c.
p
ST
Professor of Ophthalmology Harvard Medical School Director,
Immunology and Uveitis Service Massachusetts Eye and Ear Infirmary
Boston, Massachusetts
RT
VI
M.
Chief, Uveitis Division Member, Vitreoretinal Division King
Khaled Eye Hospital Riyadh, Saudi Arabia
SAUNA Harcourt Health Sciences CompanyPhiladelphia London New
York St. Louis Sydney Toronto
W.B. SAUNDERS COMPANYA Harcourt Health Sciences Compan)1
The Curtis Center Independence Square West Philadelphia,
Pennsylvania 19106
Library of Congress Cataloging-in-Publication Data
Diagnosis and treatment of uveitis / C. Stephen Foster, Albert
T. Vitale. p. em.
ISBN 0-7216-6338-9 1. Uveitis. I. Vitale, Albert T. II. Title.
[DNLM: 1. Uveitis-diagnosis. 2. Uveitis-therapy. WW 240 F754d 2001]
RE351.F67 2001 DNLM/DLC 617.7'2-de21 00-058356
Acquisitions Editor: Manuscript Editor:
Richard Lampert Carol DiBerardino Natalie Ware Lisa Lambert
Senior Production Manager: Illustration Specialist:
DIAGNOSIS AND TREATMENT OF UVEITIS Copyright 2002 by W.B.
Saunders Company.
ISBN 0-7216-6338-9
All rights reserved. No part of this publication may be
reproduced or transmitted in any form or by any means, electronic
or mechanical, including photocopy, recording, or any information
storage and retrieval system, without permission in writing from
the publisher. Printed in the United States of America. Last digit
is the print number:9
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2
I
MEHRAN A. AfSHARI, M.D., M.P..H.Assistant Professor of
Ophthalmology, Retina Service, Yale University School of Medicine,
New Haven, Connecticut Schistosomiasis (Bilharziasis)
PIK SHA CHAN, M.D.Active Consultant, Retina Service, St. Luke's
Medical Center, Institute of Ophthalmology, Quezon City; Asian Eye
Institute, Makati City, Philippines Systemic lupus Erythematosus;
Multiple Evanescent White Dot Syndrome
NASRIN AfSHARI, M.D.Assistant Professor of Ophthalmology, Cornea
Service, Duke University School of Medicine, Durham, North Carolina
Schistosomiasis (Bilharziasis)
ROXANNE CHAN, M.D.Clinical Fellow in Radiology, Tufts University
School of Medicine, Boston, Massachusetts Diagnostic Imaging
Studies for Inflammatory Diseases with Eye Manifestations; Ocular
Whipple's Disease
WILLIAM AYLIffE, foR.C.S., Ph.D.University of London; Croydon
Eye Unit, Mayday University Hospital, London, England Retinal
Vasculitis
LOUIS
J.
CHORICH III, M.D.
Assistant Professor of Ophthalmology, Ohio State University,
Columbus, Ohio Diagnosis of Uveitis; Bartonellosis
JOHN C. BAER, M.D.Omni Eye Specialists, Baltimore, Maryland
Borrelliosis
ISABELLE COCHEREAU, M.D.Professor, University of Angers; Chief
of Infectious Disease Department, Angers Hospital, Angers, France
Pneumocystosis; Human Immunodeficiency Virus-Associated Uveitis
STEfANOS BALTATZIS, M.D.Associate Professor of Ophthalmology,
Department of Ophthalmology, Athens University Medical School;
General Hospital of Athens, University Eye Clinic, Athens, Greece
Ophthalmia Nodosa
M. REZA DANA, M.D., M.P..H.Assistant Professor, Harvard Medical
School; Director, Cornea/External Disease and Ocular Immunology,
Brigham and Women's Hospital; Associate Scientist, Laboratory of
Immunology, Schepens Eye Research Institute, Boston, Massachusetts
leptospirosis
NEAL P..
BARNE~
M.D.
Associate Professor, Department of Ophthalmology and Visual
Sciences, University of Wisconsin Medical School, Madison,
Wisconsin Diffuse Unilateral Subacute Neuroretinitis
ANTHONY S. EKONGOphthalmology Department, Health Partners,
Minneapolis, Minnesota Scleroderma
RICHARD BAZIN, M.D., f.R.C.S.Clinical Professor of
Ophthalmology, Faculte de Medecine de l'Universite Laval; Member of
the Cornea and External Diseases Service, Laval University Hospital
Center, Quebec City, Quebec, Canada Rickettsial Diseases
TAMER EL-HELWFormerly, Department of Radiology, New England
Medical Center, Boston, Massachusetts Diagnostic Imaging Studies
for Inflammatory Systemic Diseases with Eye Manifestations
MARGARITA CALONGE, M.D.Full Professor of Ophthalmology,
University of Valladolid, Valladolid, Spain Medication-Induced
Uveitis
YOSUf EL-SHABRAWI, M.D.Department of Ophthalmology,
Karl-Franzens University, Graz, Austria loiasis
BARBARA l. CARTER, M.D.Professor of Radiology, Tufts University
School of Medicine; Chief of ENT Radiology, New England Medical
Center, Boston, Massachusetts Diagnostic Imaging Studies for
Inflammatory Systemic Diseases with Eye Manifestations
MELANIE
M.D.
