.28-31 used to accurately predict the location of the cone in these
Several investigators11,32 have found a similarity between two ectatic disorders. Figure 9-6 illustrates the location of
whole eye aberrations and the corneal aberrations mea- ectasia in these two diseases with the corresponding mean
sured by the corneal videokeratographer. This correlation curvature data.
is consistent with the notion that the origin of most, but While there are multiple reports of wavefront charac-
not all, of the higher-order aberrations in keratoconic eyes teristics in keratoconus eyes showing the predominance of
arise from the anterior corneal surface (Figure 9-5). vertical coma, there are only a few reports discussing the
 STUDIES OF WAVEFRONT ABERROMETRY IN CORNEAL ECTASIA 93

Figure 9-7. Shack-Hartmann wavefront

(Zywave, Bausch &Lomb, Rochester, NY)
images and Zernike coefficient elements
in a patient with keratoconus (A) and a
patient with pellucid marginal degenera-
tion (B). Coma aberrations predominate
in keratoconus, while trefoil aberrations
are highest in PMD.

wavefront aberrations in pellucid marginal degeneration.33- one such patient using the InterWave aberrometer, where
35 Oie et al35 compared the Shack-Hartmann wavefront in they describe an abnormal central blur area that corresponds
20 eyes with pellucid marginalis to 76 keratoconic eyes and to the focal, central ectasia. A formal wavefront analysis
105 normal eyes. Total higher order aberrations, trefoil, of the higher-order aberrations was not addressed in their
coma, tetrafoil, and secondary astigmatism were higher in report, but is provided in Figure 9-8 for a subject with
the ecastia groups than for controls (p<0.05). Keratoconic iatrogenic keratoectasia after LASIK. Future study of the
eyes (0.82 ± 0.39 µm) had higher coma than pellucid eyes wavefront characterisitics in these eyes would help to better
(0.56 ± 0.28 µm) (p<0.05). The magnitude of spherical describe the optical quality of vision in these patients.
aberration was of a higher magnitude and opposite in sign
in pellucid marginalis (+0.09 ± 0.10 µm) than keratoconus
(–0.03 ± 0.13 µm) (p<0.05). As discussed above, most of the CONCLUSION
retinal image degradation in ectatic eyes is derived from the
aberrated anterior corneal surface. Therefore, not surpris- The wavefront aberrations in keratoconic eyes are
ingly, the more peripherally localized ectasia in pellucid important to recognize. First, it helps us understand the
marginal degeneration is reflected in a higher degree of quality of vision in these patients and provides a basis from
trefoil, a third-order aberration that is located more periph- which to plan and monitor forms of correction available
erally in the Zernike pyramid. In contrast, the more central now or in the future. As mentioned above, these eyes have
third-order HOA, negative vertical coma, is characteristi- a substantial increase in HOAs compared to normal eyes
cally highly elevated in keratoconus (Figure 9-7). with negative vertical coma being the most predominant
mode, and these HOAs produce detrimental effects on
visual performance. Higher-order aberrations, and vertical
WAVEFRONT CHARACTERISTICS coma specifically, have been shown to decrease visual acu-
IN POST-LASIK ECTASIA ity,37-40 low-contrast visual acuity,40 and contrast sensitiv-
ity.38,41,42
The wavefront aberrations in eyes with postoperative Second, and perhaps most importantly for keratore-
ectasia after keratorefractive surgery are not thoroughly fractive surgeons, it is paramount to recognize these cor-
described in the literature, but likely resemble those found neal and whole-eye wavefront aberrations in screening for
in patients with various stages of keratoconus. Accurate forme fruste ectatic disorders when selecting appropriate
description of these whole eye waves may require an aber- refractive surgery candidates. Retrospective studies of post-
rometer that has an extended dynamic range without sacri- LASIK ectasia have led to the development of an ectasia risk
ficing sensitivity, as described by Pantanelli and colleagues.16 score system.43 The preoperative workup of these patients
Randleman et al36 discussed the wavefront aberrations in includes evaluating parameters that may put the patient
94 CHAPTER 9

at risk for postoperative ectasia (ie, abnormal topography,

low corneal thickness, younger age, high spherical equiva-
lent refractive error). The amount of specific HOAs adds
another useful piece of information to this workup that
may increase awareness as to whether the patient has a
subclinical corneal ectatic disease.13 Increased suspicion is
warranted in patients with elevated negative vertical coma
that may be found in keratoconus or keratoconus suspects.
A surgeon should also be cognizant of high degrees of
trefoil, along with against-the-rule astigmatism and a claw-
shape pattern on axial topography, that is more typical of
pellucid marginal degeneration. As these diagnoses remain
clinically based and not dependent upon any one test,
considering these characteristic wavefront signatures along
with the history, topography, and slit-lamp biomicroscopic
findings may allow ophthalmologists to improve their
diagnostic acumen, patient safety, and surgical outcomes.

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 CHAP TER 1 0

Infrared Photorefraction
Screening

Ying-Ling Ann Chen, PhD; James W. L. Lewis, PhD;

Lei Shi, MS; Ming Wang, MD, PhD; and Tracy S. Swartz, OD, MS, FAAO

A
lthough the introduction of eccentric photorefrac- for comparison with theoretical analysis. The observed
tion dates back to early 80s,1-3 most technicians irregular reflex pattern/image is described verbally, and its
are not familiar with infrared photorefraction. description in words can be vague, unclear, and obviously
Nevertheless, the dynamic infrared photorefraction (DIP) difficult to quantify. The effective use of the retinoscope
technique provides an economical, convenient, and sensi- requires an experienced examiner to skillfully operate and
tive method for detecting irregular astigmatism and high- modify optical settings according to his or her observa-
order aberrations such as keratoconus and keratoectasia tion. This absence of quantitative measures, numbers, and
in the common eye examination. Generally speaking, DIP indices contributes directly to the lack of interest in the
functions as an infrared spot retinoscope that utilizes technique among the corneal specialists.
digital registration and performs image analysis for the Because the eccentric photorefraction and retinoscopy
examiner’s visualization. Even though more sophisti- share a similar optical concept, photorefraction inherits
cated devices are usually available to corneal specialists, the capability of detecting irregular aberration but without
experienced physicians around the world are aware of the the shortcomings of the retinoscope.8 The multimeridian-
sensitivity of this common handheld device in detecting eccentricity DIP concept is illustrated in Figure 10-1. The
an irregular reflex resulting from high-order ocular aber- employment of a beam splitter is similar to that used for
ration.4-6 Prior to computerized testing methods such as retinoscopy, and the use of a camera is comparable to the
autorefraction, the retinoscope was the main method for conventional photorefraction. However, unlike these two
objective measurement of refractive error and identifica- conventional techniques, the DIP uses a two-dimensional
tion of irregular astigmatism. While a retinoscope is a (2D) light source illumination sequence that provides mea-
low-cost, simple optical device, the back-scattered retinal surements of multiple meridians and eccentricities. After
reflex integrates ocular information through all optical positioning her/his eye, the patient sees a rapid sequence
elements similar to that of a more complex wavefront of soft blinking lights from the infrared light source panel.
aberrometer.7 Shortcomings of the current commonly Multiple photographs are taken and then stored within 1
used retinoscope include the effect that the visible light second. The near infrared LED irradiance intensity is very
stimulates a pupillary response which reduces the exam- low compared to common ophthalmic measurements and
ined pupillary area in a non-mydriatic examination. Also, is therefore comfortable to the patients. The non-mydriatic
the bright illumination can be uncomfortable to patients. measurement is performed without room light to observe
Further, the broad-spectrum of the light source integrates larger pupillary area in the examination. The pupillary
chromatic aberration in the measurement and decreases areas of these images are then cropped and displayed in
image contrast and measurement sensitivity. Most of their corresponding measurement meridians on the screen.
all, retinoscopic observations are not stored in digital For a healthy eye, the combined color map exhibits an
form for discussion, sharing, or review, not to mention angular symmetry around the central coaxial image.8

Wang M, ed.
Keratoconus & Keratoectasia: Prevention, Diagnosis, and Treatment (pp.97–106) 97
© 2010 SLACK Incorporated
98 CHAPTER 10

Figure 10-1. Diagramof Dynamic Infrared Photorefraction measurement.

Figure 10-2. Comparison between Shack-Hartmann wavefront aberrometer and Dynamic Infrared Photorefraction. Keratoconus presents the so-called scissors
reflexin the multi-meridian-eccentricityDIP reflex images shown on the left.

Whereas DIP detects high-order aberrations similar to duces 2D multiple projections on the retina. To the exam-
that of the wavefront aberrometer, there are major differ- inee, they appear as small soft lights blinking across on the
ences between the two. Figure 10-2 illustrates a comparison front of the camera. With these low-intensity DIP diffuse
of DIP and the Shack-Hartmann wavefront aberrometer. illuminations, the camera detects not only the double-pass
One difference is the light source. The point source illumi- retroillumination signal but also the direct scattered and
nation in the aberrometer is replaced by the low-cost, low- diffracted signal from optical defects on cornea and lens
intensity, LED sequence of radiant illumination. Aligned to just as an ophthalmic slit-lamp does. Many cornea and
the coaxial illumination on the optical axis, the DIP pro- crystalline lens defects are revealed in the DIP raw images.
 INFRARED PHOTOREFRACTION SCREENING 99

Figure 10-3. The infrared images directly obtained fromthe DIP measurement. Fromleft to right are images of a mild cortex cataract, a keratoconus eye with
endothelium scars from healed hydrop, a case of blepharitis, a cornea metal stain imaged on the 40th day after removal of the debris, and a case of Fuch’s
endotheliumdystrophy. In each image, the white dot near the pupil center is the corneal reflection.

Some examples are displayed in Figure 10-3. From the left refractive status of the eye in conventional applications.2,3,9
to right, these images belong to an eye with a mild cortex This intensity gradient is formed because the particular
cataract, a keratoconus eye with endothelium scars from eccentric photorefraction detects a selective portion of the
∂W
healed hydrop, a case of blepharitis, an eye with a metal partial derivative of wavefront information, ____ , where the
∂x i
stain on the cornea stroma on the 40th day after removal xi indicates the illuminating meridian direction. The slope
of the metal debris, and an eye with Fuch’s endothelium appearance of an ametropic eye represents the existence of
dystrophy, respectively. In each image, the white dot near a second-order aberration of the wavefront (ie, the defo-
the pupil center is the cornea reflection, the first Purkinje cus). Negative and positive signs correspond respectively
image. It is used as an indication of proper ocular align- to the hyperopic and myopic conditions related to the neu-
ment. tralization working distance. The multi-frame integrated
The second difference in the two tecniques is the focus DIP map, therefore, presents a rotationally symmetric
lens. The micro-lenslet array of the aberrometer is replaced pattern corresponding to the DIP point light source illumi-
by a commercial camera lens in the DIP. As the figure nation around the various meridians. A centripetal or cen-
shows, for illuminations in the DIP sequence, the reflex trifugal map illustrates a hyperopic- or a myopic-shifted
wavefronts travel toward the camera lens in slightly differ- eye, respectively. An astigmatic eye presents an elliptical
ent directions that directly correspond to their illumina- appearance aligned to the two principle meridians. For an
tion eccentricities. The camera pupil in the DIP serves as eye with high-order aberration, the map appears irregular.
a spatial filter that permits a selective portion of the wave As an example, the color map at the lower left corner of
information to enter and to be focused on the camera Figure 10-2 shows a case of keratoconus map, which will be
image plane. Multi-meridian, Foucault knife-edge condi- discussed further in the following section.
tions are included in the DIP measurement.
Image registration also differs between the two tech-
niques. Multiple digital images are acquired in DIP instead CLINICAL OBSERVATION
of the single frame imaging in the aberrometer. In the aber-
rometer, the displacement of the focus point (Δx, Δy) of The following are examples that illustrate infrared pho-
each micro-lenslet image is used to determine the surface torefraction images of normal ametropic and keratoconus
normal of the wavefront, and these results are then com- condition.
bined to reconstruct the wavefront aberration map across
the pupillary area. The information stored in the pattern in Emmetropic and Mild Ametropic Eyes
each micro-image and the related intensity ratios between
micro-images are not used for analysis. In DIP, the focused Figure 10-4 exemplifies the DIP images acquired from
image from each point infrared exposure is recorded into the left eye of a 47-year-old Caucasian woman seeking pres-
a high-resolution image; each image corresponds to a byopia correction. The presented eye is 20/20 with no cor-
specified illuminating eccentricity and meridian. After rection (plano). The gray-scale DIP map on the left of Figure
the measurement, the computer identifies and crops the 10-4 illustrates the pupillary infrared reflex images that are
pupil images. The results then present these images in their arranged according to the angular orientation of the respec-
illuminating positions aligned to the coaxial image at the tive illumination sources. These reflex images show no opti-
center. For either a normal or an ametropic eye with little cal defects such as those presented in Figure 10-3. The color
high-order aberration, one typical photorefraction image map on the right illustrates a clearer visualization of the
renders a monotonic brightness change along the illumi- brightness gradient distributions of these images after the
nating meridian and forms the so-called crescent red reflex corneal reflection is removed. “Warmer” colors represent
or “slope.” The crescent or slope is used to determine the brighter signals, and cooler colors indicate a darker reflex.
100 CHAPTER 10

Figure 10-4. The integrated DIP infrared images of an emmetropic 20/ 20 Figure 10-5. DIP measurement of a myopic case with RE-6.25DS +0.75DCx
eye. Each pupil image is a cropped image of the retinal reflex image. (Left) 075 (20/ 25). Color map shows centrifugal pattern indicating myopic condition
gray-scale map. (Right) Color-coded map illustrates the intensity distribution that is greater than the neutralization.
in each reflex image. The uniformity and concentric alignment of images
demonstrates an eye with little high-order aberration.
these cases are shown in Figure 10-6. The leftmost image
shows the most common appearance of a tear wave. These
When viewing a series of reflex images along an arbitrary horizontal tear wave patterns often present shortly after
meridian, the brightness appearance emerges “against the blinking. These parallel horizontal waves may be formed
motion” similar to that observed with spot retinoscopy. by the rims of eyelids. Though not clearly revealed, the
The emmetropic condition is on the hyperopic side relative parallel tear waves can also be observed in the gray-scale
to the neutralized refraction, which is the reciprocal of the map in Figure 10-4. They are slightly more apparent in
working distance. Because of the absence of astigmatism the reflex image in the 90-degree meridian. The second
and irregular higher-order aberrations, the appearance of and third images in Figure 10-6 show wavy prints of tear
the multi-frame color map bears a resemblance to a rota- waves that are less commonly seen than the first kind. This
tionally symmetric pattern. The brighter portions appear could be the consequence of different tear composition.
toward the center, and darker portions are located periph- The two images on the right of the same figure show the
erally. The percentage of high-order aberration (third- to breakup of tear films. None of these 5 images was obtained
seventh-order) compared to the total aberration including from patients with significant dry eye problems. Although
defocus is 3.5% in this measurement. dry eye or tear film breakup can often cause difficulty or
error in the wavefront aberrometer measurement, DIP has
High Myopia no difficulty in acquiring images from patients with these
For an eye that exhibits myopia greater than the neutral- conditions. Although severe dry eye will produce a large
ization value, the DIP color map appears as a centrifugal amount of high-order aberration (such as the middle image
image. Figure 10-5 demonstrates the DIP images that were in Figure 10-3), regular tear wave conditions such as these
acquired from the left eye of a 43-year-old Asian woman. examples do not affect the rotationally symmetric appear-
Her refractive error and best-corrected visual acuity (BCVA) ance of color map in the DIP analysis. Shown in Figure 10-7
is a second measurement made on the same eye in Figure
are –6.25 DS +0.75 DC x 075 and 20/25, respectively. As the
10-5 while significant tear film breakup occurred. The
gray-scale map on the left shows, no significant optical
patient simply held the eye open long enough without blink-
defect was observed. The color map on the right of Figure
ing before the measurement. Emerging from the wobbling
10-5 demonstrates a well-defined symmetric pattern with
wavy background is a DIP color map that mimics the result
outward brighter features, and this resembles “with the
in Figure 10-5. The only difference between the two mea-
motion” behavior of the spot retinoscope of myopia. Again,
surements appears to be the noise from tear film breakups.
in each pupillary reflex image, the gradient increases out-
The percentage of high-order aberration from third- to sev-
ward and evenly along all meridians. The symmetric char-
enth-order relative to the total aberration (from second to
acteristic ensures that no significant high-order aberration
seventh) is 8.4%. When applying numerical analysis to the
is present. The percentages of myopic refraction (sphere)
results, it is found that the normal tear-film noise, as well as
and high-order aberration are 88% and 9.4%, respectively.
many fine structures observed in the reflex, appears to be in
There is a 3.1% aberration from cylinder contribution.
the much higher frequency spectral range. It is not indicated
in the first seven orders Zernike coefficients.
Observation of Tear Film The excellent repeatibilty of the DIP measurement
The DIP measurement technique is sensitive for the enables the accurate observation of successive images, such
detection of comparatively small optical variations such as those of Figures 10-5 and 10-7, to differentiate stable
as tear wave and tear film breakup. Examples of some of and transient optical defects. The image results of Figure
 INFRARED PHOTOREFRACTION SCREENING 101

Figure 10-6. Example DIP images of tear waves and tear filmbreakups.

Figure 10-7. DIP measurement of the same myopic case in Figure 10-5. Tear Figure 10-8. Color maps of two hyperopicastigmaticeyes. Manifest refractions
filmbreakup is clearlyobserved in this measurement. Color map on the right of the two eyes are measured as +5.00 DS+2.50 DCx 90 (20/ 25) and +3.50
shows the same centrifugal pattern as illustrated in Figure 10-5 indicating DS+3.75 DCx110 (20/ 30), respectively.
little high-order aberration other than tear filmbreakup.

both cases are evident from the color contours. The astig-
10-7 show an obvious example of transient events of the matism condition as manifested by the elliptically shaped
tear film and its breakup. Further, examinations of Figure contours of these 2 cases can also be observed from the 12
10-7 and more clearly of Figure 10-5 reveal a small optically eccentric images that surround the coaxial images.
opaque feature that is located at the 10 o’clock position in For a very high degree of myopic astigmatic eye, the
each pupil reflex. When the eye was dilated and examined elliptical appearance in the center, the coaxial image, is
carefully with a slit lamp, the opacity was determined to be similar to that of the high hyperopic cases of Figure 10-8.
a small cataract near the vitreous chamber. The 12 eccentric images in the color map, with brighter
portions outward, however, also form elliptical appearance
Astigmatic Appearance like the hyperopic astigmatic cases.
For an eye with refraction close to the neutralization
As the cylindrical refractive error becomes more appar-
refraction, the color contour lines are less well-defined. The
ent, the rotationally symmetric color map tends to become
coaxial image is not a clear indication for astigmatism in
elliptically shaped. For an eye with a degree of defocus that this circumstance. In this case, only the 12 eccentric images
is large relative to the value of neutralization, the DIP color can be used effectively to indicate the cylinder merid-
contours show more clearly observed or better defined ians. Shown in Figure 10-9 are the images obtained from
boundaries. The coaxial image that is located at the center of both eyes of an astigmatic patient who has a mild dry eye
the DIP map would noticeably show the elliptically shaped problem that is due to allergy. The manifest refractions are
profile with prominent astigmatic meridians. For this case, measured to be –1.50 +1.50 x 005 (20/20) for his right eye
the longer side of the ellipse in the profile corresponds to the (shown on the left) and –2.75 +2.75 x 165 (20/20) for the left
less defocused meridian. Figure 10-8 shows two examples of eye (shown on the right), respectively. The elliptical appear-
such astigmatic cases. Shown on the left of this figure is the ances formed by the 12 outer images are clearly seen. The
color map of the left eye of a 26-year-old Asian man with left eye image (on the right side) clearly shows the effect to
refractive error of +5.00 DS +2.50 DC x 90 and BCVA of be more significant than the right eye. The percentage con-
20/25. The vertical lines on the upper part of the images are tribution of astigmatic aberration in this eye is a significant
just shadows of his eye lashes. On the right of the figure is the value of 27.2%. The small dark spot on the center of the left
DIP color map that was obtained from the left eye of an 18- eye is a shadow formed by a small optical opacity.
year-old Caucasian woman with the manifest refraction of The only non-elliptical appearance of the astigmatic
+3.50 DS +3.75 DC x 110 and the best-corrected visual acuity condition occurs when the spherical equivalent of an eye
(BCVA) is 20/30. The cylinders in both coaxial reflexes in occurs at the neutralization point. Figure 10-10 shows this
102 CHAPTER 10

Figure 10-9. Color maps of two astigmatic eyes with smaller amount of Figure 10-11. Example of a typical case of LASIKeye. Manifest refraction is
spherical refractions. Manifest refractions of these two eyes are measured measured as –0.50 +1.00 x155 (20/ 20).
as –1.50 DS+1.50 DCx 005 (20/ 20) and –2.75 DS +2.80 DCx 165 (20/ 20),
respectively.
Eyes After LASIK
Figure 10-11 demonstrates a typical case of eyes after
LASIK procedures. The image was obtained from the right
eye of a 49-year-old Caucasian woman at 15 months after
the bladeless LASIK was performed. The refraction of this
eye is –0.50 +1.00 x 155 (20/20). The gray-scale map on the
left shows clean reflexes in all meridians except for a small
superficial punctate keratopathy near the center. Notably,
the interesting brightness change occurs along the peripher-
ies in all reflex images. The pupil diameters in these reflex
Figure 10-10. Example of an interesting case of astigmatic eye with dry eye images are about 7.1 mm. For the color map on the right,
syndrome. Manifest refraction is measured as –4.50DS+1.25 DCx89 (20/ 25). the rotationally symmetric pattern is observed similar to
The spherical equivalent falls right on the neutralization refraction. the emmetropic eye images that were demonstrated in
Figure 10-4, with exception of the peripheral area. The DIP
Zernike analysis shows a significant increase in the fourth-
very interesting case of astigmatism where the refractive order aberration or spherical aberration in LASIK eyes. This
errors along the two astigmatic principle meridians lay on feature is especially clear for larger pupil size. For this par-
opposite sides of the neutralization refraction. This selected ticular case, the percentage of the fourth-order aberration
eye also suffers from dry eye syndrome. Manifest refrac- is measured as 23% while the third-order and the fifth- to
tion is measured as –4.50 DS +1.25 DC x 89 (20/25). The seventh-order aberrations remain in the normal range of 4%
neutralization refraction of the device is –4.00 D in this and 3%, respectively, among the total aberration.
measurement. As a result, the eye images appear brighter
along the outward direction (against motion) on the verti- Cases of Mild to
cal meridian (ie, more myopic than –4.00 D). The image
intensity behaves oppositely in the horizontal meridian
Moderate Keratoconus
where the measured power is less myopic than –4.00 D. In The views of keratoconus DIP maps are not at all sym-
the 45-degree and 135-degree meridians, the reflex images metric, either rotationally or elliptically. Although a single
appear as merged or combined images of the two neighbor- reflex image may seem to be normal and clean and even
ing images. Although each of the 12 eccentric images still crescent- or slope-like, the multi-frame color map shows
appear as the crescent or slope reflex image, the combined clear indications of irregularity. Figure 10-12 demonstrates
color map does not resemble the rotational symmetry. the visualization of a typical keratoconus eye. This mea-
Instead, the color map forms an X-shaped figure. Other surement was acquired from the left eye of a 28-year-old
than the dry eye characteristic, no significant high-order African-American man. Although he does suffer from
aberration between third- and seventh-order is found. The slight monocular diplopia and glare, his vision in both
DIP result of percentage aberration distribution is dominat- eyes is 20/20. The patient uses only regular spectacles for
ed by an astigmatism contribution of 53% while spherical
correction. The presented measurement was obtained
refraction is 30% and high-order aberration from third- to
from his dominant eye with manifest refraction of –0.50
seventh-order contributes 17%. The smaller percentage of
DS +1.50 DC x 003 (20/20). In the gray-scaled map on the
spherical refraction as compared to cylindrical refraction is
left, the so-called scissors reflex can be observed. When
due to the smaller defocus to the neutralization.
the infrared source was illuminated from the lower side,
 INFRARED PHOTOREFRACTION SCREENING 103

Figure 10-12. Example of a typical keratoconus eye. Manifest refraction was

measured as RE–0.50 DS+1.50 DCx 003 and BCVAof 20/ 20. Scissors reflexes
are evident.

Figure 10-13. DIP images obtained frommild to moderate keratoconus eyes. The refractive errors and BCVAof the 6 eyes are indicated beloweach map.

a shadow could be seen in the middle area surrounded by cases are indicated below each DIP color map. The open
brighter upper and lower sections, resembling the image of scissors blades are normally seen with the lower illumina-
the opened blades of a pair of scissors. When the illumina- tion as a result of keratoconus cone location preference. For
tion was coaxial, the brighter sections close up. For upper the color map representation that is illustrated at the lower
illumination, the brighter area at the middle area becomes middle of Figure 10-13, this feature is less apparent due to
more intense, and the upper and lower sections become
the smaller pupil size (~4.9 mm) and the eye’s outlying
darker, resembling the closing-up of the scissors blades.
The DIP report of percentage contribution to aberration is cone. All 6 of these cases have 20/30 or better vision, and all
12% from spherical refraction, 29% of cylindrical refrac- report significant percentages of aberration contribution
tion, 44% of third-order aberration, and 15% from fourth from the third-order aberration (59%, 57%, 36%, 44%,
to seventh-order. 23%, and 41%). The mild to moderate keratoconus cases
Six similar keratoconus cases are presented in Figure 10- always reveal significant third-order aberration and this
13 for comparison. The refractive errors and BCVA of these type of behavior.
104 CHAPTER 10

Figure 10-14. Severe cases of keratoconus eyes produce protruding visualizations in the infrared photorefraction images.

Examples of Severe KC Cases

Severe keratoconus cases cannot be missed in the first
sight of the DIP measurement images. The appearances
of these cases are very disquieting even from the infrared
raw images, and normally, the reflex images, especially the
coaxial photorefraction image, render clearly protruding
features. Shown in Figure 10-14 are examples of severe KC
cases. BCVA is typically worse than 20/50. As a complete
reference, shown on the lower part of Figure 10-15 are the
gray-scale and color DIP maps obtained from the left eye Figure 10-15. Gray-scale and color DIP maps of a severe case of keratoconus.
of a 20-year-old Caucasian man who suffers from kerato- Manifest refraction was measured as –6.00 DS+5.00 DCx115 (20/ 80).
conus. The topography image of this eye shows increased
inferior steeping up to 65.60 D. Manifest refraction was
measured as –6.00 DS +5.00 DC x 115 (20/80). For this type are the DIP percentage distributions of aberrations in these
of case, the third-order aberration is no longer the domi- 59 keratoconus eyes. In comparison to the 71 normal ame-
nant measurement, but the percentage aberration extends tropic eyes shown in Figure 10-17, keratoconus eyes exhibit
into higher orders. noteworthy amounts of high-order aberrations as the color
bars indicate. Within the 59 keratoconus measurements,
Discussion and Comparison Between 35 cases in the left-most chart present, more or less, the
Ametropic and Keratoconic Eyes appearances of typical keratoconus DIP scissors as illus-
trated in Figures 10-12 and 10-13. As mentioned earlier,
The DIP color maps can easily distinguish eyes with
these types of keratoconus cases experience mild to mod-
normal refractive error and those that exhibit condi-
tions that are characterized by higher-order aberrations. erate degrees of vision destruction with BCVA measured
In general, the ametropic eyes with refractive defocus between 20/20 and 20/50. The third-order aberration,
(second-order aberration), including astigmatism, exhibit coma, emerges as the dominant measure in the eccentric
a rotational symmetry in the DIP maps. Because of this reflex images. The proportions of red bars in these cases are
symmetry, the reflex image along a specific meridian when clearly overriding the other high-order contribution.
reflected through the center yields the same reflex pattern Thirteen severe cases of KC that have a protruding
in this opposite direction. On the other hand, cases of typi- appearance, as demonstrated in Figures 10-14 and 10-15,
cal keratoconus or any high-order aberrations will reveal are illustrated in the second chart in Figure 10-16. The
the intensity-negative image in the counterpart reflex. third-order aberration (red bar) doesn’t seem to be more
With no rotation, the two counterpart reflex images will significant as the disease progresses. However, the fourth-
have the same contour outlines, but the dark area becomes order aberration (spherical aberration that is indicated with
bright and the bright area becomes dark. Figures 10-12, 10- pink bar) is relatively higher. The ratio of the fourth-order
13, and 10-15 demonstrate this trait. and the third-order aberrations is about equal among
For evaluation and differentiation, we examined DIP these severe keratoconus cases in contrast to the many-fold
results in a group of keratoconus eyes and normal ametro- dominant ratio in the 35 mild-to-moderate keratoconus
pic eyes. Within keratoconus patients, we consider both group. No evident change in even higher-order aberration is
eyes of the patients are keratoconic even if one of the two observed from the comparison between these two groups.
eyes has decent vision. In fact, more than half of these kera- The 5 keratoconus measurements that follow have irreg-
toconic eyes have BCVA 20/30 or better. The asymmetric ular, asymmetric appearance of DIP maps that are unlike
DIP characteristics are clearly observed in the measure- the 2 typical types. These 5 cases that were presented in the
ment results of keratoconus eyes. Illustrated in Figure 10-16 third chart consist of 2 eyes that were measured 1 day after
 INFRARED PHOTOREFRACTION SCREENING 105

Figure 10-16. Percentage distributions of defocus, cylinder, and high-order aberration in the DIP images of 59 keratoconus eyes. The left most chart includes
35 mild to moderate keratoconus eyes that appear with scissors reflexes in the DIP color maps. The followed 13 cases are severe cases of keratoconus eyes with
protruding features of DIP appearances. The third chart includes 5 KCcases of irregular DIP images (detail is described in the text). The last chart on the right
contains 6 KCcases that look like refractive type.

