Uveitis 2012 The Challenges Continue . . .

But the Future Is Bright
Program Directors
C Stephen Foster MD and Quan Dong Nguyen MD

In conjunction with the American Uveitis Society
McCormick Place Chicago, Illinois Saturday, November 10, 2012 Presented by: The American Academy of Ophthalmology

Uveitis 2012 Planning Group C Stephen Foster MD Program Director Quan Dong Nguyen MD Program Director Debra A Goldstein MD Russell W Read MD PhD Eric Suhler MD

Subspecialty Day Advisory Committee William F Mieler MD Associate Secretary Donald L Budenz MD MPH Daniel S Durrie MD Robert S Feder MD Leah Levi MBBS R Michael Siatkowski MD Jonathan B Rubenstein MD Secretary for Annual Meeting

Staff Melanie R Rafaty CMP, Director, Scientific Meetings Ann L’Estrange, Scientific Meetings Specialist Brandi Garrigus, Presenter Coordinator Debra Rosencrance CMP CAE, Vice President, Meetings & Exhibits Patricia Heinicke Jr, Editor Mark Ong, Designer Gina Comaduran, Cover Design

©2012 American Academy of Ophthalmology. All rights reserved. No portion may be reproduced without express written consent of the American Academy of Ophthalmology.


2012 Subspecialty Day  |  Uveitis

Dear Colleague: On behalf of the American Academy of Ophthalmology and the American Uveitis Society, it is our great pleasure to welcome you to Chicago and to Uveitis 2012: The Challenges Continue . . . But the Future Is Bright. We hope that you will find this year’s Uveitis Subspecialty Day program exciting and beneficial to your practice and your patients. We are especially honored to have planned this event, which we hope will provide clinicians with practical information that can be used to treat ocular inflammation. The international faculty for this meeting have been carefully selected to provide you with the most up-to-date and pertinent information on the current state of the art for diagnosis and treatment of ocular inflammatory diseases and uveitis, and most particularly, information gleaned from evidence-based medicine exercises as a consequence of an extensive review of the world’s peer-reviewed medical literature. This year’s program presentations will emphasize the gaps in the diagnosis and management of uveitis and ocular inflammatory diseases. What challenges do we face in managing scleritis, peripheral ulcerative keratitis, retinal vasculitis, and anterior, intermediate, and posterior uveitis, among others? What should we know, as clinician scientists caring for patients with uveitis, that we either do not know or are misinformed about? We will also emphasize again the principles of diagnosis of ocular inflammatory disorders in order to initiate appropriate, disease-directed evaluations. What happens if appropriate and timely evaluation and referral are not conducted? Based on currently recommended preferred practice patterns from recognized inflammatory disease subspecialty bodies, some of the faculty will discuss the principles of steroidal and nonsteroidal therapies in the management of ocular inflammatory diseases, as well as the important and appropriate role of immunomodulatory therapy for patients with selected, specific ocular inflammatory diseases and also for patients with steroid-dependent inflammation. Others will describe the potentially new therapeutic options and pharmacologic agents that are coming into use in our clinics, and the role of surgical management of ocular inflammatory disorders. Based on comments from past attendees, we have provided more time for Case Discussion sessions, where you will see, “live and in person,” how uveitis experts approach challenging cases! We are very grateful for the expertise that the faculty members bring to the program. In an effort to put together innovative and interesting Subspecialty Day Meetings in the future, we sincerely request that you assist us by completing the evaluation. We will carefully review all comments to better understand your needs, so please indicate the strengths and shortcomings of today’s program. Again, we welcome you to Uveitis 2012: The Challenges Continue . . . But the Future Is Bright. Please share with us any of your comments, either in the evaluation, in an e-mail at a later time, or directly to one of us during conversation. We hope to make future programs even better and more beneficial so that our patients with uveitis and ocular inflammatory diseases around the world will get the best possible care. With warmest regards,

C Stephen Foster MD Program Director Quan Dong Nguyen MD MSc Program Director

2012 Subspecialty Day  |  Uveitis 


Uveitis 2012 Contents

Section I: Section II: Section III: Section IV: Section V: Section VI: Section VII: Section VIII: Section IX:

Program Directors’ Welcome Letter   ii CME  iv Faculty Listing  vi Program Schedule  xiii The Uveitis Puzzle for the Non-uveitis Specialist   1 Uveitis Potpourris   10 External Ocular Inflammatory Diseases   15 Infectious Uveitis—How Can One Tell if the Problem Is Microbial?   23 On the Special Matter of Pediatric Uveitis   28 Puzzling White Dots—What’s a Doctor to Do?   31 The Puzzling Matter of Treatment-Resistant Uveitis   42 Potential New Therapies for Uveitis—Pharmacologic Agents in Development  46 Late Breaking News   50 Faculty Financial Disclosure  51 Presenter Index  55

Electronic version of Syllabi available at www.aao.org / 2012syllabi

org/cme. participants should be able to: • Identify the challenges in recognizing the various forms of ocular inflammatory diseases. etc. including cicatricial pemphigoid. and anterior. failure to understand the paradigm shift away from corticosteroid monotherapy to a stepladder algorithm. retinal vasculitis. NOTE: CME credits must be reported by Jan. comprehensive ophthalmologists. CME Credit Reporting Grand Concourse Level 2.Booth 508 Attendees whose attendance has been verified (see above) at the 2012 Joint Meeting can claim their CME credit online during the meeting. Attendees registered as exhibitors. among others • Describe the potential new treatments for uveitis and ocular inflammatory diseases. All persons in a position to control the content of this activity must disclose any and all financial interests. Onsite. you must either: • Register in advance. Registrants will receive an e-mail during the meeting with the link and instructions on how to claim credit. and posterior uveitis • Construct a differential diagnosis for various forms of uveitis • Classify the principles of diagnosis of ocular inflammatory disorders in order to initiate appropriate.) and allied health personnel who are involved in the management of patients with uveitis and ocular inflammatory diseases. CME transcripts that include 2012 Joint Meeting credits entered onsite will be available to Academy members on the Academy’s website beginning Dec. • Register in advance and pick up your badge onsite if materials did not arrive before you traveled to the meeting. credits can be claimed at www. Academy Resource Center. uveitis specialists. • Register onsite. Hall A . the Academy must verify your attendance at Subspecialty Day and/or the Joint Meeting. 2012 Uveitis Subspecialty Day Meeting Learning Objectives Upon completion of this activity.S. intermediate. . and also for patients with steroid-dependent inflammation • Describe the various gaps that currently exist in the management of uveitis and ocular inflammatory diseases such as failure to recognize the sight-saving benefits of pursuing durable remission. The American Medical Association has determined that non– U. objectivity and absence of commercial bias in its content. licensed physicians who participate in this CME activity are eligible for AMA PRA Category 1 Credits TM. including selected therapeutic agents in development. It seeks to promote balance. specific ocular inflammatory diseases. or • Use your ExpoCard at the meeting. The American Academy of Ophthalmology designates this live activity for a maximum of 7 AMA PRA Category 1 Credits™. 3. Academy Members: The CME credit reporting receipt is not a CME transcript. you may report credits earned during Subspecialty Day and/or the Joint Meeting at the CME Credit Reporting booth. 2013. thus enabling such physicians to maintain or improve the competence and professional performance needed to provide the best possible eye care for their patients. performance or competence. based on recent and current work and studies Attendance Verification for CME Reporting Before processing your requests for CME credit. and other ophthalmologic subspecialists (cornea. In order to be verified for CME or auditing purposes. 16.5. After the 2012 Joint Meeting. spouses or guests are not eligible to receive CME credit. 2012 Uveitis Subspecialty Day Meeting Target Audience The intended audience for this program includes general ophthalmologists. Scientific Integrity and Disclosure of Financial Interest The American Academy of Ophthalmology is committed to ensuring that all continuing medical education (CME) information is based on the application of research findings and the implementation of evidence-based medicine.iv  2012 Subspecialty Day  |  Uveitis CME Credit Academy’s CME Mission Statement The purpose of the American Academy of Ophthalmology’s Continuing Medical Education (CME) program is to present ophthalmologists with the highest quality lifelong learning opportunities that promote improvement and change in physician practices. retina. 2012. Physicians should claim only the credit commensurate with the extent of their participation in the activity. receive materials in the mail and turn in the Final Program and/or Subspecialty Day Syllabus exchange voucher(s) onsite. 2012 Uveitis Subspecialty Day CME Credit The American Academy of Ophthalmology is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. and failure to recognize the elements essential to successful control of uveitic glaucoma. The Academy has mechanisms in place to resolve all conflicts of interest prior to an educational activity being delivered to the learners.aao. disease-directed evaluations • Identify the important and appropriate role of immunomodulatory therapy for patients with selected.

but it does not provide CME credit transcripts. Nonmembers: The Academy will provide nonmembers with verification of credits earned and reported for a single Academysponsored CME activity. or for nonmembers who need it to report CME credit: • CME credit reporting/proof-of-attendance letters • Onsite Registration Form • Instruction Course Verification Visit the Academy’s website for detailed CME reporting information.2012 Subspecialty Day  |  Uveitis CME Credit v The Academy transcript cannot list individual course attendance. To obtain a printed record of your credits. . Proof of Attendance The following types of attendance verification will be available during the Joint Meeting and Subspecialty Day for those who need it for reimbursement or hospital privileges. you must report your CME credits onsite at the CME Credit Reporting booths. It will list only the overall credits spent in educational activities at Subspecialty Day and/or the Joint Meeting.

vi  2012 Subspecialty Day  |  Uveitis Faculty No photo available Massimo Accorinti MD PhD Rome. Inflammatory Eye Disease Clinic Asociación Para Evitar la Ceguera en México Professor of Ophthalmology Universidad Nacional Autónoma de Mèxico . Saudi Arabia Vitreoretinal & Uveitis Senior Academic Consultant King Khald Eye Specialist Hospital (KKESH) Clinical Assistant Professor King Saud University Medical Center Nisha Acharya MD San Francisco. Ocular Surface Diseases and Dry Eye Clinic Division of Cornea and External Diseases The Wilmer Eye Institute Hassan A Al-Dhibi MD Riyadh. PhD Sapienza Università di Roma Esen K Akpek MD Baltimore. Turkey Professor of Ophthalmology Bayindir Kavaklidere Hospital Chief of Ophthalmology Bayindir Kavaklidere Hospital Lourdes Arellanes MD Mexico City. DF. San Francisco Sofia N Androudi MD PhD Thomas A Albini MD Coral Gables. CA Associate Professor F I Proctor Foundation University of California. Mexico Chief. MD Associate Professor of Ophthalmology Johns Hopkins University School of Medicine Director. Italy MD. Greece Lecturer Larissa University Hospital. FL Associate Professor of Clinical Ophthalmology Bascom Palmer Eye Institute Thessaloniki. Greece Yonca A Akova MD Ankara.

Federal University of São Paulo Member. Histology Core National Eye Institute Rubens Belfort Jr MD PhD São Paulo. Vitreoretinal Surgeon. Immunopathology Section National Eye Institute Head.2012 Subspecialty Day  |  Uveitis Faculty Listing vii No photo available William Ayliffe MBBS London. France Professor of Ophthalmology University of Paris VI (Pierre and Marie Curie) . Belgium Chi-Chao Chan MD Alay S Banker MD Ahmedabad. Hospital São Paulo. Brazil Head Professor of Ophthalmology Vision Institute. and Uveitis Specialist Banker’s Retina Clinic and Laser Centre Bethesda. Academia Ophthalmologica Internationalis Talin Barisani-Asenbauer MD Vienna. WI Professor of Ophthalmology and Visual Sciences University of Wisconsin School of Medicine and Public Health Laure E Caspers MD Brussels. SP. MD Chief. India Director. England Professor of Medicine Gresham College London Neal P Barney MD Madison. Singapore Senior Consultant and Head of Ocular Inflammation and Immunology Singapore National Eye Centre Associate Professor Department of Ophthalmology National University of Singapore Bahram Bodaghi MD PhD Paris. Austria Associate Professor Medical University of Vienna Scientific Director Laura Bassi Centre of Expertise for Ocular Inflammation and Infection Soon-Phaik Chee MD Singapore.

MA Clinical Professor of Ophthalmology Harvard Medical School Founder and President Massachusetts Eye Research and Surgery Institution Cristobal A Couto MD Buenos Aires. FL Professor of Ophthalmology University of Miami Miller School of Medicine Director. Uveitis Service Bascom Palmer Eye Institute C Stephen Foster MD Cambridge. PGI.viii Faculty Listing 2012 Subspecialty Day  |  Uveitis No photo available David S Chu MD Newark. NJ Associate Professor of Ophthalmology New Jersey Medical School University of Medicine and Dentistry. India Professor of Ophthalmology Post Graduate Institute of Medical Education and Research Professor of Ophthalmology Advanced Eye Centre. General Hospital Klagenfurt Amod K Gupta MBBS Panchkula. MD Associate Professor of Ophthalmology The Wilmer Eye Institute The Johns Hopkins School of Medicine Debra A Goldstein MD Chicago. CA Director. Argentina Professor of Ophthalmology University of Buenos Aires Assistant Professor of Ophthalmology Catholic University of Salta James Philip Dunn Jr MD Baltimore. Haryana. The Uveitis Service California Pacific Medical Center Adjunct Clinical Professor of Ophthalmology Stanford University School of Medicine Yosuf El Shabrawi MD Klagenfurt. IL Professor of Ophthalmology University of Illinois at Chicago Emmett T Cunningham Jr MD PhD MPH Hillsborough. Austria MD. New Jersey Janet Louise Davis MD Miami. Chandigarh .

UT. Department of Ophthalmology Mount Sinai School of Medicine CEO. CT Associate Professor of Ophthalmology Yale University Careen Yen Lowder MD PhD John H Kempen MD Philadelphia. KY Evans Professor of Ophthalmology University of Louisville Chairman.2012 Subspecialty Day  |  Uveitis Faculty Listing ix Vishali Gupta MBBS Chandigarh. CO Physician and Surgeon Corneal Consultants of Colorado John J Huang MD Bethany. Faculty Practice Associates Mount Sinai School of Medicine Elisabetta Miserocchi MD Milano. France Professor and Chair Department of Ophthalmology Universite Pierre et Marie Pitie-Salpetriere Hospital . NY Professor and Chair. PA Associate Professor of Ophthalmology and Epidemiology Perelman School of Medicine University of Pennsylvania Director. Department of Ophthalmology and Visual Sciences University of Louisville Erik Letko MD Littleton. India Professor of Ophthalmology Post Graduate Institute of Medical Education and Research Henry J Kaplan MD Louisville. Italy Ophthalmologist University Vita-Salute Scientific Institute San Raffaele Phuc Lehoang MD PhD Paris. OH Full Professional Staff Cleveland Clinic Cole Eye Institute Douglas A Jabs MD MBA New York. Ocular Inflammation Service & Ophthalmic Epidemiology Scheie Eye Institute Cleveland.

and Uveitis Johns Hopkins University School of Medicine Sumru Onal MD Istanbul. AL Associate Professor of Ophthalmology and Pathology University of Alabama at Birmingham Executive Secretary American Uveitis Society . Chennai Victor L Perez MD Miami. OH Clinical Associate Professor of Ophthalmology The Ohio State University S R Rathinam MD PhD Tamil Nadu.x Faculty Listing 2012 Subspecialty Day  |  Uveitis Quan Dong Nguyen MD Baltimore. Japan Professor of Ophthalmology Kyorin University School of Medicine Russell W Read MD PhD Birmingham. CA Professor of Ophthalmology Doheny Eye Institute University of Southern California Emil Mitchel Opremcak MD Robert B Nussenblatt MD Bethesda. FL Associate Professor of Ophthalmology. MD Associate Professor of Ophthalmology Wilmer Eye Institute Diseases of the Retina and Vitreous. MD Chief Laboratory of Immunology National Eye Institute Associate Director NIH Center for Human Immunology National Institutes of Health Columbus. India Professor and Head of the Uveitis Department Aravind Eye Hospital & PG Institute of Ophthalmology Professor of Ophthalmology The Tamil Nadu Dr M G R Medical University. Microbiology & Immunology Bascom Palmer Eye Institute University of Miami Miller School of Medicine Annabelle A Okada MD Tokyo. Turkey Associate Professor of Ophthalmology Department of Ophthalmology V K Foundation American Hospital Narsing A Rao MD Los Angeles.

Uveitis Service Department of Ophthalmology The New York Eye & Ear Infirmary Assistant Professor of Ophthalmology New York Medical College Hatice N Sen MD Bethesda. MD Director. OR Associate Professor of Ophthalmology Oregon Health & Science University Cleveland. OH Staff Physician Cole Eye Institute Cleveland Clinic Foundation . CA Professor and Chairman Department of Ophthalmology University of Southern California Keck School of Medicine Doheny Eye Institute No photo available C Michael A Samson MD New York. Spain Associate Professor of Ophthalmology Hospital Clinico of Barcelona Professor of Ophthalmology Central University of Barcelona Ariel Schlaen MD Buenos Aires. NY Codirector. Argentina Staff Member Hospital Universitario Austral Staff Member Hospital de Clínicas.V. Universidad de Buenos Aires Ronald E Smith MD Los Angeles. Prasad Eye Institute Sunil K Srivastava MD Justine R Smith MD Portland. Uveitis and Ocular Immunology Fellowship Program National Eye Institute National Institutes of Health Associate Clinical Professor of Ophthalmology The George Washington University Lucia Sobrin MD Boston. Andhra Pradesh. MA Assistant Professor of Ophthalmology Harvard Medical School Attending Physician Retina and Uveitis Services Massachusetts Eye and Ear Infirmary Virender S Sangwan MBBS Hyderabad. L.2012 Subspecialty Day  |  Uveitis Faculty Listing xi Maite Sainz de la Maza MD Barcelona. India Dr.

WA Boyd K Bucey Memorial Chair. Germany Professor of Ophthalmology University of Tübingen Joseph Tauber MD Kansas City. Philippines Clinical Associate Professor of Ophthalmology University of the Philippines – Manila Consultant Uy Eye Clinics Atlanta. GA Assistant Professor of Ophthalmology Emory Eye Center Emory University School of Medicine Manfred Zierhut MD Tübingen. UT Professor of Ophthalmology Moran Eye Center University of Utah Johnny Tang MD Cleveland. OH Director Retina and Uveitis Service Louis Stokes Cleveland VA Medical Center Assistant Professor University Hospitals Case Medical Center Steven Yeh MD Harvey S Uy MD Quezon City.xii Faculty Listing 2012 Subspecialty Day  |  Uveitis Eric Suhler MD Portland. Professor. and Chairman of Ophthalmology University of Washington School of Medicine Director UW Medicine Eye Institute . MO Medical Director Tauber Eye Center Russell N Van Gelder MD PhD Seattle. OR Associate Professor of Ophthalmology Oregon Health & Science University Chief of Ophthalmology Portland VA Medical Center Jennifer E Thorne MD PhD Baltimore. MD Associate Professor of Ophthalmology Johns Hopkins University School of Medicine Associate Professor of Epidemiology Johns Hopkins University Bloomberg School of Public Health Albert T Vitale MD Salt Lake City.

2012 7:00 AM 7:50 AM 7:55 AM REGISTRATION/ MATERIAL PICKUP/ CONTINENTAL BREAKFAST Welcome and Opening Remarks Pre-test C Stephen Foster MD* Quan Dong Nguyen MD* C Stephen Foster MD* Section I: 8:00 AM 8:10 AM 8:20 AM 8:30 AM 8:40 AM The Uveitis Puzzle for the Non-uveitis Specialist Moderator: Alay S Banker MD How to Consider a Uveitic Entity and When to Refer a Patient With Uveitis How to Treat: A Stepladder Algorithm How to Orchestrate Comanagement for Immunomodulatory Therapy Managing Glaucoma in Patients With Uveitis Therapeutic Vitrectomy Douglas A Jabs MD MBA* Sofia N Androudi MD PhD Justine R Smith MD* Sumru Onal MD Emil Mitchel Opremcak MD 1 2 4 5 8 Section II: Uveitis Potpourris 8:50 AM 9:00 AM 9:10 AM 9:20 AM Moderator: Harvey S Uy MD* Recurrent Nongranulomatous Anterior Uveitis: E&M Pars Planitis: What to Do When the Intermediate Uveitis Is Idiopathic Retinal Vasculitis Case Presentations and Panel Discussion #1 (With Audience Response) Managing All the Uveitis Coming to Your Office Moderator: James Philip Dunn Jr MD Panelists: Massimo Accorinti MD PhD. Joseph Tauber MD* C Stephen Foster MD* Virender S Sangwan MBBS Esen K Akpek MD* 15 17 19 * Indicates that the presenter has financial interest. Maite Sainz de la Maza MD*. or Something More Ominous? Is Keratoconjunctivitis Sicca an Inflammatory Disease? Case Presentations and Panel Discussion #2 (With Audience Response) Inflammation of External Ocular Structures Moderator: Neal P Barney MD* Panelists: Talin Barisani-Asenbauer MD.2012 Subspecialty Day  |  Uveitis  xiii Uveitis 2012: The Challenges Continue . Harvey S Uy MD*. Albert T Vitale MD*. Victor L Perez MD*. . NOVEMBER 10. C Michael A Samson MD*. . . Erik Letko MD. No asterisk indicates that the presenter has no financial interest. Terrien’s. But the Future Is Bright In conjunction with the American Uveitis Society SATURDAY. Manfred Zierhut MD* REFRESHMENT BREAK and JOINT MEETING EXHIBITS Jennifer E Thorne MD PhD* Janet Louise Davis MD* William Ayliffe MBBS* 10 11 14 9:50 AM Section III: External Ocular Inflammatory Diseases 10:20 AM 10:30 AM 10:40 AM 10:50 AM Moderator: Maite Sainz de la Maza MD* Chronic Conjunctivitis: Is It Ocular Cicatricial Pemphigoid? Peripheral Ulcerative Keratitis: Mooren’s.

Sunil K Srivastava MD REFRESHMENT BREAK and JOINT MEETING EXHIBITS 40 3:10 PM * Indicates that the presenter has financial interest. and If So. John J Huang MD*. Steven Yeh MD Amod K Gupta MBBS Rubens Belfort Jr MD PhD* 23 26 Section V: 1:10 PM 1:20 PM 1:30 PM On the Special Matter of Pediatric Uveitis Moderator: Lucia Sobrin MD Differential Diagnosis of Uveitis in the Pediatric Population: Sarcoid. Presumed Ocular Histoplasmosis Syndrome. Lucia Sobrin MD Debra A Goldstein MD* Laure E Caspers MD 28 29 Section VI: 2:00 PM 2:10 PM 2:20 PM Puzzling White Dots—What’s a Doctor to Do? Moderator: Hassan A Al-Dhibi MD Is It Birdshot Retinochoroidopathy. Lourdes Arellanes MD.xiv Program Schedule Advocating for Patients LUNCH and JOINT MEETING EXHIBITS 2012 Subspecialty Day  |  Uveitis 11:20 AM 11:25 PM Russell N Van Gelder MD PhD*21 Section IV: 12:20 PM 12:30 PM 12:40 PM Infectious Uveitis—How Can One Tell if the Problem Is Microbial? Moderator: Russell N Van Gelder MD PhD* Herpes. and Panuveitis: Does Each of These Require Immunomodulatory Therapy? Albert T Vitale MD* Narsing A Rao MD Phuc Lehoang MD PhD* 31 37 38 2:30 PM 2:40 PM Acute Posterior Multifocal Placoid Pigment Epitheliopathy and Henry J Kaplan MD* “Ampiginous Choroiditis”: Should These Be Treated. Henry J Kaplan MD*. How Should I Treat It? What About Serpiginous Choroiditis? Is It Autoimmune? Or Herpes? Or Tuberculosis? Punctate Inner Choroidopathy. Johnny Tang MD. With What? Case Presentations and Panel Discussion #5 (With Audience Response) I Hate Those White Dots! Moderator: Russell W Read MD PhD* Panelists: Nisha Acharya MD*. Careen Yen Lowder MD PhD*. Elisabetta Miserocchi MD*. . and Beyond Juvenile Idiopathic Arthritis-Associated Uveitis: When to Move Off Corticosteroid Therapy? Case Presentations and Panel Discussion #4 (With Audience Response) How to Evaluate a Pediatric Patient With Uveitis Moderator: Bahram Bodaghi MD PhD* Panelists: Thomas A Albini MD*. Annabelle A Okada MD*. Tubulointerstitial Nephritis and Uveitis Syndrome. Syphilis. S R Rathinam MD PhD. Multifocal Choroiditis. and If So. the Most Common Problem Worldwide: What Else to Consider? Case Presentations and Panel Discussion #3 (With Audience Response) Infectious Uveitis: How Not to Miss It Moderator: Emmett T Cunningham Jr MD PhD MPH Panelists: Soon-Phaik Chee MD*. and Tuberculosis Infectious Uveitis. Hassan A Al-Dhibi MD. No asterisk indicates that the presenter has no financial interest. Ariel Schlaen.

or Malignant? The Importance of Diagnostic Surgery Current Concepts in Managing Ocular Malignancy: What Are Our Colleagues in Neuro-Oncology Doing? On the Matter of Autoimmune Retinopathy: A Diagnostic and Therapeutic Puzzle Case Presentations and Panel Discussion #6 (With Audience Response) What to Do When There Is No Response Moderator: Quan Dong Nguyen MD* Panelists: Yonca A Akova MD. No asterisk indicates that the presenter has no financial interest. John H Kempen MD* Russell N Van Gelder MD PhD*42 Chi-Chao Chan MD Hatice N Sen MD 43 44 Section VIII: Potential New Therapies for Uveitis—Pharmacologic Agents in Development 4:40 PM 4:50 PM 5:00 PM Moderator: Ronald E Smith MD* Systemic Pharmacologic Agents in Development for Uveitis: Voclosporin. Yosuf El Shabrawi MD*. Vishali Gupta MBBS*. Adalimumab. .2012 Subspecialty Day  |  Uveitis Program Schedule xv Section VII: 3:40 PM 3:50 PM 4:00 PM 4:10 PM The Puzzling Matter of Treatment-Resistant Uveitis Moderator: Yosuf El Shabrawi MD* Is It Infectious. Cristobal A Couto MD*. Autoimmune. and AIN457 Local Pharmacologic Agents in Development for Uveitis: Sirolimus and Others Novel Drug Delivery Approaches for Uveitis: Iontophoresis and Others Eric Suhler MD* Quan Dong Nguyen MD* David S Chu MD* 46 47 48 Section IX: 5:10 PM 5:20 PM 5:21 PM Late Breaking News Top 10 Mishaps in Managing Uveitis Closing Remarks and Post-test ADJOURN Robert B Nussenblatt MD C Stephen Foster MD* Quan Dong Nguyen MD* 50 * Indicates that the presenter has financial interest.