Assistant Professor, Department of Urology, University of Essen,
Essen, Germany Herpesviruses
CONTRIBUTORS
MARTIN
Ph.D.
HOANG-XUAN, M.D.Professor, University of Paris; Chief of
Ophthalmology, Bichar Hospital and Fondation Rothschild, Paris,
France Pneumocystosis, Human Immunodeficiency Virus-Associated
Uveitis
Assistant Professor, Charles University; Chairman and Director,
Cornea and Immunology Service and Department of Ophthalmology,
Prague, Czech Republic Onchocerciasis
C. STEPHEN fOSTER,Professor of Ophthalmology, Harvard Medical
School; Director, Immunology and Uveitis Service, Massachusetts Eye
and Ear Infirmary, Boston, Massachusetts Introduction; The Uvea:
Anatomy, Histology, and Embryology; Definition, Classification,
Etiology, and Epidemiology; General Principles and Philosophy;
Basic Immunology; Diagnosis of Uveitis; Diagnostic Imaging Studies
for Inflammatory Systemic Diseases with Eye Manifestations;
Treatment of Uveitis-Overview; Corticosteroids, Mydriatic and
Cycloplegic Agents; Nonsteroidal Anti-inflammatory Drugs;
Immunosuppressive Chemotherapy; Diagnostic Surgery; Therapeutic
Surgery: Cornea, Iris, Cataract, Glaucoma, Vitreous, Retinal;
Syphilis; Tuberculosis; Ocular Whipple's Disease; Measles; Rubella;
Sporotrichosis; Ocular Toxocariasis; Masquerade Syndromes:
Malignancies; Masquerade Syndromes: Endophthalmitis; Nonmalignant,
Noninfectious Masquerade Syndromes; Scleroderma; Giant Cell
Arteritis; AdamantiadesBeh~et Disease; Antiphospholipid Syndrome;
Sarcoidosis; Tubulointerstitial Nephritis and Uveitis Syndrome;
lens-Induced Uveitis
fREDERICK A. JAKOBIEC, M.D., D.Sc.(Med.)Henry Willard Williams
Professor of Ophthalmology, Professor of Pathology, and Chairman of
Ophthalmology, Harvard Medical School; Chief of Ophthalmology,
Massachusetts Eye and Ear Infirmary, Boston, Massachusetts
foreword
JAMES KAlPAXIS, M.D.Private Practice, Austin, Texas Multifocal
Choroiditis and Panuveitis
ADAM H. KAUfMAN, M.D., F.A.C.S.Director, Uveitis Service;
Director, Corneal and Refractive Surgery Service; Associate
Professor of Clinical Ophthalmology, University of Cincinnati
College of Medicine; Cornea and Uveitis Specialist, Cincinnati Eye
Institute, Cincinnati, Ohio Cysticercosis
ERIK lETKO, M.D.Harvard Medical School; Fellow, Ocular
Immunology and Uveitis Service, Massachusetts Eye and Ear
Infirmary, Boston, Massachusetts Measles; Rubella
NICOLETTE GIONEv. Krankenhaus Muelheim a. d. Ruhr, Augenklinik,
Muelheim a. d. Ruhr, Germany The Uvea: Anatomy, Histology, and
Embryology; Tubulointerstitial Nephritis and Uveitis Syndrome
CHARAlAMPOS UVIR-RAllATOS, M.D.Clinical Vitreoretinal Fellow,
Tulane University, New Orleans, Louisiana fuchs' Heterochromic
Iridocyclitis
STEPHANIE l. HARPERAssistant Professor of Ophthalmology,
Director of Residency Program, Howard University, Washington, D.C.
Diagnosis of Uveitis
NIKOS N. MARKOMICHElAKIS, M.D.Attending Ophthalmologist, Athens
Medical School; Head of Ocular Immunology and Inflammation,
Department of Ophthalmology, General Hospital of Athens, Athens,
Greece Multiple Sclerosis
KATERINA HAVRUKOVA-DUTT, M.D.SCRA, Parexel, Prague, Czech
Republic Cryptococcosis
JESUS MERAYO-llOVES, M.D.,
M.B.A.
ARND HEIUGENHAUS, Priv. Doz., M.D.Department of Ophthalmology,
University of Essen School of Medicine, Essen; Head, Department of
Ophthalmology, Inflammatory Eye Diseases, St. Franziskus Hospital,
Muenster, Germany Herpesviruses
Principal Investigator, Chief of Refractive Surgery Unit,
Instituto de Oftalmobiologia Aplicada (IOBA), Universidad de
Valladolid, Valladolid; CEO and Consultant, Ocular Immunology and
Refractive Surgery, Centro de Especialidades Oftalmologicas, Madrid
free-living Amebas and Amebiasis
EUSABETH M. MESSMER, M.D.Attending, Department of Ophthalmology,
LudwigMaximilians University Hospital, Munich, Germany Ocular
leprosy; Candidiasis
HORST HELBIG, Priv. Doz., M.D.Head, Retina Service,
Kantonsspital St. Gallen, St. Gallen, Switzerland Herpesviruses
SHAWKAT SHAfiK MICHEL, F.R.C.S.(Ed.), D.O., M.B.Ch.BPrivate
Practice, Alberta, Canada Definition, Classification, Etiology, and
Epidemiology; lens-Induced Uveitis
RAMZI K.
