Clinical Pathways in Neuro Ophthalmology An Evidence

Based Approach 3rd Edition

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To our spouses, Hilary Beaver (Lee), Liz (Brazis), and Joseph Haynes
(Smith).

To our parents, Alberto C. Lee, MD, and Rosalind G. Lee, MD; Dr. and
Mrs. Peter T. Brazis; Mr. Thomas W. Smith and Charlene Smith, MD.

To our children, Rachael and Virginia Lee; Paul and Erica Brazis.
Contents
Foreword
Preface
Acknowledgments
Contributors

1 The Diagnosis of Optic Neuropathies

Ama Sadaka, Paul D. Chamberlain, Leanne M. Little, and Shauna
Berry

2 Optic Neuritis
Leanne M. Little

3 Optic Disc Edema with a Macular Star and Neuroretinitis

Stacy V. Smith

4 Nonarteritic Ischemic Optic Neuropathy

Murtaza M. Mandviwala, Shauna Berry, Weijie V. Lin, and Ama
Sadaka

5 Arteritic Anterior Ischemic Optic Neuropathy and Giant Cell

Arteritis
Alec L. Amram

6 Traumatic Optic Neuropathy

Stacy V. Smith

7 Papilledema
Murtaza M. Mandviwala, Alec L. Amram, and Mohammed Rigi

8 Transient Vision Loss

 Austin S. Nakatsuka, Alec L. Amram, and Mohammad Obadah
Nakawah

9 Visual Field Defects

Beena M. Shah

10 Diplopia
Murtaza M. Mandviwala and Alec L. Amram

11 Third Nerve Palsies

William J. Hertzing and Alec L. Amram

12 Fourth Nerve Palsies

William J. Hertzing, Alec L. Amram, and Andres S. Parra

13 Sixth Nerve Palsies

Stacy V. Smith, Andrew G. Lee, and Paul W. Brazis

14 Supranuclear Disorders of Gaze

Alison K. Yoder

15 Ocular Myasthenia Gravis

John D. Eatman and Stacy V. Smith

16 Thyroid Eye Disease: Graves Ophthalmopathy

Grecia Rico

17 Nystagmus and Other Ocular Oscillations

Elsa Rodarte

18 Ptosis
Angeline Mariani Derham

19 Lid Retraction and Lid Lag

Benjamin A. Dake

20 Anisocoria and Pupillary Abnormalities

Noreen Shaikh

Index
Foreword
Never in the history of medicine have physicians had so many ways to both
diagnose and treat disease, and never have physicians had so many
bureaucratic barriers to performing these activities. This paradox has
necessitated a return to the days when clinical judgment was at least as
important as diagnostic testing. The challenge to all of us who care for
patients is thus to understand the signs and symptoms that distinguish
between many different local and systemic disorders so that we can perform
the most logical, expeditious, safe, and economic assessment.
Andrew G. Lee is the Chair of the Blanton Eye Institute, Houston
Methodist Hospital. He is an ophthalmology-trained neuro-ophthalmologist
and holds academic appointments at Weill Cornell Medicine (New York);
the University of Texas Medical Branch (UTMB) at Galveston; Baylor
College of Medicine (Houston); the University of Texas MD Anderson
Cancer Center (UTMDACC) in Houston; Texas A & M College of
Medicine; The University of Buffalo (New York); and the University of
Iowa Hospitals and Clinics in Iowa City, Iowa.
Paul W. Brazis is a neurology-trained neuro-ophthalmologist and was the
head of the neuro-ophthalmology service at the Mayo Clinic in
Jacksonville, Florida. He is now Professor Emeritus at Mayo Clinic.
Stacy V. Smith is a neurology-trained neuro-ophthalmologist and
headache medicine specialist at Houston Methodist Neurological Institute,
Houston Methodist The Woodlands Hospital.
The authors have extensive training and experience in the field of neuro-
ophthalmology, and have contributed singly and together to the field of
neuro-ophthalmology with numerous articles, chapters, and textbooks. In
this book, the authors provide the reader with a triumvirate of information.
First, they describe the symptoms and signs of a variety of neuro-
ophthalmologic disorders, such as anterior and retrobulbar optic
neuropathies, ocular motor nerve pareses, and other disorders of ocular
motility and alignment, and anisocoria. Second, they provide algorithms for
differentiating, both in the office and using laboratory and neuroimaging
studies, between conditions that often have overlapping clinical
manifestations. Third, they provide a basic set of references about each
subject that the reader can use to expand his or her knowledge.
By providing basic, clinically relevant information regarding various
disorders, as well as their diagnoses and treatments, this book teaches the
reader how to approach a patient with a known or presumed neuro-
ophthalmologic problem in a logical, straightforward, and cost-effective
manner. As such, it is a welcome addition to the neuro-ophthalmologic
repertoire.