Figure 10-17. Percentage distributions of defocus, cylinder, and high-order aberration in the DIP images of 71 normal ametropic and emmetropic eyes.

their Intacs (Addition Technologies, Sunnyvale, CA) pro- error, this DIP image shows dominant defocus aberration
cedures. The reflex images appeared as if the corneas were over the high-order aberrations. Coma is the second pro-
swollen and rough on the surface. The 2 data results that nounced aberration. The other 5 cases have very decent
follow were obtained from 2 eyes that were corrected with visual performance. Their manifest refractions are –1.00
well-fitted RGP contact lens. Although the vision results DS +2.50 DC x 012 (20/20), –2.50 DS +1.25 DC x 150
after these corrections were 20/20 and 20/30, respectively, (20/20), –0.75 DS +1.50 DC x 150 (20/20), +1.75 DS +1.25
the DIP maps show neither scissor reflex, nor symmetric DC x 003 (20/25+), and +2.25 DS +1.75 DC x 007 (20/20),
characteristics in them. The appearances are like parallel respectively. For keratoconus patients with small pupils
horizontal bands across the pupil reflexes. The fifth eye and relatively small cones or cones that lie away from the
result in this chart is an eye after cornea transplant (PKP). visual zone, the DIP images become more like those of the
The BCVA of this eye is 20/30. It also exhibits an irregular normal refractive eyes. Under such conditions, the patients’
DIP color map with no symmetry. daily vision suffers minimum influence from the keratoco-
The last 6 cases listed in the last chart appear rotation- nus. The cases here demonstrate this circumstance.
ally symmetric that is similar to the normal refractive Figure 10-17 shows the distributed aberrations of the 71
type. The first data result of the 6 is a keratoconus eye normal ametropic eyes. High-order aberrations are normal-
with high refractive error of –17.00 DS +2.00 DC x 025 ly less than 20% of total aberration. Defocus is clearly the
(20/50). Because of the large amount of spherical refractive main component. A few cases with a relatively larger high-
106 CHAPTER 10

TAB LE 1 0 -1

DIP MEASUREMENT C O MPARISO N O F THE ABERRATIO N PERC ENTAG E DISTRIBUTIO N

RANG ES BETWEEN 59 KERATO C O NUS EYES AND 71 NO RMAL AMETRO PIC EYES
DEFO C US C YLINDER 3 RD 4 TH 5 TH 6 TH 7 TH
59 KC e ye s 37.6±22.1% 10.4±8.0 % 32.4±17.6% 10.2±5.9% 4.8±3.7% 2.6±1.8% 2.0 ±1.2%
71 a m e tro p ic 82.6±11.7% 3.7±5.0 % 7.7±6.0 % 3.6±1.6% 0.9± 0.9 % 0.6± 0.6% 0.8± 0.8%
e ye s

order component occur when the refraction is too close to 2. Bobbier WR, Braddick OJ. Eccentric photorefraction: optical
neutralization and the defocus is therefore very small. Table analysis and empirical measures. Am J Optom Physiol Opt. 1985;
62(9):614-620.
10-1 provides the typical ranges for the aberration reading 3. Howland HC. Optics of photoretinoscopy: results from ray tracing.
between normal ametropes and keratoconus eyes. Am J Optom Physiol Opt. 1985;62(9):621-625.
Utilizing infrared and multi-meridian illumination, 4. Roth EH, Ludwig H, Schmitz F, Werner W. Retinoscopy. A multi-
DIP increases the measurement sensitivity and examination media teaching program on CD. Ophthalmologe. 2001;98(10):964-967.
5. Kim J, Netto MV. Keratoconus associated with hyperimmuno-
comfort of retinoscopy. By taking more than one measure-
globulin E syndrome. Cornea. 2004;23(1):93-96.
ment and comparing the correspondences and differences, 6. Chopra I, Jain AK. Between eye asymmetry in keratoconus in an
long-lasting and transient optical defects can be differenti- Indian population. Clin Exp Optom. 2005;88(3):146-152.
ated and identified. Although, like wavefront aberrometry, 7. Caballero MT, Furlan WD, Pons A, Saavedra G, Martinez-Corral
DIP cannot isolate and determine the corneal thickness or M. Detection of wave aberrations in the human eye using a retinos-
copy-like technique. Opt Comm. 2006;260:767-771.
corneal strength for keratoconus diagnostics, it is a conve-
8. Chen YL, Tan B, K. Baker, et al. Simulation of keratoconus observa-
nient and safe tool to screen for irregular astigmatism and tion in photorefraction. Opt Express. 2006;14:11477-11485.
high-order aberration during typical eye examination. 9. Roorda A, Campbell MC, Bobier WR. Slope-based eccentric pho-
torefraction: theoretical analysis of different light source configu-
rations and effects of ocular aberrations. J Opt Soc Am A Opt Image
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1. Kaakinen K. A simple method for screening of children with

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1979;57(2):161-171.
 CHAP TER 1 1

Assessment of Visual
Performance in Keratoconus

Konrad Pesudovs, OD, PhD

V VISUAL ACUITY
isual performance testing is a vital part of clinical
testing of the keratoconus patient. Visual perfor-
mance assessment gives an indication of the opti-
First, let us review published data on high-contrast visual
cal quality of his or her visual correction and informs the acuity in keratoconus patients. There are numerous very
clinician of the level of visual disability the patient suffers small studies, but if we confine our analysis to prospec-
in the real world. Visual performance testing helps to guide tive studies that reported data on at least 10 patients with
decision making for a change in refractive correction or keratoconus, 10 published reports of visual acuity are avail-
the need for surgical intervention. Of course, the outcome able.4-14 The data are dominated by one large study—the
of a new correction or surgery is essentially assessed with Collaborative Longitudinal Evaluation of Keratoconus Study
clinical visual testing. However, to fulfill all of these roles, (CLEK). This study was designed to investigate and docu-
comprehensive visual performance assessment is required. ment progressive changes that occur in a large sample of
While high-contrast visual acuity is the mainstay of clinical patients with keratoconus.8 The CLEK was a multi-centered
assessment, contrast domain testing or visual performance observational study with support from the National Eye
under glare may provide additional information especially Institute, Bethesda, MD.8,15 The investigators enrolled 1209
with respect to real-world functioning for many diseases.1 patients during 1995 and 1996 in 16 centers across the USA.
Inclusion of visual performance tests in the routine The patients’ mean age (± standard deviation) was 39 ± 10.9
assessment of the keratoconus patient should be evidence- years. Patients were reviewed annually and the examina-
based. The purpose of this chapter is to review the evi- tion included visual acuity (high and low-contrast), patient
reported quality of life, refractive status, corneal topography,
dence for the value of different visual performance tests in
and photo documentation of the cornea and normal rigid
keratoconus. Often, clinicians consider theory sufficient
contact lenses. There are 5 CLEK publications that report
to guide clinical activity. For example, we know that the
visual acuity data.6-10 Overall, mean visual acuity from 1682
mechanism of optical degradation of vision in keratoco- eyes was 0.12 ± 0.24 logMAR (Snellen equivalent 20/25- ±
nus is higher-order wavefront aberrations.2 We also know 2.5 lines).9 This breaks down to 0.00 ± 0.14 logMAR (Snellen
that wavefront aberrations degrade vision in the contrast equivalent 20/20- ± 1.5 lines) in the better eye and 0.15 ± 0.18
domain to a greater extent than high-contrast visual acu- logMAR (Snellen equivalent 20/25-- ± 2 lines) in the worse
ity.3 We could deduce that testing visual performance in eye.10 These studies report a mixture of spectacles or rigid
the contrast domain would be helpful in the keratoconus contact lens correction.
patient. Review of literature is more beneficial. Fortunately, The other published studies all provide similar data, but
many studies have investigated the usefulness of low-con- tending to worse visual acuity.5,11-14 Generally, the popula-
trast visual acuity, contrast sensitivity, and glare testing in tions are young, with mean ages in the 20s or 30s and a range
the keratoconus patients. from 12 years to 45 years. The mean visual acuity varied

Wang M, ed.
Keratoconus & Keratoectasia: Prevention, Diagnosis, and Treatment (pp.109–114) 109
© 2010 SLACK Incorporated
110 CHAPTER 11

between 0.16 logMAR (20/30++) and 0.5 logMAR (20/60).

These studies included patients corrected with rigid gas-
permeable (RGP) contact lenses, spectacles, or both. One
may expect that patients would see better with RGP contact
lenses than with spectacles due to the superior aberration
correction with RGP lenses.16-18 Indeed, this is the case in
a small study where 10 eyes of 5 patients were shown to see
better with RGP lenses (average visual acuity 20/25) than
with spectacles (average visual acuity 20/60).16,17 However, Figure 11-1. High and low(25%) contrast logMARvisual acuitycharts.
across most studies, there is a broad overlap in visual acu-
ity between contact lens and spectacle corrected cases. This
suggests that standardization of the staging, or severity, of LOW-CONTRAST VISUAL ACUITY
keratoconus and optical correction is an issue. In the early
stages of the disease, patients will usually simply wear spec- Low-contrast visual acuity is a measure in the contrast
tacles and only progress to RGP contact lenses when vision domain. The task is to find the threshold of letter size;
is too poor with spectacles. Therefore, RGP lens wearers but using low-contrast letters (Figure 11-1). Low-contrast
usually represent the more advanced spectrum of keratoco- visual acuity charts typically have letter contrast set at
nus. Another reason for the variation between studies may 10% or 18%, or 25% Weber contrast. There are only a few
have been chart luminance, chart design, and test protocols. studies that have reported low-contrast visual acuity in
These factors were poorly reported.6,11,19-21 keratoconus.5,7,9-11 The largest amount of data again comes
Variation aside, we should accept that high-contrast from the CLEK study, where low-contrast logMAR charts
visual acuity in an average keratoconus patient is of the were used with a contrast level of 14%. Overall, mean low-
order of 20/25 to 20/30, but may range from 20/16 to 20/60 contrast visual acuity from 1001 eyes was 0.38 ± 0.12 log-
for the majority of patients. Given this, how useful is visual MAR (Snellen equivalent 20/50+ ± 1 line).7,9 This breaks
acuity as a measure of visual performance in the keratoconus down to 0.26 ± 0.17 logMAR (Snellen equivalent 20/40++ ±
patient? On face value, one may think that these visual acu- 1.7 lines) in the better eye and 0.43 ± 0.20 logMAR (Snellen
ity data are very close to normal visual acuity; especially if equivalent 20/50- ± 2 lines) in the worse eye.10 Two other
one simply thinks of 20/20 as normal visual acuity. Only 1 of studies found similar results with average low-contrast
these studies reported an age-matched normal group where visual acuity of 20/40 and 20/40--.5,11
visual acuity was tested under the same conditions. In that Clearly, these levels of visual acuity are worse than those
study, visual acuity in normal patients was –0.18 ± 0.05 log- reported for high-contrast visual acuity, but need to be
MAR (Snellen equivalent 20/12- ± 0.5 lines).11 Other studies compared to normal values for low-contrast visual acuity.
reporting visual acuity in normal eyes, for comparable age One study reported an age-matched normal group where
groups (mean age in the 20s or 30s, with a range from the low-contrast visual acuity was tested under the same con-
teens to the mid 40s), also find average visual acuity to be on ditions. In that study, low-contrast visual acuity in normal
the order of 20/16- to 20/16++ with a range of 20/12 to 20/20 patients was –0.12 ± 0.06 logMAR (Snellen equivalent
for the majority of people.22-26 For this chapter, we then 20/16+ ± 0.6 lines).11 The results of this study are sum-
define normal visual acuity to be on the order of 20/16 for marized in Table 11-1, which shows that the difference
the young (<50 years old) eye, with an upper limit of 20/20. between normal and keratoconus groups is more striking
In which case, the vast majority of keratoconus patients fall with low-contrast visual acuity testing than high-contrast
outside of this range, suggesting that high-contrast visual visual acuity testing. This is best illustrated by calculating
acuity does effectively discriminate between normal and the difference metric “low-contrast loss”:
keratoconus. Overlap exists in those with extremely mild low-contrast loss = low-contrast VA – high-contrast VA
keratoconus, where the diagnosis is questionable and nor-
For normal patients, the difference is only 0.05 logMAR,
mal or near-normal visual performance is found clinically.
or equivalent to 0.5 lines of visual acuity. However, in
Given the published data, the difference in mean values for
keratoconus patients, the low-contrast loss is 0.15 logMAR,
normal and keratoconus is small, 20/16 vs. 20/25 to 20/30,
or 1.5 lines of visual acuity. Therefore, low-contrast visual
and given the retest reliability for visual acuity testing is acuity reveals losses of visual performance not predictable
approximately 1.5 lines,27 slightly reduced visual acuity from high-contrast visual acuity. This implies that the real
may not be evidence of true visual performance loss due to world functioning may not be as strong as suggested by
keratoconus. Moreover, a mild loss of visual acuity does not high-contrast visual acuity, and low-contrast visual acuity
imply significant visual disability. Therefore, other tests of may be a better indicator of the impact of keratoconus.
visual performance should be considered in order to better
separate normal and keratoconus patients, and to provide
further insight into functioning in the real world.
 ASSESSMENT OF VISUAL PERFORMANCE IN KERATOCONUS 111

TAB LE 11 -1

HIG H- C O NTRAST VISUAL AC UITY, LO W-C O NTRAST VISUAL AC UITY,

AND THE DIFFERENC E BETWEEN THE TWO
Lo w-c o n tra st te stin g a ffo rd s g re a te r d iffe re n tia tio n b e twe e n n o rm a l a n d ke ra to c o n u s g ro u p s.

NO RMAL (N=24) KERATO C O NUS (N=11)

Ag e 33.7 ± 8.6 35.0 ± 11.1
Visu a l a c u ity † -0.18 ± 0.05 (20/ 12-) 0.17 ± 0.22 (20/ 30+)
Lo w-c o n tra st visu a l a c u ity † -0.12 ± 0.06 (20/ 16+) 0.29 ± 0.23 (20/ 40)
Lo w-c o n tra st lo ss ‡ 0.05 ± 0.04 (0.5 lin e d iffe re n c e ) 0.15 ± 0.12 (1.5 lin e d iffe re n c e )
† p <0.0 01, ‡ p <0.01; Lo w-c o n tra st lo ss = lo w-c o n tra st visu a l a c u ity – h ig h -c o n tra st visu a l a c u ity.

Ad a p te d fro m Pe su d o vs K, Sc h o n e ve ld P, Se to RJ, C o ste r DJ. C o n tra st a n d g la re te stin g in ke ra to c o n u s a n d a fte r p e n e tra tin g

ke ra to p la sty. Br J O p h th a lm o l. 20 04;88(5):653-657.

Figure 11-2. The Pelli-Robson contrast sensitivity chart. The patient reads
down the chart as far as possible to identifythe lowest contrast level readable.
Figure 11-3. Meta-analysis of published data on contrast sensitivityin kerato-
Asimple clinical arrangement for glare testing utilizes a projector adjacent
conus and normal eyes. Contrast sensitivity is clearly reduced in keratoconus
to the chart. Repeating contrast sensitivity measurement under glare (right)
across almost all spatial frequencies.
determines the impact of glare upon the contrast threshold.

spatial frequency tested, and population, at different spatial

CONTRAST SENSITIVITY frequencies using different methods and on different pop-
ulations (some may include more severe disease than oth-
Contrast sensitivity is also a measure in the contrast ers). Despite this issue, the keratoconus group has reduced
domain, but the threshold tested is the lowest contrast contrast sensitivity across almost all spatial frequencies
level visible (Figure 11-2). Contrast-sensitivity testing can (Figure 11-3) when compared to the normal group. The
be performed for different types of targets, often sine wave normal data show the threshold contrast sensitivity peak to
gratings or letters. The size of the target can vary and is be between 2 and 4 c/deg with a gradual drop off above and
usually described in terms of spatial frequency (number below this peak. The normal and keratoconus thresholds
of sine wave cycles per degree [c/deg]). During the last 3 are comparable at low spatial frequencies (below 1 c/deg),
decades, there have been seven published reports of grating but the keratoconus group performs poorer at the peak of
contrast sensitivity in keratoconus.16,17,19,28-31 The data the curve and higher spatial frequencies. Notably, there is
from these studies have been combined in a meta-analysis a limited amount of data at the highest spatial frequencies
to determine the average contrast sensitivity in kerato- (20 to 32 c/deg). To see spatial frequencies of 20 c/deg, the
conus patients for each spatial frequency. The advantage keratoconus patient must have visual acuity of 0.1 logMAR
to combining data across studies is that, because most of or better (20/25 Snellen) which prevents many from com-
the studies have small patient numbers, this meta-analysis pleting the task. Therefore, there is a selection bias toward
allows us to build up a picture of what would happen in a the less impaired in the high spatial frequency data so it is
large population (total 51 eyes). However, combining data is likely that the numbers reported here underestimate the
hampered by variability in method of measurement, level of average contrast-sensitivity loss in keratoconus at very high
112 CHAPTER 11

TAB LE 11 -2

LO W-C O NTRAST VISUAL AC UITY WITH AND WITHO UT G LARE, PELLI-RO BSO N
C O NTRAST SENSITIVITY WITH AND WITHO UT G LARE, AND THE G LARE LO SS DIFFERENC E
G la re te stin g d o e s n o t h e lp to d iffe re n tia te b e twe e n n o rm a l a n d ke ra to c o n u s g ro u p s, a n d in d e e d , fo r
c o n tra st se n sitivity te stin g , th e a d d itio n o f g la re c a u se s a sp u rio u s im p ro ve m e n t in visu a l p e rfo rm a n c e .

NO RMAL (N=24) KERATO C O NUS (N=11)

Ag e 33.7 ± 8.6 35.0 ± 11.1

Lo w-c o n tra st visu a l a c u ity† –0.12 ± 0.06 (20/ 16+) 0.29 ± 0.23 (20/ 40)
Lo w-c o n tra st visu a l a c u ity u n d e r g la re † –0.11 ± 0.08 (20/ 16) 0.35 ± 0.28 (20/ 40 --)
G la re lo ss (lo w-c o n tra st visu a l a c u ity) 0.02 ± 0.08 (1 le tte r) 0.06 ± 0.11 (3 le tte rs)
Pe lli-Ro b so n c o n tra st se n sitivity† 1.80 ± 0.13 1.10 ± 0.28
Pe lli-Ro b so n c o n tra st se n sitivity u n d e r g la re † 1.73 ± 0.11 1.25 ± 0.46
G la re lo ss (Pe lli-Ro b so n c o n tra st se n sitivity) ‡ 0.07 ± 0.11 –0.16 ± 0.36
(1 le tte r wo rse ) (3 le tte rs b e tte r)

† p <0.0 01, ‡ p <0.05; G la re lo ss (lo w-c o n tra st visu a l a c u ity) = lo w-c o n tra st visu a l a c u ity u n d e r g la re – lo w-c o n tra st visu a l a c u -
ity, G la re lo ss ( Pe lli-Ro b so n c o n tra st se n sitivity) = Pe lli-Ro b so n c o n tra st se n sitivity – Pe lli-Ro b so n c o n tra st se n sitivity u n d e r g la re .

Ad a p te d fro m Pe su d o vs K, Sc h o n e ve ld P, Se to RJ, C o ste r DJ. C o n tra st a n d g la re te stin g in ke ra to c o n u s a n d a fte r p e n e tra tin g

ke ra to p la sty. Br J O p h th a lm o l. 20 04;88(5):653-657.

spatial frequencies. The normal data in this figure include limited experience with contrast-sensitivity testing. The
177 eyes from 5 studies,16,19,28,29,32 4 of which were pub- simplicity of this test facilitates easy incorporation into the
lished control groups to the keratoconus groups included routine clinical evaluation of the keratoconus patient.
in the keratoconus population. Despite the use of control
groups to standardize the testing methods, heterogeneity
in the data remains. GLARE TESTING
The cause of contrast-sensitivity loss in keratoconus is
the presence of elevated higher-order wavefront aberra- Few reports include glare testing of keratoconus
tions. This has been confirmed in several studies of letter patients.11,28,31,37 Each study used different glare sources,
contrast sensitivity testing.33-35 Indeed, deficits in contrast different charts, and different lighting conditions, but
sensitivity in RGP-wearing keratoconus patients have been results consistently suggest the effects of glare are small. In
shown to be due to residual wavefront aberrations.35,36 2 studies, Carney found a reduction in the contrast sensi-
Evaluating contrast-sensitivity functions at multiple spatial tivity in the presence of a glare source in some keratoconus
frequencies is time consuming, but simple clinical measure- patients who had undergone penetrating keratoplasty, but
ment of the peak of the contrast sensitivity curve may be ungrafted keratoconus patients did not show any such
accomplished using the Pelli-Robson contrast sensitivity losses.28,31 Brahma et al made contradictory observations
letter chart (see Figure 11-2). The patient simply reads down using the Mentor Brightness Acuity Tester (BAT) as the
the chart until the minimum contrast threshold is deter- glare source in conjunction with Pelli-Robson contrast
mined. In 1 study, a dramatic difference was found between sensitivity and high-contrast visual acuity charts. They
keratoconus and normals (Table 11-2).11 Normal contrast reported small levels of loss to glare in eyes with keratoco-
sensitivity of 1.80 log contrast sensitivity equates to a mini- nus (0.09 logMAR [2 letters] and 0.13 logCS [three letters]),
mum detectable contrast of 1.6% whereas contrast sensitiv- but no losses after penetrating.37
ity in the keratoconus group of 1.10 log contrast sensitivity To further investigate, Pesudovs et al11 measured both
equates to a minimum detectable contrast of 7.9%. The large low-contrast (25%) visual acuity and Pelli-Robson contrast
magnitude of this difference was highly statistically signifi- sensitivity with and without glare in normal and kerato-
cant, and the test is easily interpreted even by clinicians with conus patients (see Figure 11-2, Table 11-2). The effect of
 ASSESSMENT OF VISUAL PERFORMANCE IN KERATOCONUS 113

adding a glare source to clinical testing is best appreciated 2. Maeda N, Fujikado T, Kuroda T, et al. Wavefront aberrations mea-
using 2 derived measures of glare loss. sured with Hartmann-Shack sensor in patients with keratoconus.
Ophthalmology. 2002;109(11):1996-2003.
1. Glare loss (low-contrast VA) = low-contrast VA under 3. Applegate RA, Hilmantel G, Howland HC, et al. Corneal first
glare – low-contrast VA surface optical aberrations and visual performance. J Refract Surg.
2000;16(5):507-514.
2. Glare loss (Pelli-Robson contrast sensitivity [CS]) = 4. Zadnik K, Mannis MJ, Johnson CA, Rich D. Rapid contrast sen-
Pelli-Robson CS – Pelli-Robson CS under glare. sitivity assessment in keratoconus. Am J Optom Physiol Opt. 1987;
Normal subjects had a glare loss of 1 letter on both low- 64(9):693-697.
5. Barr JT, Yackels T. Corneal scarring in keratoconus-measure-
contrast visual acuity and Pelli-Robson contrast sensitivity
ments and influence on visual acuity. Int Contact Lens Clin. 1995;
testing. The keratoconus patients had a glare loss of 3 22(7):173-175.
letters on low-contrast visual acuity testing, but actually 6. Gordon MO, Schechtman KB, Davis LJ, et al. Visual acuity
gained 3 letters on the Pelli-Robson contrast-sensitivity repeatability in keratoconus: impact on sample size. Collaborative
chart under glare. This surprising finding was ascribed to Longitudinal Evaluation of Keratoconus (CLEK) Study Group.
pupillary constriction under glare, decreasing the higher- Optom Vis Sci. 1998;75(4):249-257.
7. Davis LJ, Schechtman KB, Begley CG, Shin JA, Zadnik K.
order wavefront aberrations and thereby paradoxically Repeatability of refraction and corrected visual acuity in kera-
increasing visual performance. toconus. The CLEK Study Group. Collaborative Longitudinal
There appears to be no value in using glare testing in Evaluation of Keratoconus. Optom Vis Sci. 1998;75(12):887-896.
patients with keratoconus. Glare is more helpful for condi- 8. Zadnik K, Barr JT, Edrington TB, et al. Baseline findings in the
Collaborative Longitudinal Evaluation of Keratoconus (CLEK)
tions where forward light scatter is a mechanism of visual
Study. Invest Ophthalmol Vis Sci. 1998;39(13):2537-2546.
loss. This is not typically the case in keratoconus, unless 9. Zadnik K, Barr JT, Edrington TB, et al. Corneal scarring and
there is significant corneal edema. Therefore, glare testing vision in keratoconus: a baseline report from the Collaborative
may be of some value after penetrating keratoplasy, when Longitudinal Evaluation of Keratoconus (CLEK) Study. Cornea.
rejection causes loss of endothelial viability and edema, 2000;19(6):804-812.
10. Zadnik K, Steger-May K, Fink BA, et al. Between-eye asymmetry in
and the resulting decreased visual performance may be
keratoconus. Cornea. 2002;21(7):671-679.
best detected under glare conditions. 11. Pesudovs K, Schoneveld P, Seto RJ, Coster DJ. Contrast and glare
testing in keratoconus and after penetrating keratoplasty. Br J
Ophthalmol. 2004;88(5):653-657.
CONCLUSION 12. Colin J, Cochener B, Savary G, Malet F, Holmes-Higgin D. INTACS
inserts for treating keratoconus: one-year results. Ophthalmology.
2001;108(8):1409-1414.
Comprehensive assessment of visual performance in 13. Burns DM, Johnston FM, Frazer DG, Patterson C, Jackson AJ.
the keratoconus patient requires a measurement of high- Keratoconus: an analysis of corneal asymmetry. Br J Ophthalmol.
contrast visual acuity as well as a measure in the contrast 2004;88:1252-1255.
domain. Visual acuity is a useful measure in differentiating 14. Chopra I, Jain AK. Between eye asymmetry in keratoconus in an
Indian population. Clin Exp Optom. 2005;88(3):146-152.
normal from keratoconic only when compared to a true
15. Zadnik K, Barr JT, Edrington TB, et al. Corneal scarring and vision
normal, better than 20/20 level of acuity. Visual acuity of in keratoconus. Cornea. 2000;19(6):804-812.
20/25 to 20/30 in a young adult should be seen as abnormal, 16. Carney LG. Visual loss in keratoconus. Arch Ophthalmol. 1982;
and this is the mean visual acuity in keratoconus. 100:1282-1285.
The difference between normal and keratoconic is 17. Carney LG. Contact lens correction of visual loss in keratoconus.
Acta Ophthalmol. 1982;60:795-802.
enhanced using low-contrast targets visual acuity and 18. Mannis MJ, Zadnik K, Johnson CA, Adams C. Contrast sen-
contrast sensitivity testing. Information provided by low- sitivity after penetrating keratoplasty. Arch Ophthalmol. 1987;
contrast visual acuity is not predictable based on high-con- 105(Sept):1220-1223.
trast visual acuity data. Contrast sensitivity testing can also 19. Hess RF, Carney LG. Vision through an abnormal cornea: a pilot
show striking differences between normal and keratoconus study of the relationship between visual loss from corneal distor-
tion, corneal oedema, keratoconus and some allied corneal pathol-
and, when measured using the Pelli-Robson chart, can be
ogy. Invest Ophthalmol Vis Sci. 1979;18:476-483.
easily incorporated into routine clinical care. Glare testing 20. Crews MJ, Driebe WT, Stern GA. The clinical management of kera-
adds little to the measurement of visual performance in the toconus: a 6 year retrospective study. CLAO J. 1994;20:194-197.
keratoconus patient and need not be included in routine 21. Lass JH, Lambach RG, Park SB, al. e. Clinical management of kera-
clinical assessment. toconus: a multi-center analysis. Ophthalmology. 1990;97:433-445.
22. Wood JM, Garth D, Grounds G, McKay P, Mulvahil A. Pupil dila-
tion does affect some aspects of daytime driving performance. Br J

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Ophthalmol. 2003;87:1387-1390.
Vanden Bosch ME, Wall M. Visual acuity scored by the letter by
letter or probit methods has lower retest variability than the line
1. Valbuena M, Bandeen-Roche K, Rubin GS, Munoz B, West SK. assignment method. Eye. 1997;11:411-417.
Self-reported assessment of visual function in a population-based 24. Rosser DA, Murdoch IE, Cousens SN. The effect of Optical Defocus
study: the SEE project. Salisbury Eye Evaluation. Invest Ophthalmol on the Test-Retest Variability of Visual Acuity Measurements.
Vis Sci. 1999;40(2):280-288. Invest Ophthalmol Vis Sci. 2004;45:1076-1079.
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25. Ohlsson J, Villarreal G. Normal visual acuity in 17-18 year olds. 33. Okamoto C, Okamoto F, Samejima T, Miyata K, Oshika T. Higher-
Acta Ophthalmol Scand. 2005;83:487-491. order wavefront aberration and letter-contrast sensitivity in kera-
26. Ucakhan OO. Predicted corneal visual acuity in keratoconus as toconus. Eye. 2008;22(12):1488-1492.
determined by ray tracing. Acta Ophthalmol Scand. 2003;81:264- 34. Pesudovs K, Coster DJ. Penetrating keratoplasty for keratoconus:
270. the nexus between corneal wavefront aberrations and visual per-
27. Rosser DA, Cousens S, Murdoch IE, Fitzke FW. How sensitive to formance. J Refract Surg. 2006;22(9):926-931.
clinical change are ETDRS logMAR visual acuity measurements? 35. Marsack JD, Parker KE, Pesudovs K, Donnelly WJ 3rd, Applegate
Invest Ophthalmol Vis Sci. 2003;44:3278-3281. RA. Uncorrected wavefront error and visual performance during
28. Carney LG, Lembach RG. Management of keratoconus: compara- RGP wear in keratoconus. Optom Vis Sci. 2007;84(6):463-470.
tive visual assessments. CLAO J. 1991;17(1):52-58. 36. Negishi K, Kumanomido T, Utsumi Y, Tsubota K. Effect of higher-
29. Zadnik K, Mannis MJ, Johnson CA. An analysis of contrast sensitiv- order aberrations on visual function in keratoconic eyes with a rigid
ity in identical twins with keratoconus. Cornea. 1984;3(2):99-103. gas permeable contact lens. Am J Ophthalmol. 2007;144(6):924-929.
30. Carney LG, Kelley CG. Visual losses after myopic epikeratoplasty. 37. Brahma A, Ennis F, Harper R, Ridgway A, Tullo A. Visual function
Arch Ophthalmol. 1991;109(4):499-502. after penetrating keratoplasty for keratoconus: a prospective longi-
31. Carney LG, Jacobs RJ. Problems remaining after successful kerato- tudinal evaluation. Br J Ophthalmol. 2000;84(1):60-66.
plasty for keratoconus. Clin Exp Optom. 1989;72(1):22-25.
32. Wicker D, Sanislo S, Green DG. Effect of contact lens correction
of sine wave contrast sensitivity in keratoconus patients after pen-
etrating keratoplasty. Optom Vis Sci. 1992;69(5):342-346.
 SECTI ON I V

Treatment of
Keratoconus and
Keratoectasia
 CHAP TER 1 2

Non-Surgical Treatment of
Keratoconus Using Contact
Lenses

Shawna L. Hill, OD, FAAO

T
he treatment of keratoconus in early stages can be However, there is a learning curve to fitting contact
managed with spectacles and soft contact lenses. lenses. The clinician should remain confident during the
Moderate to advanced cases usually require the use challenging yet rewarding process of caring for the kerato-
of gas permeable contact lenses (GPs). The optical rigidity conic patient. There are no rigid set of rules for contact lens
of a GP lens enables it to hold its shape against an irregular fitting for keratoconus. In fact, many variations exist in the
corneal surface, thereby creating a tear layer, which better philosophy of fitting and the design of lenses. There are 3
corrects for optical aberrations. The goal is to provide good fitting strategies: flat fitting (reshaping), apical clearance,
optics within the patient’s visual axis while maintaining and 3-point-touch design.
eye health and comfort. Patient consultation regarding the
instability inherent to keratoconus is required before con-
tact lens fitting. The patient must understand changes in FLAT FITTING
his or her cornea are possible, therefore making re-fitting
contact lenses inevitable. The flat-fitting method places the entire weight of the
lens on the cone while stabilization is maintained by the
There has been considerable advancement of lens designs
upper lid. Central bearing will be apparent on fluorescein
and materials of both soft and GP lenses. Recently, success
evaluation as seen in Figure 12-1. One would assume that,
has been found using aberration-correcting soft contact
over time, this can cause scarring and other apical cone
lenses.1 Marsack et al produced and evaluated custom
changes. To prospectively characterize changes in vision,
wavefront-guided soft contact lenses in GP wearers and
corneal curvature, corneal status, and vision-specific quality
found comparable visual acuity using photopic high-con- of life related to keratoconus, the Collaborative Longitudinal
trast logMAR charts.2 Another study reported 1.5 lines of Evaluation of Keratoconus (CLEK) Study was formulated.
improvement for photopic high-contrast (p=0.03) and 1 The CLEK study was an 8-year, multi-center, natural history
line for photopic low-contrast (p=0.11) over a 5-mm pupil study of 1209 patients with keratoconus who were examined
using a custom wavefront correcting contact compared annually for 8 years. “Despite the potential risk for corneal
to habitual correction.3 These lenses would be negatively scarring imposed by flat-fitting rigid contact lenses, most
affected by dry eye, and visual acuity may be sensitive to CLEK Study patients wear flat-fitting lenses. Overall, rigid
transitional errors.4 GP lenses can be fit using steep or lenses were fitted an average of 2.86 D (SD ± 3.31 D) flatter
flat base curvatures, large or small diameters, and differ- than the first definite apical clearance lens (FDACL).”5 It
ent peripheral curves. GPs have many advantages such as was found that an apical touch fitting relationship did not
high oxygen permeability, decreased bacterial and protein have an increased risk of being scarred centrally at baseline.6
adherence compared to soft lenses, dynamic tear exchange, However, factors that imply added risk for corneal scarring
and ease of care and handling. are corneal staining, contact lens wear, and the contact lens

Wang M, ed.
Keratoconus & Keratoectasia: Prevention, Diagnosis, and Treatment (pp.119–132) 119
© 2010 SLACK Incorporated
120 CHAPTER 12

Figure 12-1. Aflat-fitting GP with central bearing. Figure12-3. Dimple Veilingsecondarytosteepfittingrelationship. Compression
of bubbles maycreate a transient depression in the cornea.

central bubbles by the lens creates a transient depression

(Figure 12-3). These dimples and bubbles, if sufficient in
number, produce glare and foggy vision. It is more com-
mon in eyes with corneal transplants. Removing the lenses
for a few hours leads to resolution of the dimple veiling and
the associated symptoms.