HEMAD~
M.D.
Associate Professor, Program Director and Co-director Cornea,
Uveitis, and Refractive Surgery Services, Department of
Ophthalmology, University of Maryland School of Medicine; Chief of
Ophthalmology, Veterans Administration Hospital, Baltimore,
Maryland Rift Valley fever
EUSABETTA MISEROCCHI, M.D.University of Milan-Italy, Ospedale
San Raffaele, Milano, Italy Antiphospholipid Syndrome
CONTRIBUTORS
RON NEUMANNFormerly Fellow, Massachusetts Eye and Ear Infirmary,
Boston, Massachusetts Giardia Lamblia
MICHAEL B. RAIZMAN, M.D.Associate Professor of Ophthalmology,
Tufts University School of Medicine; Ophthalmologist, Ophthalmic
Consultants of Boston; New England Medical Center, Boston,
Massachusetts Punctate Inner Choroidopathy
QUAN DONG NGUYEN, M.D., M.Sc.Assistant Professor of
Ophthalmology, Vitreoretina Service, Wilmer Ophthalmological
Institute, Johns Hopkins University School of Medicine, Baltimore,
Maryland Traumatic Uveitis
TATIANA ROMERO RANGEL, M.D.Formerly Fellow Massachusetts Eye and
Ear Infirmary Boston, Massachusetts Ocular Toxocariasis
E. MITCHEL OPREMCAK, M.D.Clinical Associate Professor,
Department of Ophthalmology, Ohio State University; Physician and
Surgeon, The Retina Group, Columbus, Ohio Diagnostic Surgery;
Therapeutic Surgery: Cornea, Iris, Cataract, Glaucoma, Vitreous,
Retinal; Ophthalmomyiasis
LAWRENCE A. RAYMOND, M.D.Associate Professor of Clinical
Ophthalmology, University of Cincinnati College of Medicine;
Director, Retina-Vitreous Service, University of Cincinnati Medical
Center; RetinalVitreous Surgeon, Cincinnati Eye Institute,
Cincinnati, Ohio Cysticercosis
FERNANDO OREFICE, M.D., Ph.D.Professor of Ophthalmology,
Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais,
Brazil Toxoplasmosis
ALEJANDRO RODRIGUEZ-GARCIA, M.D.Associate Professor, Director,
Immunology and Uveitis Service, Department of Ophthalmology,
Hospital San Jose-TEe de Monterrey (ITESM), Monterrey, Nuevo Leon,
Mexico Serpiginous Choroiditis
TOMAS PADILLA, Jr, M.D.Clinical Associate Professor, Department
of Ophthalmology, University of the Philippines-Manila, Manila;
Associate Active Staff Member, Institute of Ophthalmology, St.
Luke's Medical Center, Quezon City; Visiting Staff, Department of
Ophthalmology, Makati Medical Center, Makati City, Philippines
Trypanosomiasis
BLANCA ROJAS, M.D., Ph.D.Associate Professor of Ophthalmology,
Facultad de Medicina, Universidad Complutense; Ophthalmologist,
Instituto de Investigaciones Oftalmologicas Ramon CastToviejo,
Madrid, Spain Subretinal fibrosis and Uveitis Syndrome
CARL H. PARK, M.D.Resident in Ophthalmology, Tufts University
School of Medicine; Resident in Ophthalmology, New England Eye
Center, New England Medical Center, Boston, Massachusetts Punctate
Inner Choroidopathy
MANOLETTE RANGEL ROQUE, M.D.Formerly, Department of
Ophthalmology, Massachusetts Eye and Ear Infirmary, Boston,
Massachusetts Sporotrichosis
MAITE SAINZ DE LA MAZA, M.D., Ph.D. BENALEXANDER A.