2005. Da Silva JA. 5. 3. Jacobs JW. Thorne JE. Thorne JE. Barnes CG. 12. et al. Thorne JE. Kijlstra A. Merayo-Lloves J. et al. 2008. 65:285-293. Zamecki KJ. 80:332-336. Birdshot retinochoroidopathy: ocular complications and visual impairment. 1996. 14. 322:281-285. et al. et al. Causes of uveitis in the general practice of ophthalmology: UCLA community based uveitis study group. Yazici H. Rothova A. The utility of routine screening of patients with uveitis for system lupus erythematosus or tuberculosis. 1996. Ann Rheum Dis. Safety of low dose glucocorticoid treatment in rheumatoid arthritis: published evidence and prospective trial data. Peters GB. 6. 11. Overall and cancer related mortality among patients with ocular inflammation treated with immunosuppressive therapy: retrospective cohort study. Foster CS. Wittenberg SE. 145:23-28. and panuveitis: the multicenter uveitis steroid treatment trial. 2009. The Standardization of Uveitis Nomenclature (SUN) Working Group. Jabs DA. 140:45-51. Dunn JP. Kempen JH. Kempen JH. Altaweel MM. HLA typing in uveitis: use and misuse. Ophthalmology 1996. Frits Treffers W. Dunn JP. Randomized comparison of systemic anti-inflammatory therapy versus fluocinolone acetonide implant for intermediate. Dunn JP. Br J Ophthalmol. Am J Ophthalmol. Wernick R. Kedhar SR. McCannel CA. Kempen JH. 4. Pazarli H. 149:189-193. 1990. 2. Dunn JP. Kirwan JR. 113:2310-2316. . 2005. Am J Ophthalmol. Dana MR. Dunn JP. Rosenbaum JT. Am J Ophthalmol. 13. 118:1916-1926. Thorne JE. 9. 2006. 10.2012 Subspecialty Day  |  Uveitis Section I: The Uveitis Puzzle for the Non-uveitis Specialist 1 How to Consider a Uveitic Entity and When to Refer a Patient With Uveitis Douglas A Jabs MD MBA Selected Readings 1. 140:509-516. Causes and frequency of blindness in patients with intraocular inflammatory disease. 8. Arch Ophthalmol. Suttorp-Van Schulten MS. Daniel E. 2010. Loss of visual field among patients with birdshot chorioretinopathy. Hair D. N Engl J Med. Am J Ophthalmol. posterior. 339:b2480. 121:35-46. Bykhovskaya I. Holbrook JT. Jabs DA. Am J Ophthalmol. 2005. Peters GB. Jabs DA. Holland GN. VogtKoyanagi-Harada disease: clinical outcomes. Standardization of uveitis nomenclature for reporting clinical data: results of the first international workshop. Brit Med J. 103:1846-1853. Am J Ophthalmol. Schaumberg DA. 108:1291-1293. Jabs DA. 7. Ophthalmology 2006. 1990. Multifocal choroiditis with panuveitis: incidence of ocular complications and loss of visual acuity. Kedhar SR. Kempen JH. et al. Jabs DA. Ophthalmology 2011. A controlled trial of azathioprine in Behçet’s syndrome. Helm CJ. Prognosticators for visual outcome in sarcoid uveitis. 140:674-678. Peters GB.

Corticosteroids are often started because they are usually able to control inflammation quickly. sex. Once treatment is initiated. The chosen drug should offer the most favorable side-effect profile and efficacy for the patient’s specific ocular disease. Dermatologic (acne. Goals of Therapy in Patients With Uveitis A. obesity. and most importantly. The Second Step The next step in the stepladder algorithm is the use of nonsteroidal anti-inflammatory drugs (NSAIDs). As needed. algorithmic approach to the treatment of noninfectious uveitis. hirsutism) viii. sodium and fluid retention) vi. a more aggressive approach in terms of therapy is required. Adamantiades-Behçet disease b. growth failure. it may be necessary to titrate the dosage. If the patient continues to have chronic or recurrent active inflammation. oncology. Steroid limitations: Poor outcomes as monotherapy in ophthalmology for: a. Current Status The vast majority of the world’s ophthalmologists do not recommend or use immunomodulatory therapy for their patients with progressive. Cataract ii. Gastrointestinal (peptic ulcer. II. Cardiovascular (hypertension. Reduce ocular and systemic morbidity We suggest a stepladder. The first step for many patients with ocular inflammation begins with the initiation of corticosteroid treatment. social and past medical history. Steroid complications a.2 Section I: The Uveitis Puzzle for the Non-uveitis Specialist 2012 Subspecialty Day  |  Uveitis How to Treat: A Stepladder Algorithm Sofia Androudi MD PhD I. oftentimes these agents are not curative. and in some patients gastrointestinal prophylaxis. V. Why not use steroids as monotherapy to control the ocular inflammation? 1. inflammatory eye disease. or discontinue the drug altogether in case of low tolerance or efficacy. Although excellent at quelling inflammation initially. with induction of immunomodulatory agents. Treatment with these drugs requires periodic monitoring of kidney and liver function. the patient must be consistently monitored to safeguard against toxicity and intolerable side effects. Neuropsychiatric (pseudotumor cerebri. aseptic hip necrosis) v. insomnia. Endocrine (adrenal insufficiency. Central serous retinopathy iv. Eliminate ocular inflammation B. or systemically. Wrong association with risks and side effects of cancer therapy B. hyperlipidemia) vii. menstrual disorders) ii. Immunologic (impaired inflammatory response. add a second or a third agent. Birdshot III. compliance factors. Glaucoma iii. and hematology). The First Step A. IV. can be the most formidable challenge to the achievement of corticosteroid-free durable remission. Susceptibility to infection 2. striae. Metabolic (secondary diabetes mellitus. Musculoskeletal (osteoporosis. this may be dispensed topically. The choice of chemotherapeutic agents is case specific and escalates in a stepwise approach. Reasons for Slow Acceptance A. Unfamiliarity of the therapeutic index of immunosuppressive therapy for the treatment of autoimmune and ocular inflammatory disease . The emotional transition to the induction of chemotherapy for most patients. intestinal perforation) iv. Juvenile idiopathic arthritis (JIA) c. blinding. mood swings. the specific ocular inflammatory disease. Cushing syndrome. Ocular i. through local injection. The process of deciding which medication to choose for treating uveitis is based upon a multitude of factors. Wegener granulomatosis d. Serpiginous e. delayed tissue healing) b. psychosis) iii. Some of these factors include age. as well as for many physicians. B. as many times patients are unable to completely wean off corticosteroid therapy without having a recurrence of their uveitis. The administration of these medications and the monitoring of these patients becomes a joint effort between the ophthalmologist and multiple subspecialists (rheumatology. Nonocular i.

F. A. Key Principles of Immunomodulatory Treatment VIII. Use immunosuppressive agents only with appropriate training and expertise. 4. 2002:177-214. H. Summary A. Keratoplasty with multiple rejections IX. Periodic complete hemograms (differential and platelet counts) C. 130:492-513. Experience with drug E. X. Memon M. Durrani K. 5. Clinical condition and systemic associations B. Ophthalmology 2008. In Foster CS. Begin early enough. Uncertainties of long-term safety F. Carefully discuss risks and benefits with the patient and family members. Leder HA. 115:1826-1832. How to Decide? The choice of immunosuppressive is individualized. adhesion molecules. Systemic therapy with conventional and novel immunomodulatory agents for ocular inflammatory disease. et al. Foster CS. Possible Indications Selected Readings 1. ed. Avoid suppressing leucocytes <3500 c/μl XII. Absolute Indications for Immunomodulatory Therapy A. Sympathetic ophthalmia VII. Other therapeutic approaches B. Therapeutic response to systemic immunosuppressive chemotherapy agents in patients with Behcet’s syndrome effecting the eyes. Surv Ophthalmol. Raizman MB. Safety and efficacy C. They should be administered by those appropriately trained in the use of such agents. In O’Duffy J. Not FDA approved/off-label use VI. Am J Ophthalmol. Polyarteritis nodosa G. A. Collaborate. Relative Indications A. 2. Close monitoring of patient: Before therapy and at 1 to 6-8 weeks intervals B. Immunosuppressive chemotherapy. Guidelines for the use of immunosuppressive drugs in patients with ocular inflammatory disorders: recommendations of an expert panel. Vitale AT. Diagnosis and Treatment of Uveitis. Siddique SS. 56:474-510. 2000. Philadelphia: WB Saunders. Galor A. C. Medical status D. Severe chronic iridocyclitis A. Cost issues G. Behçet’s Disease: Basic and Clinical Aspects. Exclude infectious or other treatable causes. 1991:581-588. C. et al. Blockade of chemokine receptors. The Future A. XIII. 2011. 3. New York: Marcel Dekker. endstage disease or when complications of steroids have developed E. They may potentially be safer than long-term corticosteroid therapy. Jabs DA. Access and cost . D. Key Principles 3 C.2012 Subspecialty Day  |  Uveitis Section I: The Uveitis Puzzle for the Non-uveitis Specialist XI. D. Ahmed M. eds. Reserving immunomodulatory treatment for severe. and transcription factors regulating the inflammatory response A. Jabs DA. JIA C. Start with low dose and titrate up. Zakka FR. E. Rosenbaum JT. Foster CS. Inexperience with immunosuppressive drugs D. B. Foster CS. Relapsing polychondritis H. More studies will elucidate some of these unknowns. Intermediate uveitis B. Severe vasculitis C. Sarcoid-associated uveitis inadequately responsive to steroid C. Foster CS. Vogt-Koyanagi-Harada D. Use a stepladder algorithm. G. Adamantiades-Behçets disease with retinal involvement B. Immunosuppressive and immunomodulatory agents play an important role in the management of ocular inflammatory disease. Ocular cicatricial pemphigoid I. Necrotizing scleritis E. Intermediate uveitis in children B. Comparison of antimetabolite drugs as corticosteroid-sparing therapy for noninfectious ocular inflammation. Do No Harm!!!!! B. E. The newer biological agents hold promise. Wegener granulomatosis F. complement components. Vitale AT.

Clearly define management responsibilities of each provider.org/find_eyemd.aao .org/ patients/list-of-specialists II. A. Refer to a uveitis specialist for advice early and often. . Multiple sclerosis: neurologist 6. Uveitis with systemic disease association 1. Pregnancy: Consult perinatologist.4 Section I: The Uveitis Puzzle for the Non-uveitis Specialist 2012 Subspecialty Day  |  Uveitis How to Orchestrate Comanagement for Immunomodulatory Therapy Justine R Smith MD I. American Uveitis Society uveitis specialist directory: www. Tubulointerstitial uveitis and nephritis syndrome: pediatric nephrologist or pediatrician A. human immunodeficiency virus infection): Consult infectious disease specialist. Seronegative spondyloarthropathy: rheumatologist 2.uveitissociety. Treatment with tumor necrosis factor blocker: rheumatologist B. IV. Treatment with alkylating agent: rheumatologist + reproductive medicine specialist 4. B. Treatment with calcineurin inhibitor: transplant specialist 3. III. Identify an appropriately qualified local physician who will work with you. Inflammatory bowel disease: gastroenterologist 4.cfm?&CFID=23517065 &CFTOKEN=48810696 B. Treatment with antimetabolite: rheumatologist 2. A. Sarcoidosis: pulmonologist or rheumatologist 3. Obtain advice on other relevant issues. Academy ophthalmologist directory: www.uveitis. herpes virus infection. Massachusetts Eye Research and Surgery Institution uveitis specialist directory: www. Juvenile idiopathic arthritis-associated uveitis: pediatric rheumatologist or pediatrician 7. Coexistent infectious disease (eg. Uveitis without systemic association 1.org/pages/specialists. Behçet disease: rheumatologist 5.html C. tuberculosis.

without increasing the rate of flare-ups of uveitis. A patient with elevated IOP due to synechial angle closure secondary to uveitis is mostly classified as having uveitic glaucoma without evidence of optic disc changes or visual field loss. Uveitic glaucoma patients often require more than one drug to control their IOP. 2. Initially thought to have a propensity to increase the activity of uveitis b. II. The overall prevalence of uveitic glaucoma ranges between 10% and 20%. Biologic therapies 1. 4. Elevated IOP is a common and significant complication in patients with uveitis treated with fluocinolone acetonide intravitreal implants. Elevation of IOP can occur with all routes of corticosteroid treatment. particularly moxifloxacin. Medical therapy 1. Relieve the discomfort of ciliary muscle spasm C. PG agonists were shown to be effective in lowering IOP in patients with uveitic glaucoma. 7. Cycloplegics 1. they exert corticosteroid-sparing effect and have the potential to induce durable remission. Uveitic Conditions Most Commonly Associated With Glaucoma A. 25% of implant-treated eyes require glaucoma surgery over 24 months. Glaucomatocyclitic crisis (Posner-Schlossman syndrome) G. and severe early IOP rise as a possible adverse drug reaction of systemic fluoroquinolone treatment. Recent studies suggest uveitis with iris transillumination. and occurs more commonly in uveitis patients than in the normal population. D. Hyperosmotic drugs B. Used to prevent or break posterior synechiae 2. C. Most of the patients respond to medical treatment.05% has superior intraocular penetration compared with other topical corticosteroids. Viral iridocyclitis F. Fuchs heterochromic iridocyclitis C. Prostaglandin (PG) agonists a. Are indicated in uveitic entities refractory to conventional IMT 2. it should be used cautiously in pediatric patients with uveitis because of a high rate of corticosteroid-induced IOP elevation in this population. 5. Sarcoid uveitis D.2012 Subspecialty Day  |  Uveitis Section I: The Uveitis Puzzle for the Non-uveitis Specialist 5 Managing Glaucoma in Patients With Uveitis Sumru Onal MD I. Introduction A. Intravitreal triamcinolone injection is associated with substantial risk of corticosteroid-induced IOP elevation. E. III. glaucoma should not be considered synonymous with elevated IOP. B. B. C. Medical Treatment of Glaucoma A. but the diagnosis should be reserved for those situations where there is either glaucomatous disc damage or visual field loss. Beta-blockers 2. only 4% to 30% of patients require surgical treatment. Treatment of Primary Disease A. pigment dispersion. Alpha-2 agonists 4. . Conventional immunomodulatory therapy (IMT) 1. Apart from controlling the intraocular inflammation. however. because these changes are inevitable without appropriate intervention. Topical difluprednate 0. 5. Juvenile idiopathic arthritis B. Raised IOP induced by corticosteroid response represents a significant proportion of IOP elevation in uveitic eyes. Corticosteroids are still the mainstay of treatment of acute intraocular inflammation. Their off-label use is the standard of care in the uveitis practice. Fluocinolone acetonide intravitreal implantation can be combined with glaucoma drainage device placement in eyes with uveitis and elevated IOP receiving maximum tolerated IOP-lowering therapy. 6. 2. Topical and oral carbonic anhydrase inhibitors 3. In a patient with uveitis. 3. Intermediate uveitis / pars planitis E. but is much more common in chronic uveitis and can be as high as 46%. Corticosteroid therapy 1. There is ongoing debate about their use as firstline therapy in certain uveitic conditions. in whom the uveitis is controlled on IMT. Specific treatment of infectious etiologies of uveitis IV.

Reserved for cases where all other efforts to lower IOP have failed. Laser Therapy A. Ongchin S. Dacey MS. e. Success rate of MMC trabeculectomy for uveitic glaucoma ranges from 50% to 90% with various criteria of success. B. 148:207-213. Disadvantages are necessity of a filtration bleb and antifibrotic use. Tugal-Tutkun I. either as the initial glaucoma surgery or when trabeculectomy fails 2. Not proven to be superior to trabeculectomy 2. B. which may reduce inflammation. Mandelcorn E. A higher percentage of pediatric uveitis patients need surgery. Holbrook JT. Not studied in uveitic glaucoma 2. and recalcitrant cases require surgical intervention. 2012. Outcome of raised intraocular pressure in uveitic eyes with and without a corticosteroid-induced hypertensive response. Am J Ophthalmol. Glaucoma drainage devices 1. a 50or 200-μm inner diameter. and possible device-related complications. a surgical iridectomy may be required if the laser iridotomy closes secondary to intense inflammation. fibrosis over the opening. 2. Glaucoma is a frequent complication of uveitis arising from the inflammatory disease process itself or from corticosteroid use or both. Random- . Habot-Wilner Z. D. 2009. Other Surgical Procedures A. Success rate is up to 94% at 1 year and 50% at 4 years with various criteria of success. V. 2011. Herlihy E. C. Others VII. Kempen JH. Argon laser trabeculoplasty 1. B. The procedure is similar to a standard trabeculectomy. IOP control is especially favorable in JIA-associated glaucoma. van Gelder RN. Nonpenetrating surgery is associated with less inflammation during the early postoperative period. Newer glaucoma implants 1. 2012. prior surgeries. Bilateral acute iris transillumination. Sheth HG. Cutan Ocul Toxicol. Bilateral uveitis associated with fluoroquinolone therapy. formation of a standard size filtration opening. et al. A low-risk and effective first-line surgery for young patients with refractory glaucoma associated with chronic uveitis 2. Main advantages are ease of insertion. 153:932-938. and elimination of the iridectomy. Used with increasing frequency in uveitic glaucoma. 5. Summary References 1. VI. A nonvalved. 3. Lightman S. Deep sclerectomy 1. Altaweel MM. A. and a rounded and beveled tip 2012 Subspecialty Day  |  Uveitis c. flow-restricting implant with a 400-μm (27-gauge) external diameter. Goniotomy 1. et al. Long-term success of trabeculectomy has increased with antimetabolic agents such as intraoperative mitomycin C (MMC) and intra-/ postoperative 5-fluorouracil. 31:111-116. Outcome is adversely affected by increased age. d. 2. Treatment should be first directed at aggressive and comprehensive control of intraocular inflammation and the underlying systemic disease.e1. 3. Onal S. Garip A. Glaucoma filtration surgery 1. et al. Improved long-term success rates are reported with glaucoma drainage implants. Arch Ophthalmol. A miniature stainless steel shunt developed for use as an alternative procedure to trabeculectomy b. Argon and/or Nd:YAG laser iridotomy 1. Filtration surgery is indicated when IOP is uncontrolled on maximum tolerated IOP-lowering therapy. Surgical Therapy VIII. Slabaugh MA. 4. 2. Uncontrolled IOP is often managed with glaucoma medical therapy. f. Indicated for pupillary block glaucoma due to a secluded pupil from extensive posterior synechiae or fibrin membrane 2. Multicenter Uveitis Steroid Treatment (MUST) Trial Research Group. Sallam A. Usually not useful in uveitic eyes 2. Ex-PRESS mini glaucoma shunt a. and aphakia.6 Section I: The Uveitis Puzzle for the Non-uveitis Specialist D. 3. C. B. Am J Ophthalmol. Has been shown to have low success rates in uveitic glaucoma patients because of angle alterations C. 129:1312-1319. In some cases. peripheral anterior synechiae. Efficacy and potential complications of difluprednate use for pediatric uveitis. Transscleral laser cyclophotocoagulation 1. Should be used cautiously because the risk of permanent hypotony is increased with a cyclodestructive procedure in uveitic eyes with compromised ciliary epithelium function A. Hinkle DM.

18. Villarón S. Singh K. Christen WB. et al. Outcome of Baerveldt glaucoma drainage implants for the treatment of uveitic glaucoma. 122(6):838-444. 23. Efficacy and safety of latanoprost in eyes with uveitic glaucoma. Flare-up rates with bimatoprost therapy in uveitic glaucoma. Herndon LW. Jaffe GJ. Muir KW. Intraoperative mitomycinC for glaucoma associated with ocular inflammation. Ophthalmology 2001. Management of uveitic glaucoma with Ahmed glaucoma valve implantation. 1997. 2004. 24:310-314. 14. Sayawat N. 11:189-196. 22. Cassoux N. Halkiadakis I. Chipman ML. J Glaucoma. Foster CS. 23:1509-1517. Trabeculectomy with antiproliferative agents in uveitic glaucoma. Ophthalmology 2002. Francis BA. Netland PA. McGehee RF. Ho CL. Herreras JM. Beck AD. LeHoang P. 118:1916-1926. Ophthalmology 2011. Maquet JA. Lin SC. 1:43-53. Georgopoulos G. Kafkala C. Parrish RK. Ceballos EM. Eye (Lond) 2010. 11. Markomichelakis NN. 2008. Derzko-Dzulynsky L. 21. Calonge M. Trope GE. Molteno AC. 2009. Novel glaucoma procedures: a report by the American Academy of Ophthalmology. Ophthalmology 2011. Ceballos EM. Fardeau C. McCluskey P. Shaer B. 20:178-183. Fortuna E. Outcome of trabeculectomy with intraoperative mitomycin C for uveitic glaucoma. Goniosurgery for glaucoma complicating chronic childhood uveitis. 2008. Kaburaki T. Chalkidou S. 2007. 7 ized comparison of systemic anti-inflammatory therapy versus fluocinolone acetonide implant for intermediate. Ophthalmology 2000. Portero A. 13. 16. Baltatzis S. Cervantes-Castañeda RA. Papadaki TG. 9:336-340. Eye (Lond). Buys YM. Kostakou A. Am J Ophthalmol. 2010. Zacharopoulos IP. Rachmiel R. 8. Doctor P. 9. Malone PE. Pederson JE. Combined fluocinolone acetonide intravitreal insertion and glaucoma drainage device placement for chronic uveitis and glaucoma. 88:33-36. Foster CS. Graefes Arch Clin Exp Ophthalmol. 6. 25. Initial trabeculectomy with mitomycin C in eyes with uveitic glaucoma with inactive uveitis. 2002. Koshino T. 17. Hynes A. 10. 19. Flanagan JG. Christen W. Bodaghi B. 108:605-613. Wong EY. et al. Carreño E. J AAPOS. 20. Vuori ML. Towler HM. Foster CS. Arch Ophthalmol. Dupas B. Da Mata A. 149:800-806. Burk SE. 2010. . 247:775-780. Noble J. 42:89-94. 106:2168-2172. 24. 43:462467. Choi J. 2009. Kawashima H. Ophthalmic Surg Lasers. 107:1822-1828. Herbison P. Otago glaucoma surgery outcome study: long-term results of uveitis with secondary glaucoma drained by Molteno implants. and panuveitis: the multicenter uveitis steroid treatment trial. 2011. Bhat P. 109:2256-2260. Acta Ophthalmol. 12. Ahmed valve implantation for uncontrolled pediatric uveitic glaucoma. 144:62-69. Lightman S. Ahmed valve implantation in glaucoma secondary to chronic uveitis. J Ophthalmic Inflamm Infect. Deschenes J. Ozdal PC. Wright MM. Can J Ophthalmol. Ophthalmology 1999. 146:876-882. 7. Deep sclerectomy and trabeculectomy in uveitic glaucoma.e1. Am J Ophthalmol. Eye 2006. posterior. Pasquale LR. Rabinovitch T. Walton DS. Surgical outcomes of uveitic glaucoma. 2005. Lynn MJ. Can J Ophthalmol. Molteno aqueous shunt as a primary surgical intervention for uveitic glaucoma: long-term results. Papakonstantinou D. Ahmed glaucoma valve implantation in uveitic glaucoma versus open-angle glaucoma patients.2012 Subspecialty Day  |  Uveitis Section I: The Uveitis Puzzle for the Non-uveitis Specialist 15. Am J Ophthalmol. Long term followup of trabeculectomy with intraoperative 5-fluorouracil for uveitisrelated glaucoma. Birt C. 28:370-376. Vianna RN. 2007. 118:1466-1480. Schiffman JC. Netland PA. Long-term results of Ahmed glaucoma valve implantation for uveitic glaucoma.

Biased. Haynes. Removal of ocular autoantigens: Type II collagen and lens antigens 2. Zambarajki. and Charteris (2006). IL-2. PPV alone in 14 patients with chronic uveitis b. Kaplan suggested PPV for intermediate uveitis over immunosuppression (1992). Clinical evidence (selected reports) a. Removal of autoreactive immune cells and cytokines (IL-1. noncontrolled. and CME was reduced from 44% to 20% (P < . Lahde. Alter the immunologic milieu with aqueous humor: ACAID a.05). Lens-induced uveitis C. Scott. Diamond and Kaplan (1978) a. e. Intermediate uveitis (46%). Scott. CME improved in 4 eyes (33%) following PPV and 1 eye (14%) with medical therapy.8 Section I: The Uveitis Puzzle for the Non-uveitis Specialist 2012 Subspecialty Day  |  Uveitis Therapeutic Vitrectomy E Mitchel Opremcak MD I. Sarra. f. Cooling. Hypotony and cyclitic membranes F. TNF-a. Randomized into PPV (n = 12) and corticosteroid/IMT (n = 11) arms c. Dickoff. and Garweg (2006) a. Algvere. Complications included retinal detachment (n = 1) and cataract (n = 1). Prospective. Inhibition of complement fixation c. Summary a. and Saari (1981) a. Trittibach. 2. Anti-inflammatory cytokines: TGF-B and VIP b.011) and 42% at 20/40 or better. Improved vision in 68%. Alanko. Retrospective review of PPV in 41 eyes in 38 patients with endogenous posterior uveitis b. and vitreous hemorrhage (1%). etc. Apoptosis 1. Vitrectomy for Repair of Structural Complications of Uveitis A. randomized. PPV is possibly relevant to the outcomes of improving vision and reducing inflammation and CME. and Charteris (2003) a. g. Theoretic mechanism of action 1. Uveitic glaucoma and posterior tube placement II. while the medical arm had no significant improvement in VA. Tranos. d.) 3. d. Traction or rhegmatogenous retinal detachment E. and reduced uveitis activity c. h. VA improved by 2 Snellen lines in 61% (P < . Ayliffe. panuveitis (32%). cataract (6%). debris. Increased vision. Pavesio. decreased CME. Pars plana vitrectomy (PPV) and lensectomy (PPL) in 15 uveitis patients b. and CME reduced from 36% to 18% e. reduced systemic medications in 57%. Literature review of PPV in 1575 uveitis patients and 1762 eyes from 44 articles b. No significant intraoperative or postoperative complications 6. e. Randomized and controlled trials are needed for PPV as an adjunct to the medical treatment of uveitis. Retrospective review of 29 eyes in 23 pediatric patients with chronic uveitis following therapeutic PPV . Complications included retinal detachment (4%). Pavesio. heterogenous diagnoses and nonstandard visual acuities (VA) d. and controlled pilot study of PPV in 23 medically unresponsive patients with intermediate or posterior uveitis b. Vitrectomy for the Control of Uveitis Activity A. Significant increase in the percentage of eyes per month that did not suffer any episodes of uveitis from 70% to 84% (P < .55 (P < .0 to 0. Based on the evidence in the literature. Epiretinal membranes and cystoid macular edema (CME) D. Intermediate uveitis in 841 eyes (48%) c. randomized and controlled B. The PPV group had statistically significant improved VA from logMAR 1. Vitreous opacification. PPV for uveitis was recommended in 41 of 44 papers (93%). Koerner. and hemorrhage B. Orr. 4.0012). Becker and Davis (1981-2005).05). Improved vision in 10 and “cells disappeared from the aqueous” 3. and posterior uveitis (22%) c. 5.