Neil R. Miller, MD
Baltimore, Maryland
Preface
The primary goal of the first edition of this book was to provide the reader
with an easy-to-follow, heavily referenced guide to the management of
common neuro-ophthalmologic conditions. In this edition, we have
specifically chosen to focus on recent references, and we emphasize the
best available clinical evidence. To this end, we include letters or case
reports if they add significant new information. We include pre-1990
references only if they are of historical significance. We have tried to be
inclusive, however, in the construction of our tables and charts, and provide
the references as needed. The secondary goal of this book is to discuss and
classify the available clinical evidence concerning the evaluation and
treatment of various neuro-ophthalmologic processes and grade the strength
of any recommendations that are made. Readers will have to judge for
themselves which is the best approach for the individual patient; the authors
emphasize that these guidelines are not meant to define any particular
standard of care for these conditions.
In this edition, we classify the clinical evidence into the following four
categories and, where appropriate, summarize the class of evidence for each
section.
1. Class I: Well-designed, randomized, power-controlled clinical trials
including meta-analyses of such trials.
2. Class II: Well-designed controlled studies without randomization
including meta-analyses of such studies.
3. Class III: Retrospective observational studies, cohort, or case–control
studies, or multiple time series with or without intervention.
4. Class IV: Expert opinion, case series, case reports.

We grade the strength of the recommendations from each section as

follows:
1. Level A: A principle for patient management reflecting a high degree of
clinical certainty (usually requires class I evidence that directly addresses
the clinical question).
2. Level B: A recommendation reflecting moderate clinical certainty based
on either class II evidence or strong consensus of class III evidence with
significant and consistent results.
3. Level C: An acceptable practice option with low clinical certainty based
on class III or class IV evidence.
4. Level U: Inconclusive or conflicting evidence, or opinion that is
insufficient to support an evidence-based recommendation.

Stacy V. Smith, MD
Andrew G. Lee, MD
Paul W. Brazis, MD (Professor Emeritus)
Acknowledgments
We would again like to thank our mentor, colleague, and friend Dr. Neil R.
Miller for his encouragement and example. Dr. Brazis would also like to
thank the following individuals for their guidance: Drs. James Corbett,
Jonathan Trobe, James Bolling, and Frank Rubino. He is appreciative of the
encouragement and support of his family, especially Elizabeth, Erica, Paul,
and Kelly Brazis.
Dr. Lee acknowledges the support and encouragement of the seven
outstanding chairmen of ophthalmology with whom he has had the honor to
serve over the years: Drs. Mort Goldberg, Dan B. Jones, Thomas Weingeist,
Keith Carter, Tim Stout, Bernard Godley, and Kevin Merkley. He thanks his
parents Drs. Alberto C. Lee and Rosalind G. Lee for instilling in a young
man the thirst for knowledge and intellectual curiosity. He is particularly
thankful to his loving, patient, and tolerant wife, Dr. Hilary A. Beaver, who
has been both a source of academic inspiration and a creative muse. Dr. Lee
also thanks his two children, Rachael Elizabeth Lee and Virginia Anne Lee,
for keeping his priorities straight and his mind and soul humble. He hopes
that one day they will join the tradition and long line of Lee family
physicians.
Dr. Smith especially thanks her mentors Drs. Deborah I. Friedman and
Andrew G. Lee for their support and guidance, as well as all the many
dedicated coauthors on this project. Dr. Smith also acknowledges the
unwavering support and encouragement of her friends and family,
especially her husband, Joseph, mother, Charlene, and father, Thomas.
We appreciate the assistance of our editors at Thieme Medical Publishers.
We thank the faculty and residents of the Departments of Ophthalmology,
Neurology, and Neurosurgery at the Houston Methodist Hospital, Baylor
College of Medicine, and UTMB as well as the faculty and staff in the
Departments of Neurology and Ophthalmology at the Mayo Clinic in
Jacksonville, Florida, for their academic support and stimulation.