PEDROFormerly Fellow, Massachusetts Eye and Ear Infirmary, Boston,
Massachusetts Acute Retinal Pigment EpitheIHtis Professor, Central
University of Barcelona School of Medicine; Clinical Associate
Professor of Ophthalmology, Hospital Clinico, Barcelona, Spain
Seronegative Spondyloarthropathies
MIGUEL PEDROZA-SERES, M.D., Ph.D.Professor, Universidad Nacional
Autonoma De Mexico; Staff, Department of Ocular Immunology and
Uveitis Service, Instituto de Oftalmologia, Conde de Valenciana,
Mexico City, Mexico Acute Posterior Multifocal Placoid Pigment
Epitheliopathy
C. MICHAEL SAMSON, M.D.Assistant Clinical Instructor, New York
Medical College, Valhalla, New York; Assistant Clinical InstructOl~
The New York Eye and Ear Infirmary, New York, New York Syphilis;
Tuberculosis; Masquerade Syndromes: Endophthalmitis
VIRENDER S. SANGWAN, M.S.(Ophthalmol.) ANDREA PEREIRA DA MATA,
M.D.Doctoral Candidate, Universidade Federal de Minas Gerais, Belo
Horizonte, Minas Gerais, Brazil; Clinical Research Ophthalmologist,
Cincinnati Eye Institute, Cincinnati, Ohio Toxoplasmosis Director,
Uveitis and Ocular Immunology Service, L.v. Prasad Eye Institute,
L.v. Prasad Marg, Banjara Hills, Hyderabad, India Ascariasis
GURINDER SINGH, M.D., M.H.A. VAKUR PINARFormerly Fellow,
Massachusetts Eye and Ear Infirmary, Boston, Massachusetts
Tubulointerstitial Nephritis and Uveitis Syndrome Associ.ate
Clinical Professor, Department of Ophthalmology, University of
Kansas Medical Center; Chief of Ophthalmology, Providence Medical
Center, Kansas City, Kansas Presumed Ocular Histoplasmosis
Syndrome
WILLIAM M.C.H.
J.
POWER, F.R.C.S., F.R.C.Ophth.,
AARON l.
M.D.
Consultant Ophthalmologist, Royal Victoria Eye and Ear Hospital,
Dublin, Ireland Sympathetic Ophthalmia
Cornea Fellow, Tulane University School of Medicine, New
Orleans, Louisiana Rift Valley fever
MASOUD
M.D.
Clinical Associate Professor of Ophthalmology and Vitreoretinal
Surgery, Shaheed Beheshti University of Medical Sciences School of
Medicine; Director, The Immunology and Uveitis Clinic, and
Associate Clinical Director of Vitreoretinal Service, Ophthalmology
Department and Eye Research Center, Labbafinejad Medical Center,
Tehran, Iran Polyarteritis Nodosa
Systemic Lupus Erythematosus; Multiple Evanescent White Dot
Syndrome
ALBERT T. VITALE, M.D.Chief, Uveitis Division, Member,
Vitreoretinal Division, King Khaled Eye Specialist Hospital,
Riyadh, Saudi Arabia Treatment of Uveitis-Overview;
Corticosteroids; Mydriatic and Cycloplegic Agents; Nonsteroidal
AntiInflammatory Drugs; Immunosuppressive Chemotherapy;
Brucellosis; Free-Living Amebas and Amebiasis; Birdshot
Retinochoroidopathy; Multifocal Choroiditis and Panuveitis;
Intermediate Uveitis
SARKIS H. SOUKIASIAN, M.D.Associate Clinical Professor, Tufts
University School of Medicine, Boston; Director: Cornea/External
Diseases Service, Ocular Infla:mmation and Uveitis Service, Lahey
Clinic Medical Center, Eye Institute, Burlington, Massachusetts
Wegener's Granulomatosis
CINDY M. VREDEVElDClinical Research Coordinator, Ocular
Immunology and Uveitis Service, Massachusetts Eye and Ear
Infirmary, Harvard Medical School, Boston, Massachusetts
Free-Living Amebas and Amebiasis
PANAGIOTA STAVROU, foR.C.S.Consultant Ophthalmic Surgeon,
Birmingham and Midland Eye Centre, City Hospital NHS Trust,
Birmingham, United Kingdom Sarcoidosis
NADIA KHALIDA WAHEED, M.D.Resident in Ophthalmology,
Massachusetts Eye and Ear Infirmary, Harvard Medical School,
Boston, Massachusetts Masquerade Syndromes: Malignancies
J. WAYNE
STREllEIN, M.D.
RICHARD PAUL
M.D.