THREE-POINT-TOUCH
Most practitioners prefer the 3-point-touch design for
fitting keratoconus patients. Here, the weight of the lens is
evenly distributed across the central and peripheral cornea.
The ideal fit shows trace apical bearing preferably with
Figure 12-2. AGP with apical clearance and bearing in the midperiphery. fluorescein coverage during a blink. Midperipheral bear-
ing appears as an annulus, shown in Figure 12-4. There is
paracentral and peripheral clearance.
fitting relationship.7 The natural history and baseline scar-
ring in keratoconus was more likely due to the steepness of
the cornea (>52.00) in more advanced disease, but the prac-
titioner can influence the progression of scarring. Zadnik
FITTING PARAMETERS
et al also found that for each diopter the GP was fit flat it
increased the risk of corneal scarring by 19%.6
Initial Base Curve
Initial base curvature value is based on keratometry.
APICAL CLEARANCE Manual keratometry is unreliable and usually difficult to
obtain in a keratoconic patient. Topography is of utmost
The apical clearance method places the weight of the importance to evaluate not only central corneal curvature
lens on the midperipheral cornea such that it vaults the but also overall toricity of the cornea. Axial and tangential
central cornea. Midperipheral bearing and central api- maps will show curvature but an elevation map will show
cal clearance is seen on fluorescein evaluation in Figure areas of depression or elevation that may cause fitting
12-2. These lenses tend to be smaller and fit very steeply problems. A GP will assume the position of least resistance,
with the intent of minimizing the trauma on the tip of the which is over the steep meridian (Figure 12-5). Realizing
cone. If decentered, glare may result due to the lens edge most cones are not centrally located, the goal is to provide
bisecting the pupil or decentration of the small optic zone. good optics by keeping the lens over the pupillary zone.
The steep lens can cause corneal edema from peripheral Diagnostic fitting is imperative for this reason. Refer to
seal-off or dimple veiling centrally from trapped bubbles. Table 12-1 for keratoconus spherical GP lens designs using
Both manifest with decreased vision. Compression of the the average keratometry value as a starting point.
 NON-SURGICAL TREATMENT OF KERATOCONUS USING CONTACT LENSES 121

Figure 12-4. Three-point-touch fitting in an attempt to spread the weight of

the lens evenlyacross the cornea.

Lens Diameter and Optical Zone

The overall diameter (OAD) and optic zone diameter
(OZD) are chosen based on type of ectasia and corneal cur-
vature. A nipple cone is classified as a small diameter (<5
mm) cone that occurs in the lower nasal quadrant within a
few millimeters of the visual axis. Oval cones are classified
as larger (>5 mm) cones that occur in the inferior temporal
quadrant. When more than 75% of the cornea is affected
(>6 mm), the cone is considered globus. Pellucid marginal
degeneration causes an area of steepening in the most infe-
rior part of the cornea but can extend to the visual axis in
moderate and severe cases.
The optic zone diameter is decreased as the cornea steep-
ens to maintain a well-centered lens. Large diameter lenses
(10 mm to 12 mm) are most successful with an inferior
decentered apex, large and globus cones, and PMD. Small
diameter (8 mm to 9 mm) lenses are most successful with
nipple cones, central/paracentral cones, and severely steep
corneas. Table 12-2 shows diameter and base curvature are
related, and the practitioner will change the parameters as B
necessary. For example, the larger the diameter of the lens,
the flatter the base curvature. Figure 12-5. (A) Lenses will decenter over the steep meridian, typicallyinferi-
The optical zone diameter should decrease as the condi- orly. (B) Axial topographyof patient in A.
tion progresses to maintain midperipheral and peripheral
alignment. One commonly used philosophy is to select an
OZD equal to the base curve radius in millimeters. For clearance is an important factor to ensure dynamic tear
example, if the base curve radius was 7.00 mm, the optical exchange.
zone diameter would also be 7.00 mm. Edge clearance is important in the long-term comfort
Multiple peripheral curves play a larger role in fitting of a GP. Minimal edge lift leads to neovascularization and
KC patients than in normal eyes because the cornea flat- molding of the cornea. Excessive edge life leads to corneal
tens rapidly from the apex of the cone to the periphery. desiccation by means of capillary action of the tears. This
Typically, 3 peripheral curves, which are flatter and reveals itself as 3 and 9 o’clock staining. The majority of
wider than conventional designs provide greater edge clear- keratoconus patients are highly myopic, requiring GPs with
ance, prevent seal-off, or an aspheric periphery has a con- thick edges. Adding a plus lenticular thins the edges, allow-
tinuous flattening of the periphery of the lens. Peripheral ing for better edge profile.
122 CHAPTER 12

TAB LE 1 2 -1

LENS FITTING G UIDE

Sta g e 1 Ave ra g e K < 45 D C o n ve n tio n a l le n s d e sig n
Sta g e 2 Ave ra g e K = 45 D to 50 D O ve ra ll d ia m e te r = 9.0 m m
OZ d ia m e te r = b a se c u rve ra d iu s
Te tra c u rve d e sig n
Sta g e 3 Ave ra g e K = 50 D to 55 D O ve ra ll d ia m e te r = 8.6 to 8.8 m m
OZ d ia m e te r = b a se c u rve ra d iu s
Te tra c u rve o r p e n ta c u rve d e sig n
Pe rip h e ra l c u rve ra d iu s = 12.00 m m
Pe rip h e ra l c u rve wid th = 0.3 to 0.4 m m
Sta g e 4 Ave ra g e K = 55 D to 60 D O ve ra ll d ia m e te r = 8.0 m m
OZ d ia m e te r = b a se c u rve ra d iu s
Pe n ta c u rve d e sig n
Pe rip h e ra l c u rve ra d iu s = 12.00 m m
Pe rip h e ra l c u rve wid th = 0.3 to 0.4 m m

Re p rin te d with p e rm issio n fro m Be n n e tt ES, Ba rr JT. Ke ra to c o n u s. In Be n n e tt ES, He n ry VA, e d s. C lin ic a l Ma n u a l o f C o n ta c t

Le n se s. 2n d e d . Lip p in c o tt Willia m s & Wilkin s, Ph ila d e lp h ia , PA, 20 0 0 :493-530.

TAB LE 12 -2

C HO O SING DIAMETER IN RELATIO NSHIP TO BASE C URVATURE

LARG E 9.3 to 10.2 0.50 fla tte r th a n fla t K
INTERMEDIATE 8.6 to 9.2 Fla t K
SMALL 8.0 to 8.5 0.50 ste e p e r th a n fla t K

Lens Material handle without symptoms. If the patient has more regular
astigmatism, a bitoric lens design can be considered. The
Lens material selection is dependent upon the need for author orders empirically from the Mandell-Moore guide
higher oxygen transmissibility in diseased eyes, but bal- (Table 12-3).
anced with the need for stability. Various parameters are
used to describe how oxygen delivery occurs during lens
wear. Oxygen permeability (Dk) measures the amount of SOFT LENSES
oxygen passing through the material from which the lens is
made and expresses the ability of the lens to let oxygen reach Soft contact lenses are attractive to patients primarily
the eye by diffusion. Low- to mid-Dk material provides
because of their initial comfort and ease of wear. However,
stability. High- and hyper-Dk materials provide increased
soft lenses typically act as drapes and cannot mask the irreg-
oxygen permeability. Oxygen transmissibility (Dk/t) is a
ularity of the corneal surface in a keratoconic. Therefore,
measure of the amount of oxygen diffusing through a con-
tact lens at a particular thickness, usually specified as center soft contact lenses are used in early disease stages where
thickness and is the parameter more commonly used. Refer correction of regular astigmatism improves the vision and
to the Gas Permeable Lens Institute at http://www.gpli. the amount of irregular astigmatism is relatively low.
info/materials.htm or refer to Tyler’s Quarterly for a list of Exceptions occur, of course. Medlens Inc (Front Royal,
all GP materials. VA) has developed a custom hydrogel lens that may mask
Determination of optical design and power evaluation irregularities in patients who have moderate to severe kera-
are the last steps of the fitting process. A front or back toconus. A diagnostic fitting set is required to determine
surface toric can be ground if there is more than 0.75 D of the base curve and toric power that is necessary for your
residual astigmatism, as this is the maximum a patient can patient. These lenses (HydraKone) incorporate a tricurve
 NON-SURGICAL TREATMENT OF KERATOCONUS USING CONTACT LENSES 123

TAB LE 12 -3

MANDELL-MO O RE G UIDE FO R EMPIRIC O RDERING O F BITO RIC G PS

MANDELL- MO O RE BITO RIC LENS G UIDE - PER EYE

1. Ke ra to m e try @ @

2. Sp e c ta c le Rx (Min u s C yl Fo rm ) x

FLATTEST K SPHERE PO WER STEEPEST K SPH+C YL PO WER

3. En te r K

4. En te r Sp e c ta c le Po we r

5. Ve rte x Ad ju st Lin e 4

6. In se rt Fit Fa c to r (–) (+) (–) (+)

Ad d Lin e s 3&6 5&6 3&6 5&6

7. Fin a l C L Rx

BASE C URVE PO WER BASE C URVE PO WER

BITO RIC LENS FIT FAC TO R

C O RNEAL C YL FIT FLAT M ERIDIAN FIT STEEP M ERIDIAN

2.0 D O n K (0 D) 0.50 D Fla tte r
2.5 D 0.25 D Fla tte r 0.50 D Fla tte r
3.0 D 0.25 D Fla tte r 0.75 D Fla tte r
3.5 D 0.25 D Fla tte r 0.75 D Fla tte r
4.0 D 0.25 D Fla tte r 0.75 D Fla tte r
5.0 D 0.25 D Fla tte r 0.75 D Fla tte r

INSTRUC TIO NS
• O n lin e s 1 a n d 2, e n te r th e p a tie n t ke ra to m e try re a d in g s a n d sp e c ta c le Rx, re sp e c tive ly.
• O n lin e 3, e n te r th e fla tte st K in th e b o x o n th e le ft sid e a n d th e ste e p e st K in th e b o x o n th e rig h t.
• O n lin e 4, e n te r th e sp h e re p o we r in th e b o x o n th e le ft a n d th e sp h e re p o we r p lu s th e c ylin d e r
p o we r in th e b o x o n th e rig h t.
• If th e p o we rs n o te d in lin e 4 a re g re a te r th a n o r e q u a l to ± 4.00 D, a n a d ju stm e n t fo r ve rte x d is-
ta n c e is e n te re d o n lin e 5. Ve rte x a d ju ste d p o we rs a re u se d to c o m p le te th e re m a in in g c a lc u la -
tio n s.
• Use th e Fit Fa c to r C h a rt a b o ve fo r th e va lu e s n e e d e d to b e e n te re d in to lin e 6. Th e a m o u n t o f
c o rn e a l c yl will d e te rm in e th e Fit Fa c to r fo r th e fla t a n d ste e p m e rid ia n s. “O n K” h a s a 0 Fit Fa c to r.
• Ad d / su b tra c t th e lin e s a s n o te d , a n d e n te r th e re su lts o n lin e 7. Th e se a re th e a c tu a l n u m b e rs
th a t yo u will g ive th e la b to m a n u fa c tu re yo u r b ito ric le n s. Th e y a re re fe rre d to a s d ru m va lu e .
124 CHAPTER 12

TAB LE 12 - 4

NUMERO US SO FT LENS DESIG NS FO R

KERATO C O NUS BY MANUFAC TURER
LAB/ M ANUFAC TURER
• Ad va n c e d Visio n Te c h n o lo g ie s In c
• C o n tin e n ta l So ft Le n s
• G e lfle x USA
• Le n s Dyn a m ic s
• Ma rie tta Visio n
• Me d le n s In n o va tio n s In c
• O c u -Ea se O p tic a l Pro d u c ts In c
• Sp e c ia lEye s LLC
Figure 12-6. Piggyback fit using a silicone hydrogel lens beneath the GP to
• Stra te g ic Le n s In n o va tio n s C o rp (SLIC) improve comfort and centration.
• Un ite d C o n ta c t Le n s In c
• X-C e l C o n ta c ts In c

posterior lens design with increased central thickness

to mask much of the regular and irregular astigmatism.
Custom design using a broad range of base curve radii,
powers, diameters, and center thickness values is avail-
able.8 These lenses are usually considered after the patient
is unsuccessful with gas-permeable designs. There are other
soft lens designs listed by manufacturers in Table 12-4.
Piggyback fitting, while not used as an initial approach
to fitting, is an important tool for the clinician. Fitting
a soft lens beneath the GP improves tolerance by acting
as a cushion between the GP and cornea, reducing cor-
neal nerve irritation. These are preferably high-Dk silicone Figure 12-7. Piggyback system requires a flatter GP base curvature. Note this
hydrogel disposable lenses in low minus or plus powers lens is too steep, evidenced by the bubble beneath the lens and thin rim of
with a steep base curve (Figure 12-6). The soft lens can be fluorescein at the edge.
fit first, and over-keratometry used to select a GP lens with
a base curve equal to the new over-K value. A flatter base
curve is normally required when using a soft lens under the parameters and risk of hypoxia even with higher oxygen-
GP (Figure 12-7). Peripheral seal-off is seen in Figure 12-8, permeable materials secondary to poor tear exchange.
where the peripheral curve is too steep. Observe for exces-
sive apical bearing or superior alignment with seal-off of
the GP, which results in a swirl staining. The patient must SCLERAL LENSES
be educated about the care of each type of lens including
wear schedule, solutions, and replacement. A hydrogen Scleral lenses are designed to vault the irregular cornea
peroxide system may be the simplest and safest option for entirely, landing on the sclera/conjunctiva. These lenses were
both types of lenses for cleaning and disinfecting. intended for more advanced cases, those patients who are GP
intolerant, or those patients who dislodge the lens with eye
movement. The advantages of scleral lens designs are good
HYBRID LENSES centration allowing for stable vision and optics. The disad-
vantages are that these very large diameter lenses can be dif-
Hybrid lenses are classified as a gas-permeable center ficult to insert and remove and there is less tear exchange.
with a soft skirt. The soft skirt allows good initial com- The fit is based on sagittal height and depth and not on
fort with the benefit of good vision from a gas-permeable the relationship of the base curve to the corneal curvature.
center. The disadvantages of these lenses are their limited Sagittal depth, the measurement from the flat plane at a
 NON-SURGICAL TREATMENT OF KERATOCONUS USING CONTACT LENSES 125

TAB LE 12 -5

SC LERAL LENS G RO UPS10

G RO UP DIAMETER ( MM)
C o rn e o -Sc le ra l 12.9 to 13.5
Se m i-Sc le ra l 13.6 to 14.9
Min i-Sc le ra l 15.0 to 18.0
Sc le ra l 18.1 to 24.0

With reverse geometry, the sagittal depth of the lens can be

changed independently of central optic zone profile and/or
Figure 12-8. Piggyback with superior peripheral seal-off of the soft lens and midperipheral/limbal zone clearance values. Sagittal depth
GP. value, midperipheral/limbal zone clearance, and lens power
are the only parameters to specify when ordering an Msd
lens as the diameter is fixed at 15.8 mm. Figure 12-10 dem-
onstrates a case of iatrogenic keratoconus after repeat hyper-
opic LASIK treatments. We fit this patient in an Msd lens.
Note the midperipheral air bubbles in Figure 12-11A that
were resolved by decreasing the sagittal depth and the mid-
peripheral/limbal zone in Figure 12-11B. The Msd thin pro-
file and design results in minimal lens edge/lid interaction,
providing excellent patient comfort and oxygen transmission
to the cornea during wear. A fenestration is incorporated in
the Msd lens, which acts as a controlled release valve for tear
Figure 12-9. Sagittal depth, the measurement from the flat plane at a given exchange and the flow of metabolic debris. The fenestration
diameter to the highest point of the concave surface of the contact lens (From inhibits the Msd lens from adhering to the eye and eases the
Blanchard Lab Inc, with permission.) removal process. These Msd lenses can be ordered with or
without a fenestration. Ideally, the Msd should fit with apical
clearance or, in the case of keratoconus, central feather touch
given diameter to the highest point of the concave surface at the corneal apex, with the midperipheral/limbal zone
of the contact lens, is important in fitting these lenses completely vaulting the limbus and aligning on the sclera.
(Figure 12-9).9 Lens vault can be manipulated by maintain- Lens movement with the Msd is often limited and may be
ing the lens diameter and increasing or decreasing sagittal difficult for the practitioner to discern.
depth. The lenses are diagnostically fit until corneal clear-
ance is achieved. The lens should also vault the limbus and
fit without blanching the conjunctival vessels with daily FITTING PROTOCOL
wear. If midperipheral or limbal touch exists, increase
the midperipheral zone of the lens to move the surface of Referring to topography, choose a diagnostic lens real-
the lens off the peripheral cornea. If midperipheral space izing it is only a starting point. The author prefers the
between the lens and cornea is too great, air bubbles will be three-point-touch technique and looks for slight (2 mm)
noted, which may cause epithelial desiccation. Decreasing central touch with fluorescein (1 point), with the blink
the midperipheral zone will minimize these issues. Small along with the annulus (the other 2 points) touching on
air bubbles in the periphery that move during lens wear, the midperipheral cornea. Select a base curve radius equal
don’t interfere with vision, or cause epithelial surface dry- to the steep “K” reading. The steep K is chosen over the
ing are acceptable and may not require lens modification. flat K in a keratoconic case because we are adjusting for
Fenestration allows for tear exchange through the pumping high corneal toricity. Some have suggested referring to the
action created by the eyelids, and debris is released more curvature that correlates with the yellow curvature on a
easily. A fenestration, however, can trap bubbles. Scleral keratometric map.11
lenses are categorized by lens diameter (Table 12-5).10 Evaluate the fluorescein pattern via a cobalt blue light in
The Mini-Scleral Design (Msd) (Blanchard Contact combination with a Wratten filter with the biomicroscope.
Lenses Inc, Manchester, NH) incorporates reverse geom- If apical clearance is present, flatten the base curve progres-
etry with specially designed optical and posterior curves. sively until minimal apical touch is present.
126 CHAPTER 12

B
Figure 12-10. Topography of iatrogenic keratoconus after repeated hyperopic
LASIKtreatments.

Next, examine the periphery using fluorescein and

cobalt filter. Alter fit as necessary until the resulting bulls-
eye pattern is attained: apical bearing, paracentral clear-
ance, midperipheral bearing, and peripheral clearance.
The lens must settle on the eye for 10 to 20 minutes,
after which time you should reassess to ensure no signifi-
cant change in the fitting with initial wear. Contact lens
over-refraction and patient education follow. When order- Figure 12-11. (A) Msd semi-scleral lens fit. Note bubbles in midperiphery (Sag:
ing, order median to high-Dk material. 3.9 Standard). (B) Good Msd semi-scleral fit. Bubbles not present after decreas-
Upon dispensing the lenses, evaluate corneal lenses after ingsagand decreasingmidperipheral/limbal zone. (Sag: 3.8 Decreased).
20 minutes. Scleral designs require more time, typically 45
minutes. Over-refraction and fluorescein pattern evalua-
tion guide any adjustments. Educate the patient on proper ous designs, which are listed by manufacturer in Table 12-6.
wear time and lens care plan. For new patients, gradually Case examples will illustrate the use of these lenses.
increase wear time. Have the patient return in 2 to 4 weeks
for an evaluation of vision and lens fitting. Case 1: Flat/Steep Option
When changing the diameter of the lens, it is important
The “flat/steep option” and the quadrant-specific tech-
to remember that changing lens shape alters the refractive
nology offered by Lens Dynamics Inc (Wheat Ridge, CO)
correction. To maintain the fitting relationship, for every
are excellent options for patients with pellucid marginal
0.5-mm increase in lens diameter, you must flatten the
degeneration (PMD). This works well with PMD because of
base curve by 0.25 D and adjust the dioptric power (add
the larger area of inferior steepening. These 11.2-mm stan-
plus). Therefore, for every 0.5 mm you decrease the lens
dard OAD with 9.4-mm OZD lenses may bear superiorly
diameter, you must steepen the base curve by 0.25 D and
and, therefore, rock along the horizontal meridian. A better
adjust the dioptric power (add minus) if you want to main-
fitting relationship can be obtained by flattening the lens
tain the fitting relationship. superiorly and steepening the lens inferiorly to decrease
edge lift. These are ordered in step increments based on
GAS-PERMEABLE the amount of edge lift or bearing present. Figure 12-12A
illustrates a patient with PMD and 10 D of curvature dif-
SPECIALTY LENSES ference from superior to inferior cornea. Therefore, a large
diameter lens design was chosen with a BC of 8.23 and the
With few exceptions, fitting of specialty lenses requires periphery ordered at 4 steps flat @ 090 (superior) and 3
the use of a diagnostic fitting set. Contact your CLMA mem- steps steep @ 270 (inferior). Figure 12-12B shows this lens
ber laboratory for fitting set information. There are numer- on the eye, and the patient’s vision is 20/20.
 NON-SURGICAL TREATMENT OF KERATOCONUS USING CONTACT LENSES 127

TAB LE 12 - 6

NUMERO US G P LENS DESIG NS BY MANUFAC TURER

LAB/ M ANUFAC TURER LENS D ESIG NS
Ab b a Se m i-Sc le ra l
Ac u ity O n e LLC So 2 C le a r
Ba u sc h & Lo m b , Bo sto n Bo sto n Sc le ra l
Bla n c h a rd C o n ta c t Le n se s In c Ro se K, Ro se K2 Irre g u la r C o rn e a , Msd
C ib a Visio n C a re So ftp e rm
Le n s Dyn a m ic s Dyn a In tra -Lim b a l, Q u a d Sym Te c h n o lo g y, Se m i-
Sc le ra l
Mid -So u th Pre m ie r C o n ta c t Le n s Ultim a Asp h e ric
Me d le n s In n o va tio n s Ju p ite r
Me tro O p tic s C o m fo rtKo n e
Pre c isio n Te c h n o lo g y Se rvic e s Ke ra to c o n u s b i-a sp h e ric
Syn e rg Eye s In c Syn e rg e ye s KC , PS
Tru -Fo rm O p tic s Tru C -Sc le ra l
X-C e l Ap e x

A B

Figure 12-12. (A) Axial topography of patient requiring flat/steep option of Dyna
Intralimbal large diameter GP. (B) Excellent vision and comfort achieved without
adverse effects on the cornea even though it appears as an imperfect fit.

Case 2: Quadrant-Specific
Technology
The quadrant-specific technology, such as the quad-
sym design from Lens Dynamics, offers the option of 4
different base curves. Figure 12-13 shows a patient with
PMD and the quad sym fitting quadrants to aid in base
curve selection. The flat/steep option did not adequately
resolve the PMD pattern in this case of peripheral seal-off
at 11- to 12- o’clock, edge lift at 2 o’clock, and bearing at 5
o’clock. Refer to Table 12-7 for the fitting information for
128 CHAPTER 12

Figure 12-13. (A) Pentacam of PMDpatient.

(B) Quad symfitting quadrants. A B

TAB LE 1 2 -7

Q UAD SYM BASE C URVATURE SELEC TIO NS

Q UADRANT C O RRELATIO N WITH C LO C K BASE C URVATURE ( D) FLAT/ STEEP O PTIO N
Q1 1:30 to 4:30 43.50 1 ste p fla t
Q2 10:30 to 1:30 42.50 1 ste p fla t
Q3 7:30 to 10:30 42.50 1 ste p fla t
Q4 4:30 to 7:30 46.75 1 ste p ste e p

this patient. Note the much steeper base curvature chosen

for the inferior quadrant. Figure 12-14 illustrates the fit-
ting and initial dispense of this lens. Note the better fitting
relationship in Figure 12-15 after a few weeks of wear. It is
important to re-evaluate after 2 weeks of continuous wear
and not to change parameters too quickly.

Case 3: Asymmetric Corneal

Technology and Peripheral Curve
The Asymmetric Corneal Technology (ACT) for the
Rose K and Rose K2 Irregular cornea (RK2IC) designs
from Blanchard Lab are an excellent choice for keratoconic
patients and those PKP or Intacs. The Rose K lenses are 8.7-
mm standard OAD and the OZ is based on a nomogram Figure 12-14. Appearance of Quad SymLens upon dispensing.
related to BC (the steeper the BC, the smaller the OZ). The
RK2IC lenses are 11.2-mm standard with a larger OZD and
aspheric optics. When fitting a keratoconic patient, the The peripheral curve is a very important factor in
inferior quadrant is significantly steeper than the superior long-term lens comfort. Figure 12-16 shows a patient with
quadrants, making inferior edge lift a common problem. PMD but a small paracentral area of elevation. Therefore,
ACT will accommodate this asymmetry and provide a a smaller diameter Rose K lens was used. Note the periph-
more accurate fit at 6 o’clock. There are 3 ACT grades num- eral clearance in excess of 0.5 to 0.7 mm 360 degrees with
bered 1 to 3 that the practitioner can specify depending on a standard peripheral curve. When re-ordering this lens, a
the edge stand off. standard steep peripheral curve will be specified. The base
curvature will not be affected.
 NON-SURGICAL TREATMENT OF KERATOCONUS USING CONTACT LENSES 129

A A

C
Figure 12-15. Quad symlens at initial fitting(A) and after 2 weeks of wear (B).
Fitting improves with time.

Case 4: Intacs fitting

Patients with Intacs (Addition Technologies, Sunnyvale,
CA) may be particularly challenging to fit. In addition to
the steep cone, Intacs introduces a second area of steep-
ening in the mid-periphery due to the segment (Figure
12-17A). The GP must be steep midperipherally to avoid
bearing over the segment, often producing inferior edge
lift. Occasionally, a piggyback approach can alleviate the
midperipheral bearing (Figure 12-17B). Figure 12-18 shows Figure 12-16. (A) Axial topographyshowingectasia. (B) Elevation map showing
a keratoconic patient following Intacs implantation fit para-central elevation, therefore choosing a small diameter Rose Klens. (C)
with a Rose K lens. To lessen edge standoff, ACT, available Need standard steep peripheral curve specified when re-ordering this lens.
from grade 1 to 3, may be successfully employed. Note the
improvement in Figure 12-19 when ACT is utilized in lens
fitting. ACT or inferior steepening will create space adja-
cent to edge of the lens, relieving bearing upon the Intac
segment.
130 CHAPTER 12

Figure 12-18. Akeratoconic patient s/p Intacs with a Rose Klens. Note the
inferior edge lift/stand off.
B

Figure 12-17. (A) GP bearing on inferior Intacs segment. (B) Piggyback fitting
used to relieve pressure of GP on INTACsegment.
Figure 12-19. To lessen the standoff, ACT is used. Note the difference and
improvement with Figure 12-17.
PROBLEM SOLVING
decentered cone. Lenses will follow the path of least resis-
tance and be drawn to the steep meridian. If there is exces-
Dry Eye sive difference between superior and inferior curvature
Patients with insufficient tear film often complain of dry- using topography, centration may be problematic.
ness and increased lens awareness. Lid margin disease or tear If there is inferior decentration, make an attempt to
insufficiency need to be treated. Three and 9 o’clock staining obtain a lid attachment design (or superior lens position)
occurs when the corneal surface isn’t adequately resurfaced by decreasing the diameter, reducing center thickness (CT),
with tears after the blink, or if blinking is incomplete. The using plus lenticular if the power is greater than –5.00 or
lens diameter can be reduced to decrease mechanical irrita- minus lenticular on all plus lenses, reducing edge thick-
tion to the limbus and cornea. Over time, you may see vas- ness, and/or flattening the base curve when possible.
cularized limbal keratitis with large-diameter lenses causing Superior decentration management requires a plus len-
chronic irritation. Edge lift can also lead to peripheral cor- ticular to thicken the edge in efforts to reduce the action
neal staining. We can manage these patients by re-fitting the of the upper lid. You can also increase the center thickness
lens to offer better centration and to minimize edge lift. and/or steepen the base curve radius.
Temporal or nasal decentration is the most difficult
Decentration to manage. The only goal is to maintain the lens over the
The symptoms of decentration include lens awareness visual axis by increasing the overall diameter and subse-
and vision varying with the blink. The main cause is a quently steepening the base curve radius.
 NON-SURGICAL TREATMENT OF KERATOCONUS USING CONTACT LENSES 131

Lens Adherence
A
Lens adherence may occur in patients with moderate
to severe dryness or peripheral seal-off. There is no lens
movement when the patient blinks. Dryness and poor
tear film quality can lead to deposits on the lens that will
cause the lens to tighten on the cornea over the course of
the day. Recommend artificial tears throughout the day to
keep the tear film clear and reduce deposits and to prop-
erly lubricate the tear lens interface. Also, have the patient
insert an artificial tear before lens removal. Flattening and
widening the peripheral curve should correct peripheral
seal-off. Some patients may need to reduce the total daily
wear time, which is difficult in cases where GPs may be the
only functioning correction.

Poor Surface Wettability

Poor surface wettability will cause the patient to notice
B
a film over his or her vision or have to remove the lenses
often to clean them. Educate the patient not to use any
soaps or lotions with lanolin prior to lens insertion. Re-
educate the patient on proper cleaning technique and
appropriate solutions.