Gupta P. In the PPV group 9 of 11 eyes (82%) had disease resolution off systemic medications at 5. improving VA.93 years. Thakuria P. d. Statistically significant with improved logMAR VA from 0.5 meds) was 32 mmHg and postoperative IOP was 13 mmHg (avg 0. Vitreous surgery in the management of chronic endogenous uveitis. 29:638-643. Letko. All 28 eyes had active uveitis on medications at PVV. Retrospective review of 28 eyes (20 patients) following vitrectomy for pediatric uveitis b. Ocul Immunol Inflamm. A well-designed.2012 Subspecialty Day  |  Uveitis Section I: The Uveitis Puzzle for the Non-uveitis Specialist 9 b. randomized.91 to 0. 27 eyes (96%) were controlled at last followup (13. There were no surgical complications with PVV. f. Three eyes developed cataract and 1 eye developed hypotony. with average follow-up of 33 months (1-204 months) . 2006. 7. Choi YJ. Yilmaz. Pavesio CE. Orr GM. 5. Scott R.69 meds) c. Eye 2010. Hinkle. Based on the evidence in the literature. Becker M. Eye 2006. 17:221-227. Thakuria. 3. Complication included choroidals (n = 1). e. Letko E. and posterior tube placement controlled both IOP and uveitis complications. a. Retina 2009. 8. and controlled clinical trial is needed to confirm these observations and conclusions. In the IMT group.021). Quinones K. Choi. Baker. Chang. and 2 patients on IMT had a reversible anemia and leukopenia. Zambarajki H. Gupta A. Am J Ophthalmol. e. d. and JIA-associated iridocyclitis (n = 5) c. Davis J. VA was was unchanged or improved in 21/32 eyes (65%). c. Tranos P. 6. 2. and Foster (2010) C. Trittibach P. 2005. Singh R. Giuliari. gas tamponade. randomized pilot study. 2. and active disease from 15 eyes (62%) to 7 eyes (30%) (P < . 4 of 7 eyes (57%) failed and required PVV. CME resolved in 3 of 3 eyes with PVV and in 2 of 3 eyes with IMT. Scott RA. Eye 2003. Cooling RJ. Perspectives: vitrectomy in the treatment of uveitis. Ayliffe W. Garweg JG. d. Koerner F.33 (P < . 20:184-190.5 months average) with reduced systemic medications following PPV. Pars planitis (n = 15). and vitreous cell reduction. Quinones. Kafkala. Vitrectomy for juvenile uveitis: prognostic factor for the long-term functional outcome. PPV. Pars plana vitrectomy versus immunomodulatory therapy for intermediate uveitis: a prospective. Hinkle DM. Sarra G-M. Retrospective review of 32 eyes (26 patients) with uveitic glaucoma treated with PPV. CME resolution in 8 of 10 eyes (P < .411-417. Conclusions References 1.042) d. 140:1096-1105. Br J Ophthalmol. Successful outcome of pars plana vitreous surgery in chronic hypotony due to uveitis. Five of 6 eyes with associated retinal vasculitis were now controlled. 2010. Chang PY. 18. Gupta V. 2. The effect of pars plana vitrectomy on cystoids macular oedema associated with chronic uveitis: a randomized controlled pilot study. PPV appears to be safe and helpful in controlling inflammation. and Foster (2010) b. tube occlusion by vitreous resolved with YAG laser (n = 2). 19/32 eyes (60%) had no recurrence of uveitis following PVV. and elevated IOP requiring cylcophotocoagulation (n = 1). f. a. and Opremcak (2012) a. 24:7-13. gas tamponade. and posterior glaucoma tube placement between 1994 and 2011. Preoperative IOP on maximal medical therapy (avg. Two eyes had intraoperative retinal tear. idiopathic panuveitis (n = 8). Kafkala C. multicentered. Haynes RJ. 9. Intermediate uveitis (n = 22) and retinal vasculitis (n = 7) c. e. Yilmaz T. Patronas. randomized pilot study on 18 eyes (16 patients) with recalcitrant intermediate uveitis b. Pars plana vitrectomy in the management of paediatric uveitis: the Massachusetts eye research and surgery Institution experience. Pavesio C. 4. 1. and 4 developed a cataract. Prospective. reducing CME. Giuliari GP. Charteris DG. IOP. Foster CS. 90:1107-1110.001). with better VA. Charteris DG. and reducing the number of medications required to control uveitis in selected patients. Foster CS. 7.

“Idiopathic” III. H. Incidence increases with age (100-300 cases/100. Topical corticosteroids B. Acute 2. Granulomatous disease may present with nongranulomatous features (eg. Systemic medications V. Epidemiology 1.000 person-years for those > 65 years old) C. Differential Diagnosis . Complications A. Drug-related uveitis F. Other considerations 1. Tubulointerstitial nephritis and uveitis (TINU) C.000 population per year 3. Recurrent (only one eye affected. 2. Workup A. Behçet disease). Most common form of uveitis 2. FTA-Abs. Incidence: 8 per 100. Lens-related: postoperative uveitis E. B. JIA). Strep 4. Posner-Schlossman syndrome (glaucomatocyclitic crisis) D. alternating. Anterior uveitis may be “beginning” of posterior disease (eg. bilateral simultaneous) 3. 3.10 Section II: Uveitis Potpourris 2012 Subspecialty Day  |  Uveitis Recurrent Nongranulomatous Anterior Uveitis: E&M Jennifer E Thorne MD PhD I. bilateral asynchronous. Dilated examination: gonioscopy with elevated IOP B. nongranulomatous D. sarcoidosis). Macular edema C. Syphilis 2. Herpetic/CMV G. Lyme 3. Other local corticosteroids C. SUN/IUSG definition: Primary location of inflammation is the anterior chamber. Treatment A. Course of uveitis 1. Anterior Uveitis A. Chronic A. Evolution into chronic uveitis B. Ocular hypertension/glaucoma D. Region-specific test IV. Chronic uveitis entities may present uncommonly as recurrent disease (eg. Cataract II. Infectious 1. chest x-ray C. Topical cycloplegics D. History-driven tests D. “The usual suspects”: HLA-B27. HLA-B27 disease B. Granulomatous vs.

Explain the possibility of other systemic disease developing later. B. iii. a. Retinal vascular leakage 1. and only 30% of sarcoid in children involves the lungs. Stage the Degree of Inflammation A. depending on other associated signs of disease (ie. Inflammation primarily involves the vitreous cavity. creatinine. this is not idiopathic but MS-related uveitis. Differential clearly includes syphilis and sarcoidosis. Consider treatment for CME. Pediatric and adolescent a. quiescent. No ANA. Sudden. Explain to your patient what “intermediate uveitis” means. If MS is present. Medical or surgical option. CBC. Severe iritis with intermediate uveitis suggests either spillover or an occult panuveitis. Neovascularization possible 4. 20/40 vision as an indication to start treatment is no longer an acceptable standard. ii. which is damaging. Fluorescein angiography 2. Cystoid macular edema (CME) common. requirement for treatment of anterior or retinal vascular inflammation) C. Impairment in vision caused by vitreous opacities is difficult to measure in the clinic. Consider treatment for symptomatic vision loss to 20/25 or worse. lesions on MRI will not lead to a diagnosis. 1. Pattern of leakage distinctive 2. Assess whether mainly collagenous or inflammatory. Radiation exposure undesirable g. Neovascularization b. Review ocular imaging II. Sarcoid is an unusual cause of intermediate uveitis in children. acute granulomatous anterior uveitis suggests MS-related uveitis. often visually disabling A. Cases with pediatric idiopathic intermediate uveitis and MS as adults are reported. c. f. Stage according to location. b. Variable anterior segment inflammation 1. Applicability to other groups is uncertain. 2. CT scan of chest with contrast originally described as having higher sensitivity than chest x-ray in elderly patients. Vision 1. Vitreous opacity 1. collagenous extracellular disease B. often extensive 1. Coats-like response d. Leukemic infiltration is a concern. III. posterior to equator worse D. Other common uveitides in this age group are juvenile rheumatoid arthritis and tubulointerstitial nephritis and uveitis syndrome. 2. No MRI of brain i. 2. A. No chest X-ray or chest CT scan e. small vessel or occlusions worse 2.2012 Subspecialty Day  |  Uveitis Section II: Uveitis Potpourris 11 Pars Planitis: What to Do When the Intermediate Uveitis Is Idiopathic Janet Louise Davis MD I. C. Retinal vascular leakage common. Peripheral retinal angioma 2. 1. 2. a. b. Syphilis is a concern at any age. Back up your explanation by reviewing the test results. OCT C. Explain to your patient what “idiopathic” means. 3. FTA b. Pars plana exudate 1. Occlusion uncommon 3. Complications that may require treatment a. ANA. but chest x-ray and angiotensin converting enzyme indicated. Consider the option to treat symptomatic vitreous opacities. Stage according to intensity. If MS is not present. d. Association with active focal vitreous opacities vs. c. Adults . Vitreous hemorrhage c. B.

and panuveitis. Pars plana vitrectomy versus immunomodulatory therapy for intermediate uveitis: a prospective. Cataract from corticosteroids. Mycophenolate mofetil or mycophenolic acid iv. Foster CS.12 Section II: Uveitis Potpourris IV. Most idiopathic intermediate uveitis does not change pattern or intensity much over time. Br J Ophthalmol. 4. Azathioprine b. 20(3):171-181. 18(5):411-417. Ossewaarde-Van Norel J. Pulmonary for those with abnormal testing C. Gregoire MA. Lightman S. 11. J Ophthalmic Inflamm Infect. 2012. Vision loss from CME B. 2(1):21-8. Rothova A. Altaweel MM. Follow-up every 3 months 1. 95(5):646-651. Galor A. Systemic therapy a. 10. and panuveitis: the multicenter uveitis steroid treatment trial. 2012. ten Cate HA. Joshi L. Holbrook JT. Retinal vasoproliferative tumors in ocular conditions of childhood. 2012. randomized pilot study. 12. Chan-Kai BT. Rothova A. Leder HA. 2012. Characterization of serous retinal detachments in uveitis patients with optical coherence tomography. Erratum in: Ophthalmology. Epub ahead of print 26 Apr 2012. Ophthalmology. Taylor SR. et al. Pagnini I. Arrange for Monitoring A. Expert Opin Investig Drugs. Reichstein D. Less often if stable and in late stages or has very mild disease B. Am J Ophthalmol. 16(1):6-9. Dunn JP. Choi JY. Am J Ophthalmol. Shields JA. 2010 to 2012 1. Ocul Immunol Inflamm. posterior. Taylor SR. Kalinina Ayuso V. Consider Subspecialty Consultation A. 9. Ocul Immunol Inflamm. 1. 6. 2. Epub ahead of print 2 June 2012. Glaucoma from corticosteroids. Camfferman LP. Yilmaz T. 2010. J AAPOS. Frediani B. Ophthalmologica 2010. Discrepancies between fluorescein angiography and optical coherence tomography in macular edema in uveitis. Broussolle C. Isa H. Corticosteroid-sparing therapy: practice patterns among uveitis specialists. Local therapy a. Assess progression 1. Cantarini L. posterior. Immunomodulatory agents i. Match the Treatment to the Disease A. If patients are stable without progression and minimal signs of disease. Young age as a risk factor for complicated course and visual outcome in intermediate uveitis in children. Kafkala C. Quinones K. Rheumatology for help with administering or monitoring drug therapy . Posterior synechiae 2. 8. observation may produce fewer complications than treatment. 3. PMID:22541651. New developments in corticosteroid therapy for uveitis [review]. Periodic angiography and OCT to check retinal inflammation Selected Readings. 118(10):1916-1926. 119(2):212. Most pediatric intermediate uveitis diminishes in adulthood. Randomized comparison of systemic anti-inflammatory therapy versus fluocinolone acetonide implant for intermediate. 3. 2. Qualitative assessment of the angiographic findings 2. Yeh S. Mashayekhi A. Jabs DA. Interferons ii. V. 21(1):1-6. Acharya NR. Cryotherapy to areas of exudative detachment b. 2011. Sugar EA. Simonini G. 2011. Characteristics of uveitis presenting for the first time in the elderly: analysis of 91 patients in a tertiary center. Letko E. et al. Cyclosporine iii. Assess severity 1. Treatment strategies for childhood noninfectious chronic uveitis: an update [review]. Biologics i. Seve P. Laser photocoagulation to peripheral retina anterior to equator adjacent to snowbanks c. Qualitative assessment of the OCT findings D. Grange JD. Neurology for those with symptoms B. Shields CL. More often if in early stages 2. Esterberg E. Lightman SL. 4. Multicenter Uveitis Steroid Treatment (MUST) Trial Research Group. 2011. Waxing and waning is possible. C. Regional steroid injection d. 2012. Kodjikian L. Methotrexate ii. 5. 2011. 152(3):441448. de Boer JH. Consider standard therapies. Periocular triamcinolone acetonide injections for cystoid macular edema complicating noninfectious uveitis. Varron L. et al. 224 suppl 1:46-53. J Ophthalmic Inflamm Infect. PMID: 22661129. especially in children 4. Galeazzi M. 19(4):219-226. The impact of macular edema on visual function in intermediate. Thorne JE. Avoid structural damage 1. Kempen JH. Cimaz R. Ocul Immunol Inflamm. especially in children 3. 7. TNF-inhibitors: TB testing and MRI prior to use 2012 Subspecialty Day  |  Uveitis VI. Simmons-Rear A. van den Does P. Pars plana vitrectomy combined with the above 2. Laboratory monitoring as appropriate for the agents used C.

Section II: Uveitis Potpourris 13 . Zierhut M. 118(1):184-190. Ocul Immunol Inflamm. Margolis TP. Loh AR. 14. Colucci A. Lin P. et al. Ocul Immunol Inflamm. Acharya NR. 2009. Am J Ophthalmol. Ophthalmology 2010. 2010. 149(3):423-432. 17. Jones NP. 18(1):60-63. Modorati G. Thorne JE. Dhawahir-Scala FE. 117(3):585-590. Mycophenolate sodium for immunosuppressive treatment in uveitis. Daniel E. Deuter CM. Quality of life in patients with uveitis on chronic systemic immunosuppressive treatment. 18. Miserocchi E. 17(6):415-419. Hatef E.2012 Subspecialty Day  |  Uveitis 13. Bandello F. Cigarette smoking as a risk factor for uveitis. Doycheva D. 15. Jalil A. e1-2. Nonprogressive tractional inferior retinal elevation in intermediate uveitis. 2010. Stuebiger N. A cross-sectional study of the current treatment patterns in noninfectious uveitis among specialists in the United States. Mycophenolate mofetil for ocular inflammation. Ocul Immunol Inflamm. 16. 2010. Mosconi P. Nguyen QD. Newcomb CW. Kayen B. Ophthalmology 2011. 18(4):297304. et al.

Retinal vasculitis is diagnosed clinically by the observation of focal. With modern treatments a substantial cohort of patients maintain their vision in the long term. Summary Retinal vasculitis is not a single disease but a response to various insults. Selected Readings 1. In general they are not used for very longterm control. Jabs DA. 2010. Smith JR. Occult causes are rare. including retinal vasculitis. Treatment Once infection has been excluded or treated and sight-threatening changes are present. Characteristics and visual outcome of patients with retinal vasculitis. retinal ischemia and its sequelae can develop. Antimetabolites—methotrexate. Eales disease.5 mg/d prednisone equivalent. 8. Investigations The major diagnostic yield comes from careful history and examination of the eyes and any other involved site. infliximab infusions. Vile RG. It is uncommon. The eye may be their herald organ. mycophenolate mofetil. Ku JH. Patients with retinal vasculitis rarely suffer from systemic vasculitis. Other tests are directed by history and geographic origin of the patient. 2012. Tabbara KF. Can J Ophthalmol. allowing smouldering disease. particularly emerging infections. Alkylating drugs. typically cyclophosphamide. 127:819-822. represent the most frequent cause. Infections of the eye. comes in some patients with posterior uveitis. and as an alternative to cryotherapy in some cases of pars planitis. 2009. More questions than answers: a call for a moratorium on the use of intravitreal infliximab outside of a well-designed trial. Infliximab therapy for refractory uveitis: 2-year results of a prospective trial. immunosuppressives. serology for syphilis. Retina 2010. Some are restricted to the eyes. If the vessels become occluded. Intravitreal administration of steroids. 2012. cases of focal ischemia. 6. A suggested basic screen would include a full blood count. Suhler EB. 2010. For Behçet’s. and therefore laboratory investigations can be limited in most patients.4% of cases. 11:1-6. require vitreoretinal intervention. cyclosporine or tacrolimus is used. Vitrectomy may be needed to clear persistent inflammatory debris or hemorrhage and to remove epiretinal membranes. Cunningham ET. 146:845-850. 130:492-513. particularly doses above 7. TNF inhibitors for uveitis: balancing efficacy and safety. perivascular sheathing of the retinal blood vessels. retinal vasculitis is also seen as a manifestation of systemic diseases such as Adamantiades-Behçet disease. Arch Ophthalmol. Semin Arthritis Rheum. These expensive drugs require careful monitoring. sarcoidosis. Ocul Immunol Inflamm. and more rarely autoimmunity or even malignancy. Surgical Intervention Retinal photocoagulation is used for obliterative vasculitides. Recent recognition of an increasing number of causes. 2. immunomodulatory therapy (IMT) is introduced. Fluorescein angiography identifies areas not visible by ophthalmoscopy alone and is therefore helpful to assess the extent of the disease and to identify areas of ischemia that may need photocoagulation. 3. Wender JD. Am J Ophthalmol. reducing by 10 mg/day each week (if no relapse) to 10 mg/day maintenance. 2008. Third-line therapy includes anti-TNF antibodies. 7. Choi D. Infliximab effects compared to conventional therapy in the management of retinal vasculitis in Behcet disease. sedimentation rate. 41(6):859-865. Pulido JS. and the therapeutic role of newer anti-inflammatory agents and cytokines is changing the way this condition is managed. Foster CS. interferon therapy has a role. A recent chart review of 1390 patients attending a North American uveitis clinic found that systemic vasculitis was the cause of retinal vasculitis in only 1. Am J Ophthalmol. 4. particularly with toxoplasmosis and herpes virus. Primary retinal vasculitis affecting the eye vasculature without evidence of any systemic or other eye disease is called idiopathic retinal vasculitis. et al. Ku J. Leakage of fluid through the normally impermeable vessel wall leads to retinal edema. Chronic use of steroids. then high-dose prednisone is commenced at 1 mg/kg/day. Guidelines for the use of immunosuppressive drugs in patients with ocular inflammatory disorders: recommendations of an expert panel. Ali A. Michet CJ. Suhler EB. 45(4):352-358. Suhler EB. Rosenbaum JT. and even biologics have been reported to improve out- . Retinal tears and detachment. and perhaps a chest x-ray or Mantoux skin test in certain endemic areas to exclude exposure to tuberculosis. Pulido JE. If disease is not controlled. Ali A. 30(1):1-5. 2000. Zierhut M. Some systemic diseases such as sarcoid or multiple sclerosis may not manifest for years after their initial presentation as retinal vasculitis. and azathioprine—have a slow onset but a low rate of serious side effects. Arch Ophthalmol. or adalimumab (Humira) injections. Low doses of anti-inflammatory drugs. lead to progressive ocular damage. et al. Giles TR. However. Al-Hemidan AI. should be avoided. Rosenbaum JT. 18(6):421-423. Cunningham ET Jr.14 Section II: Uveitis Potpourris 2012 Subspecialty Day  |  Uveitis Retinal Vasculitis William Ayliffe MBBS Introduction Retinal vasculitis is a sight-threatening inflammatory eye disease involving the retinal blood vessels. particularly cases of acute retinal necrosis. are reserved for systemic vasculitis and resistant cases. Practical approach to the use of corticosteroids in patients with uveitis. Treatment has to be timely and sufficient to control inflammation. but others represent a manifestation of systemic disease or infection. If rapid control of disease is required. 5. Rosenbaum JT. Choi D.

1996. IgA c. MG and other ductule scar 3. 93:14714-14719. Effect on signal transduction 1. Keratopathy 1. IV. Scarring 2. Linear deposits at the epithelial basement membrane zone (BMZ) a. Genetic predisposition: HLA-DQw7. Environmental trigger: drugs. Foster. IgG b. OCP Target Antigen Identification III. Uncein 8. Laminin-6 6. Keratin 7. The autoantibodies are pathogenic. Environmental trigger a. Conjunctival “shrinkage” 2. Hemler. Epi defects and ulceration A. Mucous Membrane Pemphigoid A. Livir-Rallatos. Amplification 2. Mucosal epithelial squamous metaplasia and GC dysfunction F. β4 Subunit of α6 / β4 Integrin: OCP Antigen VI. BPA 2 3. Genetic susceptibility 2. B. Microbe 1. Lesion Production A. Cytokine effects on fibroblasts a. V. Topical medication c. Fibrosis II. Two hit hypothesis 1. C3 2. Immunopathology 1. Autoantibody binding to an intracellular epitope of basal epithelial cells C. Bhol. Inflammatory cell infiltration 1. RIA. OCP Autoantibodies A. 168-kDa epi protein We have identified the β-4 subunit of α-6 / β-4 integrin as the target antigen in patients with ocular cicatricial pemphigoid (OCP). Cicatricial Pemphigoid: Pathogenesis VIII. Proc Nat Acad Sci. β-4 integrin E. OCP Susceptibility Gene Identification VII. Circulating antibodies: By IDIF. HLA-DRB1*04 2. HLA-DQB1*0301 A. or ELIZA B. TGF-β b. The binding of the autoantibody to the autoantigen of the epithelial BMZ sets in motion a complex drama in which an impressive cast of characters participates. Ocular cicatricial pemphigoid antigen: partial sequence and characterization. Stage 1: Chronic conjunctivitis and subepithelial fibrosis B. and Ahmed. Autoantibody production against a 205 kD protein in the upper lamina lucida of the BMZ A. Neovascularization 3. Systemic medication b. HLA-DRB4*0101 3.2012 Subspecialty Day  |  Uveitis Section III: External Ocular Inflammatory Diseases 15 Chronic Conjunctivitis: Is It Ocular Cicatricial Pemphigoid? C Stephen Foster MD I. Against β 4 peptide of α6/β4 integrin ± others 2. Effect on cytokines and inflammatory cell recruitment D. Laminin-5 4. We have reported that the following genes are associated with OCP: 1. virus? C. Natarajan. Autoantibodies to conjunctival BMZ can be detected in all OCP patients when the disease is active. Lash follicle misdirection 4. C. Tyagi. Autoimmune 8 different epithelial BMZ targets 1. IFN-γ 1. OCP: Ocular Manifestations . DQB1*0301 B. Autoantibody production 5. BPA 1 2. Effect on attachment molecule relationships 2.

Cytosine arabinoside G. Genital E. Imuran D. Zein G. 2005. XIV. Foster CS. Simmons RK. Dapsone B. B. 25%-50% 3. transition to IV-Ig at 6 months 2012 Subspecialty Day  |  Uveitis XIII. Esophageal F. Effective treatment of OCP requires systemic immunomodulation. OCP) is a systemic autoimmune disorder that produces progressive conjunctival cicatrization with secondary blinding keratopathy. Ruzicka T. Ahmad SR. Summary X. Trans Am Ophthalmol. Lightman S. 78% A. B. OCP Clinical Course A. 97(11):14761483. diagnosis and treatment. Mucous membrane pemphigoid: clinical aspects. Rituximab A. Eschle-Meniconi ME. 3. Hertl M. Foster CS. 16:303307. Treatment: Dapsone or MTX or CellCept or Imuran first. > 50% B. < 25% 2. immunopathological features and therapy. Wilson and Ekins. 2004. Foster CS. Cytoxan F. Dart JK. Rice BA. XI. Oral B. 4. 23:579-592. 75% 3. The autoantibodies to alpha 6 beta 4 integrin of patients affected by ocular cicatricial pemphigoid recognize predominantly epitopes within the large cytoplasmic domain of human beta 4. Foster CS. Methotrexate (MTX) C. Bruch-Gerharz D. All treatments except those that suppress abnormal (dysregulated) immune responses (autoimmune responses) have failed to stop the progressive conjunctival scarring characteristic of OCP. next add IV-Ig if necessary. 84:527-663. Mucous membrane pemphigoid: an update. Example 2 1. Ahmed AR. B. Stage 3: Symblepharon formation D. Immunopathology of cicatricial pemphigoid affecting the conjunctiva. 84:527-663. Ophthalmology 89:340-353. 1986: Foster. Mucous membrane pemphigoid affecting the eye (ocular cicatricial pemphigoid. Bhol KC. Wright P. Curr Opin Ophthalmol. Foster CS. The conjunctiva in acute and chronic mucous membrane pemphigoid: an immunohistochemical analysis. 17(3):191-200. Treatment: Cytoxan with prednisone. 2000. Prog Retin Eye Res. Presentation: Progressive disease and mild to moderate inflammation 2. J Immunol.16 Section III: External Ocular Inflammatory Diseases B. Eur J Dermatol. A. Stage 4: End stage keratinization IX. Conjunctival shrinkage at first observation 1. Cicatricial pemphigoid. 50% 2. CellCept E. Mucous Membrane Pemphigoid A heterogenous group of chronic inflammatory blistering diseases that manifest a varying constellation of lesions. 1. Leonard JN. Nasopharangeal A. Ahmed M. 100(3):339346. OCP Therapy XII. Giancotti FG. Ophthalmology 1990. 2. Dans MJ. IV immunoglobulin (IV-Ig) H. Bernauer W. Patients with disease progression in 2 years 1. Stage 2: Fornix foreshortening C. 5. 1986. Presentation: Progressive disease and marked inflammation 2. Ocular cicatricial pemphigoid: pathogenesis. Trans Am Ophthalmol Soc. Skin D. Example 1 1. proceed to rituximab + IV-Ig as needed. OCP References 1. 7. Ocular C. 1982: Foster. 2. Ophthalmology 1993. Examples . Khawaja F. 6. 2007. 165(5):2824-2829. Our ventures into this field began in 1978. A.