Charles L Schepens Professor of Ophthalmology, Harvard Medical
School; President, Schepens Eye Research Institute, Boston,
Massachusetts Basic Immunology
Associate Clinical Attending, Department of Ophthalmology,
University of Colorado, Denver, Colorado Eye Disease and Systemic
Correlates in Relapsing Polychondritis
RICHARD R. TAMESIS, M.D.Assistant Professor, Department of
Op~Ehalmology, University of Nebraska Medical Center, Omaha,
Nebraska Coccidioidomycosis
HELEN WU, M.D.Assistant Professor of Ophthalmology, Tufts
University School of Medicine; Director, Refractive Surgery
Service; Ophthalmologist, Cornea and Anterior Segment Service, New
England Eye Center, Boston, Massachusetts Acute Zonal Occult Outer
Retinopathy
KHAlED A. TAWANSYAssistant Professor of Ophthalmology,
Retina/Vitreous Service, Vanderbilt University School of Medicine,
Nashville, Tennessee Diagnostic Studies for Inflammatory Systemic
Diseases with Eye Manifestations
lIJING YAO, M.D.Clinical Fellow, Department of Ophthalmology,
Children's National Medical Center, Washington, D.C. Nonmalignant,
Noninfectious Masquerade Syndromes
NATTAPORN TESAVIBUl, M.D.Instructor in Ophthalmology,
Pramongkutklao Medical School; Chief of Ocular Immunology Service,
Department of Ophthalmology, Pramongkutklao Hospital, Bangkok,
Thailand Vogt-Koyanagi-Harada Syndrome
JEAN YANG, M.D.State University of New York-Health Science
Center at Brooklyn, Brooklyn, New York Giant Cell Arteritis
PANAYOTIS ZAFIRAKIS, M.D.General Hospital of Athens, Athens,
Greece Adamantiades-Beh~etDisease
HARVEY SlY UY, M.D.Clinical Associate Professor, University of
the Philippines College of Medicine, Manila; Active Consultant,
Retina and Uveitis Services, St. Luke's Medical Center Institute of
Ophthalmology, Quezon City, and Asian Eye Institute, Makati City,
Philippines
MANFRED ZIERHUT, M.D.Professor of Ophthalmology, University Eye
Clinic, Department of Ophthalmology, University of Tiibingen,
Tiibingen, Germany Intermediate Uveitis
The uvea is the highly pigmented, vascularized middle tissue or
tunic of the eye, sandwiched on the inside by the neuroretina and
on the outside by the collagenous sclera. If the sclera is
topographically an extension of the dura of the optic nerve, then
the uvea is an extension of the pia-arachnoid, whereas the axons of
the optic nerve ,are extensions from the innermost gangion cells of
the retina. The uvea comprises, posteriorly, the choroid; more
anteriorly, the smooth muscle of the ciliary body; and up front,
the stroma of the iris. The choroid can leak on inflammatory or
immunologic provocation to create an effusion; inflammations
situated primarily in the sclera and less often the retina may also
cause secondary choroidal inflammations and effusions. It is
interesting to note that large cell lymphoma of the retina and
brain elicits an intense non-neoplastic chronic nsmgranulomatous
inflammation of the choroid and other parts of the uvea. On the
other hand, in systemic nodal lymphoma, the neoplastic lymphocytes
settle in the choroid and hardly ever in the retina, and do not
typically incite a secondary reactive inflammatory response. In
addition to its abundant blood vessels, thechoroid possesses
scattered melanocytes and fibroblasts, the latter basically unable
to proliferate as scar tissue in the wake of inflammation or
infection. (The sclera also has limited powers of healing.) Most
true scar production featuring collagen within the eye is the
result of fibrous metaplasia of the retinal pigment epithelium
(itself, curiously, a neuroectodermal derivative) , which is on the
retinal side of Bruch's membrane. The lobular arrangement of the
fenestrated choriocapillaris, which nourishes the outer retina and
is situated right next to Bruch's membrane on the choroidal side,
can be the focus of inflammations and infections, sometimes leading
to proliferations of the pigment epithelium such as Dalen-Fuchs
nodules in sympathetic ophthalmia. There are no lymphatics in the
choroid, and none in either the retina or the sclera; thus,
immunologic events in the eye may deviate from those elsewhere in
the body ("immune privilege"). The uveal tissues of the choroid,
ciliary body and iris are all derivatives of the neural crest,
owing to the fact that there are no paired paraxial mesodermal
somites in the head and neck region. It is against the foregoing
unusual anatomic and reparative features of the choroid and other
parts of the uvea that one must analyze the idiopathic inflam,
mations and infectious diseases that cause uveitis. This textbook,
edited by Drs. C. Stephen Foster and Albert
Vitale, is the most comprehensive, scholarly and up-todate
effort at encompassing the diagnosis, etiopathogenesis, and therapy
for this often arcane spectrum of diseases. There is no doubt that
this textbook, containing 79 chapters encompassing 867 pages, will
become the dominant reference and touchstone for those with a
sophisticated and deeply committed interest in uveitis. (Dr.
Foster's earlier textbook on the Sclera [Springer-Verlag, 1994J has
already become a classic.) Having read through many chapters of
this textbook in galleys, I can testify to the richness, accuracy,
and pure pleasure attendant on reading a treatise that brings the
greatest degree of scientific precision to dissipate the miasma
that too often envelops the subspecialty of uveitis. This textbook
would have been unthinkable and undoable without its impresario Dr.
C. Stephen Foster harnessing the energy and knowledge of many of
his past and present trainees, including his coeditor Dr. Vitale. I
have long been an admirer of Dr. Foster's intellect and
accomplishments, and my other colleagues locally, regionally,
nationally, and internationally often regard his as the court of
last appeal for totally enigmatic and "hopeless" cases. I can think
of no one else who combines his intellectual capacity, knowledge,
experience, surgical skills, and powers of communication in dealing
with all facets of uveitis; he is probably in the company of no
more than six individuals internationally who can manage these
difficult problems. Through his training in ophthalmology, internal
medicine, and immunology, and his highly systematic approach to the
patient, he has mastered the cabalistic field of uveitis.