Hypersensitivity
Hypersensitivity reactions occur when patients become
sensitive to a preservative or an accumulation of a preser-
vative. They will complain of burning and redness upon
insertion and sometimes will complain of itching. This
problem is easily solved by switching chemical care regi- Figure 12-20. (A) Inferior edge lift with adjacent dimple veiling. (B) Post ACT
mens or using a preservative-free system. causing increased dimple veiling. As the edge lift was reduced by inferior
steepening, it caused greater space midperipherally, worsening the problem.
Dimple Veiling
Dimple veiling can begin by looking like a few insertion enable patients to delay surgery and maintain good visual
bubbles. If these bubbles are immobile, they exert force function.
onto the cornea, creating indentions. These will resolve
within a few hours if the lens is removed. The base curva-
ture can be flattened. In some lens designs, the problem REFERENCES
quadrant or area can be flattened to minimize the bubbles.
If this is unsuccessful or you are unable to change the lens 1. Sabesan R, Jeong TM, Carvalho L, Cox IG, Williams DR, Yoon G.
Vision improvement by correcting higher-order aberrations with
curvature, the treatment of choice is to decrease the opti- customized soft contact lenses in keratoconic eyes. Opt Lett. 2007;
cal zone size.12 Steepening of any parameter will make the 32(8):1000-1002.
problem worse as seen in Figure 12-20. 2. Marsack JD, Parker KE, Applegate RA. Performance of wavefront-
guided soft lenses in three keratoconus subjects. Optom Vis Sci.
Central Corneal Swirling 3.
2008;85(12):E1172-E1178.
Marsack JD, Parker KE, Niu Y, Pesudovs K, Applegate RA. O n-eye
This is the opposite problem of dimple veiling and performance of custom wavefront-guided soft contact lenses in a
habitual soft lens-wearing keratoconic patient. J Refract Surg. 2007;
commonly caused by a flat fitting GP. It is a swirling pat-
23(9):960-964.
tern of staining on the cornea. The base curve radius must 4. de Brabander J, Chateau N, Marin G, et al. Simulated optical per-
be steepened to alleviate this problem, which can lead to formance of custom wavefront soft contact lenses for keratoconus.
cloudy vision and possible scarring. Optom Vis Sci. 2003;80(9):637-643.
5. Edrington TB, Szczotka LB, Barr JT, et al. Rigid contact lens fit-
While fitting gas-permeable contact lenses can be chal-
ting relationships in keratoconus. The Collaborative Longitudinal
lenging, familiarizing oneself with basic fitting techniques Evaluation of Keratoconus. Optom Vis Sci. 1999;76(10):692-699.
and investigating lens materials and specialty designs may
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6. Zadnik K, Barr JT, Steger-May K, et al. Comparison of flat and 10. Sindt C. Basic scleral lens fitting and design. Contact Lens Spectrum
steep rigid contact lens fitting methods in keratoconus. The [online]. October 2008. Available at: http://www.clspectrum.com/
Collaborative Longitudinal Evaluation of Keratoconus. Optom Vis article.aspx?article=102163. Accessed June 22, 2009.
Sci. 2005;82(12):1014-1021. 11. Potter R, Wieringa J, Lotoczky J, Pole J. Using the “yellow rule” on
7. Barr JT, Zadnik K, Wilson BS, et al. Factors associated with cor- corneal topography to predict successful initial base curve selection
neal scarring in the Collaborative Longitudinal Evaluation of in keratoconic RGP lens fitting. Poster presentation at: American
Keratoconus (CLEK) study. Eye Contact Lens. 2007;33(2):103-105. Academy of Optometry; Denver, CO; 2006.
8. Caroline P, Andre M. Soft lenses for keratoconus. Contact Lens 12. McMahon T. Treatment plan dellen and dimple veiling. Contact
Spectrum [online]. 2000. Available at http://www.contactlensspec- Lens Spectrum [online]. May 2002. Available at http://www.clspec-
trum.com/article.aspx?article=101460. Accessed June 22, 2009. trum.com/article.aspx?article=12147. Accessed June 22, 2009.
9. Martin B. Home page. Available at http://www.blanchardlab.com.
Accessed June 22, 2009.
 CHAP TER 1 3

Penetrating and Lamellar

Keratoplasty Techniques

Soosan Jacob, MS, FRCS, Dip NB; Gaurav Prakash, MD;

Dhivya Ashok Kumar, MD; Athiya Agarwal, MD, DO;
Amar Agarwal, MS, FRCS, FRCOphth; Leopoldo Spadea, MD;
and Charles Wm. Stewart, OD

M
anagement of ectasia depends on the stage of pro- studies on PK with long-term follow-up have shown good
gression. Penetrating keratoplasty (PK) was con- visual results usually after 18 to 24 months.9-11 The graft
sidered the most successful surgical option for survival at 10 years for keratoconus is about 90%. Even
patients who are contact lens intolerant or unable to obtain though final visual results are good, visual rehabilitation
useful levels of vision. With the advent of newer treatment is a prolonged process due to regular and irregular astig-
options such as intra-corneal rings, collagen cross-linking matism induced by less-than-ideal graft host apposition or
with riboflavin, and development of deep anterior lamel- suturing.
lar keratoplasty techniques, PK is being reserved for select The difference in performing a keratoplasty in ectatic
indications in keratoconus and keratoectasia. disorders is that generally a same size graft is preferred to
be sutured on rather than a slightly over-sized graft as is
the norm in keratoplasties for other indications. This is
PENETRATING KERATOPLASTY to avoid post-operative increase in corneal curvature and
myopic post-op refractive results, which have been seen to
Worsening of the disease and progressive ectasia with occur when using slightly over-sized grafts.12-15 Usually
insufficient correction or intolerance to contact lenses is 7.5-mm grafts are used as this also helps in minimizing
one of the indications for keratoplasty and also central graft rejection,1 although a larger graft may be required to
scarring secondary to acute hydrops. PK for cases with remove the ectatic tissue. On the other hand, a recent study
severe thinning to prevent perforation is not justified as by Jaycock et al16 concluded that use of same-size donor
these corneas almost never perforate.1 PK was often the and recipient trephines did not reduce myopia and was also
norm for these patients, and keratoconus is one of the associated with an increased risk of post-operative compli-
most common indications for corneal transplantation in cations in the form of wound leak. This would, of course,
the developed countries with a graft survival of 97% at 5 be negated in case of deep anterior lamellar keratoplasty.
years.2-7 In the study by Sray et al conducted in a corneal Cauterization of the host before PK to reduce anterior
referral practice with long-term follow-up, 64.2% of kera- chamber depth has also been shown to reduce post-opera-
toconus patients went on to have PK in one or both eyes. tive myopia.17
Scarred corneas and those with high keratometry values Complications that may be seen following keratoplasty
more commonly underwent PK.8 include rejection, post-PK astigmatism, and a fixed, dilated
The modern goal for a successful PK is not only a clear pupil. Keratoconus has been reported to recur in the donor
cornea, but a good refractive outcome as well. Numerous graft.18-26 Various mechanisms have been proposed for this

Wang M, ed.
Keratoconus & Keratoectasia: Prevention, Diagnosis, and Treatment (pp.135–142) 135
© 2010 SLACK Incorporated
136 CHAPTER 13

phenomenon. Enzymatic degradation originating from area of endothelium was transplanted along with a large
the defective host epithelium, which replaces the donor anterior stromal lamella. This has the advantage of less sur-
epithelium within days to weeks, has been implicated in face distortion and faster healing with more than 80% of
the ectatic changes seen in the graft.27 Abnormal host recipient endothelium intact. This gives the potential of the
keratocytes gradually repopulating the donor graft, lead- host endothelium being able to repopulate the graft even in
ing to abnormal collagen production and eventual thin- cases where the graft endothelium is completely destroyed
ning of the stroma is another proposed mechanism.19,23,28 following endothelial rejection.
Another hypothesis is that if the entire extent of diseased In this procedure, on the recipient cornea, a suction tre-
tissue is not excised, it could lead to recurrence in the phine is used to make a circular incision 200 µm in depth
graft.29 Some studies have also postulated that graft kera- and 9.0 mm in diameter followed by removal of the ante-
toconus may occur because of transfer of the disease from rior lamella by hand dissection. The donor cornea is cut
the donor.18,25,26 into anterior and posterior lamellae using a 200-µm head
of the ALTK system (Moria, Paris, France). The anterior
Shaped Keratoplasties lamella is then punched to 9 mm, and the posterior lamella
Here, the corneal donor button and the recipient bed to 5.0 mm. The recipient cornea is then trephined in the
are cut in geometrical shapes with mirror cuts that make center with a 5.0-mm trephine and the button excised. The
them fit together in a jigsaw puzzle manner. The lamel- 5.0-mm donor button is then placed in the central recipient
lar surfaces increase the area of apposition between the bed over viscoelastic without suture fixation. The 9.0-mm
two, thereby improving wound healing, decreasing suture donor anterior lamella is then sutured into position with a
induced astigmatism, and therefore providing faster visual running 10-0 nylon. Air in the anterior chamber is used to
recovery than conventional PK offers. By increasing (top- facilitate central graft adhesion.
hat cofiguration) or decreasing (mushroom configuration) The IntraLase Enabled Keratoplasty software (AMO,
the posterior diameter as compared to the anterior diam- Abbott Park, Illinois) adds precision and programmability
eter, one can get a larger or smaller area of endothelium to shaped keratoplasties. It can be programmed to produce
transplanted. A mushroom keratoplasty is preferred in the different configurations with computer precision. It also
eyes of keratoconic and keratoectatic patients who gener- makes the procedure much more reproducible and creates
ally have healthy endothelium. a better fit between the donor and the recipient.32-34 This is
The nut-and-bolt PK technique was described by done using a combination of anterior side cut, ring lamel-
Busin.30 It aimed at combining the optical superior- lar cut, and posterior side cut. Here, an anterior side cut of
ity of PK with the wound-healing advantages of lamellar larger diameter and a posterior side cut of smaller diameter
keratoplasty. Here, a 0.3-mm deep incision is made with gives a mushroom-shaped resection on the graft and recipi-
a 7.0-mm Barron suction trephine on the donor cornea ent which fit together with extreme precision.
mounted on an artificial chamber. This is followed by a The technique involves programming the computer for
lamellar stromal dissection from the base of this incision to anterior side cut, lamellar cut, and the posterior side cut of
the limbus. A 9.0-mm donor button is then punched from desired dimensions. The laser procedure is then performed
the endothelial side. The resulting graft is top-hat shaped on the donor cornea, either the corneo-scleral rim mounted
with a posterior diameter of 9.0 mm and an anterior diam- on an artificial chamber or on the whole eye. Once this is
eter of 7.0 mm. The previous lamellar dissection allowed done, a mirror cut of the same dimensions is used for the
a superficial annular stromal lamella, 0.3 mm in thick- keratoconic recipient eye, but in the recipient eye, a non-
ness, to be removed in the area between 7.0 and 9.0 mm in penetrating posterior side cut is made leaving behind about
diameter. The recipient bed is prepared accordingly with 60 µm of uncut tissue toward the anterior chamber (Figure
a circular incision 0.3 mm in depth made with a 7.0-mm 13-1). This aids in safe transfer of the patient to the operat-
Barron suction trephine followed by lamellar stromal dis- ing theatre and microscope. The donor button femtosec-
section to about 1 mm peripherally. The anterior chamber ond cut can be dissected with blunt dissection. In case of
is then entered, and corneal scissors are used to complete recipient cornea, the posterior part of the uncut tissue needs
the excision of the corneal button at the peripheral end of sharp dissection with either a blade or scissors (Figure 13-2).
the posterior lamellar stromal dissection. The graft is then Alignment incisions function creates equally spaced, small
slid in under the anterior stromal lip of the recipient bed incisions along the diameter of the anterior side cut in both
and sutured in place. the donor and recipient, which can be used for decreasing
Busin et al also proposed a microkeratome-assisted astigmatism while suturing (Figures 13-3A,B and 13-4A,B).
keratoplasty31 where a central full thickness disc of about 5 It should be noted that the femtosecond laser does not cut
mm was transplanted along with a peripheral skirt of ante- through any corneal opacity adequately dense to obscure
rior stroma and epithelium. Only a relatively small central visualization of iris details (Figures 13-5 through 13-8).
 PENETRATING AND LAMELLAR KERATOPLASTY TECHNIQUES 137

Figure 13-1. (A) Mushroom-shaped cut made with

the IntraLase for performing IntraLase enabled
keratoplasty in the donor eye. (B) Mirror image,
mushroom-shaped cut made with the IntraLase
for performing IntraLase-enabled keratoplasty
in the recipient keratoconic eye. Alignment inci-
sions can be seen.

Figure 13-2. (A) Donor graft dissected with blunt

dissection. (B) Recipient cornea being dissected.
Terminal uncut portion near the anterior cham-
ber needs to be cut with sharp dissection.

Figure 13-3. (A) Donor cornea being placed on

the recipient bed. Both corneas are of same
diameter. (B) Donor cornea sutured in place.

Figure 13-4. (A) Pre-op viewof cornea showinghydrops and scar. (B) Post-operative viewwith patient seated on slit-lamp, after mushroom-shaped femtosecond
keratoplastybefore dissecting the recipient cornea. (C) Post-op viewshowing the graft host junction.

LAMELLAR KERATOPLASTY subjecting patients to the risk of immunological rejection

for the duration of their lives.2 Due to the young age of
these patients, it is important to follow a “step-by-step”
PK is the most widely used and reliable technique for therapeutic plan, selecting, when possible, the techniques
surgical treatment of keratoconus. However, this procedure that are least invasive at the beginning and thus postpon-
involves the replacement of the native corneal endothelium ing the possibility of PK. To this end, several authors have
that is typically healthy in spite of this disease, thereby suggested different techniques for anterior lamellar kera-
138 CHAPTER 13

Figure 13-5. (A) Pre-op slit-lamp viewafter making the cuts with the femtosecond laser for mushroom-shaped IEK. (B) Post-op viewshowing the graft host
interface in high magnification. (C) Post-op viewshowing outlined, the graft–host interface and mushroom-shaped graft in optical slit beam.

Figure 13-7. (A) Pre-op viewshowingthinned cornea and deep anterior cham-
ber pre-operatively in a patient with keratoconus. (B) Post-op viewshowing
increased pachymetry in the graft and decreased depth of the anterior
chamber in same patient.

Figure 13-6. (A) Anterior segment OCTshowing the mushroom-shaped inter- the electrokeratome, and Barraquer (1965) presented the
face on one side. (B) Anterior segment OCTshowing the mushroom-shaped first microkeratome with the improvement of interface
interface on the diametricallyopposite side. (C) Anterior segment OCTshow- quality and with more predictable final thickness and
ing the mushroom-shaped graft in anterior segment view. diameter.3-7
The common principles of all lamellar keratoplasty
techniques are to selectively remove only the pathological
toplasty (LK). With this technique, only the anterior por-
tissue saving the deeper corneal layers (Descemet’s mem-
tion of the cornea is excised and then replaced by a donor
brane and endothelium) and to restore the normal corneal
corneal lenticule placed onto the recipient bed. In 1877, von
thickness by implanting a lamellar graft.
Hippel tried the first LK on a human eye unsuccessfully,
but was followed by Zirm in 1906 who reported a success- Deep Anterior Lamellar Keratoplasty
ful procedure. Kraupa, Paufique, and colleagues improved
the surgical technique, and Stocker, in 1953, made a careful
(DALK)
study of the corneal endothelium. Initially, the recipient DALK refers to replacement of the host stroma and epi-
bed was prepared with a manual lamellar dissection of thelium up to Descemet’s membrane with a donor consist-
corneal tissue, with irregular interfaces and unpredictably ing of stroma and epithelium but stripped of the Descemet’s
irregular final corneal thickness. The results were not sat- membrane and endothelium. Various techniques have been
isfactory with this method. In 1958, Castroviejo invented described including Melles technique,35,36 viscoelastic dis-
 PENETRATING AND LAMELLAR KERATOPLASTY TECHNIQUES 139

Figure 13-8. (A) Pre-op pachymetry showing thinned cornea in a patient with
keratoconus. (B) Post-op pachymetryshowingbetter thickness in same patient.

Figure 13-10. (A) Superficial corneal stroma debulked. (B)

Descemet’s membrane exposed.

section,37 the big bubble technique, the small bubble tech-

nique, and so on. In the Melles technique, after injection of
air into the anterior chamber, the mirror effect, the inden-
tation effect, and the folding effect are used to determine
how close the dissection depth is to the Descemet’s mem-
brane. The most popular technique is Anwar’s big bubble
technique.38-40 Here, the recipient cornea is trephined with
a Hessburg-Barron trephine to about 300 to 350 µm, and
air is injected with force through a bent 30-gauge needle
inserted through the edge of the trephination into the
corneal stroma. The stroma can be seen to whiten, and a
big bubble is generally obtained between the Descemet’s
membrane and the stroma (Figure 13-9). The superficial
corneal stroma is then dissected off with a crescent blade,
and the anterior chamber is entered via a paracentesis.
The air bubble is then cut through, and the stromal tis-
sue over the spatula is cut into 4 quadrants with a Vannas
scissors. These flaps are then cut to completely expose the
Descemet’s membrane (Figure 13-10). A donor cornea from
which the Descemet’s membrane and the endothelium
have been stripped is then sutured in place (Figure 13-11).
Figure 13-9. (A) A30-gauge needle inserted through partially
trephined cut and directed obliquely into corneal stroma. The small bubble technique41,42 refers to injecting a
(B) Air injected into deep corneal stroma to form the big small bubble into the anterior chamber after injecting the
bubble. big bubble. If a big bubble has been successfully formed, the
140 CHAPTER 13

Figure 13-12. Anterior segment OCTin patient with ectasia following DALK.

Figure 13-11. (A) Descemet’s membrane stained with Trypan

blue stripped from the posterior corneal stroma. (B) Donor
graft stripped of Descemet’s membrane sutured onto recipi-
ent bed.
Figure 13-13. Pre- and post-operative anterior segment quad viewof anterior
segment OCTin patient with ectasia following LASIK.
Descemet’s membrane bulges into the anterior chamber, and
hence, small air bubbles are displaced toward the periphery
of the anterior chamber by the space-occupying big bubble. Despite being more time-consuming and having a
Upon moving the eye in different directions with a forceps, steeper learning curve, it offers numerous advantages over
the small bubbles do not move freely across the anterior PK. The advantages over full-thickness grafts include the
chamber but remain confined to the periphery. need for less rigorous follow-up and decreased incidence
The advantages of DALK are faster wound stabilization of endothelial rejection; only about a 10% decrease from
with suture removal possible between 6 and 12 months pre-operative levels of endothelial cell count, which is
unlike the 1.5 to 2 years required in the case of PK43,44 about half the cell loss in a PK.48 Although visual acuity
(Figures 13-12 and 13-13). Intraoperative complications following DALK is similar to that for PK, the final best
that may be encountered include, among others, Descemet’s corrected vision may sometimes be reduced in DALK sec-
membrane perforation. The rate for this complication var- ondary to interface scarring.45 The newer techniques of
ies between 9 and 20%.45,46 In case of microperforations, DALK which leave behind only Descemet’s membrane and
air or a non-expansile mixture of air and SF6/C3F8 can be thus a smooth bed in the host, and involve only stripping
injected into the anterior chamber, and one can proceed of the Descemet’s in the graft, scarring of the interface
with the procedure. Biological glues may also be used after has not been reported as a major complication.43,47,49,50
perforation in DALK.46 This also helps in preventing a sec- Astigmatism after DALK is comparable to that after PK.
ond chamber post-operatively. Larger perforations would DALK has been reported by several authors for both kera-
necessitate conversion to PK. The incidence of conversion toconus and keratoectasia.36,51
of DALK to PK has ranged from 1.3% to 8.4% of cases in
series with keratoconus.46,47
 PENETRATING AND LAMELLAR KERATOPLASTY TECHNIQUES 141

Femtosecond-Assisted Lamellar
Keratoplasty
Epithelial nebulae and anterior stromal scars may occur
in keratoconus and may also be seen as a complication in
post-refractive surgery patients. Thinning with irregular
astigmatism and inability to wear/tolerate contact lenses
is another indication for performing lamellar keratoplasty.
Manual mid-lamellar keratoplasty has been performed for Figure 13-14. Post-FALKin keratoconus patient with ectasia and superficial
ectatic disorders in the past, and average visual acuities of stromal opacity. Note the 90-degree side cut angle between the graft and
6/9 have been reported.52,53 The disadvantages of manual host unlike a meniscus cut obtained with automated lamellar keratoplasty.
mid-lamellar keratoplasty include, among others, difficult
dissection and the fact that it is difficult to control the 4. Vali A, Gore SM, Bradley BA, et al. Corneal transplantation in the
exact depth of dissection. United Kingdom and Republic of Ireland. Br J Ophthalmol. 1993;
A mid-lamellar keratoplasty in the form of femtosecond- 77:650-656.
assisted lamellar keratoplasty (FALK) may be performed 5. Legeais JM, Parc C, d’Hermies F, et al. Nineteen years of penetrat-
ing keratoplasty in the Hotel-Dieu Hospital in Paris. Cornea. 2001;
in these cases. Femtosecond technology is well known for 20:603-606.
its accuracy, safety, and efficacy.53-59 Using this technique, 6. Kang PC, Klintworth GK, Kim T, et al. Trends in the indications for
a mid-lamellar graft is performed using the femtosecond penetrating keratoplasty, 1980-2001. Cornea. 2005;24:801-803.
laser. This offers the advantages of safer surgery with fewer 7. Williams KA, Muehlberg SM, Lewis RF, Coster DJ. How successful
is corneal transplantation? (A report from the Australian Corneal
intra- or post-operative complications. Visual recovery is Graft Register). Eye. 1995;9:219-227.
faster and typically better because of the extremely smooth 8. Sray WA, Cohen EJ, Rapuano CJ et al. Factors associated with the
surface and uniform depth of the bed and the graft. Just need for penetrating keratoplasty in keratoconus. Cornea. 2002;
as in all other LKs, the risk of endothelial graft rejection is 21(8):784-786.
9. Troutman RC, Lawless MA. Penetrating keratoplasty for keratoco-
also negated. Femtosecond laser-assisted posterior lamellar
nus. Cornea. 1987;6:298-305.
keratoplasty has also been described.60 Surgery becomes 10. Lawless MA, Troutman RC. The role of penetrating keratoplasty
extremely precise with very good donor–recipient match in and epikeratoplasty in the surgical management of keratoconus.
terms of size, thickness, and shape. As mentioned by Yoo et Aust N Z J Ophthalmol. 1989;17:387-393.
al,61 FALK gives vertical side cuts rather than meniscus side 11. The Australian Corneal Graft Registry. 1990 to 1992 report. Aust N
Z J Ophthalmol. 1993;21(suppl):1-48.
cuts created by automated lamellar keratoplasty. Also, graft 12. Bourne WM, Davison JA, O’Fallon WM. The effects of oversize
and host cuts of any thickness can be obtained with the donor buttons on post-operative intraocular pressure and cor-
femtosecond unlike in the case of microkeratome-assisted neal curvature in aphakic penetrating keratoplasty. Ophthalmology.
automated lamellar keratoplasty. IntraLase femtosecond 1982;89:242–246.
13. Perry HD, Foulks GN. Oversize donor buttons in corneal transplan-
laser keratome has been reported to have depth and diam-
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eter accuracy even at increased depth settings in lamellar 14. Wilson SE, Bourne WM. Effect of recipient-donor trephine size dispar-
keratoplasty.62 Twenty percent additional thickness is added ity on refractive error in keratoconus. Ophthalmol. 1989;96:299-305.
to the donor graft to adjust for donor tissue swelling. The 15. Duran JA, Malvar A, Diez E. Corneal dioptric power after penetrat-
risks of irregular cutting and microperforation are fewer in ing keratoplasty. Br J Ophthalmol. 1989;73:657-660.
16. Jaycock PD, Jones MN, Males J, et al. Outcomes of same-sizing ver-
FALK. and there is a decreased risk of donor displacement sus oversizing donor trephines in keratoconic patients undergoing
(Figure 13-14). first penetrating keratoplasty. Ophthalmology. 2008;115(2):268-275.
Compared to manual deep anterior lamellar kerato- 17. Busin M, Zambianchi L, Franceschelli F, et al. Intraoperative cau-
plasty, the ease of surgery, quick learning curve, shorter terization of the cornea can reduce postkeratoplasty refractive error
in patients with keratoconus. Ophthalmology. 1998;105:1524-1529.
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keratoplasty. Am J Ophthalmol. 2007;143(5):737-742. Surg. 2006;32(4):679-680.
33. Holzer MP, Rabsilber TM, Auffarth GU. Penetrating keratoplasty 52. Richard JM, Paton D, Gasset AR. A comparison of penetrating
using femtosecond laser. Am J Ophthalmol. 2007;143:524-526. keratoplasty and lamellar keratoplasty in the surgical management
34. Por MY, Chuan Cheng JY, Parthasarathy A, et al. Outcomes of fem- of keratoconus. Am J Ophthalmol. 1978;86:807-811.
tosecond laser-assisted penetrating keratoplasty. Am J Ophthalmol. 53. Benson WH, Goosey CB, Prager TC, Goosey JD. Visual improve-
2008;145:772–774. ment as a function of time after lamellar keratoplasty for keratoco-
35. Melles GRJ, Lander F, Rietveld FJR, Remeijer L, Beekhuis WH, nus. Am J Ophthalmol. 1993;116:207-211.
Binder PS. A new surgical technique for deep, anterior lamellar 54. Binder PS. Flap dimensions created with the IntraLase femtosecond
keratoplasty. Br J Ophthalmol. 1999;83:327-333. laser. J Cataract Refract Surg. 2004;30:26-32.
36. Villarrubia A, Pe´rez-Santonja JJ, Palacy´n E, et al. Deep anterior 55. Nordon LT, Slade SG, Baker RN, et al. Femtosecond laser flap cre-
lamellar keratoplasty in post-laser in situ keratomileusis keratoec- ation for laser in situ keratomileusis: six-month follow-up of initial
tasia. J Cataract Refract Surg. 2007;33:773-778. US clinical series. J Refract Surg. 2003;19:8-14.
37. Manche EE, Holland GN, Maloney RK. Deep lamellar keratoplasty 56. Cheng YY, Pels E, Nuijts RM. Femtosecond laser assisted
using viscoelastic dissection. Arch Ophthalmol. 1999;117:1561-1565. Descemet’s stripping endothelial keratoplasty. J Cataract Refract
38. Anwar M, Teichmann KD. Big-bubble technique to bare Descemet’s Surg. 2007;33:152-155.
membrane in anterior lamellar keratoplasty. J Cataract Refract Surg. 57. Lubatschowski H, Maatz G, Heisterkamp A, et al. Application of
2002;28:398-403. ultrashort laser pulses for intrastromal refractive surgery. Graefes
39. Vajpayee RB, Tyagi J, Sharma N, et al Deep anterior lamellar kera- Arch Clin Exp Ophthalmol. 2000;238:33-39.
toplasty by big-bubble technique for treatment of corneal stromal 58. Kezirian GM, Stonecipher KG. Comparison of the IntraLase femto-
opacities. Am J Ophthalmol. 2007;143(6):954-957. second laser and mechanical keratomes for laser in situ keratomi-
40. Fontana L, Parente G, Tassinari G, et al. Clinical outcomes after leusis. J Cataract Refract Surg. 2004;30:804-811.
deep anterior lamellar keratoplasty using the big-bubble technique 59. Durrie DS, Kezirian GM. Femtosecond laser versus mechani-
in patients with keratoconus. Am J Ophthalmol. 2007;143:117-124. cal keratome flaps in wavefront-guided laser in situ keratomi-
41. Fontana L, Parente G, Tassinari G, et al. Simple test to confirm leusis: prospective contralateral eye study. J Cataract Refract Surg.
cleavage with air between Descemet’s membrane and stroma 2005;31:120-126.
during big-bubble deep anterior lamellar keratoplasty. J Cataract 60. Soong HK, Mian S, Abbasi O, Juhasz T. Femtosecond laser-assisted
Refract Surg. 2007;33:570-572. posterior lamellar keratoplasty. Initial studies of surgical technique
42. Parthasarathy A, Por YM, Tan DTH. Use of a “small-bubble tech- in eye bank eyes. Ophthalmology. 2005;112:44-49.
nique” to increase the success of Anwar’s “big-bubble technique” 61. Yoo SH, Kymionis GD, Koreishi A, et al. Femtosecond laser–
for deep lamellar keratoplasty with complete baring of Descemet’s assisted sutureless anterior lamellar keratoplasty. Ophthalmology.
membrane. Br J Ophthalmol. 2007;91:1369-1373 2008;115(8):1303-1307.
43. Panda A, Bageshwar LM, Ray M, et al. Deep lamellar kerato- 62. Saraya MA, Maquen E, Salz J, et al. Femtosecond laser keratome
plasty versus penetrating keratoplasty for corneal lesions. Cornea. creation of partial thickness donor corneal buttons for lamellar
1999;18:172-175. keratoplasty. J Refract Surg. 2007 Jan;23(1):58-65.
 CHAP TER 1 4

Excimer Laser Photorefractive

Keratectomy for Keratoconus

Arun C. Gulani, MD; Lee T. Nordan, MD; Noel Alpins, FRANZCO,

FRCOphth, FACS; and George Stamatelatos, BScOptom

P
atients with keratoconus are typically frustrated with While treating conditions that reduce the best-corrected
their visual limitations that negatively impact their vision acuity (BCVA) in patients with keratoconus may
lifestyle. These patients often have exhausted their be deemed “acceptable,” elective treatment of keratoconus
options with glasses and contact lenses, leading them to patients to improve unaided vision is less accepted by the
investigate surgical options. As described within this text- ophthalmic community. Reports of aberrations resulting
book, various surgical options exist but all have drawbacks. from keratoconus corrected using topographically guided
Corneal transplant is an invasive surgery with long-term and wavefront-guided treatments are scarce but do exist.
lifestyle restriction and limited ability to achieve uncorrect- Tamayo and Serrano used the VISX C-CAP method (AMO,
ed 20/20 vision. Intacs (Addition Technologies, Sunnyvale, Abbott Park, IL), a topographically customized program,
CA) is a reversible, less invasive surgery that may delay to address the topographical irregularity in keratoconus.7
or avoid transplant in many cases, but visual outcome is Koller et al used topography-guided surface ablation to sig-
unpredictable. The majority of cases require contact lenses nificantly reduce manifest refractive error, corneal irregu-
or spectacles after surgery for best correction. larity, and ghosting.8 Lin et al used the Allegretto topogra-
In addition, these patients are typically otherwise phy-guided PRK treatment (Alcon, Fort Worth, TX) in 16
healthy young adults at the prime of their professional and keratoconic eyes. They reported improvement of astigma-
personal lives, and often have expectations similar to those tism up to 5.00 D, and best spectacle-corrected visual acuity
searching for elective vision correction. We must therefore (BSCVA) unchanged or improved in 14 eyes, with 2 (12%)
balance our desire to provide an enhanced lifestyle while eyes losing 1 line of BSCVA at 6 months. Even with these
maintaining a high level of safety for these patients. results, it was not recommended unless keratoplasty was
Patients may present for surgical treatment of clinical otherwise indicated in keratoconus patients.9 Cennamo et
manifestations of keratoconus including irregular astig- al used topography-guided PRK treatments with the Zeiss
matism, scarring, nodules, and severe axial curvature Mel 70 excimer laser (Maple Grove, MN) in mild to moder-
resulting in problematic contact lens fitting. Excimer laser ate keratoconus patients (Krumeich classification, grade 2),
treatments may be applied in an effort to correct these reducing the severity of several indices used to describe the
clinical manifestations. Use of excimer treatments to reme- degree of keratoconus up to 2 years after treatment com-
diate anterior corneal pathology is not new. Its application pared to the untreated group with keratoconus.10 Use of
has been used for various conditions such as corneal scar- wavefront-guided reports may be limited by the inability of
ring,1,2 stromal dystrophies, keratoconus nodules,3 and cli- aberrometers to measure irregular corneas. Bahar et al used
matic droplet keratopathy such that transplation is avoided wavefront-supported photorefractive keratectomy (PRK) in
or delayed. Excimer treatment to reduce steepness of the keratoconus suspects. The authors reported the treatments
cone has also been reported with an increase in visual in this population appear to be effective, but 3 eyes suffered
function and no apparent progression in the disease.4-6 loss of best-corrected vision due to hazing.11

Wang M, ed.
Keratoconus & Keratoectasia: Prevention, Diagnosis, and Treatment (pp.145–151) 145
© 2010 SLACK Incorporated
146 CHAPTER 14

TAB LE 1 4 -1

G ULANI-NO RDAN C RITERIA FO R LASER PRK IN KERATO C O NUS

• Pa tie n t is sym p to m a tic with p o o r visu a l a c u ity, d o u b le visio n , o r g la re a n d c a n n o t to le ra te c o n ta c t
le n se s. O p tio n s o f g la sse s o r c o n ta c t le n se s a re lim ite d a n d / o r u n su c c e ssfu l.
• Clin ic a l e xa m in a tio n a n d sig n s su g g e stin g c o rn e a l sh a p e irre g u la rity c h a ra c te ristic o f ke ra to c o n u s.
• Be st-c o rre c te d visu a l a c u ity o f 20/ 30 o r b e tte r (e ve n if with h a rd c o n ta c t le n s tria l). Be st c o rre c te d
visio n b e lo w 20/ 40 wo u ld in d ic a te In ta c s.
• Re fra c tio n is sta b le with re vie w o f p rio r d o c u m e n te d e xa m s.
• Astig m a tism h ig h e r th a n m yo p ia / h yp e ro p ia is p re fe rre d .
• C o rn e a l th ic kn e ss is m o re th a n 400 µm a t th e th in n e st p o in t. C a lc u la tio n o f tre a tm e n t p la n d e te r-
m in e s th e th in n e st p o in t sh o u ld n o t b e le ss th a n 350 µm p o st-o p e ra tive ly.
• C o rn e a l sc a r, if p re se n t, is le ss th a n th e a n te rio r o n e -th ird in d e p th .18
• Pa tie n t’s u n d e rsta n d in g : (1) u sin g a n e xc im e r la se r in p a tie n ts with ke ra to c o n u s is a n o ff-la b e l p ro -
c e d u re ; a n d (2) th a t if d u e to la se r tre a tm e n t o r n a tu ra l p ro g re ssio n th e ir e c ta sia wo rse n s, th e y
wo u ld b e c a n d id a te s fo r o th e r c o rre c tive p ro c e d u re s, su c h a s In ta c s, la m e lla r ke ra to p la sty, o r p e n -
e tra tin g ke ra to p la sty.