ordering appropriate investigations based on the clinical features. Pellucid marginal corneal degeneration and Senile furrow degeneration are common etiologies that may seldom be confused with PUK and are differentiated by presence of an intact epithelium. non ulcerative process) d. Look for vascularization of bed (suggests chronic disease). as the diagnosis may vary from simple corneal infectious pathology to any of a gamut of systemic collagen vascular diseases that present with a peripheral ulcerative keratitis (PUK) or a number of mimics of the condition. infiltration. Table 1. Lucid interval between the epithelial defect and the limbus points toward etiologies such as phlycten and catarrhal ulcers. c.painless. Presence of infiltration mark disease to be active. The immunological basis of disease in most instances and role of immunosuppression demands a team approach with an internist for adequate immunosuppression and systemic evaluation and monitoring of these cases. or Something More Ominous? Virender S Sangwan MBBS Introduction When encountered with a central corneal ulcer. size (in terms of clock hours of involvement). Moraxella. Additionally. Appropriate microbiological investigations including smears. and an algorithm-based stepwise management provides good results in these cases. It is often a nightmare for physicians. b. It is imperative for the physician to identify various signs that would help in differentiating one from the other. it is often important to identify the underlying ocular or systemic disease and also sometimes to differentiate this condition from a number of masquerades that may mimic as PUK. cultures. The progressive nature of the disease demands aggressive therapy to curtail the devastating corneal destruction. A systematic approach that includes identification of classical clinical signs.2012 Subspecialty Day  |  Uveitis Section III: External Ocular Inflammatory Diseases 17 Peripheral Ulcerative Keratitis: Mooren’s. a peripheral corneal ulcerative pathology opens up a Pandora’s box. presence of lipid deposits with vascularization (Terrien’s disease. herpes zoster Acanthamoeba Fungal Ocular Noninfectious Causes Mooren ulcer Terrien marginal degeneration Keratoconjunctivitis sicca Blepharitis Neurotrophic keratitis Chemical injury Contact lens Trauma Systemic Infectious Causes Tuberculosis Syphilis Varicella zoster HIV Systemic Noninfectious Causes Rhematoid arthritis Giant cell arteritis Wegener granulomatosis Systemic lupus erythematosus Malignancies Rosacea Polyarteritis nodosa Sarcoidosis Behçet disease Progressive systemic sclerosis Approach to PUK We follow a systematic. with or without associated scleral inflammation. stepwise approach to PUK as summarized in following algorithm: Step 1: Assessment of corneal lesion a. Streptococcus. ulcer edges. Epithelial status: Absence of epithelial defect rules out an active PUK. . Terrien’s. However. characterized by thinning of the affected area. depth of stromal loss. PUK is classically described as peripheral crescent-shaped inflammation of corneal stroma adjacent to the limbus. and immunological tests (PCR) help to identify causative infectious organisms in case of infectious etiology. Haemophilus Viral: herpes simplex. e. Differential Diagnosis of PUK Ocular Infectious Causes Bacterial: Staphylococcus. the first differential to cross the corneal physician’s mind is usually an infectious etiology. Additionally systemic evaluation using hematological and radiological investigation may provide important clues to the diagnosis. with or without underlying systemic or ocular diseases. What makes PUK an important issue is that it is often the first sign or the presenting sign of a number of systemic collagen vascular disorders. It is important to rule out an infectious process in these cases. Look for signs of disease activity: Ulcer location. The purpose of this outline is to provide a comprehensive overview of the differential diagnosis of peripheral ulcerative keratitis and to briefly discuss our stepladder approach for management of PUK and Mooren ulcer.

et al. 91:1253-1255. 2. ANA. more than 50% stromal loss Steroid intolerance. There is essentially no scleral involvement in Mooren ulcer. Mooren’s ulcer in children. especially in cases such as Wegener granulomatosis. Surv Ophthalmol. Wang Z. Srinivasan M. single eyed. Foster CS. Chen J. A prompt identification of the underlying disease and its appropriate management is important for both visual and life salvage. > 50% stromal loss. 2000. 4. Presence of scleritis points toward underlying systemic collagen vascular disorders. Ashar J. It is an idiopathic disease seen in young healthy adults with no systemic disease. Thorough history of systemic manifestations may point toward possible underlying diagnosis: – Skin rash. 2012. Br J Ophthalmol. single eyed Bilateral. spreads circumferentially and then centrally to eventually leave only a central island of cornea or quiescence only after complete destruction of corneal stroma. single eyed. Younger patients have severe disease with bilateral involvement. et al. 3. x-ray chest. Zelefsky JR. less than 50% stromal loss Bilateral cases. Table 2. Zegans ME. less than 2 quadrants of peripheral corneal involvement. Antimicrobial therapy for infectious etiology 2. SLE – Swollen ear lobes: Relapsing polychondritis b. The disease needs an aggressive immunosuppressive regimen (described later) for control and prevention of recurrence.18 Section III: External Ocular Inflammatory Diseases 2012 Subspecialty Day  |  Uveitis Step 2: Examination of conjunctiva. Wilson LA. CRP. After ruling out infectious etiology. depigmentation: SLE – Respiratory symptoms: Wegener granulomatosis. 91:570-575. Mooren’s ulcer in China: a study of clinical characteristics and treatment. early postoperative period after keratoplasty Immunosuppression Topical steroids Oral steroids Oral methotrexate IV methylprednisolone IV methylprednisolone + IV cyclophosphamide References 1. Presence of meibomian gland dysfunction and blepharitis may be associated with marginal keratitis that may sometimes be confused with PUK. bilateral disease. ANCA. Sangwan VS. Foster CS. Ophthalmology 1984. Vasculitic peripheral ulcerative keratitis. Xie H. Mooren ulcer is an important entity. 1999. Clinical characteristics of Mooren’s ulcer in South India. 5. Immunosuppression Regimen Features Unilateral cases. The disease involves limbus. The disease has a male preponderance. more than 3 quadrants of peripheral corneal involvement. Management A stepladder approach to management of PUK provides good outcomes. Collagen vascular disorders as a cause of PUK are characterized by associated scleral involvement in the form of scleritis and scleromalaciaperforans in severe cases. easy sunburns. the following approach may be followed for autoimmune-mediated or vasculitic PUK: • Medical therapy: We prefer to use the severity-based immunosuppression regimen that is presented in Table 2. The disease is characterized by a relentless and aggressive course with multiple relapses. and lids Associated scleritis rules out etiology such as Mooren ulcer. 2007. 1. Step 3: Systemic evaluation a. VDRL Of the various etiologies associated with PUK. sclera. Br J Ophthalmol. • Surgical therapy: – Conjunctival resection with tissue adhesive and bandage contact lens – Crescentric patch graft / lamellar graft / penetrating keratoplasty – Boston keratoprosthesis . Br J Ophthalmol. perforation. impending perforation Bilateral. Forstot SL. 96:796-800. Churg-Strauss syndrome – Joint pains: RA. more than 3 quadrants of peripheral corneal involvement. more than 2 quadrants of peripheral corneal involvement. Mathur A. rheumatoid factor. young patients (< 50 years). Mortality rate in rheumatoid arthritis patients developing necrotizing scleritis or peripheral ulcerative keratitis. Messmer EM. Investigations: ESR. 84:1244-1249. 43:379-389.

” is a growing public health concern that affects as many as 17% of women and 11. As mentioned above. Thus. (Peri. and tumor necrosis factor (TNF) α were also investigated. A more recent multicenter.and postmenopausal females seem to be particularly at risk. is mediated in part by a number of intracellular kinase and phosphatase enzymes. airplane cabins. Older age and female sex seem to be the two most common risk factors for dry eye. More staining appeared in the cytokines of dry eyes compared with normal eyes. with evidence of reduced salivary secretion and a positive focus score on minor salivary gland biopsy. It is accompanied by increased osmolarity of the tear film and inflammation of the ocular surface. TNFα. Among the aqueous deficient group. hormonal studies demonstrate that sex hormones influence ocular surface conditions through their effects on aqueous tear secretion. This process appears to be mediated through activation of the c-Jun N-terminal kinases and extracellular-regulated kinase MAPK signaling pathways. Regardless of the presence of any identifiable underlying local or systemic inflammatory disorder. IL-8. and tear film instability with potential damage to the ocular surface. and the C-X-C chemokine IL-8. although it is not known whether the inflammation is the cause or the consequence of dryness. and extended visual tasks such as computer use. A recent International Dry Eye Workshop (DEWS) defined dry eye as a “multifactorial disease of the tears and ocular surface that results in symptoms of discomfort. It has been documented that activation of these stress pathways results in transcription of stress-related genes. For instance. In the same study. The study concluded that ophthalmologists caring for patients with clinically significant dry eye should have a high index of suspicion for underlying SS and a low threshold for diagnostic workup.) This suggests perhaps that dry eye is an involutional disorder. researchers concluded that hyperosmolarity induces inflammation in human limbal epithelial cells by increasing expression and production of proinflammatory cytokines and chemokines such as IL-1β.2012 Subspecialty Day  |  Uveitis Section III: External Ocular Inflammatory Diseases 19 Is Keratoconjunctivitis Sicca an Inflammatory Disease? Esen Karamursel Akpek MD Although often underrecognized and underappreciated. Stress-activated protein kinases have been identified for this purpose. These factors should not be considered important only as they relate to the pathogenesis of dry eye. patients with both SS-related dry eye as well as non-SS dry eye have identical conjunctival inflammation manifested by inflammatory cell infiltrates and upregulation of expression in markers of immune activation. Based on histopathological evaluations. There is growing evidence from the past decade that shows dry eye-related ocular surface inflammation is mediated by T-cell lymphocytes. mitogen-activated protein kinases (MAPKs) were found to stimulate the production of inflammatory cytokines and MMPs. refractive laser surgery. and conjunctival goblet cell density.” The DEWS also recognized two subgroups of dry eye syndrome based on etiopathogenesis: aqueous deficient and evaporative. the most common of which is rheumatoid arthritis. the efficacy of corticosteroids and doxycycline. and extreme hot or cold weather. and it has been suggested by one study that they might be involved in the pathogenesis or self-propagation of SS-related dry eye. following menopause) might cause dry eye. which are mostly used for treating ocular surface diseases. keratoconjunctivitis sicca. In addition. A previous retrospective study from a single tertiary eye care center determined that pSS is underdiagnosed in patients with dry eye syndrome and should be the focus of diagnostic evaluations. IL-1β. including inflammatory cytokines such as IL-1 and TNF-α and MMPs. commonly referred to as “dry eye. smoking. there are two major subclasses: Sjögren syndrome (SS) dry eye and non-SS dry eye. reactive nitrogen species have been investigated in dry eye. TNF-α. Primary Sjögren syndrome (pSS) consists of aqueous-deficient dry eye syndrome in combination with symptoms of dry mouth in the presence of autoantibodies. and prolonged reading. two forms of SS were identified. they should also be kept in mind when discussing treatment strategies. a lack of hormones (eg. and MMP-9. The source of the increased levels of IL-1 was thought to be the conjunctival epithelium. air-conditioned cars. Certain systemic medications such as diuretics or antihistamines can cause dry eye. Multiple other studies followed and demonstrated the role of inflammatory cytokines and matrix metalloproteinases (MMPs) in the pathogenesis of dry eye. The response of cells to extracellular stimuli such as ocular surface stress. This is likely an underestimate if the self-treating patients and milder/periodic cases are considered.1% of men in the United States. including IL-β. Many other factors are known to precipitate and/or exacerbate dry eye. According to the classification criteria from the European American collaboration. including increased tear film and ultraviolet light exposure. visual disturbance. In another study. meibomian gland function. Interleukin (IL)-1 is one of the most studied cytokines accompanying dry eye. In one study investigating whether exposure of human limbal epithelial cells to hyperosmotic stress activates the MAPK pathways and induces production of proinflammatory cytokines. Secondary SS (sSS) consists of the features of pSS together with the features of an overt autoimmune connective tissue disease. Recently. such as longterm contact lens wear. may be explained by their ability . IL-6. Frequent use (> 4-6 times daily) of preserved eye drops may also contribute to dry eye because of the well-established toxicity of preservatives such as benzalkonium chloride. based on multiple epidemiological studies. An increase in the proinflammatory forms of IL-1 (IL-1α and mature IL-1β) and a decrease in the biologically inactive precursor IL-1β have been found in the tear film of dry eye patients. Dry eye can also be worsened by low relative humidity conditions that are common in office environments. dry eye seems to be invariably associated with ongoing ocular surface inflammation. These results suggested that clinical symptoms of dry eye may be more dependent on T-cell activation and resultant inflammation than previously believed. hyperosmolarity is one of the factors that contribute to ocular surface inflammation. mainly MMP-9. Recognition of the role of inflammation in dry eye has been one of the most important factors to have aided dry eye treatment. prospective study confirmed these findings in a group of more than 300 patients with clinically significant aqueous deficient dry eye. television watching.

4. Lee AJ. Tolls DB. et al. 45:4293-4301. Curr Opin Ophthalmol. Selected Readings 1. et al. 22. regulation and function. Widjaja D. Classification criteria for Sjögren syndrome: a revised version of the European criteria proposed by the American-European consensus group. JAMA. Prevalence and predictors of Sjogren’s syndrome in a prospective cohort of patients with aqueous deficient dry eye. Thorne JE. 118:1264-1268. Tong L. De Paiva CS. Sullivan DA. Koh D. 5:93-107. Ocul Surf. et al. et al. 43:2609-2614. Vitali C. The modern office environments desiccate the eye? Indoor Air. et al. Pflugfelder SC. Evans JE. 42:22832292. Arch Ophthalmol. 23. Dursun D. Stern ME. Ann Rheum Dis. Lemp MA. Ocul Surf. Ang RT. et al. Hall CW.20 Section III: External Ocular Inflammatory Diseases 2012 Subspecialty Day  |  Uveitis 12. Gao J. 82:588596. Analysis of topical cyclosporine treatment of patients with dry eye syndrome: effect on conjunctival lymphocytes. 2000. 286:2114-2119. 19. Prevalence and risk factors associated with dry eye symptoms: a population based study in Indonesia. Wilson S. Ardan T. 7. Epub ahead of print 21 Sept 2012. Akpek EK. regardless of the underlying etiology. 13. 2001. Paul A. 2002. Franck C. 16. Skov P. Liew M. 10. Buring JE. Br J Ophthalmol. 2006. 2002. MAPK activation in the corneal epithelium in experimental dry eye. 12:318-322. Cell Signal. 2001. Villarreal AL. 21. Management and therapy of dry eye disease: Report of the Management and Therapy Subcommittee of the International Dry Eye WorkShop (2007). Wolkoff P. Bombardieri S. Jonsson R. Ullman MD. et al. 85:48744882. Gazzard G. 3(suppl 4):154-157. 2007. Hormone replacement therapy and dry eye syndrome. 9:403-410. Ocul Surf. 20. et al. 17. Liu Z. et al. Cornea 2009. Klein BE. In conclusion. Corticosteroid and doxycycline suppress MMP-9 and inflammatory cytokine expression. 83:526-535. Schaumberg DA. 17:10-17. 61:554-558. 2007. 70:182-186. Schwalb TA. Klimava A. Prevalence of and risk factors for dry eye syndrome. The definition and classification of dry eye disease: report of the definition and classification subcommittee of the international dry eye workshop (2007). Dry eye after refractive surgery. Akpek EK. Dana MR. 2006. et al. 2004. 18. 14. The epidemiology of dry eye disease: Report of the Epidemiology Subcommittee of the International Dry Eye Workshop (2007). Schlote T. Li DQ. Simonová Z. Nitric oxide synthase induction and cytotoxic nitrogen-related oxidant formation in conjunctival epithelium of dry eye (Sjögren’s syndrome). Dartt DA. Experimental dry eye stimulates production of inflammatory cytokines and MMP-9 and activates MAPK signaling pathways on the ocular surface. Chen Z. Exp Eye Res. Kadner G. 242:306-312. 6. 2001. 86:13471351. to suppress JNK and ERK signaling activation and inflammatory mediator production in the limbal epithelium. Exp Eye Res. Klein R. et al. et al. 16:258-265. TNF-alpha and IL-8 following hyperosmolar stress in human limbal epithelial cells. Nøjaard JK. Kunert KS. . J Clin Endocrinol Metab. Cejková J. Tsubota K. dry eye seems to be associated with chronic and perhaps subclinical inflammation that might eventually cause ocular surface damage. 11. Invest Ophthalmol Vis Sci. Tisdale AS. Br J Ophthalmol. 2002. 2007. J Am Optom Assoc. Flockencier LL. Saw SM. 2. Cermak JM. 3. Baum J. 5:163-178. 2007. Lee J. Arch Ophthalmol. 8. 2000. et al. Luo L. 5:75-92. Luo L. et al. 2005. 2004. 118:1489-1496. The influence of gender on the ocular surface. Kim E. Connor CG. Stern ME. Corrales RM. Stress-activated protein kinase signaling pathways in dry eye and ocular surface disease. Frudenthaler N. Invest Ophthalmol Vis Sci. Effect of androgen deficiency on the human meibomian gland and ocular surface. Belham CM. Nitric Oxide. 2006. Solomon A. Invest Ophthalmol Vis Sci. Novel treatments should aim toward targeting specific mediators involved in the inflammatory cascade that mediate dry eye. Zhang M. 28:493-497. Ocul Surf. 1999. 2000. Krenzer KL. Pro. Li DQ. Marked reduction and distinct pattern of eye blinking in patients with moderately dry eyes during video display terminal use. Stress-activated protein kinases: activation. Doshi A. Evaluation of patients with dry eye for the presence of underlying Sjögren syndrome. 5. Graefes Arch Clin Exp Ophthalmol. 1997. Moss SE. Baudouin C. Conjunctival T-cell subpopulations in Sjögren’s and non-Sjögren’s patients with dry eye.and anti-inflammatory forms of interleukin-1 in the tear fluid and conjunctiva of patients with dry-eye disease. 9. 15. JNK and ERK MAP kinases mediate induction of IL-1beta. de Paiva CS.

OPHTHPAC® Fund 2. The Academy’s Secretariat for State Affairs redoubled its efforts with “target” states.s but also the contributions made by ophthalmic state. in partnership with state ophthalmology societies. While Kentucky was an outlier. with narrowing practice margins making efficiency of increasing importance. were elected to Congress in 2010.D. The Academy relies not only on the financial contributions via the SSF by individual Eye M. while adding professional media training to the resources provided to prepare Eye M. which has met for the past five years in the Washington. In 2010.D. the Academy’s SSF has helped 33 state / territorial ophthalmology societies reject optometric surgery language.” it also remains firm on defining appropriate roles for the various eye care providers as demonstrated via its Surgery by Surgeons campaign. Among the significant impacts of OPHTHPAC: • Averted significant cuts to Medicare payments due to the Sustainable Growth Rate (SGR) formula • Protected Practice Expense increases for ophthalmology when attacked by other specialties • Exempted ultrasound from imaging cuts • Protected the in-office ancillary services exception • Secured physician exemption from Red Flag (creditor) rules • Secured reversal of a CMS decision to cut reimbursement for Avastin • Delayed Medicare penalties dates in health reform law • Secured appointment of full-time ophthalmology national program director in the Department of Veterans Affairs Leaders of the American Uveitis Society (AUS) are part of the American Academy of Ophthalmology’s Ophthalmic Advocacy Leadership Group (OALG). Although there was a setback in Kentucky. OPHTHPAC® Fund OPHTHPAC is a crucial part of the Academy’s strategy to protect and advance ophthalmology’s interests in key areas. Established in 1985. Thanks to the OPHTHPAC contributions made in the 2007-2010 timeframe. thalmology’s priorities as over 350 Eye M.s in advance of any anticipated legislative or regulatory move. ultimately resulting in beneficial outcomes for all Eye M. SSF contributions are completely confidential and may be made with . As health care delivery evolves.D. Academy SSF contributions are used to support the infrastructure necessary in state legislative / regulatory battles and for public education. With last year’s passage of legislation in Kentucky that allowed optometrists to perform laser surgery. including physician payments in Medicare as well as protecting ophthalmology from federal scope of practice threats. which provides financial support for campaign contributions and legislative education to elect ophthalmology-friendly candidates for the state legislature. including 2 ophthalmologists.s should consider their contributions to the following three funds as (a) part of their costs of doing business and (b) their individual responsibility in advocating for patients: 1. The AUS remains a crucial partner to the Academy in its ongoing federal and state advocacy initiatives. For example. As 2012 Congressional Advocacy Day (CAD) partners. the American Academy of Ophthalmology’s partnership with ophthalmic subspecialty and state societies in the Surgery by Surgeons campaign became even more important in protecting quality patient eye care across the country. Politico highlighted OPHTHPAC as one of the most successful health PACs in strategic giving in the 2010 election. the AUS ensured a strong presence of uveitis specialists to support oph- State Eye PAC State ophthalmology societies can not count on the SSF alone— equally important is the presence of a strong state Eye PAC.2012 Subspecialty Day  |  Uveitis Advocating for Patients 21 2012 Advocating for Patients Russell N Van Gelder MD PhD Ophthalmology’s goal in protecting quality patient eye care remains a key priority for the Academy. area to provide critical input and to discuss and collaborate on the Academy’s advocacy agenda. ophthalmology derailed O. battled optometry across the country in 2011 to protect patient access to quality medical surgical care. OPHTHPAC helps us elect friends of ophthalmology to federal leadership positions. including Tennessee and others.D.D.D. subspecialty and specialized interest societies. Contributions across the board are needed. State Eye PAC While the Academy fully supports the concept of an “integrated eye care delivery team. The SSF is a critical tool of the Surgery by Surgeons campaign to protect patient quality of care and our collective fund to ensure that optometry does not legislate the right to perform surgery. 20 physicians. all Eye M. The Academy’s Secretariat for State Affairs. Surgical Scope Fund (SSF) At the state level.s. By making strategic election campaign contributions and independent expenditures. DC. surgery initiatives in 7 states and achieved its first proactive victory in Oklahoma.s had scheduled CAD visits to members of Congress in conjunction with the Academy’s 2012 Mid-Year Forum in Washington. The AUS contributed to the SSF in 2011 and the Academy counts on its contribution in 2012. The Secretariat for State Affairs strategizes with state ophthalmology societies on target goals for state eye PAC levels. Surgical Scope Fund (SSF) 3. the Academy’s Surgery by Surgeons campaign has demonstrated a proven track record. ophthalmology realized an 8% increase in Medicare payments (other specialties experienced significant decreases). Action Requested: Advocate for Your Patients!! PAC contributions are necessary at the state and federal level to help elect officials who will support the interests of our patients. Several ophthalmic subspecialty societies also provided critical support when called upon. today OPHTHPAC is one of the largest and most successful political action committees in the physician community.

22 Advocating for Patients OPHTHPAC® Fund Ophthalmology’s interests at the federal level – Support for candidates for US Congress Campaign contributions. as well as your state ophthalmology society leaders. public education. which must be made by individuals and which are subject to reporting requirements. legislative education Contributions: Limited to $5. when they call on you and your subspecialty society to contribute. media. Please respond to your Academy colleagues who are volunteering their time on your behalf to serve on the OPHTHPAC* and SSF** Committees.legislative education 2012 Subspecialty Day  |  Uveitis Surgical Scope Fund Scope of practice at the state level Lobbyists. Advocate for your patients now! **Surgical Scope Fund Committee Thomas A Graul MD (NE) – Chair Arezio Amirikia MD (MI) Ronald A Braswell MD (MS) Kenneth P Cheng MD (PA) John P Holds MD (MO) Bryan S Lee MD PhD (MD) – Consultant Stephanie J Marioneaux MD (VA) Andrew Tharp MD (IN) Ex-Officio Members: Cynthia A Bradford MD Daniel J Briceland MD *OPHTHPAC Committee Donald J Cinotti MD (NJ) – Chair Charles C Barr MD (KY) William Z Bridges Jr MD (NC) Dawn C Buckingham MD (TX) Robert A Copeland Jr MD (Washington DC) James E Croley III MD (FL) Anna Luisa Di Lorenzo MD (MI) Andrew P Doan MD PhD (CA) Warren R Fagadau MD (TX) Michael L Gilbert MD (WA) Alan E Kimura MD (CO) Lisa Nijm MD JD (IL) Andrew J Packer MD (CT) Andrew M Prince MD (NY) Kristin E Reidy DO (NM) Ruth E Williams MD (IL) Ex-Officio Members: Cynthia A Bradford MD (OK) Gregory P Kwasny MD (WI) Michael X Repka MD (MD) .000 Contributions above $200 are on the public record Contribution limits vary based on state regulations Contributions are on the public record corporate checks or credit cards—unlike PAC contributions. administrative needs Contributions: Unlimited Contributions are 100% confidential State EyePAC Support for candidates for State House and Senate Campaign contributions.