Consequently, he has been able to restore vision to innumerable
patients who otherwise would have lost their sight. Dr. Foster's
inquisitive mind propels him to produce continually new laboratory
and clinical research at the highest levels, with enormous patient
relevancy and applicability. This textbook is a 'treasure, and will
further enlighten the ophthalmic community about many recondite
infectious and autoimmune diseases. Moreover, it also demonstrates
the unsurpassed skills of one of the world's foremost
ophthalmologists, Dr. C. Stephen Foster. FREDERICK A. ]AKOBIEC,
M.D., D.Sc. (Med.)Henry Willard Williams Professor of
Ophthalmology, Professor of Pathology, and Chairman of
Ophthalmology, Harvard Medical School; Chief of Ophthalmology,
Massachusetts Eye and Ear Infirmary
When the invitation came from W.B. Saunders Company, nearly a
decade ago, to write this textbook, it contained three primary
charges: (1) that the textbook should be comprehensive, even
"encyclopedic"; (2) that it should emphasize more modern,
aggressive approaches to treating uveitis that have evolved over
the past 20 years; (3) that it should be a single-authored text.
And although this invitation was incredibly tempting, I was
unprepared and unwilling to take on the task single-handedly.
Eventually, agreement was reached that one of my former fellows,
Dr. Albert Vitale, would coedit a multiauthored textbook with me,
and that the opportunity would be exploited to reconnect with
former fellows and colleagues who share our therapeutic
:ep.ilosophy: an attempt at total control of all inflammation and
freedom from all relapses, while at the same time eliminating the
need for chronic use of corticosteroids. The challenge posed by the
charge from the publisher has been enormous. Other books on the
subject of uveitis have met this challenge by increasing their
focus on particular matters, avoiding the problems posed by being
encyclopedic. In particular, textbooks by Opremcak,1 by Smith and
Nozik,2 by Kraus-MacKiw and O'Connor,3 by Nussenblatt, Palestine,
and Whitcup,4 and by BenEzra5 are all excellent textbooks
addressing the issue of diagnosis and therapy of uveitis. We have
met the challenge posed by the publisher through the participation
of 74 contributors, all of whom have had a relationship with the
Massachusetts Eye and Ear Infirmary Ocular Immunology and Uveitis
Service, and all of whom share in our basic philosophy of a
complete intolerance to chronic, even low-grade intraocular
inflammation, and at the same time a philosophy of steroid-sparing
anti-inflammatory therapy. The overriding philosophical principles
that underpin the writings within this textbook are as follows: (l)
Diagnosis matters; we advocate a comprehensive approach to
diagnosing the underlying cause of a patient's uveitis. (2)
Intolerance to chronic, even great low-grade inflammation; history
abundantly teaches that, eventually, such chronic inflammation
produces permanent damage to structures within the eye that are
critical to good vision. (3) Intolerance to the chronic use of
corticosteroids in an effort to control inflammation; history shows
and all physicians agree that such chronic use of corticosteroids
inevitably pro-
duces damage itself. (4) A stepladder algorithmic approach to
achieve the goal: no inflammation on no steroids. (5) Collaboration
with a rheumatologist or other individual who is, by virtue of
training and experiel1Ce, truly expert in the use of
immunomodulatory medications, so that no significant drug-induced
side effects occur in the exploitation of the stepladder
algorithmic approach to achieving the goal of no inflammation on no
steroids. The experience of writing this textbook has been
indescribable. The knowledge gained has been worth the effort
itself. The reconnection with former fellows and colleagues has
doubled the pleasure. Working with Dr. Albert Vitale has made it
all infinitely easier, and indeed has made it possible. The effort
has also refocused and sharpened my attention to many aspects in
the care of our patients. The Immunology and Uveitis Service of the
Massachusetts Eye and Ear Infirmary was established in 1977. The
first Research Fellow was accepted into the Laboratory in 1980. The
first Clinical Fellow arrived in 1984. During this same year, a
generous donation from Ms. Susan Rilles, a patient of the Service,
provided for the construction of a new, state-of-the-art immunology
laboratory: the Rilles Immunology Laboratory. A second gift from
Mr. Richard Rhodes, another of the Service's patients, enabled us
to equip an additional laboratory, the Rhodes Molecular Immunology
Laboratory, in 1990. These laboratories are described as applied
research laboratories-that is, we have attempted to bring to the
clinic as soon as practicable the discoveries and lessons learned
from the laboratory. Our hope in producing this textbook is that a
new generation of ophthalmologists will not only learn the
lessons....of the past with respect to diagnosis and treatment of
uveitis in the usual way, with corticosteroids, but will also learn
that the prevalence of blindness from uveitis, unchanged since the
improvements occurring after the introduction of cortiocsteroids,
can be further reduced by the adoption of the therapeutic
principles espoused herein.C.STEPHEN FOSTER,
M.D.
References1. Opremcak EM: Uveitis: A Clinical Manual for Ocular
Inflammation. New York, Springer-Verlag, 1995.
PREfACE2. Smith RE, Nozik Uveitis: A Clinical Approach to
Diagnosis and Management. Baltimore, Williams & Wilkins, 1989.
3. Kraus-MacKiw E, O'Connor GR: Uveitis: Pathophysiology and
Therapy. New York, Thieme Verlag, 1986. 4. Nussenblatt RB, Whitcup
SM, Palestine AG: Uveitis: Fundamentals and Clinical Practice. St.