Correction of refractive error in patients with kerato- surgery. In that case, other options such as Intacs are avail-
conus may be complicated due to the nature of the disease able.” Such a discussion underscores the honest desire to
causing instability of refractive error. However, active help keratoconic patients lead a productive life of visual
adults are inclined to request surgical improvement of their freedom knowing what may be needed in the future. This
vision. PRK in keratoconus suspects/forme fruste keratoco- may become more accepted when combined with collagen
nus has been reported with success.12-15 Successful excimer cross-linking (CXL).22
procedures have also been performed after penetrating If we approach every keratoconus patient as having
keratoplasty, deep lamellar keratoplasty,16,17 and epikera- irregular astigmatism, we can plan for increased surgical
tophakia.18 However, complications of excimer treatment and visual outcomes.23-26
have also been reported, including paradoxical responses19
and keratolysis.20 Some recommend avoiding keratorefrac-
tive procedures and correcting vision using phakic lenses CRITERIA FOR ELECTIVE
to correct high amounts of myopia commonly found in
keratoconus.21
VISION CORRECTION
While such studies suggest performing PRK for visual Using set criteria is useful when considering excimer
rehabilitation in a patient with keratoconus may be suc- treatment in a patient with early keratoconus. It guides
cessful, performing an elective procedure on a patient patient education, surgical planning, and prognosis and
whose vision may fluctuate in the future is risky. Clinical ensures the surgeon and the patient understand the goals
decision making and patient education become important of the planned procedure. We have devised a set of criteria
when a mildly keratoconic patient presents for elective for excimer laser PRK surgery for keratoconus: the Gulani-
vision correction and achieves 20/20 vision when cor- Nordan criteria (Table 14-1). If these criteria are met, we
rected. In such cases, performing Intacs implantation may feel it is safe to proceed with PRK. To validate this system,
result in a reduction of best-corrected vision and may not we applied it to a small population of patients. The authors
be the best option. Using an excimer laser surface treat- investigated PRK in keratoconic patients including 14 eyes
ment, astigmatism is addressed and uncorrected vision is of 10 patients (9 men and 5 women) ranging in age from
improved. 20-66 years with follow-up ranging from 6 months to 3
The discussion may be similar to “PRK is an option years. All cases were confirmed keratoconus with present
because you do meet the criteria for laser surgery. We can- day criteria inclusive of topography.
not guarantee how long the vision will last because your Each patient underwent excimer surface treatment
vision may drop from 20/20 to 20/40 or worse either by (PRK or advanced surface ablation) using standard proto-
natural progression or perhaps by undergoing the laser col. The technique used is previously described.27 Thirteen
 EXCIMER LASER PHOTOREFRACTIVE KERATECTOMY FOR KERATOCONUS 147

Figure 14-1. PRK for keratoconus. Pre-

operative (middle) and post-operative
(left) topographies with differential map
(right). Post-operative vision was 20/15
unaided.

A B

Figure 14-2. (A) PRKfor pellucid marginal degeneration. The pre-operative and post-operative information is presented. Post-operative vision was 20/15
unaided. (B) Differential map of same patient.

A B

Figure 14-3. (A) PRKfor keratoconus. The pre-operative and post-operative information is presented. Post-operative vision was 20/15 unaided. (B) Differential
map of same patient.

of 14 eyes achieved uncorrected vision of 20/20. The last had no complaints at night and all noted that their vision
patient’s vision was limited to 20/40 due to amblyopia. Six at night was improved compared to best corrected vision
of the 14 eyes achieved uncorrected vision of 20/15 (Figures pre-operatively.
14-1 through 14-3). In all cases, excimer laser ablation was calculated to
Subjective success of treatment was based on uncor- ensure reasonable post-operative corneal thickness to allow
rected visual acuity and patient’s subjective response. Intacs implantation at a later date should the condition
Patients were asked to compare the post-operative vision progress (Figure 14-4). One can also treat patients previous-
to pre-operative vision using a grading scale of 1 to 10 (10 ly operated with Intacs to correct residual astigmatism with
being the best). All the patients treated reported a subjec- laser vision surgery in the PRK mode, though one needs to
tive evaluation grade of 10. All patients stated that they be mindful of increased haze risk in these eyes.
148 CHAPTER 14

A A

Figure 14-4. (A) Double Intacs

segment implantation for kera-
toconus, followed by PRK for B
improvement in unaided vision.
(B) Differential topography map
of laser post-Intacs. The patient
in 14-4Aenjoyed vision unaided
of 20/ 25.

TREATMENT OF MYOPIC
ASTIGMATISM IN KERATOCONUS
USING PARK
Employing the technique of vector planning and a num-
ber of criteria for the stability of this ectatic condition, pho-
toastigmatic refractive keratectomy (PARK) has been shown Figure 14-5. (A) Calculating ORA: Polar diagramof refractive wavefront cylin-
to be safe and effective in the treatment of myopic astig- der at the positive axis and simulated keratometry from the topography. (B)
matism in forme fruste and mild keratoconus. Despite the The DAVDshowing a “doubling” of the angles without a change in the astig-
irregularity associated with keratoconic corneas, in milder matic magnitudes. (C) Polar diagramdisplaying the ORAas it would appear on
cases, there also is an underlying quantifiable regular com- the eye. (ORA=ocular residual astigmatism; R=refractive wavefront astigma-
ponent of the astigmatism that is treatable in a symmetrical tism[corneal plane]; SimK=simulated keratometryfromtopography).
manner. This regular component can commonly be gauged
by the simulated keratometry value from topography, as well
as the measured value by manual keratometry. The ORA is determined by calculating the vectorial
While zero overall astigmatism is an ideal outcome of difference between the wavefront or manifest refraction
refractive laser surgery, this result is effectively unattain- measurements for refractive cylinder and topography or
able in eyes with keratoconus due to a poorer correlation keratometry measurements for corneal astigmatism.29,30,32
between corneal (topography or keratometry) and refrac- Doubling the axes of the astigmatism while leaving the
tive (wavefront or manifest) astigmatism values compared magnitudes unchanged allows for the conversion of polar
to the values for a normal astigmatic population.28-31 This coordinates to rectangular coordinates. The ORA being
prevailing difference between these 2 astigmatic parameters a vector quantity connecting the 2 astigmatisms on this
is quantified by the ocular residual astigmatism (ORA)28-32 mathematical construct is then transferred to the origin
and where it exists in a significant amount, the eye’s optical (x=0, y=0) and halved to simulate how it would exist
system cannot be completely corrected for astigmatism by within the eye (Figure 14-5). This vectorial difference, mea-
refractive laser treatment. sured in diopters and degrees and calculated using basic
 EXCIMER LASER PHOTOREFRACTIVE KERATECTOMY FOR KERATOCONUS 149

Figure 14-6. ASSORTTreatment Planning screen shows howthe ORAof 2.20 DAx34 is apportioned 38%to eliminating the topographyastigmatismand 62%to
the refractive cylinder. Furthermore, this ORAis neutralized byan equivalent 1.37 Dat the cornea and 0.84 Dat the spectacle refraction but at an orientation
of 124 degrees.

trigonometric principles, has a proportional relationship stability over a minimum 2-year period. The minimum age
with astigmatism. As the astigmatic difference between criterion was 25 years. Those with average K readings ≥ 50.00
refractive and corneal astigmatism increases, the magni- D power, visible ectasia or scarring under slit-lamp examina-
tude of the ORA also increases. Therefore, the amount of tion, and residual stromal bed less than 300 µm (allowing for
remaining post-operative astigmatism in the ocular system epithelial thickness of 60 µm) were excluded.
will also inevitably be greater. This uncorrectable astig- The mean astigmatism values pre-operatively were
matism is left on the cornea using conventional refractive –1.39 DC ± 1.08 by manifest refraction and 1.70 D ± 1.42
techniques to neutralize the internal ocular astigmatism by topography. Post-operatively, 45 eyes were reviewed at 1
quantified by the ORA and leads to increased aberrations year, 32 eyes at 5 years, and 9 eyes at 10 years for stability in
and a reduction in the quality of vision. the corneal astigmatism and refractive cylinder measure-
Using vector planning aids in avoiding poor outcomes ments. Average corneal keratometry values were also fol-
by distributing the neutralization of the ORA between the lowed to identify signs of progressive ectasia.
cornea and the refraction. The technique of vector planning In this study group, all the treatments were optimized;
reduces a greater amount of corneal astigmatism than treat- that is, the emphasis on the ORA neutralization was deter-
ment using refractive parameters alone. As a result, fewer mined by targeting reduced corneal astigmatism optimized
second- and third-order aberrations remain.28-32 to a with-the-rule orientation of the remaining astigma-
The Alpins Method of vector planning was used for the tism in a linear relationship. As a result a beneficial effect of
treatment of astigmatism in a retrospective study of 45 eyes less astigmatism remaining overall (corneal plus refractive
with forme fruste or mild keratoconus.32 Due to the irregu- measurements) was achieved after the surgery.
lar shape of these corneas, surface ablation with PARK was By incorporating the corneal parameters as well as
performed in each case. The minimum requirements to the refractive astigmatism parameters into the overall
be eligible for surgical treatment included a best corrected treatment (Figure 14-6), less corneal astigmatism is being
visual acuity (BCVA) of better than or equal to 20/40 and targeted. In this example, shifting the emphasis for astig-
a non-progressive cone displaying refractive and corneal matism reduction “to the left” by 38 emphasis percent-
150 CHAPTER 14

age points (38% topography/62% manifest refraction) increase in corneal irregularity and progression of ectasia
increases the proportion of corneal astigmatism correction resulting in a reduction of UCVA or BCVA were detected.
by aligning the treatment more closely to the principal Using the method of vector planning, there is a potential
corneal meridian.32,34 The targeted refractive astigmatism for reduced higher-order aberrations (coma and trefoil) as
of 0.84 D may not be fully evident to the patient percep- a result of less corneal astigmatism post-operatively with
tually where a spherical equivalent of zero exists. When greater likelihood to achieve an improved BCVA more
measurements were in fact taken at 6 months, simulated frequently and avoid adverse symptomatic effects that
keratometry showed 1.25 D @ 126 degrees while manifest would likely occur with treatments based solely on refrac-
refraction measured –0.25 DC Ax 45 (less than anticipated) tive values. However, patients with keratoconus evalu-
confirming the value of this optimized approach. ated for photorefractive keratectomy should be carefully
It is important to highlight that no matter what the selected 35,36 and followed over time to determine stabil-
percentage chosen on the “emphasis” bar, the minimum ity of manifest refraction and corneal topography prior
amount of total astigmatism (corneal plus refractive), which to surgical intervention. It is extremely unlikely that the
is equal to the ORA, is being targeted at every point on the treatment of irregular corneas as a result of keratoconus
percentage scale. If the combined magnitude of the remain- can achieve universally excellent outcomes without the
ing astigmatism (corneal plus refractive) is greater than the inclusion of corneal parameters. The technique of vector
initial ORA, the surgery then fails to achieve the maximum planning is not restricted to the treatment of astigmatism
astigmatism treatment. Even though all the astigmatism in keratoconus patients but can be more routinely applied
is not correctable, results with this technique were still to the treatment paradigm of normal astigmatic corneas
significantly better than they would have been using con- when performing laser vision correction.
ventional refractive astigmatism values alone. Treatment
using refractive parameters alone would theoretically result
in 2.20 D (that is, all the ORA) remaining on the cornea. CONCLUSION
Incorporating the corneal values into the treatment profile
reduced the total astigmatism in the system post-operatively Excimer treatment appears to be successful for treat-
to 1.50 D (1.25 D corneal + 0.25 D manifest refraction). This ment of sequela of keratoconus, including scarring, steep
particular patient also had an improvement in BCVA from cones, and nodules. The treatment of myopic astigmatism
20/20 to 20/15 as well as the improvement in unaided visual is safe and effective in selected cases of forme fruste and
acuity (UCVA) from 20/200 to 20/20. mild keratoconus with careful patient education, ensuring
This favorable outcome of compounding the reduction patients meet criteria to ensure safety, and using vector
of overall total astigmatism was common in many cases planning, the treatment has less potential adverse impact
within the group of 45 eyes and also evident in the aggre- upon visual outcome and progression.
gate results where topography values have been incorpo-
rated into the treatment plan.
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apex syndrome’. Br J Ophthalmol. 1996;80(1):25-28. 31. Goggin M, Alpins N, Schmid L. Management of irregular astigma-
16. Pedrotti E, Sbabo A, Marchini G. Customized transepithelial pho- tism. Current Opinion in Ophthalmology. 2000;11:260-266.
torefractive keratectomy for iatrogenic ametropia after penetrat- 32. Alpins NA, Stamatelatos G. Customized PARK treatment of myo-
ing or deep lamellar keratoplasty. J Cataract Refract Surg. 2006; pia and astigmatism in forme fruste and mild keratoconus using
32(8):1288-1291. combined topographic and refractive data. J Cataract Refract Surg.
17. Leccisotti A. Photorefractive keratectomy with mitomycin C after 2007;33:591-602.
deep anterior lamellar keratoplasty for keratoconus. Cornea. 2008; 33. Alpins NA. Wavefront Technology: A new advance that fails to
27(4):417-420. answer old questions on corneal vs. refractive astigmatism correc-
18. Xie L, Gao H, Shi W. Long-term outcomes of photorefractive tion. J Cataract Refract Surg. 2002;18:737-739.
keratectomy in eyes with previous epikeratophakia for keratoconus. 34. Alpins NA, Vector analysis of astigmatism changes by flattening,
Cornea. 2007;26(10):1200-1204. steepening, and torque. J Cataract Refract Surg. 1997; 23:1503-1514.
19. Fraenkel G, Sutton G, Rogers C, Lawless M. Paradoxical response 35. Binder P, Lindstrom R, Stulting R, et al. Keratoconus and corneal
to photorefractive treatment for postkeratoplasty astigmatism. J ectasia after LASIK. J Cataract Refract Surg 2005; 31: 2035-2037.
Cataract Refract Surg. 1998;24(6):861-865. 36. Colin S, Velou S. Current surgical options for keratoconus. J
20. Lahners WJ, Russell B, Grossniklaus HE, Stulting RD. Keratolysis Cataract Refract Surg. 2003;29:379-386.
following excimer laser phototherapeutic keratectomy in a patient
with keratoconus. J Refract Surg. 2001;17(5):555-558.
21. Kamiya K, Shimizu K, Ando W, Asato Y, Fujisawa T. Phakic toric
Implantable Collamer Lens implantation for the correction of high
myopic astigmatism in eyes with keratoconus. J Refract Surg. 2008;
24(8):840-842. Financial Disclosure: Dr. Alpins is the founder of ASSORT Pty Ltd.
 CHAP TER 1 5

Topography-Guided Excimer
Laser Treatment

Aleksandar Stojanovic, MD, and Xiangjun Chen, MD

K
eratoconus (KC) is usually accompanied by visu- as an integral part of CA, seems to be the most logical
ally disturbing refractive errors that lead to poor approach 20 if one considers that the epithelium in KC has
vision, not readily correctable with spectacles or an uneven thickness due to its continuous remodeling,21,22
soft contact lenses. Despite being commonly considered manifested as thinning over the elevations and thickening
contraindicated because of the danger of causing further over the depressions in stroma (Figures 15-1A and 15-2A).
thinning of an already thin and unstable cornea, excimer Removal of the remodeled epithelium before the custom
laser correction of the refractive errors in KC has been laser ablation would reveal a stromal surface with optical
attempted.1-8 Introduction of custom ablation (CA) with characteristics that no longer match the corneal surface
its capability to deliver asymmetric ablation patterns measured preoperatively (upon which the ablation had
complementary to corneal or wavefront irregularities has been planned) (Figure 15-1B). Hence, the laser treatment
further raised the potential of the excimer laser to deal after de-epithelialization techniques used with most of
with the optical problems inherent to KC.9-14 Concerning the common surface strategies (PRK, LASEK, EpiLASIK)
the surgical technique, photorefractive keratectomy (PRK) will result in reduced predictability of outcomes (Figure
in carefully selected patients with forme fruste and mild 15-1C).20 A transepithelial technique where de-epitheli-
KC,1-7 as well as in a few cases of advanced KC,8 has shown alization is an integrated part of a CA will circumvent this
to be effective in reducing myopia and astigmatism, only problem (Figure 15-2). Furthermore, the boundaries of the
infrequently leading to activated progression of the dis- removed epithelium will precisely conform to the bound-
ease.1,4 Nevertheless, the most popular keratorefractive aries of the custom ablation (Figure 15-3B) occupying a
technique, laser in situ keratomileusis (LASIK), seems to be smaller area, compared to standard de-epithelialization
less suitable for treatment of biomechanically unstable KC. (Figure 15-3C), because only the absolutely necessary area
The LASIK cut alone, in most such cases, will destabilize of epithelium will be removed. This technique seems less
the cornea, while an ablation in the stroma underneath the invasive compared to other types of surface ablations and
flap will further increase the danger of destabilization and shortens the postoperative healing time.20
progression of KC.15-19

TOPOGRAPHY-GUIDED
TRANSEPITHELIAL SURFACE CUSTOM ABLATION (TGCA)
ABLATION
Although wavefront-guided custom ablation (WGCA) is
Not all types of surface ablation techniques are suitable most commonly associated with CA in virgin eyes, it seems
for effective and predictable treatment of irregular astigma- to be less suitable for treatment of highly irregular corneas
tism in KC. Transepithelial surface ablation, programmed in KC. Only the fact that the source of the irregular optics

Wang M, ed.
Keratoconus & Keratoectasia: Prevention, Diagnosis, and Treatment (pp.153–158) 153
© 2010 SLACK Incorporated
154 CHAPTER 15

Figure 15-1. Surface ablation in forme fruste keratoconus (FFKC) with use of Figure 15-2. Surface ablation in FFKCwith use of transepithelial technique.
common deepithelialization technique. (A) Preoperative, (B) after epithelial (A) Preoperative, (B) after epithelial removal, and (C) after refractive stromal
removal, and (C) after refractive stromal ablation. ablation.

Figure 15-3. Area of de-epithelialization in surface abla-

tion. (A) Custom ablation area, (B) common surface ablation
de-epithelialization technique, and (C) integrated custom
transepithelial ablation.

in KC clearly resides on the cornea makes the WGCA an Traditionally, the laser ablates a concave, convex, or toric
indirect and limiting approach, because it is based on aber- lenticule from the cornea to establish the desired refractive
rometry measurements of the optics of the whole eye, in result independent of the preoperative corneal shape, mim-
the area limited by the pupillary opening. Additionally, the icking the effect of a contact lens. Most of the current CA
range of sensitivity, as well as the number of points in aber- profiles keep this approach by only modifying this lenticule
rometry appears to be inadequate for mapping of the high by refining its shape with wavefront refractive information.
optical irregularities commonly present in KC, making it Most of the few existing TGCA systems construct their
virtually impossible to acquire good quality aberrometry ablation by converting their corneal surface elevation into
measurements for use in CA. This effectively excludes the Zernicke polynomials and then subtracting those from an
WGCA as a realistic treatment option in KC, even if one imaginary ideal wavefront in order to finally construct a
overlooks the first argument. “custom” lenticule. Hence, those systems remove them-
 TOPOGRAPHY-GUIDED EXCIMER LASER TREATMENT 155

Figure 15-6. Triangulation technique used in Scheimpflug-based topography

for 3-Delevation corneal mapping (Courtesyof Dr. Alesandro Mularoni).

Figure 15-4. Asymmetric corneal optics along the eye’s original fixation axis
results in a distorted image.

Figure 15-7. Flow-chart showing the current choices for customablation.

than correct it. Doing so may result in significant tilt and

unnecessary removal of the corneal tissue.23 Figures 15-4
and 15-5 illustrate the situation where a patient fixating
with an eye with distorted corneal optics reduces his/hers
visual disturbances by rotating the eye into a tilted posi-
tion. Figure 15-5 shows that the information contained in a
single image of a fixating eye with decentered corneal optics
is referenced to an adapted eye position, with a significant
tilt and decentration of the corneal intercept of the fixation
axis. In conclusion, if a highly irregular cornea is to be treat-
Figure 15-5. Eye with asymmetric corneal optics tilted into a newposition “in
ed, an ideal corneal surface, based on three-dimensional (3-
search” for a less distorted image.
D) elevation acquired by triangulation (Figure 15-6) should
selves from the main problem of irregular corneal shape at be software generated and subtracted from 3-D map of the
a very early stage in the treatment planning process. They actual surface, in order to make a reliable ablation plan.
base their custom information on a monocular placido Figure 15-7 represents a flow-chart showing current choices
topography image, taken along the fixation axis of an eye for custom ablation of irregular astigmatism.
with aberrated optics. Importantly, an aberrated eye with
decentered optics such as in KC will suffer from fixation
axis that is both tilted and decentered compared to the same iVIS SUITE
eye’s axis if the corneal optics were regular.23 Hence, an
ablation plan that fails to consider true elevation of the cor- Combining its Scheimpflug-based topographer/tomog-
neal surface acquired by triangulation that is independent rapher (Precisio), dynamic pupilometer (pMetric), topog-
on the fixation axis may actually worsen the situation rather raphy-based ablation planning software (CIPTA), and
156 CHAPTER 15

Figure 15-9. Constant frequency per area (CF/A) for constant effective abla-
tion rate (5 Hz/mm2) assures an increase in ablation predictabilityof complex
shapes and increase of ablation smoothness.

sels recognition and positive eye identification with respect

to the preoperative data. Uniquely, the iRES attenuates the
delivery frequency so that a constant number of pulses per
second (frequency) are delivered per area (CF/A) (Figure
15-9) throughout the ablation to efficiently mitigate the
effects of plume and achieve a very smooth surface. Unlike
software used in other systems, CIPTA uses true elevation
Figure 15-8. The iVISSuite concept for correction of irregular astigmatism. data disconnected from the adaptive fixation axis (see
Figure 15-4 and 15-5). It assesses the cornea’s structure and
shape to determine the most suitable axis, perpendicular
high-resolution 1 KHz flying spot laser (iRES) in its to which the targeted surface is fitted. This is especially
transepithelial mode (cTEN), the iVIS Suite custom abla-
important in eyes with complex corneal irregularities such
tion system (iVIS Technologies, Taranto, Italy) attempts to
as keratoconus.
address the requirements for treatment of complex cases
The transepithelial ablation technique (cTEN) is a fea-
with irregular astigmatism (Figure 15-8). Unlike other
ture of the iVIS suite that is reliant on the following critical
custom ablation systems that rely on third-party supplied
topographers that are actually not constructed for surgical, technologies: CA software for integrated, one-step ablation
but rather for diagnostic purposes, the iVIS Suite’s topog- inclusive of epithelium; laser system with optimized flu-
rapher is specifically designed as a highly repeatable, statis- ence and shot pattern delivery for achieving almost the
tically validated, custom surgical data acquisition device. It same ablation rate for epithelium and stroma; and a high
is fine tuned for registering precise 3-D morphology of the laser repetition rate to shorten the treatment time (ultrafast
cornea with resolution, sensitivity, and specificity suited ablation is necessary for transepithelial technique because
for detecting the details relevant for treatment of irregular the epithelial component adds around 500% to the total
astigmatism. The patient’s refraction, anterior and pos- ablation volume). These refinements also create a very
terior corneal elevations, pachymetry, pupillometry, and smooth ablation surface, to minimize the chances of post-
detailed registration data using a “signature” of pupil, iris, operative haze.24,25
and scleral information are imported into a surgical design
application, CIPTA. With CIPTA, the surgeon compiles an
ablation with the aim of transforming the detected cor- COMBINING TGCA
neal shape into a regular aspheric shape within a desired
treatment zone. The curvature of the targeted corneal
AND CORNEAL COLLAGEN
surface is decided by the amount of the desired refractive CROSS-LINKING (CXL)
change from the preoperative curvature. CIPTA also allows
customization of parameters such as centration, tilt, and Excimer laser refractive surgery, even when performed
asphericity of the targeted corneal surface, as well as the as surface ablation, has been known to induce keratoec-
size of the optical and transition zones, making it possible tasia,26-29 and, therefore, its use in treatment of KC has
for the surgeon to choose and fit the desired corneal shape been limited and controversial, while a safer alternative
in a variety of ways. The CIPTA-generated ablation plan has been sought. A treatment combining CXL and TGCA,
is then transferred to the dual (0.6 mm) flying-spot, iRES to both halt the progression of keratoectasia and regular-
excimer laser, which delivers an effective frequency of up to ize the distorted corneal optics in KC, was first attempted
1 KHz (2 x 500 Hz) at the corneal plane. The laser features by Kanellopoulos.30 However, in his combined procedure
a synchronized eye-tracking system with intraoperative Kanellopoulos first applied CXL and TGCA 12 months later,
cyclotorsional compensation based on iris and scleral ves- effectively removing the previously CXL-treated, stiffened
 TOPOGRAPHY-GUIDED EXCIMER LASER TREATMENT 157

Figure 15-10. Preoperative curvature maps in a patient with mild keratoconus.

Figure 15-12. Axial curvature map of the same eye in

Figure 15-11, 12 months after surgery.