Fundus photograph (a) and fluorescein angiograph (b) of a 43-year-old male with decreased vision in right eye for 20 days (6/12) who presented with syphilitic neuroretinitis. if managed in a timely manner. frequently associated with corneal involvement in the form of corneal scar or active keratitis. the anterior segment was quiescent. The retinal vessels show staining of the vessel walls. the placoid lesions show hypofluorescence during the dye transit that becomes hyperfluo- Herpes Herpetic anterior uveitis is commonly caused by herpes simplex virus (HSV) and varicella zoster virus (VZV). especially in the United States. especially in men having sex with men. There are no pathognomonic signs of syphilitic uveitis. and Tuberculosis The Challenges Continue. Uveitis is one of the most common manifestations of ocular syphilis but requires a very high index of suspicion because of a wide spectrum of clinical manifestations. (a) Anterior segment photograph of a 18-year-old male with herpetic anterior uveitis in the right eye with pigmented keratic precipitates. Patients with HIV infection and higher reagin titers also present with more severe inflammation. All patients with syphilitic uveitis should be treated as neurosyphilis with intravenous crystalline penicillin 4 M units given every 4 hours for 2-3 weeks. Canada. PCR may yield a positive result from the aqueous or vitreous fluid. Epstein-Barr virus (EBV) and human herpes virus (HHV). WBC counts. and significant vitritis. The disease is sight-threatening because of rapid necrosis of retina causing atro- . Human immunodeficiency virus infection may coexist in 60%-70% of patients with syphilis.2012 Subspecialty Day  |  Uveitis Section IV: Infectious Uveitis—How Can One Tell if the Problem Is Microbial? 23 Herpes. If treatment is delayed. with yellow-white retinitis lesions that are tongue-shaped. The diagnosis is primarily clinical. FTA-Abs) may be ordered. In posterior uveitis. Necrotizing retinitis may be seen uncommonly. posterior. followed by cytomegalovirus (CMV). ARN is characterized by peripheral necrotizing retinitis involving all retinal layers. Unlike the autoimmune uveitides. rescent in the late frames. the former tests may be negative. the infective uveitides require a high index of suspicion and pattern recognition. Since uveitis is often seen in patients with neurosyphilis. Concomitant use of oral/topical corticosteroids is recommended. and Aman Sharma MD It is critical to differentiate autoimmune uveitis from masquerades and the infective uveitides. intermediate. Patients with HIV infection may develop uveitis in early or late stages of syphilis and present more often with posterior uveitis. Optic disc hyperemia and peripapillary retinal swelling may be significant (see Figure 1). nausea. On fundus fluorescein angiography. has reemerged in the last decade. Posterior segment may show leopard skin lesions. Up to 5% of patients with tertiary syphilis may develop ocular syphilis. Syphilis This sexually transmitted bacterial disease. ARN usually occurs in immunocompetent individuals and PORN in severely immunocompromised persons. He received intravenous penicillin for 2 weeks and recovered 20/20 visual acuity with mild optic disc pallor. and unsteady gait. It is characterized by a recurrent. and late stages show optic atrophy. Posterior segment involvement may occur in the form of acute retinal necrosis (ARN) or progressive outer retinal necrosis (PORN). or panuveitis. Men are predominantly affected. have good visual outcomes. Uncommonly. Serological tests are diagnostic. If treated promptly. In patients with HIV infection. and advance circumferentially. but a negative PCR does not rule out the diagnosis. Scleritis has been recently reported to be associated with herpetic infection. complaining of night blindness and optic atrophy. they may complain of headache. Retinal vessels may show occlusive changes. PCR from aqueous fluid was positive for HSV. Ocular syphilis may be the presenting symptom of HIV infection. Vishali Gupta MBBS. Figure 2. deafness. Since these patients frequently have neurosyphilis. Syphilis. the infective uveitides. and several European countries. but the Future Is Bright Amod Gupta MBBS. uveitis carries a good prognosis for visual recovery. creamy. punctate retinitis and preretinal infiltrates may be seen. patients may permanently lose vision. begin in periphery. Reema Bansal MBBS. Uveitis may have either acute or insidious onset and if untreated may run a chronic course. which require long-term corticosteroid / immunosuppressive therapy and tend to recur and often run a chronic course. patients may present with single or multifocal yellow. It is usually unilateral but may be bilateral in a few cases. However. and protein estimation from CSF is ordered. serological tests. (b) Three weeks after initiating oral antiviral therapy. caused by Treponema pallidum and once considered on the wane. occlusive vasculitis predominantly arteritis. and increasing numbers are being reported. Patients may present with bilateral anterior. There may be variable exudative retinal detachment. Both nontreponemal such as VDRL and RPR and specific treponemal (TPHA. HSV and VZV have been known to be the common viruses causing ARN. placoid lesions with overlying significant vitritis. granulomatous iridocyclitis. Figure 1. Iris atrophy and transiently raised IOP due to trabeculitis are common (see Figure 2).

and HAART if patients are HIV infected.. Tuberculosis Tuberculosis (TB) has long been recognized as a cause of uveitis—with increasing reports. Besides fulminant necrotizing retinitis. 2011. Li JZ. Treatment is started with 4-drug antitubercular therapy for the first 2-3 months. corroborative indirect evidence of a latent TB infection. PCR was positive for M TB. choroidal tubercules (see Figure 4). In patients not responding to acyclovir. interferon-gamma release assays (IGRAs). A low-dose aspirin (100 mg/day) is beneficial in view of occlusive retinal arteritis. retinal vasculitis. tapered gradually over the next few months. and protein b. Fawzi AA. . UK) have found significant use in detection of TB uveitis. due to HSV and VZV. Inc. Syphilis: reemergence of an old adversary. showing a choroidal tuberculoma with surrounding exudative retinal detachment. Using 3 primers in intraocular fluids has shown a high sensitivity and specificity for diagnosing TB uveitis (unpublished data). Other drugs that can be used include valaciclovir and foscarnet. Ophthalmology 2006. and tapered gradually. 113:20742079. oral famciclovir or ganciclovir have been recommended. Recently. followed by 2-drugs for at least 7 more months. MPB64. and should be started at a high dose (1 mg/kg/day). particularly from endemic regions of the world. and exclusion of other specific uveitic entities. The role of prophylactic laser photocoagulation is controversial. Fundus autofluorescence in serpiginouslike choroiditis can reliably monitor lesions as they evolve from the acute to the healed stage. Patients on therapy should be monitored for hepatotoxicity. The patients should be monitored for renal function tests. IS6110. followed by oral acyclovir 800 mg 5 times/day for at least 6 weeks. Right eye of a 45-year-old female with a positive tuberculin skin test. Fellow eye may get involved within 6 weeks. et al. Australia) and ELISpotPLUS (T-SPOT. Vitritis is minimal. intravitreal ganciclovir. such as the QuantiFERON-TB Gold In-Tube (QFT) (Cellestis. Khurana RN. 2. It usually occurs in the absence of any systemic evidence of TB. Treatment is with intravenous acyclovir. It is usually bilateral. or neuroretinitis as common clinical signs. Recurrences are known to be significantly reduced with administration of antitubercular therapy. Rao NA. The diagnosis is usually presumptive. References Syphilis 1. which increase the risk of developing retinal detachment. with chronic recurrent granulomatous anterior uveitis. The diagnostic accuracy is known to improve with their use. Real-time PCR and multitargeted PCR (MPCR) are newer diagnostic aids for TB uveitis. PORN is characterized by large areas of necrosis with deep retinal opacification and minimal involvement of retinal vessels (see Figure 3). Vitreous surgery is indicated for retinal detachment or prophylactic for debulking the inflammatory cells and releasing vitreous traction. The clinical spectrum is extremely wide. Figure 4. Hemorrhagic retinitis lesions and perivascular infiltration near the posterior pole may be seen affecting one or more quadrants. Ocular syphilis among HIVinfected patients: a systemic analysis of the literature. Abingdon. namely. Sex Transm Infec. Tucker JD. Corticosteroids are tapered depending upon the clinical response. The tuberculin skin test (TST) is the most common laboratory test performed. based on clinical findings.TB. CMV retinitis is commonly associated with AIDS. Oral corticosteroids are used to control active inflammation. MPCR uses 3 target genes simultaneously for diagnosis of TB. Fundus photograph of right (a) and left (b) eyes of a 45-yearold male showing progressive outer retinal necrosis with visual acuity 6/9 in both eyes.24 Section IV: Infectious Uveitis—How Can One Tell if the Problem Is Microbial? 2012 Subspecialty Day  |  Uveitis phic retinal holes. These measure interferon-gamma response produced by the T cells after antigenic stimulation. Intravenous acyclovir is recommended. Chao JR. with an initial dosage of 15 mg/kg 3 times daily for 10 days. Reddy HS. Chest radiography has a very limited role. and any part of the eye can get affected. 87:4-8. The diagnosis is often clinical. The posterior pole is affected early because of confluence of progressing lesions. Oxford Immunotec. Robbins GK. He had undergone renal transplant 5 years ago and had developed chicken pox a month before becoming visually symptomatic. Direct evidence by PCR is gaining worldwide use. slow-progressing necrotizing and non-necrotizing variants have also been recognized. Figure 3. and direct microscopic or histopathologic evidence of intraocular TB by demonstration of acid-fast bacilli (AFB) on direct smear or culture of mycobacteria from ocular fluids or tissue specimens is extremely rare. serpiginouslike choroiditis.

Wickremasinghe S. Clin Infect Dis. 2009. Belair ML. 12. Kim SJ. 2008. 30: 559-565. Ocular signs predictive of tubercular uveitis. 23:285-290. Puklin JE. Long-term preservation of vision in progressive outer retinal necrosis treated with combination antiviral drugs and highly active antiretroviral therapy. Standard diagnostic criteria for the acute retinal necrosis syndrome. 10. Retina 2012. Gupta A. Fundus autofluorescence in serpiginouslike choroiditis. 32:16611673. Dunn JP. Stawell R. Syphilitic uveitis: an Asian perspective. Altinkurt E. Arora S. Cheng CL. Presumed tubercular serpiginouslike choroiditis: clinical presentations and management. Sharma A. 5. Bansal R. 13. Marra CM. Gupta V. et al. 32(4):814-825. Herpes 7. 2010. Int Ophthalmol. 2007. 2001. Chee SP. Ormerod LD. 9. 149:562570. 15. Bansal R. Ling C. 116:1195-1200. Syphilitic posterior uveitis: correlative findings and significance. Spencer DB. Ang M. 1994. Holland GN. Chee S-P. Syphilitic punctate inner retinitis in immunocompetent gay men. Gupta V. 117:663-667. 11. Gupta A. Retina 2001. et al. Arora S. Gupta V. Ophthalmology 2009. 8. Sobel JD. Therapy for acute retinal necrosis. Gupta V. Ophthalmology 2003.2012 Subspecialty Day  |  Uveitis Section IV: Infectious Uveitis—How Can One Tell if the Problem Is Microbial? Tuberculosis 25 3. Am J Ophthalmol. 21:435-444. Bambery P. . 116:1391-1396. Mochizuki M. PCR-positive tubercular retinal vasculitis: clinical characteristics and management. 2008. 11:127-134. Update on neurosyphilis. Am J Ophthalmol. Sharma A. Clinical features and prognosis of herpetic anterior uveitis: a retrospective study of 111 cases. Diagnosis of tubercular uveitis: clinical application of an interferon-gamma release assay. Kawaguchi T. Br J Ophthalmol. Anshu A. 6. 2010. Gupta A. 4. 15(6):425-427. 92:594-597. 14. Fine HF. Otuk-Yasar B. Tugal-Tutkun I. et al. Equi R. Ocul Immunol Inflamm. Semin Ophthalmol. the Executive Committee of the American Uveitis Society. 110:1744-1749. Curr Infect Dis. Ophthalmology 2009. Htoon HM. Gupta A.

• Marked differences globally Risk factors • Socio economic conditions • Water. glaucoma and cataract. There is no treatment to avoid recurrences. Wrong Concepts in Ocular Toxoplasmosis All cases are congenital. virus. PCR (aqueous humor and vitreous). gondii). retinal vasculitis. All patients need antitoxoplasmic drugs for 4-6 weeks.26 Section IV: Infectious Uveitis—How Can One Tell if the Problem Is Microbial? 2012 Subspecialty Day  |  Uveitis Infectious Uveitis. Therapy for Ocular Toxoplasmosis Weeks to months. Cristina Muccioli MD Infectious Uveitis Classic and emerging infectious agents Infectious uveitis comprises 10 to 60% of cases. Cats and meat are the only source. retinal neovascularization. Many concepts related to OT have changed in the last years (see Table 2). and anterior uveitis. Folinic acid: during pyrimethamine therapy Diagnosis Pattern of uveitis. New diagnostic techniques (such as panmicrobial microarrays) confirm higher number of pathogens as cause of uveitis until recently diagnosed as “noninfectious” (eg.) • Geographic distribution patterns Table 1. Immunosuppressed patients have a tendency to present bilateral lesions with diffuse retinitis and less vitreous involvement. Laboratory Serology (circulating antibodies to T. • • • • • Background Necrotizing retinochoroiditis satellite lesion adjacent to old hyperpigmented scars accompanied by vitreous inflammation. Fuchs heterochromic cyclitis caused by rubella or toxoplasma and anterior uveitis caused by cytomegalovirus). Ocular Toxoplasmosis (OT) Caused by an obligate. In any patient with uveitis. Table 3. retinal detachment. Bacteria. an infectious cause should be ruled out first. vitreous hemorrhage. Diagnosis Based on the clinical picture. the Most Common Problem Worldwide: What Else to Consider? Rubens Belfort Jr MD. vascular occlusion. Prevention of recurrences Combination of trimethoprim / sulfamethoxazole given for many months may decrease the number of recurrences and may be considered in higher-risk patients. plus specific epidemiological data confirmed by the presence of immune response to the specific pathogen or the identification of it preferably in the eye. intracellular protozoan parasite (Toxoplasma gondii) and the most important and frequent cause of infectious retinal disease and posterior uveitis. etc.” Vertical transmission (pregnancy) occurs only once in life. . genotyping. Must present as a “retinochoroiditis. Complications Macular edema. depending on clinical picture and response Systemic steroids always associated to antitoxoplasmic drugs Pyrimethamine + sulfadiazine (or trimethoprim + sulfamethoxazole) – Systemic or intraocular clindamycin and combination of trimethoprim/sulfamethoxazole have also been used. Recurrences are related only to persistent retinal cysts. Examples of Important Infectious Uveitis Toxoplasmosis Cytomegalovirus Tuberculosis Syphilis Herpes DUSN Toxocariais Bartonella Borrelia Dengue Fever Leprosy Leptospirosis Onchocerciasis Rickettsiosis West Nile virus infection Rift valley fever Chikungunya Candidiasis Table 2. food and soil contamination • Health conditions of population (such as HIV infection. epiretinal and subretinal neovascular membranes. parasites and fungi More than 100 etiologies (see Table 1) Direct invasion to the eye or uveitis secondary to infection and immunologic changes elsewhere. Treatment Antitoxoplasmic drugs associated with steroids (decrease the inflammation and improve vision).

Identification of new pathogens in the intraocular fluid of patients with uveitis. Ocular Toxoplasmosis. Perry LJP. Nussenblatt RB. Whitcup S. 4. In: Ryan SJ. allows individuals to discontinue their CMV therapy but some develop uveitis secondary to the immune recovery. Commodaro AG. Arevalo JF. Ganatra J. Durand M. et al. retinal hemorrhages. 2013. Kestelyn P. extensive iris atrophy. prompt hospital-based treatment of systemic complications and avoid aspirin Diffuse Unilateral Subacute Neuroretinitis (DUSN) Background Caused by nematodes. retinal detachment. et al. Am J Ophthalmol. 2011. Rathinam SR. Unusual abundance of atypical strains associated with human ocular toxoplasmosis. choroidal vasculopathy and neuropathy. et al. 5. Treatment Systemic or intraocular therapy with anti-CMV drugs. Int Ophthalmol Clin. erosion. eds. Int Ophthalmol Clin. transplanted patients receiving immunosuppressive medications). J Infect Dis. vascular sheathing. and frosted-branch angiitis. 2010. as well as protection of anesthetic corneas from exposure. Zuurveen S. 6. Posterior uveal involvement is rare. 184(5):633-639. Tends to occur in older children and young adults as unilateral disease. Uveitis in the Developing World. Boothroyd JC. narrowed retinal vessels. and intractable glaucoma. Mebendazole or diethylcarbamazine kill the nematode larvae. 104(2):345-350. 7. HAART leads to recovery of immune function. posterior uveitis. . Toxocariasis Background Caused by the ingestion of larvae of Toxocara canis or cati. Advances in detection and treatment of ocular infections. 150(5):628-636.2012 Subspecialty Day  |  Uveitis Section IV: Infectious Uveitis—How Can One Tell if the Problem Is Microbial? 27 Dengue Fever Background Arthropod-borne viral disease (transmitted by Aedes mosquitoes) in over 120 countries. and before the third decade of life Ocular disease Mild vitritis. Ocular toxoplasmosis: an update and review of the literature [review]. Grigg ME. granular. and ulceration in the face of lagophthalmos. De Groot-Mijnes JD. usually unilateral. Oxford. bilateral choroidal effusion. Decreased vision. posterior pole and pars plana granulomas. 53(4). et al. Diagnosis Clinical picture and serum antibodies to Toxocara Treatment/prognosis Visual outcome is usually poor due to late diagnosis. Mosby. pigment epithelial stippling and visual field loss Diagnosis Slitlamp retinal exam that discloses a worm moving under the retina Treatment Photocoagulation of the worm or systemic antihelmintic agents (albendazole or thiabendazole) Cytomegalovirus (CMV) Retinitis and Anterior Uveitis Ocular disease Progressive retinitis with vasculitis and hemorrhages in immunocompromised hosts (AIDS. 50(2). Chee SP. Treatment Treatment of iridocyclitis is mandatory. Belfort Jr R. vitreous opacities. floaters. Three clinical forms: Necrotizing. Selected Readings 1. Leprosy Background Important and neglected cause of blindness Ocular disease Chronic anterior uveitis with iris pearls (represent miliary lepromas). 3. It may follow or not clinical visceral larva migrans syndrome. de Visser L. UK: Saunders. cotton wool spots. 2001. progressive optic atrophy. Uveitis. Silveira C. 2009. including the Southern United States Ocular disease Asymmetric-bilateral. Retina. Preface. retinal hemorrhages. Mem Inst Oswaldo Cruz. 2004. Three basic forms of ocular involvement: diffuse (endophthalmitis). Belfort RN. CMV has also been recognized as the etiology of anterior uveitis and endotheliitis in nonimmunosuppressed individuals. Muccioli C. 3rd ed. Prednisone should be used as an adjunct to anti-helminthic therapy in patients with ocular active inflammation. Rizzo LV. Chodosh J. Laboratory diagnosis Circulating IgM specific antibodies Treatment Systemic steroids. 2010. 2. Cunningham ET Jr. capillary occlusion.

28 Section V: On the Special Matter of Pediatric Uveitis 2012 Subspecialty Day  |  Uveitis Differential Diagnosis of Uveitis in the Pediatric Population: Sarcoid. and Beyond Debra A Goldstein MD N otes .Tubulointerstitial Nephritis and Uveitis Syndrome.

2012 Subspecialty Day  |  Uveitis Section V: On the Special Matter of Pediatric Uveitis 29 Juvenile Idiopathic Arthritis Associated Uveitis: When to Move Off Corticosteroid Therapy? Laure Caspers MD. Treatment has not been standardized. SCST. The age of patients at diagnosis of JIA uveitis ranged from 0. and Le Phu Quoc Introduction Approximately 6% of all cases of uveitis arise in children. TCST was used in all the patients. Xavier Janssens. SCST. and these patients had SCST for mean duration of 4.5 to 11. ranged from 1. Onset peaks at age 2 years.4 The use of biologics in JIA is now well known and include adalimumab Results Eighteen patients (14 F) with JIA diagnosed by a rheumatologist were included. duration of follow-up. and systemic. IMT were started and ended. The age of patients at end of follow-up ranged from 4 to 40 years. Cataract was observed in all but 2 patients.75 to 11. total duration of TCST. two had etanercept (Enbrel) and one had infliximab (Remicade). ANA positivity. seronegative. presence of uveitis consistent with JIA-associated uveitis. The duration of follow-up ranged from 4 to 36 years. The use of immunosuppressive therapy has been shown in a retrospective study to be associated with an important reduction of severe side effects of JIA-associated uveitis. Eight patients had a final VA < 20/40 at least in one eye. None of the authors have a financial interest. initial and final visual acuity (VA) with a significant VA change above 2 Snellen lines.2 years. Discussion The medical treatment of JIA-associated uveitis has changed with time. Fifteen patients had an IMT constituted of at least methotrexate. There is a progressive morbidity with 30%-40% of patients with severe loss of vision as leading to possible blindness. Most side effects of corticosteroids were reversible except in 1 patient who had a osteonecrosis at the age of 35 years. 11 patients had an oligoarticular subtype. while those with a final VA ≥ 20/40 had SCST for a mean duration of 3. Systemic-onset JIA has a very low risk for uveitis. when other causes have been excluded. Irina Balikova.6 Cyclosporine has limited value in the treatment of JIA-associated uveitis.6 years.7 For patients requiring chronic therapy. subtype of arthritis. SCST IMT. Uveitis is the most common manifestation of JIA after arthritis and is seen in up to 30% of antinuclear antibody (ANA)-positive patients with JIA. of at least 3 months duration. and time to relapse after withdrawal. An elevated IOP was observed in 14 patients. We had no severe Cushingoid syndrome like those sent to our clinic after years of SCS treatment as unique therapy. with a mean of 3. family history of JIA. polyarticular. Among the 4 patients with normal IOP. (mycophenolate mofetil and azathioprine). the various IM drugs used. Florence Duchateau. It is also more common in girls (3:1). 12 patients tested positive for ANA. adalimumab (Humira) or infliximab (Remicade) or etanercept (Enbrel) followed by adalimumab (Humira) and infliximab (Remicade) and 1 patient who had no anti-TNF alpha treatment.2 JIA. Chronic iridocyclitis occurs in 10%-20% of all patients with JIA. About 75% of these patients test positive for antinuclear antibody (ANA). It is classified by 1 of 3 types of onset:3 oligoarticular (pauciarticular).6 years. age at diagnosis of uveitis and arthritis.8 years. Little is known about when systemic corticosteroid treatment (SCST) should be introduced and arrested in uveitis-related JIA.1 The most frequent cause of chronic intraocular inflammation among children is juvenile idiopathic arthritis (JIA)-associated uveitis. Ten patients had a SCST. and peripheral) before age 16 years. with a mean of years 3. Flare-up was frequently observed after SCST withdrawal. Oligoarticular onset of JIA (40%-60%) is more common in girls (5:1). All but 1 of them had also additional methotrexate. One of these patients was at the end of very long followup and the 2 others had only SCST but no IMT and were probably less severe patients. and the onset peaks around the age of 3 years. Seven patients had hypotony. side effects. IMT. followed by immunomodulatory therapy (IMT). Four patients had a family history of JIA. Four patients had retinal detachment and had all 4 TCST and SCST.8 years. Inactivity was observed at the end of follow-up with ongoing IMT in 10 patients and was observed without IMT in 3 patients still under TCST. which was then replaced by IMT.9 years. as defined by the American Rheumatism Association (ARA). All but 1 patient with a final VA < 20/40 at least in one eye had methotrexate treatment. The age of patients at diagnosis of JIA arthritis . SCST were stopped because of temporary remissions in most patients but also because of toxicity in 3 cases. all but 1 had SCST and 2 of them had 2 or 3 successive anti-TNF alpha treatment.3 It is typically asymptomatic.13 years. Corticosteroid was injected intravitreously or periocularly in 6 patients. and the goal of the study is to assess this question. Two drugs were associated in 4 cases and 3 drugs were associated in 4 cases in order to better control inflammation and prevent toxicity. Methods Chart review of 18 patients with JIA-associated chronic or recurrent uveitis with an ongoing follow up in the Brussels University Hospitals was done. no SCST was used in 2 of them and no TCST or TCST was used in 1 of them. Inclusion criteria were disease onset between the age of 1-16 years. the initial agents of choice are typically antimetabolites including methotrexate. The data collected for each patient were gender. Alice Ferster. with a mean age of 19 years. is the presence of arthritis (chronic.3 The polyarticular onset JIA (20%-40%) has an intermediate risk for uveitis. and this retrospective study was approved by the IRB of the hospital. Approximately 40% of these patients test positive for ANA. Remission was defined as < 1+ cells in the anterior chamber or vitreous. François Willermain. while in patients with a final VA ≥ 20/40. with a mean of 10. Five of these patients had no anti-TNF alpha treatment. age at which TCST. Emmanuelle Leys. diagnosis of JIA by a rheumatologist. reasons for withdrawal of TCST. The mainstay of initial treatment for uveitis remains corticosteroids. Eleven patients had an anti-TNF alpha treatment. This mode of onset has a high risk for uveitis. Topical corticosteroid therapy (TCST) remains the first choice.

Kempen JH. References 1. Tappeiner C. Daniel E. A recent largescale retrospective cohort study by Kempen et al5 included 7957 U. Int Ophthalmol Clin. Patients who took antimetabolites. infliximab (Remicade). but some patients with JIA-related uveitis were occasionally referred to our clinic after years of SCST as a unique therapy with high level of toxicity and absolutely needed to move off their SCST. BMJ. This needs to be further evaluated. TNFalpha blockers. and corticosteroids had overall and cancer-related mortality similar to patients who never took immunosuppressive medications and similar to the general U. The combination of several IMT with or without low dosage of SCST as a bi. particularly in children with JIA. 2010. the long-term safety profile of these treatments becomes important. Long-term toxicity of antimetamolites has been evaluated in adults. et al. Nguyen QD. JAMA. Long-term safety of biologic treatment is a concern. 5. Acharya NR. Juvenile idiopathic arthritis associated uveitis.30 Section V: On the Special Matter of Pediatric Uveitis 2012 Subspecialty Day  |  Uveitis (Humira). Roesel M. Setlur V. et al. especially since children with JIA require years of treatment. Uveitis in children: population-based study in Finland.S. 21(6):468-472.S. . Eye (Lond). Severe hypotony and retinal detachement were more often observed in patients with SCST and methotrexate than in those treated with antiTNF. 2009. SCST. 1998. et al. Woreta F. 7. Our preliminary results did suggested that most patients are still treated with ongoing IMT and TCS at the end of follow-up and that the 3 patients without IMT at the end of follow-up still needed topical treatment.or tri-therapy was found to be effective and helpful to prevent toxicity. Kedhar SR. Heinz C. Saari KM. As more patients receive immunosuppressive therapy for ocular inflammatory disease. JIA-associated uveitis remains a challenging disease to treat. 48(3):21-38.7 Prospective randomized clinical trials are currently under way to investigate the effectiveness of TNF-alpha inhibitors for JIAassociated uveitis. Päivönsalo-Hietanen T. 2000. 4. Conclusion Cataract and glaucoma were observed in most patients with JIA uveitis independently from therapeutic regimen. Most side effect of corticosteroids were reversible except one patient who had a osteonecrosis at age of 35 years. 2007. Foster CS. 280(13):1133-1134. 2009. Retinal detachments and hypotony might be related to corticosteroid treatment. of whom 2340 received immunosuppressive therapy. Bi-therapy and tri-therapy were both used in 4 cases to avoid side effect of SCST and IMT. Dunn JP. Cushingoid changes. Cataract and glaucoma were observed in most patients and did not appear to be related to corticosteroids. Kesen MR. and abatacept (Orentia) a T cell activation. Goldstein DA. Juvenile idiopathic arthritisrelated uveitis.  6. Am J Ophthalmol. Limited value of cyclosporine A for the treatment of patients with uveitis associated with juvenile idiopathic arthritis. 143(5):840-846. population. Juvenile idiopathic arthritisassociated uveitis: incidence of ocular complications and visual acuity loss. 3. Curr Opin Ophthalmol. Saving the vision of children with juvenile rheumatoid arthritis-associated uveitis. 2008. with ocular morbidity lasting well into adulthood. who may require systemic treatment for decades. Corticosteroids’ long-term use in children has many well-known severe side effects including growth decrease. Qian Y. The early addition of anti-TNFalpha to ledertrexate with or without SCST might have been the most effective treatment is those patients. 339:b2480. Randomized controlled trials are needed to assess the efficacy and safety of antimetabolites. Tuominen J. T cell inhibitors. residents with noninfectious ocular inflammatory disease. Patients who took TNF-alpha inhibitors had increased overall and cancer-related mortality. Thorne JE. Acta Ophthalmol Scand. 23(5):1192-1198.5 The MERSI study presented at ARVO in 2012 suggested that treatment of chronic recurrent JIA-associated uveitis at a younger age and soon after the diagnosis with IMT for a 2-year period of quiescence on IMT and off all corticosteroid therapy increases the odds of the patient to maintain remission after IMT is discontinued. 2. Overall and cancer related mortality among patients with ocular inflammation treated with immunosuppressive drugs: retrospective cohort study. and osteoporosis. 78(1):84-88. Long standing high dosage of corticosteroids were never used in our referral center. and etanercept (Enbrel. as these remain the first-line treatment for chronic JIA-associated uveitis.