Louis, Mosby-Year Book, 1996. 5. BenEzra D: Ocular Inflammation:
Basic and Clinical Concepts. London, Blackwell Science, 1999.
It has been an honor and a privilege to participate in the
creation of this text. This work represents much more than the
concerted efforts and efficient teamwork of a group of individuals
dedicated to a multiauthored book; it is the product of an extended
family bound by similar philosophical values in their care for
patients with ocular inflammatory disease. Indeed, the essence of
this philosophy, the pleasure of reconnecting and collaborating
with the current and former fellows of the Ocular Immunology and
Uveitis Service of the Massachusetts Eye and Ear Infirmary, and
the
refocusing and crystallization of the state of the art with
respect to many aspects of patient care as a result of this effort
have all been articulated in Dr. Foster's preface. What is not
mentioned is the personal and professional respect and gratitude
that I, myself, and the members of this extended family share for
our association with Dr. Foster. The ultimate and most important
beneficiaries, of course, are our patients who suffer from
uveitis.ALBERT
T. VITALE, M.D.
We wish to thank here the thousands of patients with uveitis who
have entrusted their care to us. It is through them that the
inspiration for this textbook arises, and it is for them primarily
to whom this textbook is dedicated. We also acknowledge and thank
the support staff at the Massachusetts Eye and Ear Infirmary, its
clinics and its operating rooms, for their loyalty and support in
our care of patients. In particular, Ms. Cindy Vredeveld and Ms.
Audrey Melanson are acknowledged and thanked for their assistance,
Cindy for her unstinting dedication to editorial assistance and
organizational efforts in this multi-authored text, and Audrey for
her help in assembling many of the photographs employed in the
text. We acknowledge the help of and are grateful to the many
fellows who participate on the Ocular Immunology and Uveitis
Service; without their help the day's work could not be done. We
also acknowledge the help of Dr. Tongzhen Zhao, Chief Technician in
the Hilles Immunology Laboratory, whose help in processing tissue
and fluid specimens for analysis is invaluable. Finally, we would
like to extend our thanks and acknowledgment to all the referring
physicians, not only in New England but across th~ United States
and throughout Europe, who have consistently referred patients to
this Service.C. STEPHEN FOSTER, M.D.
I would like to thank the medical staff secretaries of the King
Khaled Eye Specialist Hospital, especially Mrs. Yvonne Brine, for
their tireless dedication and support in preparing the manuscript
for this work.ALBERT
T.
VITALE,
M.D.
Color Plates
II. NONSTEROIDAL ANTI-INFLAMMATORY DRUGS Albert T. Vitale and C.
Stephen Foster 12. IMMUNOSUPPRESSIVE CHEMOTHERAPY C. Stephen Foster
and Albert T. Vitale
167
BASIC PRINCIPLESI. INTRODUCTION C. Stephen Foster 2. THE UVEA:
ANATOM'Y, HISTOLOG'Y, AND EMBRYOLOGY C. Stephen Foster and
Nicolette Gion 3. DEFINITION, CLASSIFICATION, ETIOLOGY, AND
EPIDEMIOLOGY Shawkat Shafik Michel and C. Stephen Foster
177
113. DIAGNOSTIC SURGERY E. Mitchel Opremcak and C. Stephen
Foster 3 14. THERAPEUTIC S.URGERY: CORNEA, CATARACT, GLAUCOMA,
VITREOUS, RETINAL C. Stephen Foster and E. Mitchel Opremcak
215
222
17
4. GENERAL PRINCIPLES AND
PHILOSOPHy.................................... 27 C. stephen Foster
5. BASIC IMMUNOLOGY C. Stephen Foster and j. Wayne Streilein
THE UVEITIS SYNDROMESInfectious15. SyPHILiS C. Michael Samson
and C. Stephen Foster 16. BORREUOSIS John C. Baer . 237
34
245
PRINCIPLES OF THERAPY
AND
17. BARTONELLA Louis j. Chorich m 18. TUBERCULOSIS C. Michael
Samson and C. Stephen Foster 19. LEPTOSPIROSIS M. Reza Dana 20.
BRUCELLOSIS Albert T. Vitale 21. OCULAR WHIPPLE'S DISEASE Roxanne
Chan and C. Stephen Foster
260
6. DIAGNOSIS OF UVEITiS Stephanie L. Harper, Louis j. Chorich
III, and C. Stephen Foster
!.......
. 264
79
273
7. DIAGNOSTIC IMAGING STUDIES FOR INFLAMMATORY SYSTEMIC DISEASES
WITH EYE MANIFESTATIONS Roxanne Chan, Khaled A. Tawal1SY, Tamer
El-Helw, C. Stephen Foster, and Barbara L. Carter
278
104
287
10. MYDRIATIC AND CYCLOPLEGIC AGENTS . Albert T. Vifctle and
C.Stephen Foster
....... 159
24. HERPESVIRUSES 315 Arnd Heiligenhaus, Horst Helbig, and
Melanie Fiedler
25. RIFT VALLEY FEVER Aaron L. Sobol and Ramzi K Hemady 26.
MEASLES Erik Letko and C. Stephen Foster 27. RUBELLA Erik ,Letko
and C. Stephen Foster 28. PRESUMED OCULAR HISTOPLASMOSIS SYNDROME
Gurinder Singh 29. CAND'IDIASIS Elisabeth M. Messmer
333
44. SCHISTOSOMIASIS (BILHARZIASIS) Mehran A. Afshari and Nasrin
Afshari 45.