Figure 15-11. CIPTAablation planningwindowshowingimported preoperative

elevation and calculated ablation map, as well as treatment parameters and
postoperative pachymetry.

corneal tissue (which resides in the superficial layers of the Figure 15-13. Difference anterior elevation map between 1 and 12 months
stroma) and leaving the cornea with a reduced strength/stiff- after surgery.
ness in the ablation area. The authors of this chapter used a
combined procedure where the order was reversed; the CXL
even if larger than the preoperative state, and by reducing the
was performed immediately after TGCA to stiffen the stroma
treatment zone. Immediately after the ablation, the stroma
at a uniform depth, before the ectatic process had a chance
was saturated by topically-applied riboflavin solution, and,
to progress (submitted for publication). Another advantage
of the “single combined procedure” approach compared after the corneal saturation was confirmed, the cornea was
to the sequential approach of Kanellopoulos is that the irradiated by UVA light for 30 minutes. All 12 eyes showed
patient avoids 2 de-epithelializations. Finally, the temporary an improvement in UCVA and BSCVA, as well as decreased
keratocyte loss after CXL31 might diminish the chance for astigmatism. Topographic symmetry improved, and, impor-
haze/scarring that might otherwise occur if the surface abla- tantly, there was no sign of ectasia progression detected
tion is performed at a later time. The authors treated 12 eyes throughout the 18-month observation time. There were no
with advanced stages of progressive keratoectasia, all with complications and no postoperative haze graded higher than
seriously reduced vison, which could no longer be improved trace observed at any of the follow-up examinations. Figures
by the use of spectacles and/or contact lenses. A CIPTA- 15-10, 15-12, and 15-13 show preoperative and postoperative
designed transepithelial TGCA in “minimal ablation” mode Precisio maps, while Figure 15-11 shows CIPTA ablation
was used to allow maximal reduction of irregularities and planning window for 1 of the cases.
astigmatism but with minimal tissue consumption. This CXL stiffens the stroma and halts the ectatic process,
was achieved by accepting any postoperative spherical error, but it does not directly address the optical error. The TGCA
158 CHAPTER 15

reduces the visually disturbing irregularity, but it reduces 14. Bahar I, Levinger S, Kremer I. Wavefront-supported photorefrac-
the corneal tissue strength and is mainly contraindicated tive keratectomy with the Bausch & Lomb Zyoptix in patients with
in the advanced cases of KC. Therefore, the idea of these 2 myopic astigmatism and suspected keratoconus. J Refract Surg.
2006;22(6):533-538.
procedures complementing each other is very appealing. It
15. Abad JC, Awad A, Kurstin JM. Hyperopic keratoconus. J Refract
has been shown that CXL increases the human corneal bio- Surg. 2007;23(5):520-523.
mechanical rigidity in vitro (calculated by Young modules) 16. Javadi MA, Mohammadpour M, Rabei HM. Keratectasia after LASIK
by a factor of 4.5.32 However, there is currently no standard- but not after PRK in one patient. J Refract Surg. 2006;22(8):817-820.
ized method for in vivo measurements of corneal rigidity, 17. Kymionis GD, Tsiklis N, Karp CL, Kalyvianaki M, Pallikaris AI.
which would allow an accurate estimate of both the amount Unilateral corneal ectasia after laser in situ keratomileusis in a
of weakening after a certain tissue ablation and the amount patient with uncomplicated photorefractive keratectomy in the fel-
of strengthening after the consecutive CXL. Until in vivo low eye. J Cataract Refract Surg. 2007;33(5):859-861.
18. Rao SK, Srinivasan B, Sitalakshmi G, Padmanabhan P.
measurements are available, the indication for the procedure
Photorefractive keratectomy versus laser in situ keratomileusis to
has to be left solely to the surgeon’s clinical judgment.
prevent keratectasia after corneal ablation. J Cataract Refract Surg.
In conclusion, visually disturbing irregular astigmatism 2004;30(12):2623-2628.
in KC may be treated with transepithelial, 3-D elevation- 19. Klein SR, Epstein RJ, Randleman JB, Stulting RD. Corneal ectasia
topography-guided custom ablation in relatively early after laser in situ keratomileusis in patients without apparent pre-
cases, where the corneal biomechanical strength is esti- operative risk factors. Cornea. 2006;25(4):388-403.
mated to allow this. Both in these and in more advanced 20. Stojanovic A, Jankov M. Treatment of irregular astigmatism—devel-
cases of KC, a combination with CXL might prove to be a oping an ideal corneal surface. In: Wang M. Irregular Astigmatism:
Diagnosis and Treatment. Thorofare, NJ: SLACK Incorporated;
safer and more effective solution.
2007:211-218.
21. Reinstein DZ, Archer T. Combined Artemis very high-frequency

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tectomy and wavefront-guided treatment following multiple corneal
refractive procedures. J Cataract Refract Surg. 2006;32(11):1870-1876.
1. Kasparova EA, Kurenkov VV. Combination of photorefractive and 22. Reinstein DZ. Ultrasound proves worth in screening for keratoco-
phototherapeutic keratectomy in the treatment of keratoconus. nus. Eurotimes. 2008;March:18-19.
Vestn Oftalmol. 2000;116:10-12.
23. Stojanovic A, Suput D. Strategic planning in customized ablation
2. Bilgihan K, Ozdek SC, Konuk O, Akata F, Hasanreisoglu B. Results
treatment of secondary irregular astigmatism. J Refract Surg. 2005;
of photorefractive keratectomy in keratoconus suspects at 4 years. J
21:369-376.
Refract Surg. 2000;16:438-443.
3. Appiotti A, Gualdi M. Treatment of keratoconus with laser in situ 24. Vinciguerra P, Azzolini M, Airaghi P, Radice P, De Molfetta V. Effect
keratomileusis, photorefractive keratectomy, and radial keratoto- of decreasing surface and interface irregularities after photorefrac-
my. J Refract Surg. 1999;15:240-242. tive keratectomy and laser in situ keratomileusis on optical and func-
4. Kremer I, Shochot Y, Kaplan A, Blumenthal M. Three year results tional outcomes. J Refract Surg. 1998;14(2 Suppl):S199-203.
of photoastigmatic refractive keratectomy for mild and atypical 25. Vinciguerra P, Azzolini M, Radice P, Sborgia M, De Molfetta V.
keratoconus. J Cataract Refract Surg. 1998;24:1581-1588. A method for examining surface and interface irregularities after
5. Mortensen J, Carlsson K, Ohrstrom A. Excimer laser surgery for photorefractive keratectomy and laser in situ keratomileusis: pre-
keratoconus. J Cataract Refract Surg. 1998;24:893-898. dictor of optical and functional outcomes. J Refract Surg. 1998;14(2
6. Mortensen J, Ohrstrom A. Excimer laser photorefractive keratec- Suppl):S204-S206.
tomy for treatment of keratoconus. J Refract Corneal Surg. 1994; 26. Navas A, Ariza E, Haber A, Fermón S, Velázquez R, Suárez R.
10:368-372.
Bilateral keratectasia after photorefractive keratectomy. J Refract
7. Kasparova EA, Kasparov AA. Six-year experience with excimer
Surg. 2007;23(9):941-943.
laser surgery for primary keratoconus in Russia. J Refract Surg.
2003;19:250-254. 27. Leccisotti A. Corneal ectasia after photorefractive keratectomy.
8. Cochener B, Le FG, Volant A, Colin J. Is there a role for excimer laser Graefes Arch Clin Exp Ophthalmol. 2007;245(6):869-875.
in the treatment of keratoconus?. J Fr Ophtalmol. 1997;20:758-766. 28. Malecaze F, Coullet J, Calvas P, et al. Corneal ectasia after pho-
9. Alpins N, Stamatelatos G. Customized photoastigmatic refractive torefractive keratectomy for low myopia. Ophthalmology. 2006;
keratectomy using combined topographic and refractive data for 113(5):742-746.
myopia and astigmatism in eyes with forme fruste and mild kerato- 29. Randleman JB, Caster AI, Banning CS, Stulting RD. Corneal ecta-
conus. J Cataract Refract Surg. 2007;33:591-592. sia after photorefractive keratectomy. J Cataract Refract Surg. 2006;
10. Koller T, Iseli HP, Donitzky C, Ing D, Papadopoulos N, Seiler T. 32(8):1395-1398.
Topography-guided surface ablation for forme fruste keratoconus. 30. Kanellopoulos AJ, Binder PS. Collagen cross-linking (CXL) with
Ophthalmology. 2006;113:2198-2202. sequential topography-guided PRK: a temporizing alternative for
11. Dausch D, Schroder E, Dausch S. Topography-controlled excimer keratoconus to penetrating keratoplasty. Cornea. 2007;26:891-895.
laser photorefractive keratectomy. J Refract Surg. 2000;16:13-22.
31. Mazzotta C, Balestrazzi A, Traversi C, et al. Treatment of pro-
12. Cennamo G, Intravaja A, Boccuzzi D, Marotta G, Cennamo G.
gressive keratoconus by riboflavin-UVA-induced cross-linking of
Treatment of keratoconus by topography-guided customized pho-
torefractive keratectomy: two-year follow-up study. J Refract Surg. corneal collagen: ultrastructural analysis by Heidelberg Retinal
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ALLEGRETTO WAVE Excimer Laser. J Refract Surg. 2008;24(4): human and porcine corneas after riboflavin-ultraviolet-A-induced
S439-S445. cross-linking. J Cataract Refract Surg. 2003;29:1780-1785.
 CHAP TER 1 6

Intacs for the Treatment of

Keratoconus and Keratoectasia

George O. Waring IV, MD; Jason E. Stahl, MD;

Brian Boxer Wachler, MD; and William B. Trattler, MD

I
mplantation of Intacs corneal prescription inserts vascularization to the suture site, foreign body sensation,
(Addition Technology Inc, Sunnyvale, CA) for the segment movement or extrusion, intralamellar deposits,
treatment of keratoconus was first performed and epithelial plugs or ingrowth, infectious keratitis, peripheral
described by Colin in 1997.1 The original design, manufac- haze, perforation into the anterior chamber during place-
tured by KeraVision, was a 360-degree ring called the intra- ment, and keratolysis.
stromal corneal ring. The design evolved into semicircular Intacs are a pair of semicircular polymethyl methac-
segments, called Intacs, which were easier to implant and rylate (PMMA) arcs with a positioning hole at one end of
explant and provided more flexibility with refractive out- the arc. Each piece has a hexagonal transverse shape with
comes. Intacs Corneal Implants were originally approved external diameter of 8.10 mm, internal diameter of 6.77
by the U.S. Food and Drug Administration for the correc- mm, and circumference arc length of 150 degrees. Available
tion of low to moderate myopia (–1.0 to –3.0 diopters [D]) thickness ranges from 0.25 mm to 0.45 mm in 0.05 mm
in 1999 and received New Humanitarian Device Approval increments and thickness modulates refractive outcome.
by the FDA for the treatment of keratoconus in 2004. Since
Recently, a new segment design called Intacs SK has been
then, multiple studies in keratoconic eyes have demonstrat-
developed for the treatment of moderate to severe kerato-
ed that Intacs can reduce corneal steepening, astigmatism,
ectasia (keratometry > 57.00 D). Intacs SK have an inner
and topographic irregularity while improving uncorrected
diameter of 6.00 mm and available thicknesses of either
visual acuity (UCVA), best-corrected visual acuity (BCVA),
0.40 or 0.45 mm.
mean refractive spherical equivalent (MRSE), and contact
lens tolerance.2-9,13,14,23 Intacs achieve refractive adjust- Indications for Intacs implantation include low myo-
ment through an arc-shortening effect of the corneal pia, keratoconus, pellucid marginal degeneration, corneal
lamellae that produces flattening in the central cornea in ectasia after LASIK, and myopic regression after LASIK.
accordance with Barraquer’s thickness law, which describes Candidates should have a clear central cornea, a corneal
a central corneal flattening with addition of material to thickness of at least 400 µm, and be typically considered
the peripheral cornea (Figures 16-1 through 16-3).11,12 contact lens intolerant. Alio et al demonstrated that patients
Keratoconic corneas are flattened more easily than nor- with mild to moderate keratoconus (average keratometry
mal corneas as the relatively thin tissue is more flaccid. < 53 D) have better outcomes than advanced stages of the
Intacs have the advantages of being minimally invasive, disease.7,15,16 Although a clear central cornea has classically
reversible, and not violating the visual axis of the cornea.13 been considered an inclusion criteria, Boxer Wachler et al
Implantation of Intacs can delay or avoid penetrating reported a series of patients with corneal scars that showed
keratoplasty in patients with keratoconus. Infrequent but 3 lines of improvement in visual acuity after implantation
possible adverse effects include poor refractive results, neo- of Intacs.23

Wang M, ed.
Keratoconus & Keratoectasia: Prevention, Diagnosis, and Treatment (pp.161–167) 161
© 2010 SLACK Incorporated
162 CHAPTER 16

Figure 16-2. The same patient’s preoperative topography (Image courtesy of

WilliamB. Trattler, MD).

Figure 16-1. Slit-lamp photography of a patient with keratoconus who under-

went Intacs implantation 2 years ago, now with cataract formation (Image
courtesyof WilliamB. Trattler, MD).

CHANNEL CREATION: MANUAL

CHANNEL MAKER
The surgery is preformed under sterile conditions with
Figure 16-3. Topography after Intacs insertion showing reduction in astigma-
administration of perioperative topical antibiotics and
tism(Image courtesyof WilliamB. Trattler, MD).
topical anesthetic. The geometric center of the cornea is
identified with an 11.0-mm zone marker and is marked
with a Sinskey hook. The incision mark of the zone marker patency. Next, align the vacuum centering guide with the
is typically placed on the flat meridian in the temporal geometric center of the cornea. The intrastromal tunnels
quadrant (at the 9 o’clock position in right eyes and the 3 are formed using a clockwise and counterclockwise dissec-
o’clock position in left eyes), though the incision marking tor under vacuum-suction. After creation of the tunnels,
and placement varies with surgeon preference and tech- the vacuum is deactivated, and the dissectors are removed.
nique. The temporal radial incision should be approxi- In post-LASIK patients, the 7.0-mm optical zone of the
mately 70% of the corneal thickness and 1.0 mm long. For Intacs should lie central and deep to the LASIK flap edge.
easier entry, or first cases, consider making an incision of
1.1 mm to 1.2 mm, though some surgeons create incisions
up to 1.8 mm long. Central and peripheral pachymetry FEMTOSECOND LASER CHANNEL
should be performed to ensure adequate corneal thickness
and to determine optimal channel depth. Set a diamond
DISSECTION
blade to 70% of the mean peripheral thickness of multiple Surgeons can utilize femtosecond lasers to create chan-
measurements. Jorge Alio describes a method of taking 7 nels for Intacs safely and precisely. Femtosecond lasers
readings, discarding the highest and lowest, and setting create lamellar channels with plasma-generated micro
the diamond blade to 70% of the mean of the remaining 5 bubbles by the principle of photo disruption. The IntraLase
measurements. Alternatively, this can be done by averag- (Advanced Medical Optics, Abbott Park, IL) offers soft-
ing the pachymetry in the areas over the intended segment ware to custom program the Intacs channel parameters,
placement to ensure that the Intacs will not be implanted in and recommended parameters are presented in Table 16-1.
less than 50% of the thickest area. Position the implanted Like the manual technique, it is important to check central
segment so that it embraces the steepest meridian accord- pachymetry and peripheral pachymetry over the incision.
ing to the topography. The intended result is to lift the Ensure that a depth of 400 µm is sufficient as this may be
ectatic cornea and induce maximal flattening. Once the considered the reliable depth limit of IntraLase channel
incision is made, the stromal tunnels are initiated with 2 creation. Similar to creating a femtosecond LASIK flap,
Sinskey hooks and a stromal spreader. A guide blade is then centration is critical. Identify and mark the geometric cen-
placed into the incision to assess incision length and pocket ter of the cornea as described earlier. To aid with centration
 INTACS FOR THE TREATMENT OF KERATOCONUS AND KERATOECTASIA 163

TAB LE 1 6 -1

REC O MMENDED SETTING S FO R FEMTO SEC O ND C HANNEL C REATIO N

WITH THE INTRALASE
PARAMETERS DEFAULT M IN M AX
De p th in c o rn e a (µm ) 400 0 600
O u te r d ia m e te r (m m ) 8.3 4.0 10
In n e r d ia m e te r (m m ) 6.7 4.0 9.9
Sta rtin g p o sitio n (IN/ O UT) IN – –
Rin g ta n g e n tia l sp o t se p a ra tio n (µm ) 12 1 30
Rin g ra d ia l sp o t se p a ra tio n (µm ) 10 1 30
Rin g e n e rg y (µJ) 6.0 1 15
Nu m b e r o f rin g la ye rs 1 1 10
Rin g la ye r se p a ra tio n (µm ) 6 1 30
En try c u t e n e rg y (µJ) 8.5 1 15
En try c u t le n g th (m m ) 1.0 1.0 15.0
En try c u t th ic kn e ss (µm ) 1 0 50
In c isio n a xis (d e g ) Ba se d o n in te n d e d 0 359
se g m e n t lo c a tio n

En try c u t sp o t se p a ra tio n (µm ) 7 1 30

En try c u t lin e se p a ra tio n (µm ) 1 50
En try c u t la ye r se p a ra tio n (µm ) 6 1 50
De p th in c o n ta c t g la ss 60 0 300
Ve rtic a l e n try c u t o ve rla p (µm ) 20 0 100
Z Ra d iu s (m m ) 0.0 0.0 50.0
X-o ffse t 0.000 –5.000 5.000
Y-o ffse t 0.000 –5.000 5.000

during docking, consider the additional step of using a 3- to

4-mm circular marker around the center mark. Apply the
Comparison of Channel Creation
suction ring under a surgical microscope with low magni- Techniques and Channel Dimension
fication and a Mastel light (Rapid City, SD) to best visualize A number of potential advantages for channel creation
centration. Transfer the patient under the laser, ensure the with the femtosecond laser exist. A more precise channel
patient’s face is parallel with the applanation surface, and
depth decreases the chance of a superficial channel and
lower the docking cone while stabilizing the suction ring
possible subsequent segment extrusion, or deep channels
clip. Modify centration with initial cone contact, not after
leading to accidental anterior chamber perforation. The
full applanation, as the flaccid, ectatic cornea will distort
laser’s ability to customize dimensions that can allow for a
with full applanation if the surgeon attempts to center on
the pupil. Once centered and fully applanated, unlock the tighter fit. A bladeless procedure may decrease the chance
suction ring, securing the suction ring to the applanation of infectious keratitis and parachannel edema and decrease
cone. Increasing the intensity of the illumination light can the risk of epithelial defects due to less manipulation of the
aid in identification of the centration marks after docking. corneal surface. An inner to outer diameter setting of 6.7
Center the cursor, activate the laser, and observe the pat- mm by 8.3 mm is commonly used, though opinions vary
tern. Once the channels are complete, release suction of on optimal inner to outer diameter.18 When implanting
the suction ring, reclip the suction ring, loosening it from a 0.25-mm segment, or if a tighter fit is desired, decrease
the applanation cone, and raise the laser head. Because of the outer diameter by increments of 0.1 mm. For a nar-
the precise channel dimensions and ability to create tighter row channel, consider programming a 6.6-mm by 7.6-mm
channels, it may be possible to forgo suture placement. inner to outer diameter. Rabinowitz et al published the first
164 CHAPTER 16

TAB LE 16 -2

REC O MMENDED THIC KNESS NO MO G RAM FO R KERATO C O NUS ( MM)

TYPE O F C O NE PREO P SE ≤ 3.0 0 D PREO P SE ≥ 3.0 0 D
Asym m e tric a l 0.35/ 0.40 0.40/ 0.45
Hig h ly Asym m e tric 0.25/ 0.40 0.25/ 0.45
G lo b a l 0.40/ 0.40 0.45/ 0.45
C e n tra l 0.40/ 0.40 0.45/ 0.45
SE=sp h e ric a l e q u iva le n t
Ad a p te d fro m C o lin J. Eu ro p e a n c lin ic a l e va lu a tio n : u se o f In ta c s fo r th e tre a tm e n t o f ke ra to c o n u s. J C a ta ra c t Re fra c t Su rg .
20 06;32:747–755.

comparison of femtosecond and mechanical methods of

channel creation. The results suggested superior outcomes
ASYMMETRIC SEGMENT
with the femtosecond laser group; however, no statistical IMPLANTATION
difference between groups was found.19 A large retrospec-
tive study by Ertan et al demonstrated statistically better Because the majority of keratoconus is topographically
refractive outcomes when the channels were created with a asymmetrical with inferotemporal steepening, patients
femtosecond laser compared to the mechanical method.20 may benefit from placement of a thicker segment inferiorly
The same group published comparative refractive results of or a single segment inferiorly to induce maximal flattening
2 different channel sizes created with a femtosecond laser in this area.23 In the original reports on treatment of kera-
and found refractive outcomes to be similar at 6 months toconus with Intacs, the inferior and superior segments
postoperatively.18 were of the same thickness, as they are in the treatment
of myopia.1,2 Since Colin’s first description of asymmetric
segment placement of the thicker segment inferior and
IMPLANTATION TECHNIQUE thinner segment superior, multiple reports have described
AND POSTOPERATIVE CARE variations on asymmetric implantation including single
segments, thick segment implantation superiorly and thin
inferiorly, and vertical segment placement.8,15,23,24 Alio et
Once the channels are created, reopen the incision with
al reported improvement in corneal steepening, astigma-
a Sinskey hook and use an insertion forceps to place the
tism, and BSCVA with both single and double segments.
segment into the channel with a slight arc-like rotation.
Several reported studies suggest that patients with ectasia
Once half of the length of the segment is inserted, nudge
after LASIK benefit from a single inferior INTACS with
the tip of the segment with a Sinskey hook. Insert the seg-
improvement in BCVA and UCVA.27-30 Boxer Wachler and
ment into the tunnel approximately 1.5-mm beyond the
Sharma compared single- versus double-segment Intacs
incision, aiming for a 2-mm space between segments. The
for patients with post-LASIK ectasia and keratoconus
incision is closed with a single buried 10.0-nylon suture.
and demonstrated that patients with single segments had
Postoperatively, topical antibiotic and steroid are applied 4
improved UCVA and BCVA, which was felt to be due to
times a day, in addition to frequent preservative-free arti-
the differential flattening of the inferior meridian and
ficial tears, for 1 to 2 weeks, based on surgeon’s preference.
steepening of the superior meridian.23 In general, thicker
The suture is usually removed 2 weeks postoperatively to
segments are used for more advanced disease. A treatment
minimize induced neovascularization or induced astigma-
nomogram for recommended thickness was proposed by
tism. Induced neovascularization may occur after a suture
Colin in 2006 and takes into account the spherical equiva-
has been left in place for more than 3 weeks and is typically
lent refraction, cone location, and asymmetric astigmatism
clinically insignificant and self-limited after suture remov-
(Table 16-2).15 Reports suggest that patients do not benefit
al.25 To remove a segment, relocate the lamellar channel
from placing the thicker segment superiorly and, in fact,
plane, engage the segment hole with a Sinskey hook, and
may do worse with this technique.8,22
gently remove the segment with a slight arc-like rotation.
 INTACS FOR THE TREATMENT OF KERATOCONUS AND KERATOECTASIA 165

REPORTED LONG-TERM
OUTCOME DATA
Multiple studies are published reporting data with 2
to 5 years of postoperative follow-up.2,6,26,31 Kymionis
et al followed 17 eyes with post-LASIK ectasia for 5 years
and found statistically significant reduction in MRSE,
improvement in UCVA in 87.5% of eyes, and improvement
of BCVA in 100% of eyes.31 Colin et al published the results
of 100 eyes with 2-year follow-up and found statistically
significant improvement in UCVA, BCVA, MRSE, mean
keratometry readings, and contact lens tolerance.2 Alio et
al reported on a 13 eyes with 36-month follow up and 6
eyes with 48-month follow-up and found a statistically sig-
nificant improvement in mean BSCVA, as well as a statisti-
cally significant decrease of inferior-superior asymmetry
and average keratometry value.6 Ibrahim et al reported on
186 eyes with 5-year follow-up and found improvement in Figure 16-4. Preoperative corneal topography. Note the inferior cone and
UCVA in 85.2% and BCVA in 87.9% of patients.26 the high irregular astigmatism of 13.35 D(Image courtesy of Brian S. Boxer
Wachler, MD).

COMBINATION THERAPY:
INTACS, CONDUCTIVE Case Report: Combination Therapy
KERATOPLASTY, AND CROSS- for Advanced Keratoconus
LINKING FOR ADVANCED A 53-year-old man presented with keratoconus, high
myopia, and irregular astigmatism. Preoperative mani-
KERATOCONUS fest refraction (MRx) in right eye was –8.75 –14.75 x 075
producing 20/50. Uncorrected visual acuity (UCVA) was
Although new collagen formation and increased kera- count fingers. Preoperative topography showed 13.35 D
tocyte density has been observed around Intacs in ani- of astigmatism at axis 071 (Figure 16-4). A single segment
mal models, and reasonable stability has been shown in inferior Intacs (0.35 mm) was placed, and care was taken
long-term studies, Intacs alone do not completely halt the when marking the center of the cornea with a Sinskey
progression of the biomechanically weakened collagen hook to not indent epithelium as indentation may affect
responsible for keratoconus.24 Alio et al reported a series accuracy of subsequent topography for CK titration. The
of eyes with progressive keratometric steepening after patient was escorted out of the surgery room where topog-
Intacs insertion up to 36 months postoperatively.6 Corneal raphy and autorefraction was repeated to use a gauge for
collagen cross-linking is a photodynamic treatment that CK. Three CK spots were placed at 8-mm optical zone
combines the photosensitizing effects of riboflavin and (OZ) in 075 degree axis to reduce the astigmatism. The
ultraviolet A light to increase the stiffness of a keratoconic patient was taken out of room for repeat topography and
cornea. Chan et al were the first to report the combination autorefraction, which showed astigmatism reduced to only
treatment of corneal cross-linking with Intacs and found 11.34 D (Figure 16-5). Three additional superior spots were
improvement in refractive outcomes when compared to added at 7 mm OZ which reduced astigmatism to 3.09 D
treatment with Intacs alone.27 One possible explanation (Figure 16-6). Three additional CK spots were applied at
for the synergy between corneal cross-linking and Intacs 9-mm OZ, which has less effect as it is a larger OZ to give
is that intrastromal channels allow the riboflavin to con- a small overcorrection of the astigmatism. Corneal cross-
centrate locally around the segments, resulting in a focal linking was then used to stabilize CK effect, as CK without
parasegment stiffening effect. The following case report the cross-linking will lead to near complete regression of
illustrates the potential benefit of combining Intacs with the CK effect. On the first postoperative day, there was
corneal cross-linking and conductive keratoplasty (CK). dramatic improvement in astigmatism (Figure 16-7), and
manifest refraction at 3 months postoperatively was –6.75
–5.75 x 105, which produced a BCVA of 20/30, and the
corresponding topography showed stability of improved
astigmatism (Figure 16-8).
166 CHAPTER 16

Figure 16-5. Corneal topography with 11.34 Dof irregular astigmatism after Figure 16-7. Preoperative corneal topography (lower left) and 1-day post-
single inferior Intacs segment inserted and 3 superior CKspots were applied operative topography (upper left) with 10 D of astigmatism correction and
at 8-mmOZ(Image courtesyof Brian S. Boxer Wachler, MD). difference map (right) (Image courtesyof Brian S. Boxer Wachler, MD).

Figure 16-6. Corneal topography after 3 additional superior CKspots were Figure 16-8. Preoperative corneal topography(lower left) and 3-month post-
applied at 7-mm OZreducing astigmatismto 3.09 D(Image courtesy of Brian operative topography(upper left) with over 8 Dof astigmatismcorrection and
S. Boxer Wachler, MD). difference map (right) (Image courtesyof Brian S. Boxer Wachler, MD).

CONCLUSION of this treatment modality, Intacs will continue to serve

as a therapeutic pillar for treatment of keratoconus and
keratoectasia.
During the last few years, technological advances for the
treatment of keratoconus and keratoectasia have occurred,
and our understanding of novel therapeutic approaches has
improved dramatically. Increased selection in intracorneal
REFERENCES
segment dimensions, femtosecond lasers, and corneal col- 1. Colin J, Cochener B, Savary G, Malet F. Correcting keratoconus
lagen cross-linking have given surgeons tools to improve with intracorneal rings. J Cataract Refract Surg. 2000;26:1117-1122.
outcomes for keratoconic patients who traditionally had 2. Colin J, Malet FJ. Intacs for the correction of keratoconus: two-year
very few therapeutic options. Given the safety and efficacy follow-up. J Cataract Refract Surg. 2007;33:69-74.
 INTACS FOR THE TREATMENT OF KERATOCONUS AND KERATOECTASIA 167

3. Guell JL, Are intracorneal rings still useful in refractive surgery? 19. Rabinowitz YS, Li X, Ignacio TS, Maguen E. Intacs inserts using
Curr Opin Ophthalmol. 2005;16:pp. 260-265. the femtosecond laser compared to the mechanical spreader in the
4. Siganos CS, Kymionis GD, Kartakis N, et al. Management of kera- treatment of keratoconus. J Refract Surg. 2006;22:764-771.
toconus with Intacs. Am J Ophthalmol. 2003;135(1):64-70. 20. Ertan A, Colin J. Intacs for Keratoconus: Comparison of Mechanical
5. Chan SM, Khan HN. Reversibility and exchangeability of intrastro- Versus Femtolaser Channel Dissection. Presented at Annual meet-
mal corneal ring segments. J Cataract Refract Surg. 2002;28:676-681. ing of the American Academy of Ophthalmology: Las Vegas,
6. Alió JL, Shabayek MH, Artola A. Intracorneal ring segments for Nevada; November 2006.
keratoconus correction: long-term follow-up. J Cataract Refract 21. Colin J, Cochener B, Savary G, et al. Intacs inserts for treating kera-
Surg. 2006;32:978-985. toconus; one-year results. Ophthalmology. 2001;108:1409-1414.
7. Alió JL, Shabayek MH, Belda JI, Correas P, Feijoo ED. Analysis of 22. Chan CC, Wachler BS. Reduced best spectacle-corrected visual
results related to good and bad outcomes of Intacs implantation for acuity from inserting a thicker Intacs above and thinner Intacs
keratoconus correction. J Cataract Refract Surg. 2006;32:756-761. below in keratoconus. J Refract Surg. 2007;23:93-95.
8. Alio JL, Shabayek MH. Intracorneal asymmetrical rings for kera- 23. Sharma M, Boxer Wachler BS. Comparison of single-segment and
toconus: where should the thicker segment be implanted? J Refract double-segment Intacs for keratoconus and post-LASIK ectasia. Am
Surg. 2006;22:307-309. J Ophthalmol. 2006;141:891-895.
9. Levinger S, Pokroy R, Keratoconus managed with Intacs: one-year 24. Twa MD, Ruckhofer J, Kash RL, et al. Histologic evaluation of cor-
results. Arch Ophthalmol. 2005;123:1308-1314. neal stroma in rabbits after intrastromal corneal ring implantation.
10. Twa MD, Karpecki PM, King BJ, et al. One-year results from the Cornea. 2003;22:146-152.
phase III investigation of the Kera Vision Intacs. J Am Optom Assoc. 25. Alió JL, Artola A, Hassanein A, et al. One or 2 Intacs segments for
1999;70:515-524. the correction of keratoconus. J Cataract Refract Surg. 2005;31:943-
11. Barraquer JI. Queratoplastia refractiva, estudios e informaciones. 953.
Oftalmologicas (Barcelona). 1949;2:10-30. 26. Ibrahim TA. After 5 years follow-up: do Intacs help in keratoconus?
12. Barraquer JI. Modification of refraction by means of intracorneal Cataract Refract Surg Today–Europe. 2006;1:45-48.
inclusion. Int Ophthalmol Clin. 1966;6(1):53-78. 27. Chan CC, Sharma M, Wachler BS. Effect of inferior-segment Intacs
13. Colin J, Cochener B, Savary G, et al. Intacs inserts for treating kera- with and without C3-R on keratoconus. J Cataract Refract Surg.
toconus: one-year results. Ophthalmology. 2001;108:1409-1414. 2007;33(1):75-80.
14. Boxer Wachler BS, Chandra NS, Chou B, et al. Intacs for keratoco- 28. Lovisolo CF, Fleming JF. Intracorneal ring segments for iatrogenic
nus. Ophthalmology. 2003;110:1031-1040, errata, 1475. keratectasia after laser in situ keratomileusis or photorefractive
15. Colin J. European clinical evaluation: use of Intacs for the treat- keratectomy. J Refract Surg. 2002;18:535-541.
ment of keratoconus. J Cataract Refract Surg. 2006;32:747-755. 29. Kymionis GD, Siganos CS, Kounis G, et al. Management of post-
16. Kanellopoulos AJ, Pe LH, Perry HD, Donnenfeld ED. Modified LASIK corneal ectasia with Intacs inserts; one-year results. Arch
intracorneal ring segment implantations (Intacs) for the manage- Ophthalmol. 2003;121:322-326.
ment of moderate to advanced keratoconus: efficacy and complica- 30. Pokroy R, Levinger S, Hirsh A. Single Intacs segment for post-
tions. Cornea. 2006;25:29-33. laser in situ keratomileusis keratectasia. J Cataract Refract Surg.
17. Ratkay-Traub I, Ferincz IE, Juhasz T, et al.First clinical results with 2004;30:1685-1695.
the femtosecond neodymium-glass laser in refractive surgery. J 31. Kymionis GD, Siganos CS, Tsiklis NS, et al. Long-term follow-up of
Refract Surg. 2003;19:94-103. Intacs in keratoconus. Am J Ophthalmol. 2007;143:236-244.
18. Ertan A, Kamburoğlu G, Akgün Ü. Comparison of outcomes of 2
channel sizes for intrastromal ring segment implantation with a
femtosecond laser in eyes with keratoconus. J Cataract Refract Surg.
2007;33:648-653.
 CHAP TER 1 7

Corneal Cross-Linking With

Riboflavin and Ultraviolet
Irradiation
Ronald R. Krueger, MD, MSE; Karolinne Maia Rocha, MD, PhD;
and Mirko R. Jankov II, MD, PhD

P CROSS-LINKING
rogressive corneal ectasia can occur secondary to
corneal disorders such as keratoconus and pellucid
marginal degeneration or be surgically induced as PHARMACOKINETICS
post-laser iatrogenic ectasia. In both these natural and
iatrogenic conditions, the corneal stroma is structurally Experimental evidence has show that the photosensitzer
weakened and biomechanically unstable. Due to this insta- riboflavin and UVA led to corneal tissue strengthening by
bility, the alternatives for correction of irregular astigma- increasing collagen covalent bonds, similar to photopoly-
tism are few, expectations are limited, and consequences merization in polymers.11 Collagen cross-linking induces
may be unpredictable, anatomically and functionally.1 an increase in the formation of intra- and interfibril-
Corneal collagen cross-linking (CXL) is a new method to lar covalent bonds by photosensitized oxidation, which
stop the progression of keratoectasia and may reduce the leads to a biomechanical stabilization of the cornea.11-13
need for penetrating keratoplasty.2 The first landmark The basis of the idea came from scientific evidence that
article on this therapy demonstrated clinically significant the natural cross-linking effect of glucose increases cor-
stiffening of the corneal stroma in keratoconus patients neal resistance in young diabetic patients.3 Interestingly, in
after cross-linking, by reporting a mean keratometric these conditions, keratoconus rarely occurs.
regression of 2 diopters (D) over the course of 23 months Corneal collagen cross-linking has been shown to modify
with just 30 minutes of ultraviolet A (UVA) exposure and the biomechanical properties of the cornea as demonstrated
topical application of riboflavin.3 Potential applications of by ex vivo stress-strain experiments using porcine and human
the cross-linking technique include the treatment of kera- corneas.14 Corneal stiffness has been shown to increase by
toconus,3-5 keratoectasia,6 and even refractory, non-heal- 300% in some of these experiments.14 The stiffening effect
ing corneal ulcerations.7 of the riboflavin/UVA treatment is similar to formaldehyde-
Although advancements in laser vision correction have induced tissue stiffening and fixation in pathologic speci-
begun to offer us better tools for managing irregular mens, also caused by collagen cross-linking.15
astigmatism,8-10 the new technologies used to regularize Corneal cross-linking leads to a significant increase
the corneal surface in these irregular eyes do not assume in collagen fiber diameter, which indirectly confirms the
or predict the stabilty of the underlying stroma. Hence, change in its structure and rigidity. Immunofluorescence
a primary intervention, such as collagen cross-linking, confocal microscopy has shown a pronounced compaction
would first be required, ensuring stabilization of the cor- of collagen fibers in the anterior stroma of porcine corneas
nea, before or even immediately after the laser ablation in after riboflavin and UVA exposure.16 However, the compac-
these cases.2 tion of the collagen fibers was only observed in the absence
of the epithelium, due to a limited penetration of riboflavin
through the epithelial tight junctions into the stroma.