The Editors
Contributors
Alec L. Amram, MD
Resident
Department of Ophthalmology
University of Texas Medical Branch
Galveston, Texas

Shauna Berry, DO
Pediatric Ophthalmology and Adult Strabismus Fellow
University of California, Los Angeles
Los Angeles, California

Paul W. Brazis, MD
Neuro-ophthalmologist
Professor Emeritus
Departments of Neurology and Ophthalmology
Mayo Clinic
Jacksonville, Florida

Paul D. Chamberlain
Medical Student
Baylor College of Medicine
Houston, Texas

Benjamin A. Dake, MD
Resident
Department of Ophthalmology
University of South Florida
Tampa, Florida

Angeline Mariani Derham, MD

Ophthalmology Resident
New York Medical College
Jamaica Hospital Medical Center
Queens, New York

John D. Eatman, MD
Assistant Professor
University of Missouri-Kansas City School of Medicine
Neurologist
Saint Luke's Neurology
Kansas City, Missouri

William J. Hertzing
Medical Student
University of Texas Medical Branch
Department of Ophthalmology and Visual Sciences
Galveston, Texas

Andrew G. Lee, MD
Chairman
Department of Ophthalmology
Blanton Eye Institute
Houston Methodist Hospital
Houston, Texas
Professor of Ophthalmology, Neurology, and Neurosurgery
Weill Cornell Medical College
New York, New York
Professor of Ophthalmology, UTMB and UT MD
Anderson Cancer Center and Texas A & M College of Medicine (Adjunct)
Houston, Texas
Adjunct Professor
Baylor College of Medicine and The Center for Space Medicine
Houston, Texas
Adjunct Professor
The University of Iowa Hospitals and Clinics
Iowa City, Iowa
Adjunct Professor
The University of Buffalo
Buffalo, New York

Weijie V. Lin
Medical Student
Baylor College of Medicine
Houston, Texas

Leanne M. Little
Medical Student
Baylor College of Medicine
Houston, Texas

Murtaza M. Mandviwala
Medical Student
University of Texas Medical Branch
Galveston, Texas

Austin S. Nakatsuka, MD
Resident
Department of Ophthalmology
University of Texas Medical Branch
Galveston, Texas

Mohammad Obadah Nakawah, MD

Neurologist
Department of Neurology
Houston Methodist Neurological Institute
Weill Cornell Medical College
Houston, Texas

Andres S. Parra, BA
Medical Student
Baylor College of Medicine
Houston, Texas

Grecia Rico, MD
Graduate Research Fellow
Department of Pathology and Genomic Medicine
Houston Methodist Hospital
Houston, Texas

Mohammed Rigi, MD, MS

Resident
Department of Pathology
University of Alabama at Birmingham
Birmingham, Alabama

Elsa Rodarte, MD
Resident
Department of Neurology
The University of Texas Health Science Center at Houston
Houston, Texas

Ama Sadaka, MD
Assistant Professor
Ophthalmologist
Lebanese AmericanUniversity Medical Center Rizk Hospital
Beirut, Lebanon

Beena M. Shah, BBA

Medical Student
Baylor College of Medicine
Houston, Texas

Noreen Shaikh, MD
Ophthalmology Resident
MedStar Georgetown University Hospital/Washington Hospital Center
Washington, DC

Stacy V. Smith, MD
Neuro-ophthalmologist
Assistant Professor
Department of Neurology
Houston Methodist Neurological Institute
Houston Methodist The Woodlands Hospital
The Woodlands, Texas

Alison K. Yoder
Medical Student
Baylor College of Medicine
Houston, Texas
1 The Diagnosis of Optic Neuropathies
Ama Sadaka, Paul D. Chamberlain, Leanne M. Little, and Shauna Berry

Abstract
Optic neuropathy refers to disease or damage to the optic nerve, typically
characterized by decreased visual acuity, decreased color vision, visual field
defect, relative afferent pupillary defect, optic disc edema, and/or optic disc
atrophy. Possible etiologies include hereditary, inflammatory, infiltrative,
ischemic, demyelinating (optic neuritis), toxic, and compressive optic
neuropathies. This chapter discusses the clinical pathway for evaluating and
diagnosing optic neuropathy, reviewing the literature in detail.
Keywords: optic neuropathy, hereditary optic neuropathy, radiation optic
neuropathy, compressive optic neuropathy, toxic/nutritional optic
neuropathy

1.1 Introduction
The diagnosis of an optic neuropathy is usually made on clinical grounds
alone. Several excellent references discuss in detail the anatomy of the optic
nerve as well as examination techniques.1,2,3 The clinical features of optic
neuropathies include decreased visual acuity, decreased color vision, visual
field defect, relative afferent pupillary defect (RAPD), optic disc edema,
and/or optic disc atrophy. Other more complex (and time-consuming)
testing for optic neuropathy, such as visual evoked potentials (VEPs),
flicker fusion, formal color vision testing, and contrast sensitivity, can be
performed but in general are not required to establish the clinical diagnosis
of optic neuropathy and are not discussed here.
Once the diagnosis of optic neuropathy has been made, it is important to
consider a wide differential diagnosis of possible etiologies, including
hereditary, inflammatory, infiltrative, ischemic, demyelinating (optic
neuritis [ON]), toxic, and compressive optic neuropathies. We refer the
reader to the specific chapter on each type of optic neuropathy for further
details.