480
336485
34346. OPHTHALMIA NODOSA Stefanos Baltatzis
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FIGURE 3-1. Relative frequency of the most common causes of
anterior uveitis. (Data from Rodriguez A, Calonge M, Foster CS, et
al: Referral patterns of uveitis in a tertiary eye care center.
Arch Ophthalmol 1996;114:593-596.)
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CHAPTER. J: DEFINITION, CLASSIFICATION,80 70 60 50 40 30 20 10
0Idiopathic Sarcoidosis Multiple sclerosis Lyme disease
AND EPIIDE:MI,DLOG
.. The most common causes of panuveitis are idiopathic, 22.2%;
sarcoidosis, 14.1 %; multifocal choroiditis and panuveitis, 12.1%;
ABD, 11.6%; systemic lupus matosus, 9.1 %; syphilis, 5.5%;
Vogt-Koyanagi-Harada syndrome, 5.5%; HLA-B27 associated, 4.5%;
sympathetic ophthalmia, 4.0%; tuberculosis, 2.0%; fungal retinitis,
2.0%. Other causes of panuveitis include bacterial panophthalmitis,
intraocular IYJ.TIphoma, relapsing polychondritis, polyartertitis
nodosa, leprosy, dermatomyositis and progressive systemic sclerosis
(Fig. 3-4). The above-mentioned percentages and figures were
obtained from a study of 1237 uveitis patients referred to the
Uveitis and Immunology Service of the MEEI,11 Harvard Medical
School, from 1982 to 1992. The study was published in 1996. These
figures were found to be similar to the results of other studies of
tertiary referral centers from different parts of the world,9, 11,
19, 25 especially those of developed countries. Most uveitis cases
are first seen and treated by the general (comprehensive)
ophthalmologists, who mayor may not refer the patients to a uveitis
specialist. In a. study26 comparing the epidemiologic differences
between community-based patients (seen by comprehensive
ophthalmologists) and university referral patients (seen by a
uveitis sub-specialist) in the University of California at Los
An.geles (UCLA) community (Table 3-8), the results showed that
anterior uveitis was much more common in the community-based
population, whereas the other anatomic types of uveitis were more
common in the university referral patients, highlighting the
referral bias of the more difficult, vision-threatening cases to
the specialist (Fig. 3-5). There were no significant differences in
the mean age at presentation or sex and race distribution. 26 The
influence of genetic factors on the etiopathogenesis of uveitis is
clearly shown by the close relationship of some specific uveitic
entities and the MHC. Some
FIGURE 3-2. Relative frequency (%) of the most common causes of
intermediate uveitis, (Data from Rodriguez A, Calonge M, Foster CS,
et al: Referral patterns of uveitis in a tertiary eye care center,
Arch Ophthalmol 1996;114:593-596,)
.. The most common causes of intermediate uveitis are
idiopathic, 69.1 %; sarcoidosis, 22.2%; multiple sclerosis, 8.0%;
and LYlue disease, 0.6% (Fig 3-2). .. The most common causes of
posterior uveitis are toxoplasmosis, 24.6%; idiopathic, 12.3%;
cytomegalovirus retinitis, 11.6%; systemic lupus erythematosus,
7.9%; birdshot retinochoroidopathy, 7.9%; sarcoidosis, 7.5%; acute
retinal necrosis syndrome, 5.5%; Epstein-Barr virus
retinochoroiditis, 2.9%; toxocariasis, 2.5%;
Adamantiades-Beh~et'sdisease (~D), 2.0%; syphilis, 2.0%; acute
posterior multifocal placoid pigment epitheliopathy (APMPPE),
.2.0%; and serpiginous choroidopathy, 1.65%. Other causes of
posterior uveitis include punctate inner choroidopathy (PIC),
multiple evanescent white-dot syndrome (MEWDS), multiple sclerosis,
temporal arteritis, presumed ocular histoplasmosis, fungal
retinitis, and leukemia (Fig. 3-3).
30,.--------------------------25+---------------------------
20 15 10
FIGURE 3-3. Relative frequency (%) of the most common causes of
posterior uveitis, (Data from Rodriguez A, Calonge M, Foster CS, et
al: Referral patterns of uveitis in a tertiary eye care center.
Arch Ophthalmol 1996;114: 593-596,)
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CHAPTER J: DEFINITION, CLASSIFICATION, ETIOLOG'f, AND
EPIDEMIOLOGY
25--------------,-------------20
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10FIGURE 3-4. Relative frequency (%) of the most common causes
of panuveitis (Data from Rodriguez A, Calonge M, Foster CS, et al:
Referral patterns of uveitis in a tertiary eye care center. Arch
Ophthalmol 1996;114:593-596.):;::; '(j)
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