93% specific B. Ophthalmic Findings A. 96% sensitive. no organisms C. photopsias 3. CNVM (6%) 5. Gass (1981) B. Ovoid. HLA-A-29 + (80%-98%) 2. RPE atrophy A. Nyctalopia .A29*02 (Caucasian) b. Indistinct borders 3. Northern European 4. Not correlated with BCVA 8. Epiretinal membranes (19%) 4. phase of study B. Old lesions: No significant window defects D. Atopy 5. Indirect ophthalmoscopy 7. Retinal vasculitis 2. 7% general white population a. ↑ expression self peptides to T cells A29 molecule? 2. Floaters. Antigen specific vs. Epidemiology 1. Pathogenesis A. Symptoms 2. HLA . CME (60%) 3. Nyctalopia 1. Similarity between birdshot retinochoroidopathy and experimental autoimmune uveitis 3. Late findings 1. Mixed T and B cells in choroidal lesions. Later onset: mean age 50 years (35-70) 3.2012 Subspecialty Day  |  Uveitis Section VI: Puzzling White Dots—What’s a Doctor to Do? 31 Is It Birdshot Retinochoroidopathy.9% PU tertiary setting 2. Level of the choroid or retinal pigment epithelium (RPE) 4. How Should I Treat It? Albert T Vitale MD I. Hypertension b. vibrating VA b. Retinal autoimmunity 1. Optic-nerve edema 4. nasal 6. nonspecific bystander activation D. Pigmentation associated with symptoms a. Attenuated retinal vessels 2. Polymorphisms in linkage disequilibrium with HLA-A29? 3. VA poor surrogate for disease severity 1.A29*01 (Asian) 3. Inconsistent findings: Depends on age lesion. Active disease IV. Post-equatorial fundus 5. Blurred visual acuity (VA) 2. Lesion characteristics 1. Clinical findings C. Fluorescein Angiography (FA) b. cream-colored 50-1500 mm 2. Lymphocyte proliferation to retinal S antigen 2. Mild nongranulomatous iritis 5. CNV II. Frequently excellent VA B. Mechanism 1. Borrelia burgdorferi III. HLA . Radial distribution. Ryan and Maumenee (1980). Caucasian. CME. Molecular mimicry with microbial antigen? a. Highly sensitive for detection disease activity: Optic nerve (ON) leakage. Female predominance (50%-70%) 5. History and Epidemiology A. segmental phlebitis. Diffuse vitritis with precipitates on the vitreous face E. Paracentral scotomas 4. Blurred. Presentation 1. Early lesions: Early hypofluorescence with subtle late staining C. and If So. Immunogenetics 1. No consistent systemic disease association a.2%-7. Optic atrophy 3. 50-fold to 224-fold risk 4. Uncommon: 1. Abnormal color 6.

nyctalopia. inflammatory entity causing multifocal choroidal lesions A. Sarcoidosis 2. Reversible? VI. Linear hypoautofluorescent streaks along retinal blood vessels 1. Improvement retinal function with systemic treatment 2. Multiple foci. Differential Diagnosis . Choroid and maybe RPE damaged independently. Required 1. 75% (48 eyes) at presentation of at least 1 (I-4) isopter 2. Supportive 1. multifocal choroiditis/panuveitis (MCP) 2. Mean deviation related to disease characteristics VII. OCT 2012 Subspecialty Day  |  Uveitis E. Guide to initiate therapy 4. SFU) 3. Hypofluorescent round lesions. color.18/EY 3. Vogt-KoyanagiHarada syndrome (VKH) D. Loss third highly reflective band OCT a. Fundus Autofluorescence (FAF) A.11 to 0. Placoid hypoautofluorescence macula. vibration c. Variety abnormalities despite normal BCVA 1. subretinal fibrosis with uveitis. Fuzzy. More numerous than IVFA. Keratic precipitates 2. VKH F. Visual field (VF) loss common over time. B. Immunomodulatory therapy (IMT) may reverse VF loss. arcuate defects 2. Complimentary to FA B. Photoreceptors inner/outer segment junction b. Scotopic bright flash amplitudes reduced a. F. May reflect degree retinal vasculopathy B. Retinal vasculitis 3. White dot syndromes (APMPPE. Inflammatory 1. punctate inner choroidopathy. Posterior synechiae 3. Perimetry XI.05) E. Electronegative maximal ERG. Bilateral 2. Electrophysiology A. neoplastic. Corresponding visible changes at RPE D. Abnormal Goldmann VF score 1. Low grade vitreous inflammation B. HLA-A29 positivity 2. Inner retinal dysfunction rod and cone systems 1. exam 1.32 Section VI: Puzzling White Dots—What’s a Doctor to Do? V. no visible RPE change 1. BCVA (N = 80) 1. Loss of third highly reflective band on OCT 1. Macular RPE atrophy as measured by FAF predictor ↓ central VA A. 30 HZ flicker implicit time delay 2. indistinct choroidal vessels and late-diffuse choroidal hyperfluorescence during active disease C. Objective tool to assess disease activity 3. Rate 0. intermediate phase 1. D. ↓ b/a ratio 3. Birdshot lesions ≥ 3 inferior or nasal to ON 3. Exclusion 1. Associated with retinal damage a. MCP. Serial ERG 1. May better reflect loss of function than VA C. late B. Distributed along choroidal vessels 1. BCVA. Hypoautofluorescence due to RPE atrophy B. Research Diagnostic Criteria VIII. Smaller than acute multifocal placoid pigment epitheliopathy (AMPPE). Objective measure to follow disease activity IX. Predictor of disease recurrence during taper of IMT A. Nonuniform correspondence hypoautofluorescence/ birdshot lesions C. Correlated with BCVA ≤ 20/50 (P < . Remain hypofluorescent / become isoflourescent. Blurred VA. Standardized Humphrey VF (Fastpac 30-2) X. Low grade anterior chamber inflammation 4. Symptoms: Blurry VA. CME C. Other infectious. Not clustered around ON A. Indocyanine Green Angiography A. Larger than multiple evanescent white dot syndrome. Macular thickness: Increased or decreased 3. loss of contrast sensitivity G. color contrast sensitivity 2. Vascular leakage 2.

2012 Subspecialty Day  |  Uveitis

Section VI: Puzzling White Dots—What’s a Doctor to Do? 2. Preservation, reversal of VF loss, ERG parameters


4. Sympathetic ophthalmia 5. Idiopathic retinal vasculitis, systemic vasculitides 6. Posterior scleritis B. Infectious: Syphilis, TB, toxoplasmosis, brucellosis C. Masquerade syndromes: Lymphoma, metastatic carcinoma, myelodysplasia

3. Reduction of risk of CME: Prevalence reduced 80% 4. Disappearance of classic birdshot spots B. Induction of long-term remission A. Antimetabolites 1. Methotrexate 2. Mycophenolate mofetil 3. Azathioprine B. T-cell transduction inhibitors 1. Cyclosporine 2. Tacrolimus 3. Combination with MTX, mycophenolate mofetil C. Biologics 1. Infliximab 2. Adalimumab 3. Daclizumab D. IVIG E. Fluocinolone acetonide implant F. Emerging therapies 1. Voclosproin 2. Anti-interleukin-17 monoclonal 3. Interferon alpha-2a A. Symptomatic patient: Photopsias, floaters, nyctalopia, altered color perception B. Vitritis C. Retinal vasculitis: IVFA, ICG D. CME: OCT E. Peripheral retinal dysfunction: VF, ERG A. Randomized, double masked study of CSA compared to prednisolone in the treatment of endogenous uveitis (Nussenblatt RG, et al. Am J Ophthalmol. 1991; 112:138-146.)

XII. Natural History A. Multiple exacerbations and remissions B. Progressive visual loss 1. Structural complications: CME (10% EY), ERM, cataract, glaucoma, optic neuropathy 2. Global retinal dysfunction: VF loss, ERG dysfunction 3. Longer duration of disease 4. Independent of previous oral corticosteroid therapy A. Few maintain good VA without treatment B. VA ≤ 20/200 affected eye 1. 8% onset 2. 30% at 5 years 3. 39% at 10 years (Rothova A, et al. Ophthalmology 2004; 111:954-959.) C. 20% ≤ 20/200 (Thorne JE, et al. Am J Ophthalmol. 2005; 140:45-51.) 1. 20% 5 year cumulative incidence 2. VA ≤ 20/50: 13% per eye-year (EY) incidence rate 3. VA ≤ 20/200: 4% per EY incidence rate A. Periocular/intravitreal/systemic corticosteroids 1. Short-term management vitritis, CME 2. Inconsistent efficacy long- term a. Maintainence > 15 mg/day to prevent CME recurrence b. Steroid resistance, intolerance, severe adverse effects 1. Inherent anti-inflammatory effect 2. Steroid sparing (< 10 mg/day) 3. Extended treatment anticipated A. Preservation of visual function 1. Reduction of inflammation, recurrences

XVI. Therapeutic Options

XIII. Visual Prognosis

XVII. Treatment Indications

XIV. Treatment

XVIII. Cyclosporine 10 mg/kg Day

B. Early introduction of IMT

1. 5 patients with BSRC 2. 2 treated with CSA with good response B. 21 patients (42 eyes) BSCR (Le Hoang P, et al. Transplant Proc. 1998; 20:128-130.) 1. 10 mg/kg CSA (16 patients), 5mg/kg (5 patients) 2. Marked ↓ intraocular inflammation (vitritis) in all eyes

XV. Treatment Outcomes


Section VI: Puzzling White Dots—What’s a Doctor to Do? 3. Dramatic ↓ retinal vasculitis, retinal vascular leakage

2012 Subspecialty Day  |  Uveitis

2. Median total patient follow-up: 52.6 months (19.7-153.5) B. 12-month time point

4. ↑ VA 23 (54.8%) eyes, stabilization in 11 (26.2%) 5. Nephrotoxicity, hypertension A. 19 patients (35 eyes) 1. 8 patients CSA (2.5-5.0 mg/kg) 2. 5 patients CSA plus azathioprine (1.5-2.0 mg/kg day) 3. 6 patients systemic/periocular steroids B. Vitreous inflammation controlled in 23 (88.5%) eyes C. VA improved or stabilized in 20 (83.8%) D. Reduction inflammatory recurrences E. No nephrotoxic side effects (Vitale AT, et al. Ophthalmology 1994; 101:822-831.) F. 28 patients BSRC (mean follow-up: 81.2 months) G. All treated with systemic IMT 1. CSA (93%) alone or in combination with: a. Mycophenolate mofetil (68%) b. Azathioprine (18%) c. Methotrexate (11%) d. Daclizumab (7%) XIX. Cyclosporine 2.5-5.0 mg/kg day

1. ↓ Vitreous inflammatory scores O.D./O.S. (P < .0001; P < .0001) 2. ↓ CME, angiographic leakage O.D./O.S. (P < .025; P < .001) 3. No ↓30 HZ amplitude/implicit times O.D./O.S. (P = .14, P = .17) 4. 37 (92.5%) inflammatory control off systemic corticosteroids 5. 24 (64.9%) long-term remission, no relapses 6. 13 (35.1%) at least 1 relapse, require change in IMT 7. Mean logMAR VA not statistically different O.U. (Cervantes-Castaneda RA, et al. Eur J Ophthalmol. 2009; 19(1):118-123.) A. 8 patients BSRC refractory to conventional IMT 1. 1mg/kg IV every 2 weeks 2. Follow-up mean: 25.6 months B. Outcomes 1. 7 stabilization/improvement of VA O.U.; complete resolution of vitritis 2. 6 resolution vasculitis on IVFA 3. 4 discontinued other IMT while on daclizumab

XXII. Daclizumab

H. VA stable or improved in 78.6% (O.D.), 89.3% (O.S.) I. ERG 1. Stable bright flash scotopic amplitudes 2. 30 Hz flicker implicit times in majority of patients during follow-up (Kiss S, et al. Ophthalmology 2005; 112:1066-1071.) A. 76 patients HLA-A29 BSRC; 46 followed for 5 years, 18 for > 10 years B. Treatment regimes / yearly change logMAR VA 1. None / - 0.020 P = .034 2. Corticosteroids / 0.034 P = .71 3. Low dose MTX / 0.028 P = .006 C. Initial MTX treatment 1. Gradual increased VA contrast to other groups (P = .003) (Rothova A, et al. Retina, 2011.) A. 40 patients (80 eyes) 1. Median time CSA/MM treatment: 25.6 months (12-96.6)

4. ↓30 HZ implicit times and bright scotopic amplitudes in some despite effective inflammatory control (Sorbin L, et al. Arch Ophthalmol. 2008; 126:186-189.) C. High doses (8 mg/kg followed by 4 mg/kg) 1. 2 patients to achieve more rapid control inflammation (Yeh S, et al. J Autoimmun. 2008; 31:9197.) A. 22 patients with BSRC refractory to conventional IMT 1. Mean duration disease pre infliximab 58.62 months 2. Mean duration infliximab therapy 13.55 months 3. Previous BMR 10 pts B. Outcomes (baseline / 6 months /12 months) 1. Inflammatory: control / 81.82% / 75% 2. CME: 22.73% / 13.89% / 5.56% 3. VA ≥ 20/40: 84.09% / 91.67% / 94.44% 4. Three patients had active inflammation during therapy.

XX. Methotrexate

XXIII. Infliximab

XXI. CSA/Mycophenolate Mofetil

2012 Subspecialty Day  |  Uveitis

Section VI: Puzzling White Dots—What’s a Doctor to Do?


5. Six patients developed adverse events requiring drug discontinuation: Neuropathy, drug-induced lupus, allergic reaction, fungal infection (Artornsombudh P, et al. Ophthalmology 2012; in press,) A. IVIg used treatment of human autoimmune disease

C. Treatment threshold, markers of progressive disease 1. Clinical indices of intraocular inflammation 2. Imaging modalities (IVFA, ICG, OCT, FAF) 3. Visual fields (GVF, HVF) 4. Electroretinograph indices of retinal dysfunction A. Initial treatment with prednisone 1 mg/kg day 1. Up to 60 mg daily for 3-4 weeks 2. Taper off if possible, and if not, < 10 mg/day B. Initial treatment with antimetabolite 1. CellCept 1 gm b.i.d.; maximum 1.5 gm b.i.d. failing prednisone taper 2. Methotrexate 15 mg/weekly with 1 mg folic acid daily; maximum 25 mg/weekly failing prednisone taper 3. Consider initial combined CSA/ mycophenolate mofetil C. Adjunctive periocular/intravitreal steroid for CME D. Add CSA (2.5-5.0 mg/kg/day) or tacrolimus (0.10– 0.15 mg/kg/day) to antimetabolite with significant inflammatory recurrence/failure prednisone taper. E. Advance to TNF inhibitor (infliximab, adalimumab) failing combined IMT with significant inflammatory recurrence/failure prednisone taper. Discontinue CSA/tacrolimus. F. Consider fluocinolone acetonide implant. Systemic steroid/IMT failure or intolerance

XXIV. Intravenous Immune Globulin (IVIg) 1. Guillain-Barré, Kawasaki, juvenile dermatomyositis 2. Uveitis 3. Cancer-associated retinopathy B. Mechanism action not known 1. Blunt B-cell responses, alter cytokine production, inhibit phagocytosis, neutralize C3a, C5b 2. Prevent expression EAU, induce peripheral T-cell anergy C. 18 patients (36 eyes), follow-up mean 39 months D. IVIg monotherapy 1. 1.6 g/kg every 4 weeks for 6 months 2. Subsequent IVIg 1.2 to 1.6 g/kg every 6-8 weeks E. 14/26 (53.8%) ↑ VA ≥ 2 lines; 2/26 ↓ VA F. Decreased CME in 17/23, improved VF in 20/26 G. Benign side effects in 12 patients: Transient HTN, HA, eczematous lesions, hyperthermia (LeHoang et al. Occul Immunol Inflamm. 2000; 8:49-57.) A. 22 patients (36 eyes) HLA-A29 + BSRC 1. Follow-up: 3 years 2. 19 (32 eyes) completed 1 year B. Outcomes baseline: 1 year 1. Vitreous haze of 0 26% (7/27) / 100% (30/30) 2. CME 36% (13/36) / 6% (2/32) 3. VA (median) 20/50 20/40 (P = .15) 4. IMT 82% (18/22) / 5% (1/19) (P < .001) C. Complications 1. Cataract Sx: All except for 5/24 phakic eyes exit baseline 2. Ocular HTN: 100% 3. Glaucoma Sx: 33% (12/36) (Rush RB, et al. Am J Ophthalmol. 2011; 151:630-636.) A. BSRC chronic progressive, sight-threatening disease B. Early and aggressive IMT 1. Limit ocular structural damage 2. Preserve global visual function 3. Induction of long-term remission

XXVII. Treatment Protocol

XXV. Fluocinolone Acetonide Implant

Selected Readings
1. Ryan SJ, Maumenee AE. Birdshot retinochoroidopathy. Am J Ophthalmol. 1980; 89(1):31-45. 2. Gass JD. Vitiliginous chorioretinitis. Arch Ophthalmol. 1981; 99(10):1778-1787. 3. Shah KH, et al., Birdshot chorioretinopathy. Surv Ophthalmol. 2005; 50(6):519-541. 4. Priem HA, Oosterhuis JA. Birdshot chorioretinopathy: clinical characteristics and evolution. Br J Ophthalmol. 1988; 72(9):646659. 5. Kiss S, et al. Long-term follow-up of patients with birdshot retinochoroidopathy treated with corticosteroid-sparing systemic immunomodulatory therapy. Ophthalmology 2005; 112(6):1066-10671. 6. Monnet D, et al. Longitudinal cohort study of patients with birdshot chorioretinopathy: I. Baseline clinical characteristics. Am J Ophthalmol. 2006; 141(1):135-142. 7. Thorne JE, et al. Birdshot retinochoroidopathy: ocular complications and visual impairment. Am J Ophthalmol. 2005; 140(1):4551. 8. Becker MD, et al. Long-term follow-up of patients with birdshot retinochoroidopathy treated with systemic immunosuppression. Ocul Immunol Inflamm. 2005; 13(4):289-293. 9. Rothova A, et al. Birdshot chorioretinopathy: long-term manifestations and visual prognosis. Ophthalmology 2004; 111(5):954-959.

XXVI. Summary

Ophthalmology 1994. Kaye DB.36 Section VI: Puzzling White Dots—What’s a Doctor to Do? 2012 Subspecialty Day  |  Uveitis 10. 133(5):622-629. 31. Ophthalmology 1999. Arch Ophthalmol. 41. Nussenblatt RB. 13. et al. 2006. et al. Oh KT. Indocyanine green angiography in birdshot chorioretinopathy. double-masked study of cyclosporine compared to prednisolone in the treatment of endogenous uveitis. 86(12):1439-1441. 20(3 suppl 4):128-130. 2008. 2004. 2011. 31(2):91-97. 1999. et al. 33. Arnold AC. et al. 115(2):149-153. Jabs DA. 38. Zacks DN. 130(4):492-513. Am J Ophthalmol. Herbort CP. Yeh S. Foster CS. 2010. et al. 2002. 32. Ophthalmology 1996. Rodriguez A. et al. Am J Ophthalmol. 11. Am J Ophthalmol. 19. 2000. 2002. 1993. et al. 30. 37. 14. Sobrin L. Fundus autofluorescence imaging of the white dot syndromes. 25. et al. 1992. Low-dose cyclosporin A therapy in treating chronic. 31(6):1150-1155. LeHoang P. 39. Ocul Immunol Inflamm. Cheung MK. 94(2):147-158. Spaide RF. Control of visual symptoms in two men with birdshot retinochoroidopathy using low-dose oral corticosteroid therapy. et al. 128(1):116-118. Br J Ophthalmol. Guidelines for the use of immunosuppressive drugs in patients with ocular inflammatory disorders: recommendations of an expert panel. Monnet D. Fardeau C. 2000. Yeh S. J Autoimmun. Human leukocyte antigen A29 subtypes associated with birdshot retinochoroidopathy. Chan CC. 16. Ladas JG. discussion 373-374. Gordon LK. Palestine AG. 128(1):46-56. 42. 8(1):49-57. 112(2):138-146. Koizumi H. Am J Ophthalmol. Am J Ophthalmol. Macular imaging at baseline. 23. Jabs DA. 126(2):186-191. Sobrin L. et al. Birdshot retinochoroiditis: long term follow-up of a chronically progressive disease. 15. 18(6):470-471. Christmas NJ. J Ocul Pharmacol. High-dose humanized anti-IL-2 receptor alpha antibody (daclizumab) for the treatment of active. Cyclosporine therapy for uveitis: long-term followup. Transplant Proc. et al. Proc Natl Acad Sci U S A. et al. Crawford JB. 24. 28. Longitudinal cohort study of patients with birdshot chorioretinopathy. 141(1):185-187. Electroretinographic monitoring in birdshot chorioretinopathy. 27. et al. Am J Ophthalmol. LeHoang P. 1985. Am J Ophthalmol.2 subtype associated with birdshot retinochoroidopathy. Nussenblatt RB. 1(4):369382. 144(6):829-837. Foster CS. et al. 151(4):630-636. 22. 115(5):e15-20. Vitale AT. Differential inflammatory involvement in retina and choroid in birdshot chorioretinopathy. 18. Levinson RD. 2002. Histopathology of birdshot retinochoroidopathy. Daclizumab for treatment of birdshot chorioretinopathy. 14(6):325-332. 1982. 138(4):631-634. Randomized. Outcomes of birdshot chorioretinopathy treated with an intravitreal sustained-release fluocinolone acetonide-containing device. Ocul Immunol Inflamm. noninfectious uveitis. Levinson RD. 2006. et al. Am J Ophthalmol. 40. 221(5):351-356. Am J Ophthalmol. Research criteria for the diagnosis of birdshot chorioretinopathy: results of an international consensus conference. Longitudinal cohort study of patients with birdshot chorioretinopathy: III. et al. 12. Am J Ophthalmol. Ophthalmology 2008. 26. HLA-A29. et al. Gulati N. 36. 2008. Zamecki KJ. 2007. Ocul Immunol Inflamm. 2008. 35. et al. 113(1):33-35. et al. Loss of visual field among patients with birdshot chorioretinopathy. Jabs DA. Rush RB. 2010. 17. 1991. Outcome of uveitis patients treated with long-term cyclosporine. Restoration of retinal architecture following systemic immunosuppression in birdshot chorioretinopathy. 140(1):52-64. Callanan DG. Birdshot chorioretinopathy and Lyme borreliosis. 21. et al. Klin Monbl Augenheilkd. Intravenous immunoglobulin (IVIg) for the treatment of birdshot retinochoroidopathy. 2005. HLA typing in uveitis: use and misuse. 29. Cyclosporine in the treatment of birdshot retinochoroidopathy. Rothova A. et al. 103(3):365-373. et al. 145(1):23-28. Am J Ophthalmol. IV. Martin DF. Rodriguez A. 149(2):189-193 e2. Folk JC. 2007. Suttorp-Schulten MS. Forooghian F. 35:2094. Thorne JE. 144(6):818-828. Am J Ophthalmol. Visual field results at baseline. Am J Ophthalmol. Graefes Arch Clin Exp Ophthalmol. Pozzoni MC. Gaudio PA. et al. non-infectious uveitis. Efficacy of low-dose methotrexate treatment in birdshot chorioretinopathy. 101(5):822-831. 240(8):601-607. Nussenblatt RB. 1994. 93(8):3466-3470. Am J Ophthalmol. Low-dose cyclosporine therapy in the treatment of birdshot retinochoroidopathy. Holland GN. Standardized visual field assessment for patients with birdshot chorioretinopathy. 34. 2004. Am J Ophthalmol. Arch Ophthalmol. 2010. Birdshot retinochoroidopathy associated with HLA-A29 antigen and immune responsiveness to retinal S-antigen. et al. 106(10):1928-1934. Electroretinograms as an indicator of disease activity in birdshot retinochoroidopathy. Le Hoang P. Definition of the HLA-A29 peptide ligand motif allows prediction of potential T-cell epitopes from the retinal soluble antigen. Gordon LK. 20. Vitale AT. 1988. 1996. Invest Ophthalmol Vis Sci. Retina 2011. . a candidate autoantigen in birdshot retinopathy. Fundus autofluorescence in birdshot chorioretinopathy. Boisgerault F.

which are likely related to infectious etiology. In contrast the simulating SC are associated with infectious etiology. Narayana KM. Others III. Geographic distribution B. retinal pigment epithelium (RPE). Madhavan HN. 2. The typical SC reveals choroidal inflammation extending from juxtapapillary choroid with recurrences progressing in centrifugal pattern with minimal or no inflammatory vitreous reaction. 2. and they display multifocal lesions. I. and HLA-DW3. There appears to be a subset of patients with atypical features mimicking SC. 2007. the latter is seen in relatively older individuals from non-tuberculosis endemic regions with or without mild vitreous inflammatory reaction and negative history of exposure to tuberculosis and negative TST and γ-interferon release assay test results (QuantiFERON Gold TB or similar tests) and negative chest x-ray. 4. 128(7):847-848. (b) infectious etiology. Surv Ophthalmol. and current ocular imaging studies support the inflammatory nature of the SC with predominant involvement of inner choroid. Molecular studies (PCR) 3. 10(4):247261. Rao PK. Relentless placoid chorioretinitis C. primarily tuberculosis in endemic regions of this infection or herpetic viral infection without restrictions to a particular geographic part of the world. 1900. therapeutic intervention studies suggest SC could be autoimmune or idiopathic inflammatory process. and (c) idiopathic. . C. Differential Diagnosis A. Herpes infection (VZV and HSV) 1. there are 3 likely inflammatory mechanisms that could induce this recalcitrant choroiditis. Rao NA. Reiser BJ. Davies JB. there are several distinct differences. Association with pulmonary tuberculosis 4. Arch Ophthalmol. Tuberculosis 1. Association of herpes viruses in the aqueous humor of patients with serpiginous choroiditis: a polymerase chain reaction-based study. Ocul Immunol Inflamm. Rao NA. Although variations in clinical features of SC have been amply described. Response to antiviral agents A. Ampiginous B. Although superficially these infectious serpiginous-like choroiditis may be mistaken for the typical SC. Case reports based on tuberculin skin test (TST) and interferon gamma release assays 3. HLA-A2. Response to anti-TB agents 6. It is essential to differentiate classic SC from mimicking conditions of infectious etiology for proper treatment. including macular variant and simulating SC. Gupta A. HLA-B8. Histopathology B. 2002. Gupta V. Infectious Etiology Primarily presents as multifocal serpiginoid choroiditis. however. Favorable response to immunosuppressive agents B. Sohn EH. 52(6):561-587. Biswas J. Vasconcelos-Santos DV. A. 3. HLA association: HLA-B7. there are distinct differences in the clinical features of typical SC compared to the simulating SC. 2010. Saptagirish R. Limited histopathologic studies of eyes with SC revealed a chronic inflammatory process. Serpiginous choroiditis in scrofulous subjects: choroidal lupus. usually sparing the juxtapapillary choroid during initial presentations and moderate vitreous inflammatory response. the suggestive mechanisms include (a) organ-specific autoimmune process. Autoimmune Etiology A. among which Mycobacterium tuberculosis and varicella zoster virus are likely causes. Molecular studies (PCR) IV. Intraocular tuberculosis: an update. Rao NA. Clinical features of tuberculous serpiginous-like choroiditis in contrast to classic serpiginous choroiditis. choriocapillaris. Hutchinson reported infectious etiology over a century ago.2012 Subspecialty Day  |  Uveitis Section VI: Puzzling White Dots—What’s a Doctor to Do? 37 What About Serpiginous Choroiditis? Is It Autoimmune? Or Herpes? Or Tuberculosis? Narsing A Rao MD Serpiginous choroiditis (SC) is a posterior uveitis displaying a geographic pattern of choroidal changes typically extending from juxtapapillary choroid in a centrifugal pattern and a recurrent progressive choroiditis from margins of healed choroidal lesions. Priya K. T-cell immune response to retinal S-antigen II. Association with herpes zoster ophthalmicus 2. Selected Readings 1. such as multifocal serpiginoid choroiditis (multifocal serpiginous-like choroiditis) and serpiginous-like choroiditis. Although the etiology of SC is not clear. 11:126-135. Idiopathic Studies seeking a unifying etiology are inconclusive. Hutchinson J. and outer retina. Arch Surg (Lond). Molecular studies (PCR) 5.

