Global Ophthalmology What Today’S Volunteers Do Differently

EyeNetJANUARY 2018

Global Ophthalmology What Today’s Volunteers Do Differently

How to Spot and Manage Iris Cysts

Outer Retinal Tubulation: What It Is and What It Means

PEARLS Central Retinal Vein Occlusion Call for Abstracts

Instruction Courses and New Skills Labs December 14, 2017 – January 9, 2018

Papers/Posters and Videos Join Your Colleagues March 8, 2018 – April 10, 2018 in Chicago

Like Chicago, ophthalmology is a global community of innovators in art and science. Join us at AAO 2018, where you can contemplate the finer points of cross-linking, intraocular knot-tying and lenticule extraction — or Monet, van der Rohe and Chagall.

AAO 2018 October 27 – 30

Subspecialty Day October 26 – 27

AAOE Program October 27 – 30 aao.org/2018

Where All of Ophthalmology Meets®

In conjunction with the Pan-American Association of Ophthalmology 100% PRESERVATIVE-FREE

ORDER FREE SAMPLES

Go to either website and select “Request Sample” www.Zioptan.com www.CosoptPF.com

Cosopt is a registered trademark of Merck Sharp & Dohme Corp and is used under license. ZIOPTAN is a registered trademark of Merck Sharp & Dohme Corp and is used under license.

ZIOPTAN is licensed by Santen Pharmaceutical Co., Ltd.

TRS-5100 Product/Model name: REFRACTOR RT-5100

The OPD-Scan III provides integrated wavefront aberrometry and corneal assessment with topography, pupillometry, autorefraction and keratometry. In just 10 seconds, per eye, over 20 diagnostic metrics are integrated. AND DESIRED OUTCOMES

Mitchell A. Jackson, MD Larry Patterson, MD Charles Collins, MD Faisal Haq, MD Lake Villa, Illinois Crossville, TN Middleton, RI Plano, Texas

The TRS-5100 rapidly The TRS-5100 takes The TRS-5100 is highly The TRS provides our practice completes all refractions accuracy to a new level valued. It is extremely with a diagnostic tool that both and the split prism and provides the ultimate accurate and I’m very improves clinical outcomes while allows immediate patient refraction information that confident in the quality increasing patient flow and overall comparison and verification we’ve been seeking. Now, of refraction. It is such a efficiency. The investment that pays of old vs. new prescriptions we have fewer remakes timesaver, has cut down for itself. Wait times are reduced, – without flipping through with more satisfied on remakes, reduced our we see more patients, and we’re lenses and asking “which is patients who enjoy shorter frustrations and increased performing more surgery than ever. better, 1 or 2?” refraction exam times. our bottom line.

Designed and Manufactured by NIDEK - Represented by Marco 800-874-5274 • marco.com

634 TRS Testiml-MD-EN.indd 1 12/6/17 11:13 AM CONTENTS JANUARY 2018 VOLUME 22 • NUMBER 1

FEATURE 40-45 Volunteering Abroad Medical missions aren’t what they used to be. Here’s how to make a long-lasting, sustainable contribution to eye care in communities around the world.

CLINICAL INSIGHTS 17-19 News in Review Neuro-ophthalmology Remyelination in multiple sclerosis. Cataract Retinal detachment after cataract surgery. 40 Glaucoma Gene editing with CRISPR. Oncology Coming to consensus on retino blastoma screening.

21-25 Journal Highlights Key findings fromOphthalmology, Ophthal- mology Retina, AJO, JAMA Ophthalmology, and more. 17 27 27-32 Clinical Update Anterior Segment Iris cysts: what you need to know about identification and management. Retina Outer retinal tubulation: a hallmark of 31 33 neurodegeneration.

33-35 Ophthalmic Pearls CRVO Review the risk factors, diagnosis, and management of central retinal vein occlusion.

EyeNet® Magazine (ISSN 1097-2986) is published monthly by the American Academy of Ophthalmology, 655 Beach St., San Francisco, CA 94109-1336, as a membership service. Subscription is included in U.S. members’ annual dues. International Member, IMIT, $135 per year. Nonmember in U.S., $150 per year. Nonmember outside U.S., $210 per year. Periodicals Postage Paid at San Francisco, CA, and at additional mailing offices. POSTMASTER: Send address changes toEyeNet , P.O. Box 7424, San Francisco, CA 94120-7424. American Academy of Ophthalmic Executives®, EyeSmart®, EyeWiki®, IRIS® Registry, and ONE® Network are trademarks of the American Academy of Ophthalmology®. All other trademarks are the property of their respective owners.

EYENET MAGAZINE • 5 CLINICAL INSIGHTS 37-39 Morning Rounds A Case of Aches and Pains and Blurry Vision A 28-year-old woman had flulike symptoms followed by red, painful, photophobic eyes and decreased vision. What’s your diagnosis?