Wang M, ed.
Keratoconus & Keratoectasia: Prevention, Diagnosis, and Treatment (pp.169–174) 169
© 2010 SLACK Incorporated
170 CHAPTER 17

SAFETY
With riboflavin as a photosensitizer, the cornea absorbs
a very high percentage of the irradiation intensity. Without
riboflavin, the UVA light would be absorbed within the
cornea by approximately 30%, with more than 50% UVA
transmitted to the lens.17 This never happens because, with
a stromal saturation of riboflavin 0.1%, the 3 mW/cm 2
of UVA irradiance at the corneal surface is considerably
reduced by 95%, to a noncytotoxic irradiance of 0.15 mW/
cm 2 at the level of the endothelium.18 Anteriorly, in the
corneal stroma, keratocyte apoptosis leads to a repopula-
tion that has been shown by confocal microscopy to start
after 1 month, reaching its preoperative morphology and
number by 6 months after the treatment.19 Figure 17-1. UVAirradiation (370nm; Peschkemed, Huenenberg, Switzerland) is
applied at a 1-cmworkingdistance for 30 minutes followingapplication of ribo-
In experiments with rabbit eyes, the cytotoxic threshold
flavin solution. (Reprinted with permission fromWangM.Irregular Astigmatism.
irradiance for the endothelial cell apoptosis after combined
Diagnosis and Treatment. Thorofare, NJ: SLACKIncorporated; 2007.)
riboflavin/UVA treatment is 0.36 mW/cm 2 (~0.65 J/cm 2),
which may be reached with a corneal thickness of less than
400 µm using 3 mW/cm 2 irradiance (~5.4 J/cm 2) projected
onto the corneal front surface.20 Therefore, preoperative of UVA light. The UVA irradiation (370 nm; Peschkemed,
pachymetry is essential and must be measured in all cases. Huenenberg, Switzerland) is applied at a 1-cm working
Usually, the central corneal thickness in keratoconus is not distance for 30 minutes using a 3 mW/cm 2 irradiance (~5.4
reduced to less than 400 µm. In corneas with less then 400 J/cm 2) (Figure 17-1). After the treatment, an antibiotic eye-
µm, the cross-linking treatment should be avoided using drop is applied, and a bandage contact lens is fitted to the
these dosage parameters, and a hypotonic solution of ribo- corneal surface until re-epithelialization.
flavin in physiological solution (without Dextran T-500)
should be applied in order to swell the cornea before and
during the irradiation. CLINICAL OUTCOMES
Considering the crystalline lens, the UVA dose of 0.65
J/cm 2 (0.36 mW/cm 2) at the level of the endothelium is far Based on the principle that increasing the number of
below a cataractogenous level of 70 J/cm 2, and with further covalent bonds between the collagen fibers might enhance
absorption of UVA by the riboflavin in the anterior cham- the biomechanical stability of ectasic corneas, the chief
ber, the exposure to the lens is even lower.21 In addition, indication for the cornea collagen cross-linking procedure
lens damage is usually induced by UVB light (wavelength is to halt the procession of ectasia in keratoconus and pellu-
range of 290 to 320 nm), which has a higher energy than cid marginal degeneration. Collagen cross-linking may also
UVA. Regarding retinal phototoxicity, UVA levels in the be effective in the treatment and prophylaxis of iatrogenic
posterior segment are negligible and comparable to ambi- keratoectasia, resulting from laser in situ keratomileusis.
ent sun exposure. The first prospectively designed clinical study that
included 23 eyes with moderate or advanced progressive
keratoconus showed collagen cross-linking as effective in
SURGICAL TECHNIQUE halting the progression of keratoconus over a period of up
to 4 years.3 In the study, a mean preoperative progression
Topical anesthetic should be applied before the pro- of keratometry (max K) by 1.42 D in 52% of eyes over a
cedure. The central 7-mm of the corneal epithelium is 6-month period was followed by a postoperative decrease
removed using a blunt knife or 30 seconds of application of in 70% of eyes, revealing a reduction of mean keratometry
20% alcohol. As a photosensitizer, riboflavin 0.1% solution by 2.01 D. Moreover, the postoperative spherical equivalent
in dextran T-500 20% solution is applied 15 minutes before refraction (SEQ) was reduced by an average of 1.14 D, while
the irradiation and every 2 to 3 minutes during the irra- at the same time, 22% of the untreated fellow control eyes
diation. Alternatively, a smaller area of epithelium may be had a postoperative progression of keratoectasia by 1.48 D.
removed, provided that the time of application of ribofla- The prospective results from our group in Serbia (MRJ as
vin is increased, and the presence of riboflavin in the ante- surgeon) was studied for 38 keratoconic eyes of 19 patients,
rior chamber is confirmed by the presence of a yellow flare where the more advanced eye was treated and the fellow eye
under the slit-lamp examination prior to the application served as a control. Postoperatively at 6 months, there was
 CORNEAL CROSS-LINKING WITH RIBOFLAVIN AND ULTRAVIOLET IRRADIATION 171

a statistically significant mean decrease in max K by 1.75 ± (photochemical reaction, not photosensitizing reaction). It
1.24 D, spherical equivalent refraction (SEQ) by 1.94 ± 3.30 also has augmentation properties (forms hydrogel material
D, and refractive cylinder by 1.31 ± 1.96 in the treated eyes, within the cornea) and is not purely creating intrastromal
while the fellow eyes had a mean increase in max K by 0.24 cross-links. In comparison to standard cross-linking, we
± 0.97 D, SEQ by 0.13 ± 1.00 D, and cylinder by 0.06 ± 0.83 demonstrated similar efficacy with flash-linking in stiffen-
(p<0.01). Both the UCVA and BSCVA increased by 0.01 ± ing the cornea, when measured with surface wave elastom-
0.12 and 0.04 ± 0.22 (LogMAR), respectively, in the treated etry.27 The advantage of the flash-linking over riboflavin
eyes, while the fellow eyes decreased by 0.03 ± 0.23 and is the reduction of UVA exposure time from 30 minutes
0.02 ± 0.17, respectively, but without statistically significant to only 30 seconds. However, further studies are necessary
difference. Regarding safety, the endothelial cell counts before it can be introduced into the clinical practice. In
decreased by 64 ± 158 c/mm 2 in the treated eyes and 20 addition to tissue stiffening, our group (RRK and KMR)
± 44 c/mm 2 in the fellow eyes without reaching statistical also presented at ARVO 2008 the novel mixture of riboflavin
significance. Meanwhile, the IOP increased by 1.92 ± 2.22 and type 1 collagen for cross-linking of a clear collagen gel
mmHg in the treated eyes and 0.08 ± 2.25 mmHg in the into an adherent and resilient anterior stromal substitute
fellow eyes with a high statistically significant difference for corneal reconstruction after lamellar graft dissection.
(p<0.01). This latter finding was not a safety concern, but Photochemical corneal augmentation by the cross-linking of
rather demonstrated the efficacy of cross-linking, because a collagen gel mixture in porcine corneas has demonstrated
a stiffer, more elastic cornea measures at a higher IOP,22 good optical clarity and strong tissue adhesive properties.28
similar to the observed IOP measurement increases with Beyond keratoectasia, CXL can also be used in treating
thicker than thinner corneas.23 corneal melting conditions or infectious keratitis, as the
In a randomized controlled trial of 49 patients carried cross-linking strengthens a collagenolytic cornea and UVA
out in Australia, the 1-year outcome was recently reported irradiation sterilizes the infectious agents. Furthermore,
in 33 eyes with documented progression of keratoconus UV-radiation with riboflavin has been shown to stop
treated with riboflavin/UVA cross-linking procedure.24 In the keratolytic process in eyes with progressive corneal
this study, flattening of the steepest simulated keratometry ulceration. In 4 patients suffering from various melting
by a mean value of 1.45 D (p=0.002) was reported at 12 ulcerations of the cornea, collagen cross-linking, using a
months. There was also an improvement in best spectacle- similar protocol, led to a halting of the progression in 3 of
corrected visual acuity (BSCVA) and stability of endothe- the 4 patients.29
lial cell density. Intrastromal delivery of riboflavin after creating 2 fem-
Corneal cross-linking has also been used successfully in tosecond laser pockets at 350 and 150 µm depth followed by
stopping the advancement of iatrogenic ectasia in eyes with CXL with high irradiance UVA (15 mW/cm 2 for 7 minutes)
aggressive excimer laser ablation. In a published German was clinically helpful in reducing the corneal thickness
study of collagen cross-linking following post-LASIK ecta- and symptomatology of corneal edema secondary to bul-
sia, the biomechanical status of the cornea was stabilized lous keratopathy.30 The procedure was able to postpone a
with a halting of the refractive and topographic progres- corneal transplant in an 84-year-old woman with bullous
sion of ectasia over a period of 18 months.25 Furthermore, keratopathy.
intrastromal corneal ring segments (INTACS) implanted
within an externally created channel in the cornea followed
by CXL treatment may represent a novel combined treat- CLINICAL SIDE EFFECTS
ment for postoperative ectasia.26
To date, there have been no remarkable clinical side
effects or complications noted during clinical trials and
NEW COMPONENTS AND studies performed at multiple centers. Mild transient
edema is common with a mild cotton-like hazy appearance
FUTURE APPLICATIONS within the corneal stroma, which usually resolves after 4 to
6 weeks with the usual treatment (Figures 17-2 and 17-3).
Beyond the standard riboflavin-based cross-linking One case has been reported with focal corneal edema over
methods and dosing for ectactic disease, we have introduced a small area that had a reduced endothelial cell count and
a new, rapid method of cross-linking (flash-linking) by the focal endothelial haziness. Retrospectively, this eye was
use of a customized photoactive cross-linking agent.27 The found to be below the minimal thickness range and prob-
flash-linking agent is a multicomponent (>3) photochemi- ably developed localized endothelial damage. A week later,
cal mixture, which is activated with UVA exposure in a however, the cornea returned to its usual appearance due
non-thermal reaction to form a hydrogel that can absorb to the compensatory migration of surrounding endothelial
80% water. In contrast to riboflavin-UVA cross-linking, it cells, and there was no further sign of endothelial damage
is oxygen-independent and requires little UVA exposure visible during the slit-lamp examination.
172 CHAPTER 17

Figure 17-2. Third postoperative day. After the removal of the contact lens, Figure 17-3. Under the slit-lamp a faint demarcation line between the swollen
one can observe transient stromal and epithelial edema with a mild cotton- anterior and normal posterior cornea can be seen on the third day(left). This
like hazy appearance within the corneal stroma. (Reprinted with permission line can hardly be seen after 3 months (right). (Reprinted with permission
fromWang M. Irregular Astigmatism. Diagnosis and Treatment. Thorofare, NJ: fromWang M. Irregular Astigmatism. Diagnosis and Treatment. Thorofare, NJ:
SLACKIncorporated; 2007.) SLACKIncorporated; 2007.)

A delay in re-epithelization had been noted in an

eye receiving coricosteroid medication during the period
CONCLUSIONS
of epithelization and bandage soft contact lens wear.
Clinical and experimental studies on riboflavin/UVA
Following withdrawal of the corticosteroid medication,
corneal cross-linking have provided sufficient peer-
re-epithelization was complete within 24 hours, and the
reviewed evidence in support of the safety and efficacy of
eye suffered no adverse consequences afterwards. A few
this technology in not only halting the progression of the
anecdotal reports have been made of small sterile corneal
keratoconus, but even reducing corneal curvature, spheri-
infiltrates developing under the contact lens, all of which
cal equivalent refraction, and refractive cylinder. Future
are believed to be related to the use of non-steroidal anti-
indications of CXL in other corneal disorders, such as
inflammatory eye drops. The infiltrates did not progress
infectious keratitis, bullous keratopathy, and as a stromal
after the contact lenses were removed, and disappeared
substitute in corneal augmentation procedures, expand the
with 1 to 2 weeks of intense topical steroid therapy, leaving
scope of potential application for this technology around
only faint visually insignificant opacities.
the world.

CASES REFERENCES
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uncorrected visual acuity (UCVA) of 20/2000. The BSCVA perspective. Refract Corneal Surg. 1990;6:441-454.
with –0.50 –7.75 x 70 was 20/70. After CXL treatment, the 2. Kanellopoulos AJ, Binder PS. Collagen cross-linking (CCL) with
UCVA was 20/400. Best spectacle corrected visual acuity sequential topography-guided PRK: a temporizing alternative for
keratoconus to penetrating keratoplasty. Cornea. 2007;26(7):891-
improved to 20/50 with a refraction of –1.25 –6.25 x 75.
895.
Maps are shown in Figure 17-4. 3. Wollensak G, Spoerl E, Seiler T. Riboflavin/ultraviolet-a-induced
A 28-year-old patient with a history of keratoconus had collagen cross-linking for the treatment of keratoconus. Am J
a pre-operative UCVA of 20/60. A refraction of +1.50 –2.50 Ophthalmol. 2003;135(5):620-627.
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new hope. Curr Opin Ophthalmol. 2006;17(4):356-360.
the UCVA was 20/50 , and BSCVA of 20/30 was obtained 5. Kymionis G, Portaliou D. Corneal cross-linking with riboflavin
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Figure 17-5. 2007;33(7):1143-1144.
6. Hafezi F, Kanellopoulos J, Wiltfang R, Seiler T. Corneal collagen
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A B

C D

Figure 17-4. (A) Preoperative keratometric maps for a keratoconic patient. (B) Preoperative elevation maps for a keratoconic patient. (C) Postoperative kerato-
metric maps following CXLtreatment. (D) Postoperative elevation maps following CXLtreatment. (Courtesyof Aleks Stojanovic, MD.)

7. Spoerl E, Wollensak G, Seiler T. Increased resistance of crosslinked 16. Bottós KM, Dreyfuss JL, Regatieri CV, et al. Immunofluorescence
cornea against enzymatic digestion. Curr Eye Res. 2004;29(1):35- confocal microscopy of porcine corneas following collagen cross-
40. linking treatment with riboflavin and ultraviolet A. J Refract Surg.
8. Mrochen M, Krueger RR, Bueeler M, Seiler T. Aberration-sensing 2008;24(7):S715-719.
and wavefront-guided laser in situ keratomileusis: management of 17. Wollensak G, Spoerl E, Reber F, Seiler T. Keratocyte cytotoxicity of
decentered ablation. J Refract Surg. 2002;18(4):418-429. riboflavin/UVA-treatment in vitro. Eye. 2004:1–5.
9. Knorz M. Topographically-guided laser in situ keratomileusis to 18. Wollensak G, Spoerl E, Wilsch M, Seiler T. Keratocyte apoptosis
treat corneal irregularities. Ophthalmology. 2000;107:1138-1143. after corneal collagen cross-linking usingriboflavin/uva treatment.
10. Jankov MR, Panagopoulou SI, Aslanides IM, Hajitanasis GI, Cornea. 2004;23:43-49.
Pallikaris GI. Topography-guided treatment or irregular
19. Mazzotta C, Balestrazzi A, Traversi C, et al. Treatment of pro-
astigmatism with the WaveLight excimer laser. J Refract Surg.
gressive keratoconus by riboflavin-UVA-induced cross-linking of
2006;22(4):335-344.
corneal collagen: ultrastructural analysis by Heidelberg Retinal
11. Spoerl E, Huhle M, Seiler T. Erhöhung der Festigkeit der Hornhaut
Tomograph II in vivo confocal microscopy in humans. Cornea.
durch Vernetzung. Ophthalmologe. 1997;94:902-906.
2007;26(4):390-397.
12. Spoerl E, Schreiber J, Hellmund K, Seiler T, Knuschke P.
Untersuchungen zur Verfestigung der Hornhaut am Kaninchen. 20. Wollensak G, Spoerl E, Wilsch M, Seiler T. Endothelial cell damage
Ophthalmologe. 2000;97:203-206. after riboflavin–ultraviolet-A treatment in the rabbit. J Cataract
13. Spoerl E, Huhle M, Seiler T. Induction of cross-links in corneal tis- Refract Surg. 2003;29:1786-1790.
sue. Exp Eye Res. 1998;66:97-103. 21. Wollensak G, Spoerl E, Seiler T. Riboflavin/ultraviolet-a–induced
14. Wollensak G, Spoerl E, Seiler T. Stress-strain measurements of collagen cross-linking for the treatment of keratoconus. Am J
human and porcine corneas after riboflavin-ultraviolet-A-induced Ophthalmol. 2003;135:620-627.
cross-linking. J Cataract Refract Surg. 2003;29(9):1780-1785. 22. Krueger R, Ramos Esteban J. How might corneal elasticity help us
15. Spoerl E, Seiler T. Techniques for stiffening the cornea. J Refract understand diabetes and intraocular pressure? J Refract Surg. 2007;
Surg. 1999;15:711-713. 23:85-88.
174 CHAPTER 17

A B

C D

Figure 17-5. (A) Preoperative keratometric maps for a keratoconic patient. (B) Preoperative elevation maps for a keratoconic patient. (C) Postoperative kerato-
metric maps following CXLtreatment. (D) Postoperative elevation maps following CXLtreatment (Courtesyof Aleks Stojanovic, MD).

23. Doughty M, Zaman M. Human corneal thickness and its impact 28. Krueger RR, Rocha KM, Ventura J, Ramos-Esteban J, Herekar S.
on intraocular pressure measures: a review and meta-analysis Photochemical corneal augmentation of experimental lamellar
approach. Surv Ophthalmol. 2000;44:367-408. graft dissection by cross-linking of collagen gel into a corneal tissue
24. Wittig-Silva C, Whiting M, Lamoureux E, Lindsay RG, Sullivan substitute. Invest Ophthalmol Vis Sci. 2008; E-abstract 2346.
LJ, Snibson GR. A randomized controlled trial of corneal collagen 29. Schnitzler E, Sporl E, Seiler T. Irradiation of cornea with ultra-
cross-linking in progressive keratoconus: preliminary results. J violet light and riboflavin administration as a new treatment for
Refract Surg. 2008;24(7):S720-S725. erosive corneal processes, preliminary results in four patients. Klin
25. Kohlhaas M, Spoerl E, Speck A, et al. A new treatment of keratec- Monatsbl Augenheilkd. 2000;217(3):190-193.
tasia after LASIK with riboflavin/UVA light cross-linking. Klin 30. Krueger RR, Ramos-Esteban JC, Kanellopoulos AJ. Staged intra-
Monatsbl Augenheilkd. 2005;222(5):430-436. stromal delivery of riboflavin with UVA cross-linking in advanced
26. Kamburoglu G, Ertan A. Intacs implantation with sequential col- bullous keratopathy: laboratory investigation and first clinical case.
lagen cross-linking treatment in postoperative LASIK ectasia. J J Refract Surg. 2008 Sep;24(7):S730-S736.
Refract Surg. 2008;24(7):S726-729.
27. Rocha KM, Ramos-Esteban JC, Qian Y, Herekar S, Krueger RR.
Comparative study of riboflavin-UVA cross-linking and “flash-
linking” using surface wave elastometry. J Refract Surg. 2008;24(7):
S748-S751.
 CHAP TER 1 8

New and Future Treatments

Excimer Laser Lamellar Keratoplasty and Advanced Cross-Linking

Leopoldo Spadea, MD; Dale P. Devore, PhD; Richard A. Eiferman,

MD, FACS; Bruce DeWoolfson, PhD; Charles Wm. Stewart, OD; Tracy
Swartz, OD, MS, FAAO; and Ming Wang, MD, PhD

S
urgical options for patients with ectasic disorders resulted in the least amount of adjacent tissue damage and
continue to evolve. Collagen cross-linking and Intacs created a smoother ablation compared to longer wave-
(Addition Technologies, Sunnyvale, CA) hold prom- length lasers.10,11 Argon fluoride lasers (also called excimer
ise for delaying or avoiding transplantation. Laser applica- lasers as an acronym for excited dimer) were subsequently
tions to previously manual procedures bring new precision developed for keratorefractive procedures. At a 193 nm
to tissue modifications and visual rehabilitation Here, we wavelength, high-energy photons break organic molecular
discuss new technologies that may strengthen weak cor- bonds of the superficial corneal tissue in a process called
neas to address ectasia and advanced vision correction pro- ablative photo-decomposition. Particles are expelled at
cedures to aid those with keratoconus and keratoectasia. high velocity, which helps to dissipate much of the energy.12
Other important properties of the laser were also explored,
including the optimum irradiance levels and repetition
EXCIMER LASER LAMELLAR rates. The optical principles for the laser correction of
KERATOPLASTY ametropia have been developed and are straightforward.4
At the same time, therapeutic uses of the excimer laser have
The use of the excimer laser to sculpt the cornea has also been developed. In the phototherapeutic keratectomy
been the most important advancement in the field of (PTK) procedure, an excimer laser is used as an adjunctive
refractive surgery. With reports of epithelial sensitivity tool to surgically treat a variety of superficial corneal dis-
to ultraviolet lasers and precise etching properties using orders. With PTK, a uniform depth ablation of the surface
various substrates, in 1983, Trokel et al studied the effect corneal tissue is executed over a wide area that is typically
of the excimer laser on bovine corneas.1,2 They demon- from 8 to 11 mm. This technique produces a smooth sur-
strated that far ultraviolet laser emissions (between 150 face and clear visual axis and minimizes tissue removal.5
and 200 nm) could precisely remove corneal stroma with- Due to these specific characteristics of the PTK procedure,
out apparent thermal trauma to the adjacent tissue.3- 8 The some authors have proposed the use of the PTK mode for
laser did not create adverse alterations of wound healing lamellar keratectomy instead of the microkeratome.4,5 The
processes including cellular migration, proliferation, or overriding advantage of using the excimer laser for lamellar
production of new tissue.9 This landmark report started a keratectomy is its ability to remove tissue with microscopic
multitude of investigations into the use of laser for refrac- precision that is unattainable with other procedures. The
tive surgery. The 193-nm ultraviolet light from the argon depth of ablation is then adjusted as necessary by the sur-
fluoride laser demonstrated the critical characteristic of geon so that a very thin, keratoconic cornea with extreme
having the least transmission through corneal tissue. This curvatures can undergo a laser lamellar keratectomy, miti-

Wang M, ed.
Keratoconus & Keratoectasia: Prevention, Diagnosis, and Treatment (pp.177–185) 177
© 2010 SLACK Incorporated
178 CHAPTER 18

gating risks that were associated with historical techniques.

These properties of the excimer laser are ideal for the surgi-
cal treatment of corneal ectasia, such as keratoconus.
The laser lamellar keratectomy for keratoconus began
in the 1990s based upon previous experiences with epik-
eratoplasty. In this technique, donor corneal tissue is pre-
lathed into the proper shape and sutured onto a recipient,
de-epithelialized cornea in which Bowman’s layer and the
stroma have been left intact. The change in curvature of
the anterior surface from the lenticule provides the refrac-
tive correction. Unfortunately, despite various changes in
this technique, the refractive results were disappointing.
Many authors have demonstrated the utility and accuracy
of the excimer laser for reproducible corneal photoablation
in lamellar keratoplasty.6,7 To improve the anatomical and
functional outcome of lamellar keratoplasty for patients Figure 18-1. The iRESlaser system.
with early stage keratoconus, the excimer laser lamellar
keratoplasty (ELLK) with augmented thickness technique
was developed.7 ELLK is a procedure in which a deep plano cornea as a function of corneal thickness differentials
excimer laser ablation is performed on the host cornea and (pachymetric-link) or with corneal aberrations (topoaber-
a donor button is sutured into the recipient bed. No ther- rometric-link). The concept of customized ablation was
mal or mechanical damage to the cornea in the areas adja- developed in the mid 90s,14 and it seemed useful to apply
cent to the ablation was observed on light microscopy.13 the made-to-measure, custom ablation strategy to lamel-
Additionally, the laser did not create adverse alteration lar keratoplasty to improve the surgical technique and the
of wound healing responses including cellular migration, results. Corneal Lamellar Ablation for Transplantation
proliferation, and production of new tissue.13 Excimer (CLAT; iVIS Tecnologies, Taranto, Italy) was developed
laser-assisted keratoplasty for keratoconus provides an for therapeutic surgery in order to restore the normal
adequate improvement of corneal thickness, which is use- corneal pachymetric gradient utilizing devices that pro-
ful to restore the corneal optic integrity and structure. vide highly repeatable anterior elevation, posterior eleva-
Laser lamellar keratectomy seemed to be a simple and tion, and pachymetry data. For this technique, a custom
safe technique: in PTK-mode with an ablation area of 10- refractive surgery platform is used that is an integrated
mm diameter, the treatment was centered on the pupil system of devices and software to customize refractive and
and executed using a non-ablative ring mask to protect therapeutic surgery specific to each patient’s unique and
the peripheral cornea. The ablation depth was planned individual needs. The iVIS Suite (iVIS Technologies) is an
to leave a 200-µm thickness at the thinnest point, avoid- integrated platform that consists of software applications
ing any consequences with the endothelium. A peripheral for CLAT; Precisio (iVIS Technologies) high-resolution sur-
pocket was then created and the lamella positioned on the gical tomographer; pMetrics (iVIS Technologies) dynamic
recipient bed to restore a regular anterior corneal surface. pupillometer; and a high-resolution ablation delivery plat-
Functional and anatomic improvements were evident, but form using the iRES 1.000-Hz laser (Figure 18-1). A funda-
in some cases the mechanical effects of the recipient’s origi- mental premise in the design concept of these diagnostic,
nal keratoconus persisted, especially with advanced and design, and delivery systems is to provide highly repeat-
decentered ectasia. These disadvantages limited the use of able, high-definition data appropriate for the demands of
this technique to only mild or moderate keratoconus cases. high-resolution custom refractive and custom therapeutic
Other disadvantages of excimer laser lamellar keratoplasty corneal surgery. CLAT is a paradigm shift allowing the sur-
were vision-limiting interface problems. To further reduce geon to execute a totally automated, customized lamellar
the mechanical effects and improve these cases, new meth- transplantation of the cornea.
ods were necessary to regularize the ectasia and to create CLAT is a 3-step surgical process (Figure 18-2) to create
unique ablations, customizing the lamella and recipient both a thin, uniform thickness receiving bed and a dimen-
bed. sionally matched donor lamella. When the shaped donor
The introduction of a new-generation excimer laser with lamella is placed within the receiving bed, a full-thickness
a comprehensive surgical planning application specific for regularized cornea results, which importantly preserves
laser lamellar transplantations allowed the surgeon to cre- the patient’s endothelium, Descemet’s membrane, and the
ate customized ablations for both the receiving bed and posterior stroma. Unlike microkeratome or laser-keratome
the lamella as complements. Specifically, this provided the lamellar surgeries, CLAT removes the irregularities in the
capability to plan different ablation depths in the same cornea in preparation for receiving the matched uniform
 NEW AND FUTURE TREATMENTS 179

Figure 18-2. CLAT Surgical Process. The recipient cornea (A) is prepared to
remove the irregular, keratoconic thickness (B), resulting in the formation of a
uniformthickness receiving bed (C). The laser first thins the donor cornea (D),
and then shapes the donor perimeter to a matching circumference using laser Figure 18-3. Biomicroscopic image of a 21-year-old man at 1 month of follow-
trephination (E). The completed donor (F) as a complement to the planned up after customized lamellar keratoplasty in the right eye. The preoperative
recipient bed is then sutured in place (G) yielding a full-thickness, regularized BSCVAwas 0.1; the 1-month postoperative BSCVAwas 0.3.
postoperative condition. An optional perimetral saddle is not illustrated.

thickness donor. This process yields significantly improved characteristics of the bed will cause the bed to be posi-
refractive characteristics of the resultant postoperative tioned along the isostatic line that eliminates the deforma-
cornea. Keratome or laser-keratome based surgeries which tion induced from the corneal pathology.7
reference the anterior surface, leave or mirror all of the pre- At this moment, local anesthesia is achieved with a
operative corneal irregularities in the postop cornea and peribulbar injection of 10 cm 3 of bupivacaine 0.5% and
therefore develop a significantly more aberrated refractive mepivacaine 4% combination. Each patient is prepared and
condition. draped in the usual fashion. Several drops of a 5% povi-
The donor cornea is positioned on a specialized concave done-iodine solution are instilled in the inferior fornix,
support with the endothelial side exposed. The surgeon and a lid speculum is inserted to keep the eye wide open.
then uniformly reduces the donor cornea thickness with the With a circular movement using a disk knife a 2.5-mm
excimer laser. The donor cornea is then positioned on a con- stromal pocket is obtained around the 360-degree circum-
vex support with the epithelial side exposed for excimer laser ference of the ablation floor.
trephination, using a donor mask of equal (or 0.25-mm larg- The donor lamella is then secured into the recipient
er) diameter to the recipient’s ablation. A perimetral saddle bed with 4 10-0 nylon cardinal sutures at the 6, 12, 9, and
with depth and width defined by the surgeon is performed 3 o’clock positions, and then, after the introduction of the
by positioning a secondary mask with a smaller diameter. wing of the donor lamella into the stromal pocket, 16 inter-
The receiving bed is created by utilizing a three- rupted 10-0 nylon sutures are placed. Finally, the knots are
dimensional (3-D) pachymetry map and calculating the buried, and intraoperative suture adjustment is performed.
intersection of an ideal, uniform thickness corneal bed for At the end of surgery, the speculum is removed, and the eye
the patient uniquely referencing the posterior surface of is patched. The patch is removed the day after the surgery.
the cornea. The irregular volume above this ideal surface The postoperative therapy consists of topical ofloxacin 3%
is removed with the iRES laser (gaussian flying-spot 650 3 times daily until re-epithelialization is completed. Topical
µm, 1000 Hz, 193 nm; iVIS Technologies, Taranto, Italy) dexamethasone 0.1% is administered for at least 1 month,
with the patient under topic anesthesia (ropivacaine 1%). and then tapered and titrated. Within 3 months from sur-
A round, non-ablatable plastic mask (from 7.5 mm to 8 gery, all patients stop their medication. Preservative-free
mm in diameter) is placed on the cornea to create a verti- artificial tears (sodium hyaluronate 0.2%) are used for up
cal edge to the ablation and then the ablation is performed to 6 months in each case. An image of a typical patient at 1
transepithelially. The choice of the mask’s diameter is sec- month postoperatively is shown in Figure 18-3.
ondary to the Ideal Pupil dimension (iVIS Technologies) Two months after surgery, the sutures responsible for
that is calculated from the patient’s pMetrics pupillometry major graft distortion are starting to be removed, as
study. The minimal estimated residual stromal thickness of indicated by corneal topography analysis (example of the
the completed receiving bed is usually specified to be 200 change in topography is shown in Figure 18-4). Over the
µm. At this uniformly thin dimension, the remaining tis- following 3 months, all the remaining sutures are selec-
sue takes on membrane properties with no cross-sectional tively removed to achieve as regular corneal curvature as
rigidity. When the ablation is complete, the new membrane possible. A biomicroscopy image of a patient at 3 months
180 CHAPTER 18

Figure 18-6. Preoperative and postoperative mean UCVA(decimal).