They suffer from unpredictable recurrent choroiditis with possible development of secondary choroidal neovascularization. both of which can threaten the macula. azathioprine. Presumed Ocular Histoplasmosis Syndrome. the involvement of the foveola. metamorphopsia. therefore. punched-out. Anti-inflammatory agents either by local or systemic routes (corticosteroids. and particularly upon the possible development of submacular choroidal neovascularization (CNV). immunosuppressive drugs). multifocal choroiditis and panuveitis are three rare type of choroiditis of unknown origin. MFCPU. scotomas. microglia. Several papers have reported beneficial effects of various immunomodulating agents (methotrexate. although it can be observed worldwide in nonendemic regions. predominantly of Caucasian extraction. Destruction of the new vessels (direct laser photocoagulation. cyclophosphamide. accompanied by vitritis and anterior uveitis requiring a complete uveitis workup. early detection of a macular threat warrant a close follow-up with repeated patient’s self-evaluations (blurred vision. photopsia). with bilateral involvement in more than 60% of the cases. but only in 5% of patients with histo spots at the earliest stage of the disease. peripapillary pigment alterations. Peripapillary alterations of the retinal pigment epithelium and vitritis are absent. the treatment can combine three approaches in selected patients (lesions at the posterior pole threatening the macula. presumed ocular histoplasmosis syndrome (POHS). Although unpredictable. in 70% of punctate inner choroidopathy. deep yellow-white lesions evolving toward atrophic and pigmented spots. fundus pictures (including FAF) and angiograms (FA. with the absence of systemic findings although POHS was initially thought to be related to Histoplasma capsulatum infection. • PIC generally shows multiple. Some characteristics can help to differentiate one entity from another: • POHS frequently occurs in histoplasma endemic areas in the United States. Therefore. IFN beta 1A) in a limited number of patients with PIC. and multifocal choroiditis with panuveitis (MFCPU) is linked to the involvement of the macula. OCTs. presumed ocular histoplasmosis syndrome. They are scattered throughout the fundus and. and Panuveitis: Does Each of These Require Immunomodulatory Therapy? Phuc Lehoang MD PhD Introduction The visual prognosis of punctate inner choroidopathy (PIC). 2. CNV occurs in 28% of multifocal choroiditis. similar to those observed in the POHS. They share common features: Patients are frequently myopic. cytokines. may respond to anti-inflammatory agents and to immunomodulatory therapy. and a clear vitreous. rapamycin.38 Section VI: Puzzling White Dots—What’s a Doctor to Do? 2012 Subspecialty Day  |  Uveitis Punctate Inner Choroidopathy. cyclosporine. Because proangiogenic growth factors and cytokines released during chronic inflammation are both thought to contribute significantly to CNV formation. However. Several studies clearly demonstrate the important role of inflammatory mechanisms in the development of CNV in AMD and moreover in uveitic conditions. explaining why the term “presumed” has appeared in its name. a randomized controlled trial is difficult to set up because of the rarity of those entities. Although warranted. mycophenolate mofetil. oxidative stress inflammatory products). Anti-angiogenesis therapy (intravitreal injections of antiVEGF agents) 3. thalidomide. small. immunomodulatory therapy should be considered in order to limit the number of recurrences of CNV and reduce the risk for developing any posterior pole complication during follow-up. It is characterized by the presence of disseminated atrophic “histo” spots. particularly fungal infection in POHS). photodynamic therapy) Prognosis The visual prognosis of these three entities depends upon the rate of inflammatory recurrences. Background Punctate inner choroidopathy. CNV develops in direct response to low-grade chronic intraocular inflammation and. Rationale for an Anti-inflammatory and Immunosuppressive Treatment Any treatment should aim at decreasing the rate of inflammatory recurrences and the risk of CNV. Multifocal Choroiditis. These mechanisms involve inflammatory cells (macrophages. presence of CNV): 1. In fact the causative role of the fungus Histoplasma capsulatum is unclear. There is no standardized treatment for these three entities. and in 100% of presumed ocular histoplasmosis syndrome if one includes a macular disciform . their action is transient and their administration cannot be prolonged because of severe side effects. in most cases. a maculopathy. They can be effective in treating the inflammatory lesions during the acute stages. Corticosteroids has been proven effective in limiting and decreasing the CNV either locally or by systemic route. • MFCPU is characterized by multiple creamy chorioretinal lesions in their active phase before becoming atrophic scars. chemokines. lesion from CNV in the definition of the POHS. lymphocytes) and inflammatory factors (complement factors. Their distribution is mostly limited to the posterior pole. or POHS with regression of CNV and improvement or maintenance of vision (provided to exclude any infectious component. ICG-A) when indicated.

1998. Punctate inner choroidopathy: a survey analysis of 77 persons. . Br J Ophthalmol. 2011. Systemic therapy with conventional and novel immunomodulatory agents for ocular inflammatory disease. Forrester JV. Essex RW. Majid MA. Pavesio C. et al. 58(1):3-10. Rentiya ZS. Foster CS. 2007. The treatment of multifocal choroiditis associated choroidal neovascularization with sirolimus (rapamycin). 19(4):286-292. Arch Ophthalmol. 81(1):7-11. and CNV. et al. Ocul Immunol Inflamm. 56(1):36-53. 113(12):2310-2316. Acta Ophthalmol Scand. Arch Ophthalmol. Rothova A. Sobrin L. Wittenberg S. Immunosuppressive treatment of choroidal neovascularization associated with endogenous posterior uveitis. O’Toole L. Lois N. Inflammatory choroidal neovascular membrane in posterior uveitis-pathogenesis and treatment. Durrani K. 114(6):1201-1204. or POHS suffering from frequent inflammatory recurrences. early and aggressive therapy with immunosuppressive drugs may help to preserve good visual acuity in selected patients with PIC. Zakka FR. Selected Readings 1. Surv Ophthalmol. Dees C. 2005. Jirawuthiworavong G. Suttorp-Schulten MS. Tufail A. 2011. 56(6):474-510. limit the number of recurrences of CNV and prevent the occurrence of CNV in the contralateral eye Therefore. Chang PY. et al. 2010. Bailey CB. 116(11):14561461. Bollemeijer JG. Arnold JJ. Management of choroidal neovascularization in uveitis. Turkcuoglu P. Kelly S. 6. Memon M. Nussenblatt RB. Dick AD. 5. Punctate inner choroidopathy. Jabs DA. Thorne JE. 3. 2010. 128(8):982-987. choroidal lesions threatening the macula. Coleman H. Ahmed M. 1997. 2011.2012 Subspecialty Day  |  Uveitis Section VI: Puzzling White Dots—What’s a Doctor to Do? 39 Conclusion Immunosuppression appears to: • Prevent the recurrence of progressive choroiditis and reduce the risk for developing posterior pole complications during follow-up • Facilitate the regression of CNV. Surv Ophthalmol. Dhingra N. 11. Multifocal choroiditis with panuveitis incidence of ocular complications and of loss of visual acuity. 8. 85(2):230-231. Thorne JE. Bos PJ. 9. 45(2):157-177. Presumed ocular histoplasmosis in The Netherlands: an area without histoplasmosis. Punctate inner choroidopathy: clinical features and outcomes. 7. Dick AD. 4. Ophthalmology 2006. et al. 2. MFCPU. Siddique SS. Mycophenolate mofetil and fundus autofluorescence in the management of recurrent punctate inner choroidopathy. Amer R. Ophthalmology 2007. Fraser-Bell S. 10. et al. Int Ophthalmol Clin. Gerstenblith AT. Wong J. Indian J Ophthalmol.

40 Section VI: Puzzling White Dots—What’s a Doctor to Do? 2012 Subspecialty Day  |  Uveitis Acute Posterior Multifocal Placoid Pigment Epitheliopathy and “Ampiginous Choroiditis”: Should These Be Treated. Stage 1a hyperacute phase: Demarcated domeshaped elevation of the inner segment/outer segment (IS/OS) junction. Distribution of lesions – periphery (mid and far) and macula 2. biologics III. varying in size. yellowish-white. Complications differed a. Healthy young adults affected. hepatitis B vaccine. Mild vitritis (25%) 4. Prolonged relapsing course: 35%-65% within 6 months to 5 years 5. Morphology of lesions 3. Stages of disease by spectral domain OCT15-22 . placoid lesions. but may be asymmetric 4. With What? Henry J Kaplan MD I. Should either of these diseases be treated? D. Diagnosis 1. Fluorescein angiography: Hypofluorescent early (blocked). viral prodrome 2. lesions fade over course of time. pulmonary TB. Characteristic fundus findings a. T cell inhibitors. optic disc swelling. Chronic suppression of immunity: Immunomodulatory therapy (IMT)—alkylating agents. Associated with multiple conditions: Lyme disease. What is acute posterior multifocal placoid pigment epitheliopathy (APMPPE)? A. but ≤ 20/40 2. antimetabolites. What is ampiginous choroiditis? Clinical Presentation23-25 A. Stage 4 resolution phase (~ 3 months after onset): Two bands of IS/OS junction and RPE regain normal appearance. at level of retinal pigment epithelium (RPE). Associated ocular conditions: central retinal vein occlusion. Variant of APMPPE and serpiginous choroiditis = relentless placoid chorioretinitis B. Uncommon condition 2. Fundus autofluorescence: Foveal hypofluorescence – visual acuity (VA) impairment e. paracentral and central scotomas 5. ICG angiography: Hyperreflective lesions in outer photoreceptor layer d.5-6 months later): Disruption of IS/OS junction. thickening of IS/OS junction. exudative NSD 1. CNV.14 papillitis. periphlebitis. Stage 3 late phase (from 1. group A streptococcal infection. invoke autoimmunity and inflammation as the cause. new lesions may be observed over several weeks from onset b. Treatment choices 1. Visual in 58% eyes prognosis3: Relatively benign.” B. corticosteroids) 2. Characteristic clinical presentation (as above) 2. frequently with influenza-like illness (30%) 3. systemic necrotizing vasculitis. Wegner granulomatosis. Absent: episcleritis. retinal detachment 6. subretinal fluid. Rationale for treatment of disease Kaplan’s modification of Occam’s razor: “Treat the cause and If you don’t know the cause. mumps. Acute suppression of immunity (ie. Etiology: Unknown4-12 1. ulcerative colitis. increased hyperreflectivity of RPE 5. with atrophy and hypertrophy of RPE. HLA-B7. flat. and If So.2 1. gradually. increased reflectivity of ONL 3. DR213 C. Stage 2 subacute phase (2 weeks later): + SRF with separation of IS/OS junction and RPE. Present: subretinal fibrosis and epiretinal membrane b. Stage 1b acute phase (2-4 days later): Flattening of dome. Funduscopy: Multiple. photopsias. Distinguishing features on presentation 1. hyperfluorescent late (staining) c. sarcoid. except for minimal persistent irregularity in RPE B. fading of hyper-reflectivity of ONL 4. Possible association with systemic autoimmune disease A. Bilateral. Rapid onset of blurred vision. Clinical presentation1. ± SRF (yellowish-gray fundus lesion) II.

10. Goldstein DA. Yeo IY. Chiquet C. et al. In either case. Quercioli P. 14. Choromokos EA. 19. 18(1):46-51. Davis JB. Multifocal placoid epitheliopathy and anti-hepatitis B vaccination. Goldenberg D. 23. Loewenstein A. Iaccheri B. 24. Wolf MD. 128:644-646. Acute posterior multifocal placoid pigment epitheliopathy associated with Wegener’s granulomatosis. Goldberg MF. 244:1219-1223. Folk JC. Correlation between optical coherence tomography and autofluorescence in acute posterior multifocal placoid pigment epitheliopathy. 106:796-800. 21. Lofoco G. Wolf MD. Blair MP. et al. J Fr Ophthalmol. 23:64-68. Marks SJ. 11. Jampol LM. 118:931-938. Koh A. . Habot-Wilner Z. 1990. Am J Ophthalmol. Retina 2005. 1992. Subretinal fluid in acute posterior multifocal placoid pigment epitheliopathy. Ocular coherence tomography in acute posterior multifocal placoid pigment epitheliopathy [letter]. Lowder CY. 2004. 6. Kalpana B. Harlan JB. Lauer AK. Optical coherence tomography findings in a case of acute multifocal posterior placoid pigment epitheliopathy (AMPPPE). Laurens C. Gaetano D. Birnbaum AD. Fiore T. Scheufele Ta. Ampiginous choroidopathy: forme fruste of serpiginous choroidopathy C. Webb L. Goeken NE. Anderson K. mycophenolate mofetil or azathioprine) 2. Yannuzzi LA. Lee BW. 13. Relentless placoid chorioretinitis. 2012. Acute posterior multifocal placoid pigment epitheliopathy as the initial manifestations of sarcoidosis. 5. 16. et al. Retina 2010. Dutton GN. J Ophthal Vis Res. 30:810-814. 22. Limon S. 1996. 1998. Arch Ophthalmol. 126:309-312. Hillenkamp J. multifocal. Quillen DA. 6:189-193. Gutman FA. 2011. Piguet B. Retina 2012. Witkin AJ. 2000. Arch Ophthalmol. Bodaghi B. Retina 1999. 1968. Arch Ophthalmol. placoid. 108:698-700. Patel KR. Jones BE. Lee GE. 2006. Gora F. If central macular involved or VA ≤ 20/25: Systemic corticosteroids with IMT monotherapy (methotrexate. Smith JR. Goldstein M. and visual outcome of ampiginous choroiditis. Relentless placoid chorioretinitis: a new entity or an unusual variant of serpiginous chorioretinitis? Arch Ophthalmol. 1998. Fawzi AA. AIOC 2006 proceedings. Lumbroso L. Photoreceptor changes in acute and resolved acute posterior multifocal placoid pigment epitheliopathy documented by spectral-domain optical coherence tomography. 1998. 2011. Borruat FX. Am J Ophthalmol. Foster RE. Hsu CT. 20. 32(7):1403-1410. Tessler HH. Gottlieb JL. Acute posterior multifocal placoid pigment epitheliopathy: outcome and visual prognosis. Arch Ophthalmol. 6(4):338-343. Acute posterior multifocal placoid pigment epitheliopathy following mumps. Schocket LS. Eur J Ophthalmol. Ciucci F.2012 Subspecialty Day  |  Uveitis Section VI: Puzzling White Dots—What’s a Doctor to Do? 41 3. Dunn JP. 80(2):177-185. 17. Mathian A. Biswas J. 137(3): 538-550. Jafferji SS. Perspective: the white dot syndromes. Panknen CA. Gordon SM. Sheppard R. Watzke RC. Steigerwalt RD. 19:42-47. Acute posterior multifocal placoid pigment epitheliopathy. Gass JD. Acute posterior multifocal placoid pigment epitheliopathy after acute group A streptococcal infection. Ocul Immunol Inflamm. Darugar A. Clinical profile. 9. 29:994-1001. Herbort CP. 25:11091112. et al. Androudi S. 2012. Bardocci A. 7. If VA > 20/25 and central macular not threatened: Watchful waiting 3. HLA-B7 and HLADR2 antigens and acute posterior multifocal placoid pigment epitheliopathy. Am J Ophthalmol. 21:696-700. Acute posterior multifocal placoid pigment epitheliopathy associated with a systemic necrotizing vasculitis. 19:309-313. treatment. References 1. 2006. 25. 80:186. 15. Spectral domain optical coherence tomography classification of acute posterior multifocal placoid pigment epitheliopathy. Spectral domain optical coherence tomography and autofluorescence in a case of acute posterior multifocal placoid pigment epitheliopathy mimicking VogtKoyanagi-Harada disease: case report and review of literature. Photoreceptor atrophy in acute posterior multifocal placoid pigment epitheliopathy demonstrated by optical coherence tomography. Retina 2009. posterior. Sudharshan S. et al. 4. 34:810-812. 1998. Treatment recommendations 1. 3. pigment epitheliopathy and Lyme disease. Retina 2003. Wilson CA. Rao NA. 2005. Arch Ophthalmol. 15(1):143-147. Ocul Immunol Inflamm. Graefes Arch Clin Exp Ophthalmol. Nelson JA. 122:115-117. Kazi S. Folk JC. Clin Experiment Ophthalmol. Acute posterior multifocal placoid pigment epitheliopathy with bilateral central retinal vein occlusion. Souka AA. 2. Alle SD. Lim LL. 18. with judicious use of serial OCT examinations (remembering that Medicare and insurance companies will probably not pay for the studies) 12. Acute posterior multifocal placoid pigment epitheliopathy and cerebral vasculitis. Acute posterior multifocal placoid pigment epitheliopathy associated with pulmonary tuberculosis. If patient older than 50 years of age (has a lesion resembling serpiginous choroidopathy): Very watchful waiting 4. Jyotirmay B. 1996. Denis P. Pisella PJ. Ocul Immunol Inflamm. 8. follow the patient closely. Peeples ME. Bourges JL. Acute. 110:750. Cheung CM. LeHoang P. Br J Ophthalmol.

Endoretinal biopsy IV. Techniques for Diagnostic Surgery A. 87(6):588-601. Applications of the polymerase chain reaction to diagnosis of ophthalmic disease. Gram stain. 2001. Viral PCR/quantitative PCR 2. Surv Ophthalmol. V. and the Goldmann-Witmer coefficient to diagnosis of atypical toxoplasmic retinochoroiditis. Emerging deep sequencing techniques 3. Laboratory Testing for Diagnostic Tap A. 5. Scott IU. 7. Background II. 47(7):2131-2135. Ophthalmology 2010. 10. Fine-needle aspiration biopsy and other biopsies in suspected intraocular malignant disease: a review. Paris L. 16S universal bacterial PCR 3. Epub ahead of print. Rothova A. 9. 2012. 8. et al. and real-time PCR using aqueous humor samples for diagnosis of ocular toxoplasmosis. Brown GC. 117(9):1851-1857. Asseraf M. Infectious uveitis in immunocompromised patients and the diagnostic value of polymerase chain reaction and Goldmann-Witmer coefficient in aqueous analysis. Contributions of immunoblotting. Touafek F. Westeneng AC. Am J Ophthalmol. Clinical features and diagnostic significance of the intraocular fluid of 217 patients with intraocular lymphoma. and sensitivity C. et al. Mazier D. McCallum RM. Jpn J Ophthalmol. 19(3):218-224. 2008. Mruthyunjaya P. 2007. Curr Opin Ophthalmol. 145(2):369-374. Van Gelder RN. Diagnostic vitrectomy for the diagnosis and management of posterior uveitis of unknown etiology.42 Section VII: The Puzzling Matter of Treatment-Resistant Uveitis 2012 Subspecialty Day  |  Uveitis Is It Infectious. Comparison of immunoblotting. Int Ophthalmol Clin. culture. Indications for Diagnostic Surgery III. de Visser L. 2. Goto H. Talabani H. or Malignant? The Importance of Diagnostic Surgery Russell N Van Gelder MD PhD I. Vitreous tap/diagnostic vitrectomy C. Aqueous tap B. Histology B. Sobrin L. 56(4):383-389. Small-gauge pars plana vitrectomy: a report by the American Academy of Ophthalmology. . Bodaghi B. J Clin Microbiol. 51(4):25-31. Jaffe GJ. Polymerase chain reaction (PCR) 1. Scott AW. real-time PCR. 6. 2009. 4. Brown MM. Autoimmune. de Groot-Mijnes JD. Margolis R. 144(5):781785. Eide N. Acta Ophthalmol. 18S universal fungal PCR 4. Kimura K. 2008. 2008. de Boer JH. Case Examples Selected Readings 1. Recchia FM. 2009. Yera H. Diagnosis of ocular toxocariasis by establishing intraocular antibody production. Cytokine Analysis VII. calculation of the Goldmann-Witmer coefficient. Intraocular Antibody Testing VI. 21 Mar 2012. 46(6):1965-1967. Am J Ophthalmol. Fekkar A. Graefes Arch Clin Exp Ophthalmol. Diagnostic yield of vitreous biopsy in presumed sarcoidosis-related posterior segment inflammation. de Boer JH. J Clin Microbiol. Rothova A. Ip MS. 11. Walaas L. Le Hoang P. 2011. 46(3):248-258. Ho AC. The Japanese Intraocular Lymphoma Study Group. New diagnosis and treatment paradigms in acute retinal necrosis. Usui Y. Kanoff J.

Ocular Malignancies in Neuro-Oncology A. although systemic treatment may not be excluded. Consideration of whole-brain radiotherapy in conjunction with ocular radiotherapy in those who have failed systemic therapy and are too debilitated or do not meet criteria for more aggressive therapy such as ASCT . chemotherapy C. B. B. 2. Optic sheath meningioma: radiation II. radiation. Careful and close follow-up for CNS disease D. Consult ophthalmologist III. Only 1 eye involved: Use local therapy—whether it is local intravitreal methotrexate and rituximab alone or carefully given between 30-35 Gy external beam is still in contention. Reserve systemic therapy for those with CNS disease. The optimal therapy for PVRL is not defined. A. Local therapy for disease confined to the eye C. High-dose methotrexate-based therapy (possibly with systemic rituximab) in conjunction with local therapy given the limited penetration of systemic agents into the vitreous cavity 2. Optic nerve glioma: surgery. Recommendations A. With CNS involvement 1. Addition of intravitreal chemotherapeutic agents in addition to the systemic therapy would be considered. Both eyes involved: There is still a preference toward local therapy. Without CNS or systemic involvement 1.2012 Subspecialty Day  |  Uveitis Section VII: The Puzzling Matter of Treatment-Resistant Uveitis 43 Current Concepts in Managing Ocular Malignancy: What Are Our Colleagues in Neuro-Oncology Doing? Chi-Chao Chan MD I. Primary vitreoretinal lymphoma (PVRL) B.

outlined above are critical to diagnosing nonparaneoplastic AIR. the presence of antiretinal antibodies alone is not sufficient for the diagnosis of this ill-defined ocular disorder. There is usually minimal or no clinically detectable intraocular inflammation. These antiretinal antibodies can target any retinal cell type. antimetabolites such as mycophenolate mofetil. recoverin and enolase are the most extensively studied antigens in AIR. common clinical features in AIR patients include retinal vascular attenuation. Differential diagnoses of AIR include paraneoplastic AIR (eg. Evidence from paraneoplastic retinopathies suggests that AIR may be triggered by molecular mimicry between retinal proteins and presumed viral or bacterial proteins.8. cancer-associated retinopathy. may be deceivingly good. On examination the fundus may appear unremarkable. has its own limitations. and the term “paraneoplastic retinopathy” was first used by Klingele et al in 1984. some of these are retinaspecific (recoverin) and others are not (enolase). retinal degenerative disorders such as RP. Among these. Some uveitis syndromes can also demonstrate antiretinal antibodies. Paraneoplastic AIR was described by Sawyer et al in 1976. or photoaversion. retinal pigment epithelial (RPE) changes. and adding to the challenges in the management is the lack of parameters to guide treatment.9 Less frequently. Ancillary testing with fluorescein angiography (FA) or OCT may show mild retinal vascular staining or leakage. but most of these syndromes have typical fundus findings that help differentiate them from AIR. AIR is usually bilateral but it can be asymmetric. clinical and laboratory. or cystoid macular edema (CME) in some cases.9 Diagnosis and Differential Diagnosis Diagnosis of AIR is a challenge because there are no standardized diagnostic criteria.8-11 Seemingly most important factor in diagnosis. photoreceptor dysfunction. immunomodulatory therapy can be considered empiric at this time. azathioprine. but the mechanisms by which these antibodies cause retinal dysfunction are not entirely understood. A family or a personal history of systemic autoimmune disease can be common among patients with AIR. the ambiguity in diagnosis creates an enormous challenge in the management of AIR. There is a female preponderance (63%-66%). has also been used in the treatment of AIR. Early treatment attempts would require establishing a clear diagnosis using sensitive and specific assays and more definitive clinical criteria that can only be achieved with a better understanding of the disease. However.7 Visual field testing shows constricted visual fields and central or paracentral scotomas.44 Section VII: The Puzzling Matter of Treatment-Resistant Uveitis 2012 Subspecialty Day  |  Uveitis On the Matter of Autoimmune Retinopathy: A Diagnostic and Therapeutic Puzzle Hatice Nida Sen MD Introduction and Definition Autoimmune retinopathy (AIR) is an inflammatory retinopathy characterized by vision loss. and whether timing of therapy is important or whether autoantibodies can be used to guide therapy is still unclear. Visual acuity.17 The benefit of immunosuppressive therapy in AIR is unclear at this time. and the presence of circulating autoantibodies against retinal antigens. Firstly. AIR can be studied in two groups: paraneoplastic and non-paraneoplastic.2 This presentation will focus on nonparaneoplastic form of AIR. and T-cell inhibitors such as cyclosporine. cone-rod dystrophy and noninfectious and infectious uveitis syndromes. A long-term treatment is usually needed in most cases. including photoreceptor cells. and therapy is unlikely to be helpful once widespread retinal degeneration occurs. Clinical Findings Patients with AIR typically present with subacute vision loss. melanoma-associated retinopathy). intravenous immunoglobulin (IVIG). Common approaches include systemic or local corticosteroids. western blot (WB) and immunohistochemistry (IHC) are the more commonly performed techniques.1. such as antiCD20 monoclonal antibody (rituximab). or plasmapheresis. it is important to differentiate paraneoplastic AIR from non-paraneoplastic AIR. scotomas. and electroretinogram (ERG) can show abnormalities in rods. their presence does not always indicate pathogenicity.6. Despite the heterogeneity in their circulating antiretinal antibodies. antiretinal antibody detection. which makes differentiating these two entities with overlapping features very difficult. There are no prognostic indicators. and secondly. particularly acute zonal occult outer retinopathy. Multiple retinal proteins have been found to be antigenic. the techniques used to detect these antibodies are not highly sensitive or specific. RP patients can have very similar clinical features to AIR and some demonstrate antiretinal antibodies. diffuse retinal atrophy. visual field deficits. Because of limitations in diagnostic testing and lack of our understanding of the underlying mechanisms. and even in healthy subjects. Most AIR patients may have been diagnosed with retinitis pigmentosa (RP) prior to presentation. white-dot syndrome spectrum disorders. Most of the knowledge regarding therapy comes from paraneoplastic retinopathy. Absence of malignancy and family history of RP and the presence of antiretinal antibodies in the setting of appropriate clinical findings as . The overlap of clinical features with other degenerative retinal disorders and the lack of standardized diagnostic criteria. However. and waxy disc pallor. other ocular diseases. various forms of immunomodulatory approaches have been tried. Some of these antiretinal antibodies can be found in multiple autoimmune diseases. may be contributing to underestimation of its prevalence. Treatment Because of the presumed autoimmune nature of AIR.8.3-5 Although it is believed to be rare. photopsias. targeted B-cell therapy. particularly in the earlier stages. scotomas. nyctalopia.16. cones.12-15 Regardless of its caveats. AIR presumably results from an immunologically mediated attack on the retina by antiretinal autoantibodies. and average age at diagnosis appears to range from 51 years to 56 years. or bipolar cell responses or a combination of these. ganglion cells. the prevalence of AIR is currently unknown. Because of significant implications. or bipolar cells. and dyschromatopsia.