Figure 18-4. Preoperative anterior elevation map (top right), 3-month post-
operative anterior elevation (bottom right), and differential map (left) of a
29-year-old patient. The preoperative BSCVAwas 0.3; the postoperative BSCVA
at 3 months was 0.8. The preoperative apexcorneal thickness was 402 µm; the
maximumrecipient corneal ablation was 390 µm, the minimumwas 180 µm.

Figure 18-7. Preoperative and postoperative mean BSCVA(decimal).

Figure 18-5. Biomicroscopicimage of a 49-year-old man at 3 months of follow- Figure 18-8. Preoperative and postoperative mean manifest refractive spheri-
up after customized lamellar keratoplasty in the left eye. The preoperative cal equivalent (MRSE).
BSCVAwas 0.5; the postoperative BSCVAat 3 months was 0.9.

484); the mean preoperative keratometric astigmatism was

post-ELLK is shown in Figure 18-5. In all patients, suture 5.78 D ± 3.11 SD (range from 1.65 to 7.47 D) with a mean
removal has been completed by the 6-month follow-up keratoconus apex power of 67.64 D ± 9.96 SD. The mean
examination. preoperative endothelial cell density was 1954 cell/mm 2 ±
Subsequent to 6 years of experience using standard ELLK 214 SD (range from 1919 to 2489), the mean photopic pupil
on 80 keratoconic eyes, 30 eyes of 30 patients (mean age 34.9 diameter was 3.66 mm ± 0.45 SD; the mean scotopic pupil
± 8.4 years; range 21 to 55) affected by mild to moderate diameter was 6.34 mm ± 0.57 SD; the mean Ideal Pupil
keratoconus underwent CLAT procedures. The follow-up diameter was 5.44 mm ± 0.53 SD.
examinations were performed at 1, 3, 6, 9, 12, and 24 months The mean donor ablation depth was 271 µm ± 59.4
postoperatively. The mean preoperative uncorrected visual SD (range from 100 to 420); the mean recipient ablation
acuity (UCVA) was 0.10 ± 0.11 SD, and mean preoperative depth was 198 µm ± 30.4 SD (range from 138 to 260).
best spectacle-corrected visual acuity (BSCVA) was 0.46 ± Surgeries were performed by one surgeon (LS) always
0.20 SD, with a mean manifest refraction spherical equiva- specifying a minimum estimated residual corneal bed of
lent (MRSE) of –4.73 D ± 4.25 SD. The mean preoperative 200 µm. Statistical analysis was performed using the paired
corneal thickness was 414 µm ± 24 SD (range from 382 to Student’s t-test. The results obtained are shown in Figures
 NEW AND FUTURE TREATMENTS 181

migration, proliferation, and production of new tissue.13

The depth of laser ablation is set by the surgeon in relation
to the preoperative corneal thickness of the eye and laser
lamellar keratectomy can be performed with minimized
risk. In our procedures, preoperative planning of the laser
ablation with a safety margin of 200 µm of residual corneal
bed was always considered. No endothelial damage has
developed during the 2 years of follow-up. A normal thick-
ness (>500 µm) was restored in all patients by implanting
a donor lamella thicker than the tissue ablated from the
recipient cornea. The improvement in the corneal curva-
Figure 18-9. Preoperative and postoperative mean keratometric astigma- ture (<50 D) was obtained by the flattening effect of the
tism. sutures placed as described for other lamellar techniques,
such as epikeratophakia.15
In our series, the patients have shown a slow but steady
improvement in their visual acuity after surgery. The final
visual results were satisfying and similar to those achieved
with other lamellar keratoplasty techniques, such as micro-
keratome-assisted LK16 and PK.17-19 Buratto et al6 reported
a mean BCVA of 20/30 in 20 keratoconus patients after
ELLK. Recently, Bilgihan et al20 obtained similar results
after treating 5 keratoconus patients with ELLK. These
results could have been affected by the use of old-genera-
tion lasers and the photoablation of the stromal side of the
Figure 18-10. Preoperative and postoperative mean endothelial cellular donor grafts.
density. The slowness of visual recovery could be due to vari-
ous factors, such as 1) haze of graft-bed interface, 2) lower
ability of the host keratocytes to colonize the rehydrated
lamella, and 3) small folds in the recipient bed caused
by mechanical tensions of the suture on the lamella. We
suppose that, in our patients, these factors have improved
spontaneously and steadily over time. The early removal of
sutures, and in all cases within the fifth month from sur-
gery, may have affected the patients’ refraction because of
changes in both the spherical equivalent and the refractive
cylinder observed during the follow-ups.
Keratoconus patients who need surgery are often young
Figure 18-11. Preoperative and postoperative mean corneal pachymetry. and CLAT does not rule out the possibility of a PK in the
future. CLAT, as other types of anterior LK, has addi-
tional advantages over penetrating keratoplasty in the eye
18-6 to 18-11. No immunologic rejections were observed. banking procedures: a quality donor endothelium is not
There were no cases of corneal vascularization or infection. required, and this reduces the problem of tissue availabili-
ty. Donor corneas discarded for endothelium problems and
The subjective symptom frequently reported was a foreign
not suitable for PK can instead be used for lamellar proce-
body sensation, but only in the first week after surgery.
dures. Moreover, the corneal lamella can be dehydrated in
In our experience, excimer laser-assisted dissection has a silicone gel and stored for longer times.
proved to be a reproducible technique requiring a short
In conclusion, our 2-year experience indicates that the
surgical time. The diameter of recipient photoablation was optical pachymetry-guided customized corneal lamellar
from 7.5 to 8 mm with a very regular contour in all cases, transplantation using an ultrafast excimer laser can be a
despite the wide range of preoperative corneal curvatures technique to consider when treating moderate to advanced
and degrees of surface irregularity. The overriding advan- keratoconus with a minimal corneal thickness of 350 µm.
tage of excimer laser use for lamellar keratectomy is its In these cases, CLAT can be a valuable alternative to pen-
ability to remove tissue with a microscopic precision that etrating keratoplasty, with similar efficacy and less inva-
is unattainable with other procedures. The laser does not siveness. Importantly, the preservation of the recipient’s
interfere with wound healing processes, including cellular healthy endothelium creates a higher safety profile. The
182 CHAPTER 18

use of excimer laser has allowed us to standardize lamellar collagen aggregation was accompanied by loss of tyrosine
keratoplasty by simplifying the surgical process, shortening and formation of dityrosine.23
the surgical time, and decreasing intraoperative and post- More recently, Seiler and Spoerl successfully utilized
operative complications. riboflavin as a photoinitiator for ultraviolet light (UVA)
treatment of the cornea to cross-link corneal tissue.24,25
This technique is currently being evaluated in a world-
ADVANCED COLLAGEN wide clinical study to evaluate the safety and efficacy of
CROSS-LINKING riboflavin/UVA light corneal cross-linking in patients with
progressive keratoconus or corneal ectasia after previous
refractive surgery.
The human cornea’s optical transparency and mechani-
cal strength are attributed to the well-organized matrix
architecture composed of approximately 200 parallel sheets
Novel Methods to Strengthen
of narrow-diameter collagen fibrils arranged orthogonal Corneal Structure
to neighboring fibril sheets. Corneal fibrils are primarily Porcine eyes were treated with acetic anhydride and then
composed of Type I collagen co-assembled with Type V were exposed to either 1, 3, and 4 10-second bursts of UV
collagen. However, there are other minor elements such light at an intensity of 1000 mW at a band pattern of 310
as fibril-associated collagens with interrupted triple heli- to 400 nm; there was a 10-second period of non-exposure
ces (FACIT) and small leucine-rich proteoglycans (SLRP) between UV bursts. The eyes were flushed with neutral pH
that modify the structure and function of collagen fibrils phosphate buffer and mounted in a stress/strain analyzer.
and contribute to corneal integrity. FACITS include Types A single exposure increased the strength by 400%
XII and XIV collagen, and primary SLRP include decorin, A similar study was performed on feline eyes using the
lumican, keratocan, and mimican. SLRP molecules such as Reichert Ocular Response Analyzer (ORA) to measure
decorin are critical for maintaining corneal transparency corneal hysteresis. Corneas were pretreated with a photo-
and corneal strength. initiator, 0.05 M sodium persulfate, and then exposed to
A weakened, ectatic cornea may be strengthened by 33.7 mW/cm 2 UV irradiation for 2 or 4 seconds. Results
linking its collagen fibers. These can be accomplished by are shown in Table 18-1. There was a slight decrease in CH
treatment with chemicals, heat, ultraviolet irradiation, for the control eye at 60 days, a dramatic increase in CH
and interaction with naturally occurring molecules. Many for the 2-second UV-treated eye immediately after treat-
reagents are capable of cross-linking collagen such as ment, and a 11unit increase after 60 days. The 4-second
glutaraldehyde, glyceraldehyde, dianhydrides, and bis-iso- UV-treated eye demonstrated a dramatic decrease in CH
cyanates. In addition, collagens and collagen-based mate- immediately following exposure. However, after 60 days,
rials have been cross-linked using carbodiimides and poly the CH returned to near baseline levels.
(glycidyl) ether. However, these chemicals have not been
specifically used to cross-link intact body tissues and are Stabilization of Cornea
quite toxic. Formulations containing serum albumin and by Application of Human
glutaraldehyde are approved to seal vascular anastomosis
(BioGlue [CryoLife Inc, Kennesaw, GA]). However, their Recombinant Decorin
intended use is not to cross-link treated tissues. Decorin is a member of a family of small leucine-rich
It was noted in the early 1960s that exposure to ultravio- repeat proteoglycans (SLRPS). Decorin is an approximately
let light altered collagen. Specifically, 254-nm UV increased 100 kDa proteoglycan consisting of a 40 kDa core protein
tensile strength by the induction of collagen cross-links. and 1 chondroitin sulfate or dermatan sulfate glycosami-
However, the effects of ultraviolet irradiation are extremely noglycan chain. Decorin interacts with collagen Type I and
variable, ranging from polymerization to depolymeriza- II, fibronectin, thrombospondin, and TGFβ.
tion depending on many conditions including wavelength, Decorin is a horse-shoe shaped proteoglycan that binds
intensity, exposure time, and distance from the light source to collagen fibrils in human cornea forming a bidentate
to the collagen composition. Riboflavin is well known as ligand attached to 2 neighboring collagen molecules in the
a photoinitiator for photopolymerization of monomers in fibril or in adjacent fibrils, helping to stabilize fibrils and
the presence of oxygen. Delzenne et al studied the kinetics orient fibrillogenesis.26 Decorin appears to be a ubiquitous
of polymerization of acrylic monomers using riboflavin component of extracellular matrices linking collagen fibrils
as the initiating redox system in the presence of oxygen.21 at specific binding sites.27 Corneal transparency is depen-
Needles examined photopolymerization of acrylic mono- dent on the size and arrangement of collagen fibrils in
mer solutions in the presence of protein or amino acids.22 the corneal stroma. Decorin binding is critical in limiting
Kato et al studied the mechanism of riboflavin-sensitized collagen fibril growth and in controlling the arrangement
photodynamic modification of collagen and suggested that of collagen fibrils to produce a transparency.28 Studies of
 NEW AND FUTURE TREATMENTS 183

TAB LE 1 8 -1

EFFEC T O F SHO RT-EXPO SURE UV O N C H VALUES O F FELINE C O RNEA

UNIT C HANG E
C O NDITIO NS C H VALUES AT 2 MO NTHS

Ba se lin e Im m e d ia te ly 60 -Da ys
Pre -Tre a t Po st-Tre a t Po st-Tre a t
C o n tro l-n o UV 4.5 ND 4.3 -0.2

2.3 se c e xp o su re @
33.7 m W/ c m 2 2.88 6.34 3.9 +1 u n it
4 se c e xp o su re @
33.7 m W/ c m 2 7.95 4.33 7.53 -0.4

A chemical enhancer was developed to allow penetration

A B of decorin. Confocal micrographs shown in Figure 18-12
demonstrate the ability of the penetration enhancer agent to
disrupt epithelial cell junctures so that human recombinant
decorin (MW approximately 40,000 daltons) can diffuse
into the cornea following direct application to the central
cornea. As shown, decorin penetration into the control
cornea was limited to the epithelium when it was applied
directly to the central cornea, and the epithelial cell junc-
tures were not disrupted. Conversely, decorin penetrated
the corneal stroma of the cornea pretreated with a penetra-
tion enhancer agent. Thus, penetration enhancer agent suc-
Figure 18-12. Confocal micrographs demonstrate the ability of the penetration cessfully disrupted the epithelial cell junctures, permitting
enhancer agent to disrupt epithelial cell junctures so that human recombinant diffusion of the 40,000 dalton decorin molecules.
decorin (mWapproximately40,000daltons) can diffuse intothe cornea following
direct application to the central cornea. Transmission Electron Microscopy to
Observe Decorin Binding to Collagen
effects of decorin on in vitro collagen fibrillogenesis show Fibers in a Feline Model
inhibition of collagen fibril growth and increase in colla-
gen fibril diameter.29 One eye from each group was treated with deco-
Stabilization occurs due to ionic binding of these mole- rin. Decorin penetration into the corneal stroma was
cules between adjacent collagen fibrils, forming a cross-link determined utilizing transmission electron microscopy.
(or bridge) between such fibers. However, the penetration Corneas treated with decorin were reacted with Quinolinic
of these extracellular matrix molecules is limited due to the Blue Stain (Cupromeronic blue) in buffered formalin.
fact that the intrinsic conjunctional epithelial tissue layer This reagent stains small proteoglycan structures such as
forms tight junctions with high resistance to ocular delivery decorin.
of hydrophilic molecules greater than 500 daltons. In addi- As shown in Figure 18-13, increased bridges were noted
tion, binding sites for the exogenous stabilization molecules between collagen fibrils in the decorin-treated eyes.
on collagen fibers are limited because the sites are inher- Decorin also increased corneal hysteresis in the feline
ently occupied by natural extracellular matrix molecules. model as shown in Table 18-2. As shown, treatments with
Thus, in order to enhance delivery of stabilization the chemical penetration enhancer reduced corneal hyster-
agents and thereby maximize stromal stabilization, meth- esis (CH), indicating “softening” of corneal structure due
ods have been developed to 1) open the epithelium to allow to dissociation of molecular links between collagen fibers.
intrastromal penetration of the stabilization agents and Subsequent application of decorin increased CH values to
2) dissociate inherent binding of extracellular molecules levels greater than initial values, indicating “strengthen-
between adjacent collagen fibers in stromal tissue. ing” of corneal structure.
184 CHAPTER 18

Figure 18-13. TEMS of control and decorin-treated cornea. Increased bridges

were noted between collagen fibrils in the decorin treated eyes.

TAB LE 18 -2

C O RNEAL HYSTERESIS O F FELINE C O RNEA FO LLO WING PRE-TREATMENT WITH AN

O C ULAR PENETRATIO N ENHANC ER AND DEC O RIN TREATMENT
TREATMENT ANIMAL IBT4 ANIMAL Q KU8 ANIMAL Q NO 6
C o n tro l Tre a te d Tre a te d Tre a te d C o n tro l Tre a te d
In itia l ND 4.0 6.4 7.0 ND 6.3
Po st-Pro p a ra c a in e * ND 7.0 8.0 7.5 ND 7.0
Po st-En h a n c e r #1 ND 3.3 5.3 6.4 ND 6.4
Po st–En h a n c e r #2 ND 3.2 7.0 4.8 ND 5.7
Po st-De c o rin ND 4.6 7.9 – ND –

* Pro p a ra c a in e a d m in iste re d to p ro vid e a n e sth e sia b e fo re tre a tm e n ts with p e n e tra tio n e n h a n c e rs a n d d e c o rin .

TAB LE 18 -3

C O RNEAL HYSTERESIS VALUES O F FELINE C O RNEA FO LLO WING TREATMENT

WITH DEC O RIN DRO PS
TREATMENT ANIMAL AHH3 ANIMAL Q J D4 ANIMAL RAF6 ANIMAL BEA4 ANIMAL IRH6

In itia l 8.75 6.9 5.88 3.65 7.98

Po st-O c u la r
5.73 3.9 4.15 – –
En h a n c e r
Po st-De c o rin 7.3 6.3 5.18 4.8 8.03

A second study was conducted to examine the effects of subject animals were included in this study. One eye of each
decorin treatment on stabilizing “weakened” cornea. Four animal was treated while the contralateral eye served as the
subject animals were included in this study. One eye of each control. Control and treated eyes were evaluated for corneal
animal was treated with the contralateral eye serving as the hysteresis using the Reichert Ocular Response Analyzer at
control. Eyes were evaluated for corneal hysteresis using the baseline and then after treatment with Proparacaine HCL,
Reichert Ocular Response Analyzer before treatment and proprietary ocular enhancer solution, and decorin.
then after treatment with proparacaine HCL, ocular pene- Corneal hysteresis (CH) results are shown in Table
tration enhancer, and decorin. As shown in Table 18-3, treat- 18-4. As in previous studies, the corneal hysteresis values
ments with proprietary ocular enhancer solution reduced increased following treatment with human recombinant
CH values, indicating corneal softening. Subsequent appli- decorin solution.
cation of human recombinant decorin increased CH values, These studies suggest that topical decorin may be
indicating stabilization of corneal structure. valuable in the treatment of keratoconus and post-LASIK
A third study was conducted to examine the effects of ectasia. It may also be possible to reshape the cornea using
decorin on strengthening or stabilizing corneal structural decorin and orthokeratology lenses to correct refractive
integrity using the Reichert Ocular Response Analyzer. Two errors. Finally, it is conceivable that decorin or similar
 NEW AND FUTURE TREATMENTS 185

TAB LE 18 - 4

C O RNEAL HYSTERESIS VALUES FO LLO WING DEC O RIN ADMINISTRATIO N

ANIMAL C O RNEAL HYSTERESIS VALUE (AVG . OF 4 MEASUREMENTS)

Ba se lin e Po st-d e sta b iliza tio n Po st-d e c o rin tre a tm e n t

PMC 3 4.2 2.75 3.9
PMG 4 3.35 1.75 3.0

molecules can be used to delay presbyopia by altering the 15. Kaufman HE, Werblin TP. Epikeratophakia for the treatment of
cornea or scleral architecture. keratoconus. Am J Ophthalmol. 1982;93:342-347.
16. Busin M, Zambianchi L, Arffa RC. Microkeratome-assisted
lamellar keratoplasty for the surgical treatment of keratoconus.

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 Index

Abba, lens manufacturer, 127 clinical features of keratoconus, 33–41

aberrometry, wavefront, in corneal ectasia, 89–95 epidemiology, 34–36
corneal wavefront aberrations, 90–92 family studies, 37
pellucid marginal degeneration, 92–93 keratoconus, vs. pellucid marginal degeneration, 39
wavefront characteristics, post-LASIK ectasia, 93 recurrence in graft, 37–39
whole eye wave aberrations, 89–90 unilateral keratoconus, 39
Acuity One LLC, lens manufacturer, 127 clinical features of keratoectasia, 43–48
advanced collagen cross-linking, 182–185 anatomy, and biomechanical considerations, 44–46
advanced keratoconus, 23–25 biomechanics, 44–46
anatomy, 3–10 clinical presentation, 44
Apex, lens design, 127 epidemiology, 43–48
Artemis VHF digital ultrasound, corneal evaluation, 77–86 optical consequences, 46
case examples, 83–84 patient demographics, 44
epithelial thickness profiles, 79–83 clinical interpretation, ocular response analyzer, 25
epithelial thickness profiles, 83 collagen cross-linking, 182–185
keratoconic eyes, 80–83 collagen fibers, decorin binding to, 183–185
normal eyes, 80 ComfortKone, lens design, 127
three-dimensional epithelial pachymetric topography, 80 conductive keratoplasty, 165–166
asymmetric corneal technology, 128 contact lenses, non-surgical treatment of keratoconus,
asymmetric keratoconus, 20–23 119–132
asymmetric segment implantation, 164 apical clearance, 120
central corneal swirling, 131
Bausch & Lomb, lens manufacturer, 127 decentration, 130
biomechanics, clinical, 13–28 dimple veiling, 131
Blanchard Contact Lenses Inc., lens manufacturer, 127 dry eye, 130
Boston Scleral, lens design, 127 fitting parameters, 120–122
Bowman’s layer, 5 initial base curve, 120–121
lens diameter, 121–122
channel creation techniques, comparison of, 162–164 lens fitting guide, 122
Ciba Vision Care, lens manufacturer, 127 lens material, 122

187
188 INDEX

optical zone, 121–122 design of lenses, 127

fitting protocol, 125–126 dimple veiling, 131
flat fitting, 119–120 dry eye, 130
gas-permeable speciality lenses, 126–130 Dyna Intra-Limbal, lens design, 127
asymmetric corneal technology, 128
flat steep option, 126–127 ectatic disease, ocular response analyzer, 13–28
Intacs fitting, 129–130 elective vision correction, criteria for, 146–148
quadrant-specific technology, 127–128 electron microscopy, decorin binding to collagen fibers,
hybrid lenses, 124 183–185
hypersensitivity, 131 emmetropic ametropic eyes, 99–100
lens adherence, 131 endothelium, 7
poor surface wettability, 131 epithelial thickness profiles, 79–83
problem solving, 130–131 epithelial thickness profiles, 83
scleral lenses, 124–125 keratoconic eyes, 80–83
soft lenses, 122–124 normal eyes, 80
three-point-touch, 120 three-dimensional epithelial pachymetric topography, 80
corneal biomechanical properties, clinical measurement epithelium, 4–5
of, 15–16 excimer laser lamellar keratoplasty, 177–182
corneal changes, posterior, 69–75 excimer laser photorefractive keratectomy, 145–151
corneal cross-linking, with riboflavin, ultraviolet irradia- elective vision correction, criteria for, 146–148
tion, 169–174 PARK, myopic astigmatism in keratoconus using, 148
case studies, 172 excimer laser treatment, topography-guided, 153–158
clinical outcomes, 170–171 combining TGCA and corneal collagen cross-linking,
cross-linking pharmacokinetics, 169 156–158
future applications, 171 iVIS Suite, 155–156
new components, 171 topography-guided custom ablation, 153–155
and future applications, 171 transepithelial surface ablation, 153
safety, 170
side effects, 171–172 femtosecond-assisted lamellar keratoplasty, 141
surgical technique, 170 femtosecond laser channel dissection, 162–164
corneal evaluation, Artemis VHF digital ultrasound, 77–86 flat steep option, 126–127
case examples, 83–84 future treatments, 177–185
epithelial thickness profiles, 79–83
epithelial thickness profiles, 83 gas-permeable speciality lenses, 126–130
keratoconic eyes, 80–83 asymmetric corneal technology, 128
normal eyes, 80 flat steep option, 126–127
three-dimensional epithelial pachymetric topography, Intacs fitting, 129–130
80 quadrant-specific technology, 127–128
corneal innervation, 8 gross anatomy, 3–4
corneal material properties, 13–15 Gulani-Nordan criteria for laser PRK, 146
corneal structure strengthening, novel methods, 182
corneal topography, 61–62 human recombinant decorin, 182–183
corneal wavefront aberrations, 90–92 stabilization of cornea with, 182–183
criteria for elective vision correction, 146–148 hybrid lenses, 124
crosslinking for advanced keratoconus, 165–166
iatrogenic ectasia, 65–67
DALK. See Deep anterior lamellar keratoplasty infrared photorefraction screening, 97–106
decorin, recombinant, 182–183 ametropic, keratoconic eyes, compared, 104–106
decorin binding to collagen fibers, 183–185 astigmatic appearance, 101–102
deep anterior lamellar keratoplasty, 138–140 cases, 102–103
Descemet’s membrane, 6–7 clinical observation, 99–106
 INDEX 189

emmetropic ametropic eyes, 99–100 keratoectasia, 43–48, 51–57

high myopia, 100 case examples, 53–55
LASIK, eyes after, 102 clinical features, 43–48
mild ametropic eyes, 99–100 anatomy, 44–46
severe cases, examples of, 104 biomechanics, 44–46
tear film observation, 100–101 clinical presentation, 44
“innocent” topography, natural ectasia development from, epidemiology, 43–48
19–20 optical consequences, 46
Intacs, 129–130, 161–167 patient demographics, 44
asymmetric segment implantation, 164 Intacs for treatment of, 161–167
case report, 165–166 legal issues, 55–56
channel creation, 162 medical issues, 55–56
combination therapy, 165–166 ocular response analyzer in, 16–17
conductive keratoplasty, 165–166 risk analysis, 53
crosslinking for advanced keratoconus, 165–166 risk factors, 52–53
femtosecond laser channel dissection, 162–164 topography, 61–67
implantation technique, 164
long-term outcome data, 165 lamellar keratoplasty, 135–142
manual channel maker, 162 laser lamellar keratoplasty, 177–182
postoperative care, 164 LASIK, eyes after, 102
irradiation, corneal cross-linking with, 169–174 legal issues, keratoectasia, 55–56
case studies, 172 lens designs, 127
clinical outcomes, 170–171 Lens Dynamics, lens manufacturer, 127
cross-linking pharmacokinetics, 169 lens fitting guide, 122
future applications, 171
new components, 171 manual channel maker, 162
safety, 170 manufacturers, 127
side effects, 171–172 Medlens Innovations, lens manufacturer, 127
surgical technique, 170 Metro Optics, lens manufacturer, 127
iVIS Suite, 155–156 microscopic anatomy, 4–8
Mid-South Premier Contact Lens, lens manufacturer, 127
Jupiter, lens design, 127 molecular biology, 3–10
Myopic astigmatism in keratoconus using PARK, 148
keratectomy, photorefractive, 145–151
elective vision correction, criteria for, 146–148 natural ectasia development from “innocent” topography,
PARK, myopic astigmatism in keratoconus using, 148 19–20
keratoconus, 33–41, 62, 69–70
clinical characteristics, 33–41 ocular response analyzer, 13–28
clinical presentation, 36–37 clinical interpretation, 25
epidemiology, 34–36 ocular response analyzer in keratoectasia, 16–17
recurrence in graft, 37–39
unilateral, 39 PARK, myopic astigmatism in keratoconus using, 148
vs. pellucid marginal degeneration, 39 pellucid marginal degeneration, 92–93
excimer laser photorefractive keratectomy, 145–151 vs. keratoconus, 39
Intacs for treatment of, 161–167 penetrating keratoplasty, 135–142
non-surgical treatment, contact lenses, 119–132 pharmacokinetics, cross-linking, 169
topography, 61–67 photorefraction screening, infrared, 97–106
visual performance, 109–114 ametropic, keratoconic eyes, compared, 104–106
keratoconus bi-aspheric, lens design, 127 astigmatic appearance, 101–102
keratoconus-like topographic patterns without ectasia, cases, 102–103
17–19 clinical observation, 99–106
190 INDEX

emmetropic ametropic eyes, 99–100 Softperm, lens design, 127

high myopia, 100 strengthening of corneal structure, novel methods, 182
LASIK, eyes after, 102 stroma, 5–6
severe cases, examples of, 104 SynergEyes Inc., lens manufacturer, 127
tear film observation, 100–101 Synergeyes KC, PS, lens design, 127
photorefractive keratectomy, 145–151
elective vision correction, criteria for, 146–148 tear film, 7–8
PARK, myopic astigmatism in keratoconus using, 148 TGCA. See Topography-guided custom ablation
physiology, 3–10 thickness profiles, epithelial, 79–83
poor surface wettability, 131 epithelial thickness profiles, 83
posterior corneal changes, 69–75 keratoconic eyes, 80–83
Precision Technology Services, lens manufacturer, 127 normal eyes, 80
three-dimensional epithelial pachymetric topography, 80
Quad Sym Technology, lens design, 127 three-dimensional epithelial pachymetric topography, 80
quadrant-specific technology, 127–128 three-point-touch, 120
topographic diagnosis, 61–67
radiation, corneal cross-linking with, 169–174 corneal topography, 61–62
case studies, 172 iatrogenic ectasia, 65–67
clinical outcomes, 170–171 indices, 62–64
cross-linking pharmacokinetics, 169 keratoconus, 62
future applications, 171 progression tracking, 64–65
new components, 171 refractive surgery patient screening, corneal topogra-
and future applications, 171 phy, 61–62
safety, 170 screening software, 62–64
side effects, 171–172 topographic evaluation, keratoectasia, 51
surgical technique, 170 topography-guided custom ablation, 153–155
recombinant decorin, 182–183 topography-guided excimer laser treatment, 153–158
refractive surgery patient screening, corneal topography, combining TGCA, corneal collagen cross-linking, 156–
61–62 158
riboflavin, corneal cross-linking, 169–174 iVIS Suite, 155–156
case studies, 172 topography-guided custom ablation, 153–155
clinical outcomes, 170–171 transepithelial surface ablation, 153
cross-linking pharmacokinetics, 169 transepithelial surface ablation, 153
future applications, 171 transmission electron microscopy, 183–185
new components, 171 decorin binding to collagen fibers, 183–185
and future applications, 171 Tru C-Scleral, lens design, 127
safety, 170 Tru-Form Optics, lens manufacturer, 127
side effects, 171–172
surgical technique, 170 Ultima Aspheric, lens design, 127
risk analysis, keratoectasia, 53 ultraviolet irradiation, corneal cross-linking with, 169–174
risk factors, keratoectasia, 52 case studies, 172
Rose K, Rose K2 Irregular Cornea, lens design, 127 clinical outcomes, 170–171
cross-linking pharmacokinetics, 169
S/P LASIX, posterior corneal power, 70 future applications, 171
scleral lenses, 124–125 new components, 171
screening software, 62–64 safety, 170
Semi-Scleral, lens design, 127 side effects, 171–172
shaped keratoplasties, 136–137 surgical technique, 170
So2 Clear, lens design, 127 visual performance assessment, 109–114
soft lenses, 122–124 contrast sensitivity, 111–112
 INDEX 191

glare testing, 112–113 wettability, 131

low-contrast visual acuity, 110–111 whole eye wave aberrations, 89–90
visual acuity, 109–110
X-Cel, lens manufacturer, 127
wavefront aberrometry in corneal ectasia, 89–95 X-offset, 163
corneal wavefront aberrations, 90–92
pellucid marginal degeneration, 92–93 Y-offset, 163
wavefront characteristics, post-LASIK ectasia, 93
whole eye wave aberrations, 89–90 Z radius, 163
Wait…There’s More!
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Corneal Topography in the Wavefront Era: Irregular Astigmatism: Diagnosis and

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Ming Wang MD, PhD Ming Wang MD, PhD
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Prevention, Diagnosis, and Treatment Understanding Ophthalmology, Second Edition
Ming Wang MD, PhD Janice K. Ledford, COMT
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