a photoreceptor-specific calcium-binding protein. Kelman SE. 84(2):90-101. et al. Adamus G. Weleber RG. Jun 4:4:5. 2004. Weinstein JM. Arijs I. 2009. 2007. 4(4):239-245. 54(3):534-541. 1976. A clinical triad to diagnose paraneoplastic retinopathy. Vermeulen N. Anti-alpha-enolase antibody as a serologic marker and its correlation with disease severity in intestinal Behçet’s disease. Klingele TG. et al. 6. et al. Recoverin. 7. 56(3):812-818. Burde RM. Arch Ophthalmol. 2004. 15. Mahdi N. Ren G. Forooghian F. Lee JH. Cho SB. et al. Am J Ophthalmol. Blindness caused by photoreceptor degeneration as a remote effect of cancer. Macular and retinal dysfunction of unknown origin in adults with normal fundi: evidence for an autoimmune pathophysiology. Khan NW. Sen HN. 23:161-167. 13. 81:606-613. Management of autoimmune retinopathies with immunosuppression. 18(4):322-323. 101:12361243. 1984. Paraneoplastic retinopathy. 12. Sen HN. 3. 2. is expressed by the tumor of a patient with cancer-associated retinopathy. Bang D. 11. Jayasundera T. 51: E-Abstract 6375. Gottlieb CC. 4. Jacobson DM. Ann Neurol. Ferreyra HA. A case of autoimmune retinopathy associated with thyroid carcinoma.2012 Subspecialty Day  |  Uveitis Section VII: The Puzzling Matter of Treatment-Resistant Uveitis 45 References 1. 2008. Dig Dis Sci. Clin Exp Rheumatol. Shin SJ. 5. et al. Zein WM. Witkowska D. Human anti-alpha-enolase antibody in sera from patients with Behçet’s disease and rheumatologic disorders. Polans A. Haley T. Paraneoplastic retinopathy associated with antiretinal bipolar cell antibodies in cutaneous malignant melanoma. 27(2 suppl 53):S63-66. Goodwin J. Ophthalmology 2004. 92:9176-9180. et al. . J Clin Neuroophthalmol. Cellular targets of anti-alpha-enolase autoantibodies of patients with autoimmune retinopathy. 245(8):1077-1084. Larson TA. Adamus G. Sproule M. Enolase autoantibodies and retinal function in multiple sclerosis patients. Kim BC. Sawyer RA. Clin Chem. 2011. Am J Ophthalmol. 8. Autoimmune retinopathy: prognosis and treatment. et al. et al. Joossens S. Rappazzo JA. Clinical and electrophysiologic characterization of paraneoplastic and autoimmune retinopathies associated with antienolase antibodies. et al. Watzke RC. Zimmerman LE. 1990. 127(4):390-397. Kim TI. Adamus G. Caruso RC. Bresnick GH. Shults WT. Graefes Arch Clin Exp Ophthalmol. Selhorst JB. Ophthalmology 1994. et al. Ocul Immunol Inflamm. 2009. Ren G. Ramchand KV. Thirkill CE. 111(3):535539. 17. Mantel I. Faia LJ. Tipping SJ. Nussenblatt RB. 9. et al. et al. 10. Holder GE. et al. Weleber RG. Invest Ophthalmol Vis Sci. 2010. J Autoimmun. Exp Mol Pathol. 1995. 2005. Autoantibodies against retinal proteins in paraneoplastic and autoimmune retinopathy. 2010. Waldenström’s macroglobulinemia-associated retinopathy. 2008. Chan CC. 14. Anti-alpha-enolase antibodies in patients with inflammatory bowel disease. 16. BMC Ophthalmol. 139(5):780-794. 28:162-167. Proc Natl Acad Sci U S A.

and AIN457 Eric Suhler MD N otes . Adalimumab.46 Section VIII: Potential New Therapies for Uveitis 2012 Subspecialty Day  |  Uveitis Systemic Pharmacologic Agents in Development for Uveitis: Voclosporin.

with a half-life of 8-9 days. become minimally quantifiable. Napoli KL. was isolated in the 1970s from Streptomyces hygroscopicus in soil samples from Easter Island. It is also important to recognize that the lowest therapeutic levels of sirolimus in organ transplant and cardiac patients is 5-15 ng/ml. Ophthalmology 1985. Roberge F. approved for improving coronary luminal diameter in patients with symptomatic ischemic disease. Owing to its unique mechanism of action and favorable side effects profile. 3. 1998. including cyclosporin and methotrexate. 2. Nussenblatt RB. Invest Ophthalmol Vis Sci. 92:467-471. . an immunosuppressive agent used in renal transplant patients. Selected Readings 1. Sirolimus is an immunosuppressant that works through inhibition of the mammalian target of rapamycin (mTOR) by binding to the immunophilin FK protein 12 (FKBP-12). by Day 14 and beyond. By Day 7. Following intravitreal administration. pharmacologic agents. although its side effects with systemic administration are also recognized. 4. Chronic non-infectious uveitis in the elderly: epidemiology. Rapamune (RAPA. 5. The interim results of the SAVE (Sirolimus as a Therapeutic Approach for Non-Infectious UVEitis) studies will be discussed. The depot subsequently dissolves slowly and sirolimus diffuses through the vitreous humor to other ocular layers. 4-31. Details will be discussed if public information is available. Other Agents Several other immunomodulatory therapeutic agents. 53:3198. employing Ca2+dependent or Ca2+-independent pathways. sirolimus blood levels decrease to less than 3 ng/ml and subsequently. Sehgal SN. 2001. Sirolimus is the active ingredient in two FDA-approved products. based on preclinical animal toxicity and pharmacokinetic studies. Palestine AG. 2012. rapamycin. Clin Biochem. 23:535-558. sustained-release. In order to allow higher target tissue levels and reduce systemic exposure. Intravitreal administration of ocular formulation of sirolimus in rabbits and humans. et al. we have set forth to evaluate the potential role of locally administered sirolimus in noninfectious uveitis. thus interrupting the inflammatory cascade that leads to T-cell activation and proliferation. a proprietary local formulation of sirolimus was developed that. a drug depot is formed that subsequently dissolves slowly and diffuses across sclera based on the physicochemical properties of sirolimus. Chan CC. pathophysiology and management.2012 Subspecialty Day  |  Uveitis Section VIII: Potential New Therapies for Uveitis 47 Local Pharmacologic Agents in Development for Uveitis: Sirolimus and Others Quan Dong Nguyen MD Sirolimus Sirolimus. is amenable to both intraocular (intravitreal [IVT]) and extraocular (subconjunctival [SCJ]) injection. Gupta R. After intravitreal administration of 352 µg. Blood levels of sirolimus after SCJ administration peaks on Day 0 to dose-dependent levels: 3. 23:559-586. specifically Rapamune. Mudumba S. if at all. are being developed as locally delivered. also known as rapamycin. When administered by SCJ injection. Taylor PJ. Based on the current knowledge of sirolimus and its potential anti-inflammatory effect. It also suppresses T-cell proliferation through the inhibition of IL-2. Takanaga H. Standardization of vitreal inflammatory activity in intermediate and posterior uveitis. Murray PI. From beach to bedside: history of the development of sirolimus. Bezwada P. the formulation forms a nondispersive depot in the vitreous and localizes in the inferior portion of the vitreous humor. and IL-15. IL-4. Drugs and Aging 2006.32 ng/ml for a dose of 1320 µg. sirolimus): mechanism of action immunosuppressive effect results from blockade of signal transduction and inhibition of cell cycle progression. with the highest concentration in vitreous followed by retina and choroid and lowest concentration in sclera and blood with detectable ocular tissue levels extending for 60 days after a single intravitreal administration. Ther Drug Monit. and the CYPHER Sirolimuseluting Coronary Stent. sirolimus blood levels peaks to < 2ng/mL by the second day and decreases subsequently over the following days.62 ng/ml for a dose of 440 µg and 9. sirolimus has been increasingly proposed as an alternative immunosuppressant in organ transplantation.

Delivery of anesthetic through skin 2. Many of the published studies lacked carefully controlled trials and details on toxicity. Herpes simplex keratitis 4. Macular degeneration 7. 2. G. Many reports until about 1960. Treatment of uveitis can potentially be more effective and safer with more efficient drug delivery methods. but usefulness in ophthalmology seemed to be overestimated. II. Unwanted systemic side effects C. The techniques were limited by the technological development of the devices and ocular electrodes. Potential advantages 1. cataract formation. Dry eye 2. Leduc demonstrated transcutaneous iontophoretic administration of strychnine in rabbits in early 1900s. Uveitis Therapy . Studied for treatment of: 1. Administration of acetylcholine and sodium nitroprusside for assessing risk of development and progression of cardiovascular disease D. Renewed interest in ophthalmic use H. Studied and used in many fields early on F. IV. Iontophoresis Technology V. Bacterial keratitis 3. Safety 2. the bloodretinal barrier and the lens-iris diaphragm further complicate drug delivery to the posterior segment. Avoids systemic toxicity 3.48 Section VIII: Potential New Therapies for Uveitis 2012 Subspecialty Day  |  Uveitis Novel Drug Delivery Approaches for Uveitis: Iontophoresis and Others David S Chu MD I. Requires repeated injections 4. Need to overcome blood-retinal barrier 3. Need to overcome blood-retinal barrier 2. Topically: eye drops and ointment 1. Administration of vitamin C for treating melasma G. Glaucoma 6. In the literature 1. Dermatologic 1. Based on the physical principle that like charges repel each other C. glaucoma and others A. Need to overcome epithelium and the rest of cornea and conjunctiva 3. I. Systemic 1. Corneal graft rejection 5. May require frequent instillation to achieve therapeutic level B. In addition. E. Administration of verapamil for treating Peyronie disease F. Physician-controlled dosing D. III. H. 1989: Lam et al showed transscleral dexamethasone delivery more effective than drops and subconjunctival injections. It was never adopted as a standard procedure in ophthalmology. Periocular injections 1. Clinical Applications A. Primary focal hyperhidrosis B. Administration of nonsteroidal anti-inflammatory drugs or corticosteroids for musculoskeletal disorders E. 1997: Behar-Cohen et al developed rat uveitis model treated with iontophoresis of dexamethasone. Uveitis A. 4. Tear physiology: Aqueous production and blood flow can affect efficacy. Standard Drug Delivering Options for Eyes With Uveitis A. Introduction The eye presents anatomical and physiologic challenges in ocular drug delivery: the cornea and conjunctival epithelium and tear drainage. Advancement of technology I. Sweat test by pilocarpine iontophoresis for the diagnosis of cystic fibrosis C. Cataract formation and glaucoma D. Risk of retinal detachment. Least invasive 2. Risk of globe injury 2. Use of electrical current to facilitate delivery of medication or ions into the tissue for therapeutic purposes B. Intravitreal implants and intraocular injections 1.

prednisolone acetate i. Evaluation of dexamethasone phosphate delivered by ocular iontophoresis for treating noninfectious anterior uveitis. et al. double-masked. Pouliquen Y. J. Arch Ophthalmol. Lam TT. Sakai T. 82:657-663.6 mA-min dose was the most effective and revealed an inverse dose response. Double-masked placebo controlled 49 B. Parel JM. Multicenter.6 mA-min group vs. Treatment of experimental autoimmune uveoretinitis with poly(lactic acid) nanoparticles encapsulating betamethasone phosphate. placebo iontophoresis treatment with accompanying prednisolone acetate ophthalmic suspension (1%) (positive control) eye drops iii. 107(9):1368-1371. Edward DP. J Control Rel. 2004. Extended release of dexamethasone from silicone-hydrogel contact lenses containing vitamin E. effective. . de Kozak Y. Results (a) 19 of 40 patients (48%) achieved anterior chamber cell score of 0 at Day 14. randomized clinical trial iii. Phase 3 a. 3. Selected Readings 1. (b) 1. Tamoxifen-loaded nanoparticles injected intravitreally have been shown to be effective in treating experimental autoimmune uveitis models whereas nonencapsulated tamoxifen had no effect. 1997. Contact lens i. 148:110-116. Ophthalmology Jan. Study design (a) 40 subjects with diagnosis of noninfectious anterior segment uveitis studied for 28 days (b) Four treatment groups with a single treatment of ocular iontophoresis (~4 min) with EGP-437 (c) No concurrent uveitis treatments during study (d) Rescue therapy with prednisolone acetate. Currently enrolling b. 24 of 40 patients (60%) achieved score of 0. 31 days in the 14.2012 Subspecialty Day  |  Uveitis Section VIII: Potential New Therapies for Uveitis 3. By Day 28. 34:3702-3712. Nanoparticles i. 2010. EyeGate – FDA Trials 1. i. Intraocular injection of tamoxifen-loaded nanoparticles: a new treatment of experimental autoimmune uveoretinitis. iii. Iontophoresis system: First commercial ocular iontophoresis system developed by EyeGate Pharma 2. Cohen et al. Exp Eye Res.0 mA-min at 1. Iontophoresis of dexamethasone in the treatment of endotoxin-induced–uveitis in rats. iontophoretic doses of EGP-437 (dexamethasone phosphate formulated for iontophoresis) in patients with noninfectious anterior uveitis and to evaluate systemic drug exposures ii. Zhu XA. et al. 4. Eur J Immunol. 2012. Chauhan A.5 mA) on Day 0 and Day 7 with accompanying placebo eye drops vs. Ishihara T. Phase 1/2 a. 2006. Dexamethasone phosphate solution (EGP437) delivered by iontophoresis treatment (4. Andrieux K. ii.5 days in the 1. 2. median days to an ACC score of 0 were 11. (c) All ocular adverse events deemed possibly or probably related to device or procedure. Transscleral iontophoresis of dexamethasone. Silicon-hydrogel loaded with vitamin E has been shown to increase dexamethasone release period to from 1 day to 7 to 9 days. Ability to absorb drugs and release over a period of time ii. Betamethasone-encapsulated particles have successfully treated EAU models. Potential advantages: Ability to penetrate tissue better. more controlled release of drug over longer duration ii. Kohno H. parallel group. et al. Villarroya H. (d) Mean IOP remained within normal range and mean best-corrected visual acuity at 4 meters remained relatively stable. Peng CC. c. if needed iv. Exp Eye Res. 1989. 5. EGP-437 vs. no adverse events were deemed related to study medication.0 mA-min group. To determine safe. Tso MO. Kim. 65:533. Behar-Cohen FF.

but don’t fall back on systemic tests if your clinical impression tells you otherwise.  Avastin to treat active uveitis. 5. .  MRI: Repeat and repeat. It’s not always easy. 6. 8. A good history and evaluation is critical. The problem of reacting to reactivations rather than prevention.  PPD positivity and ocular disease masquerading a masquerade. whether to add systemic medication or surgery. acute retinal necrosis.50 Section IX: Late Breaking News 2012 Subspecialty Day  |  Uveitis Top 10 Mishaps in Managing Uveitis Robert Nussenblatt MD 1. 3. 7. 4.  No therapy for relatively mild.  Undertreating anterior segment disease in children. We know that it is a matter of time before the vision will decrease. 2. 9. risk of infection. with serious consequences if a mistake is made.  The use of short-term intraocular or periocular steroids to treat chronic disease.  Following intraocular inflammation with no therapy if vision remains good because of good vision. Intraocular injections can certainly be helpful but beware of infections. 10. particularly when it comes to children.  Behçet vs. This can have a very negative effect on outcome. The phakic patient’s eye will not usually permit enough steroid to get to the posterior pole. Under the right circumstances these can be similar. chronic disease such as birdshot.  Topical therapy to treat posterior pole disease.  Triamcinolone therapy in severe uveitis. We always wish to minimize.

All contributors to Academy educational activities must disclose any and all financial relationships (defined below) to the Academy annually. objectivity. or • involvement in any for-profit corporation where the Contributor or the Contributor’s family is a director or recipient of a grant from said entity. including consultant fees.2012 Subspecialty Day  |  Uveitis  51 Financial Disclosure The Academy’s Board of Trustees has determined that a financial relationship should not restrict expert scientific. Category Consultant / Advisor Code Description C Consultant fee. contributor. child or spouse of a child. honoraria. As an Accreditation Council for Continuing Medical Education (ACCME) accredited provider of CME. • financial support or funding from third parties. The term “family” as used above shall mean a spouse. even if they have not been exercised or they are not currently exercisable. the Academy seeks to ensure balance. including research support from government agencies (e. travel fees or reimbursements when speaking at the invitation of a commercial entity (for the past one year) Equity ownership/stock options of publicly or privately traded firms (excluding mutual funds) with manufacturers of commercial ophthalmic products or commercial ophthalmic services Patents and/or royalties that might be viewed as creating a potential conflict of interest Grant support for the past one year (all sources) and all sources used for this project if this form is an update for a specific talk or manuscript with no time limitation Employee Lecture fees E L Equity owner O Patents / Royalty P Grant support S . or reviewer has reported with any manufacturers of commercial products or providers of commercial services within the past 12 months • any meeting presenter. parent. or employer by: • direct or indirect commission. or spouse of a brother or sister. or nonclinical presentation or publication. • stock options and/or warrants in the producing company. domestic partner. • ownership of stock in the producing company. clinical. and funded travel. sister. author. provided that appropriate disclosure of such relationship is made. business partners. or a brother. and/or pharmaceutical companies. contributor. independence.. device manufacturers.g. and scientific rigor in all individual or jointly sponsored CME activities. or reviewer (hereafter referred to as “the Contributor”) who report they have no known financial relationships to disclose For purposes of this disclosure. of the Contributor. paid advisory boards or fees for attending a meeting (for the past one year) Employed by a commercial entity Lecture fees (honoraria). The ACCME requires the Academy to disclose the following to participants prior to the activity: • any known financial relationships a meeting presenter. NIH). a known financial relationship is defined as any financial gain or expectancy of financial gain brought to the Contributor or the Contributor’s family. author.

: C. Inc. Inc.: C.S Allergan. Inc.L Melanie Rafaty None Debra Rosencrance None Quan Dong Nguyen MD Abbott Pharmaceuticals.: S Santen.: S Optos.: S .S Eyegate Pharmaceuticals.: O.S Alcon Laboratories.52  2012 Subspecialty Day  |  Uveitis 2012 Uveitis Planning Group Financial Disclosures C Stephen Foster MD Abbott Medical Optics: C. Inc. Inc.S Beth Wilson None Russell W Read MD PhD EyeSight Foundation of Alabama: S International Retinal Research Foundation: S Research to Prevent Blindness: S Eric Suhler MD Abbott Pharmaceuticals: C. Inc.: S Regeneron Pharmaceuticals. Inc.S Novartis Pharmaceuticals Corp.S AAO Staff Brandi Garrigus None Ann L’Estrange None Debra A Goldstein MD Abbott Pharmaceuticals: C Allergan. Inc.S Bristol-Myers Squibb: S EyeGate: S Genentech: S Lux Bio: C.: C.: S Bausch + Lomb Surgical: C Genentech: S Heidelberg Engineering: S Lux Biosciences.S Novartis Pharmaceuticals Corp. Inc.: C. Inc.S Lux Biosciences.: L Bausch + Lomb Surgical: C.: S Pfizer.: C. Inc.

: C..: C GlaxoSmithKline: C Novartis Pharmaceuticals Corp. Inc.: S Lourdes Arellanes MD None James Philip Dunn Jr MD None William Ayliffe MBBS Santen.: L Alay S Banker MD None C Stephen Foster MD Abbott Medical Optics: C. Inc.: C Bausch + Lomb Surgical: C Lux Biosciences: S Novartis Pharmaceuticals Corp. Inc.: C.S Neal P Barney MD Alcon Laboratories. Inc. Inc.: C Roche Pharmaceuticals: C Nisha Acharya MD Bausch + Lomb: S GlaxoSmithKline: C National Eye Institute: S Research to Prevent Blindness: S Xoma: C Chi-Chao Chan MD None Soon-Phaik Chee MD Bausch + Lomb Surgical: C. Inc.: C Allergan.: C Allergan Pharmaceutical Corp. Inc.: C.: C.: C Assenti: O Caremark: C Pfizer.S Bayer: C Debra A Goldstein MD Abbott Pharmaceuticals: C Allergan. Inc.L Allergan.: C Yosuf El Shabrawi MD Allergan: C Merck & Co.: C Celtic: C Eyegate: S Food and Drug Administration: S Harbor: C Lux Biosciences: C Mackall Foundation: S National Eye Institute: S Research to Prevent Blindness: S University of Pennsylvania: E Xoma: C Sofia N Androudi MD PhD None Janet Louise Davis MD Santen.: S Esen K Akpek MD Alcon Laboratories.P Alcon Laboratories.S Eyegate Pharmaceuticals.L Careen Yen Lowder MD PhD Allergan: C Bahram Bodaghi MD PhD Allergan. Inc.2012 Subspecialty Day  |  Uveitis  53 Faculty Financial Disclosures Massimo Accorinti MD PhD None Laure E Caspers MD None Douglas A Jabs MD MBA Abbott Laboratories: C Alcon Laboratories.: S Allergan. Inc.S Alcon Laboratories.: S Henry J Kaplan MD Advanced Ocular Technology: O.S Lux Biosciences. Inc.: C Regeneron Pharmaceuticals. Inc.: C Santen.: C Thomas A Albini MD Alcon Laboratories.P Santen. Inc.: C Corcept Therapeutics: C Genentech: C Genzyme Corp. Inc. Inc. Inc. Inc.: L Bausch + Lomb Surgical: C. Inc. Inc.: S Xoma: C Amod K Gupta MBBS None Elisabetta Miserocchi MD Abbott Immunology: C Allergan: C Bausch + Lomb: C Lux Biosciences: L Teva: C Vishali Gupta MBBS None John J Huang MD Allergan: C .: C.L Yonca A Akova MD None David S Chu MD Alcon Laboratories.: C Applied Genetic Technologies Corp.: S Erik Letko MD None Rubens Belfort Jr MD PhD Alcon Laboratories.: O.: C.: C Novartis Pharmaceuticals Corp.L.: C.S Talin Barisani-Asenbauer MD None Phuc Lehoang MD PhD Allergan. Inc.: C. Inc. Inc. Inc.S Novartis Pharmaceuticals Corp.L HOYA Medical Singapore Pte. Inc.S Allergan.: C RegenaSight: O.S Allergan.L Analysis Group. Ltd. Inc.: C.L.: C Eyegate: S Lux Bioscience: S Novartis Pharmaceuticals Corp. Inc.: C.L Technolas Singapore Pte Ltd: C.: C Bausch + Lomb Surgical: L Cristobal A Couto MD Allergan: L Hassan A Al-Dhibi MD None Emmett T Cunningham Jr MD PhD MPH None John H Kempen MD Alcon Laboratories. Inc.

: C C Michael A Samson MD CLS Pharmaceuticals: C. Inc.S Novartis Pharmaceuticals Corp.S Bausch + Lomb: C Albert T Vitale MD Aciont.: C. Inc.. Inc.: S Bausch + Lomb Surgical: C Genentech: S Heidelberg Engineering: S Lux Biosciences.: C.: L Allergan: L Bausch + Lomb: L Russell W Read MD PhD EyeSight Foundation of Alabama: S. Inc. Inc. Inc. Inc.: S .S Novartis Pharma Japan: L Novartis Pharmaceuticals Corp.: C Pfizer Japan: L XOMA: C Ariel Schlaen MD None Hatice N Sen MD None Harvey S Uy MD Alcon Laboratories. International Retinal Research Foundation: S Research to Prevent Blindness: S Eric Suhler MD Abbott Pharmaceuticals: C.: S Regeneron Pharmaceuticals.: C Bausch + Lomb Surgical: C Lucia Sobrin MD None Narsing A Rao MD None Sunil K Srivastava MD Allergan: S Bausch + Lomb Surgical: C.: S Chromologic.L.L LensAR: L Justine R Smith MD Collins Medical Trust: S National Eye Institute: S Sumru Onal MD None Russell N Van Gelder MD PhD Alcon Laboratories.E.: C. Inc.: L Johnny Tang MD None Joseph Tauber MD Allergan.O Lux Biosciences: C PCAsso: O Robert B Nussenblatt MD None Virender S Sangwan MBBS None Jennifer E Thorne MD PhD Allergan: C National Eye Institute: S Research to Prevent Blindness: S Xoma: C Annabelle A Okada MD Mitsubishi Tanabe Pharma: L. Inc.: L Allergan: L Merck & Co.L Bausch + Lomb: C Biolase: C Eleven Bio: C Merck & Co. Inc.: S Pfizer.S Bristol-Myers Squibb: S EyeGate: S Genentech: S Lux Bio: C. LLC: S PanOptica: C Photoswitch Therapeutics: S Emil Mitchel Opremcak MD None Ronald E Smith MD Calhoun Vision.54 Faculty Financial Disclosures 2012 Subspecialty Day  |  Uveitis Quan Dong Nguyen MD Abbott Pharmaceuticals..S Maite Sainz de la Maza MD Alcon Laboratories.: O Clarity Vision: O Lacrimal Gland Device: P Victor L Perez MD Alcon Laboratories.: S Santen.: S Optos.: C. Inc. Inc. Inc. Inc. Inc.S Novartis Pharmaceuticals Corporation: S Steven Yeh MD None S R Rathinam MD PhD None Manfred Zierhut MD Abbott Pharmaceutical Co.

Hatice N  44 Smith*. Rubens  26 Caspers. Henry J  40 Lehoang*. Virender S  17 Sen. Russell N  21. Quan Dong  47 Nussenblatt. Emil Mitchel  8 Rao. Sofia N  2 Ayliffe*. Amod K  23 Jabs*. Esen K  19 Androudi. Phuc  38 Nguyen*. Sumru  5 Opremcak. Eric  46 Thorne*. William  14 Belfort*. Albert T  31 * Indicates that the presenter has financial interest. 42 Vitale*. Janet Louise  11 Foster*. Debra A  28 Gupta. . Douglas A  1 Kaplan*. Jennifer E  10 Van Gelder*. C Stephen  15 Goldstein*. Narsing A  37 Sangwan. Robert B  50 Onal. No asterisk indicates that the presenter has no financial interest. Chi-Chao  43 Chu*. Laure E  29 Chan. Justine R  4 Suhler*. David S  48 Davis*.2012 Subspecialty Day  |  Uveitis  55 Presenter Index Akpek*.