IN PRACTICE 51-52 Savvy Coder Audit! How Should Staff Respond? You need a written protocol. Here’s what it should address. 53-55 Practice Perfect 37 Social Media and Low Vision Help your patients to avoid depression. From PQRS to MIPS To enjoy continued success with the IRIS Registry, meet the Jan. 15 deadline and avoid these mistakes.

FROM THE AAO 57-60 Academy Notebook State societies honored. l D.C. Report: Major Quality Program changes and stable ophthalmology payments. l And more. 57

VIEWPOINTS 9 Letters How to shift perspective. l More on low vision. 10 Opinion Can you practice part time? 12 Current Perspective Sexual harassment and ophthalmology. 14 President’s Statement The value of education and giving back.

MYSTERY IMAGE 62 Blink What do you see? COVER PHOTOGRAPH 62 Marc Safran, MD xx

® COPYRIGHT © 2018, American Academy of Ophthalmology, Inc.® All rights reserved. No part of this publication may be reproduced without written permission from the publisher. Letters to the editor and other unsolicited material are assumed intended for publication and EyeNet are subject to editorial review, acceptance, and editing. Disclaimer. The ideas and opinions expressed in EyeNet are those of the authors, and do not necessarily reflect any position of the editors, the publisher, or the American Academy of Ophthalmology. Because this publication provides information on the latest developments in ophthalmology, articles may include information on drug or device applications that are not considered community standard, or that reflect indications not included in approved FDA labeling. Such ideas are provided as information and education only so that practitioners may be aware of alternative methods of the practice of medicine. Information in this publication should not be considered endorsement, promotion, or in any other way encouragement for the use of any particular procedure, technique, device, or product. EyeNet, its editors, the publisher, or the Academy in no event will be liable for any injury and/or damages arising out of any decision made or action taken or not taken in reliance on information contained herein.

6 • JANUARY 2018 A doctor doesn’t give a hospital its reputation. A team of doctors do.

When the world demands the best, it looks to Wills Eye. With the nation’s highest clinical volume of annually referred patients, we’ve always been at the forefront of eye disease treatment. Our expertise and advanced capabilities are what defined the field in 1832, and continue to redefine it today.

840 Walnut Street willseye.org Philadelphia, PA 19107 1-877-289-4557 EDITORIAL BOARD ®

MAGAZINE CATARACT Steven L. Mansberger, MD, MPH Michael F. Chiang, MD Kevin M. Miller, MD, Ronit Nesher, MD Jane C. Edmond, MD David W. Parke II, MD Section Editor Richard K. Parrish II, MD Frank Joseph Martin, MD Editor-in-Chief William R. Barlow, MD Sarwat Salim, MD, FACS Federico G. Velez, MD Ruth D. Williams, MD Kenneth L. Cohen, MD LOW VISION REFRACTIVE SURGERY Chief Medical Editor Kendall E. Donaldson, MD Lylas G. Mogk, MD George O. Waring IV, MD, Dale E. Fajardo, EdD, MBA Jason J. Jones, MD John D. Shepherd, MD Section Editor Publisher Boris Malyugin, MD, PhD Damien Gatinel, MD NEURO-OPHTHALMOLOGY Patty Ames Cathleen M. McCabe, MD Soosan Jacob, FRCS Executive Editor Randall J. Olson, MD Leah Levi, MD, Section Editor A. John Kanellopoulos, MD Marie Jose Tassignon, MD J. Bradley Randleman, MD Carey S. Ballard Kimberly Cockerham, MD, FACS Art Director / COMPREHENSIVE Karolinne M. Rocha, MD Helen V. Danesh-Meyer, Production Manager Marcony R. Santhiago, MD OPHTHALMOLOGY MBCHB, MD Preston H. Blomquist, MD, Chris McDonagh, Jean Shaw Prem S. Subramanian, MD, PhD RETINA/VITREOUS Section Editor Senior Editors Julia A. Haller, MD, Sherleen Huang Chen, MD OCULOPLASTICS Section Editor Catherine Morris Evan H. Black, MD, April Y. Maa, MD Neil M. Bressler, MD Associate Editor / Section Editor Content Manager Linda M. Tsai, MD Kimberly A. Drenser, MD, PhD Elizabeth A. Bradley, MD CORNEA AND EXTERNAL Sharon Fekrat, MD Lori Baker-Schena, MBA, EdD; Femida Kherani, MD Leslie Burling-Phillips; DISEASE Mitchell Goff, MD Don O. Kikkawa, MD Peggy Denny; Miriam Karmel; Christopher J. Rapuano, MD, Lawrence S. Halperin, MD Mike Mott; Linda Roach; Section Editor OPHTHALMIC ONCOLOGY Gregg T. Kokame, MD Lynda Seminara; Annie Stuart Kathryn A. Colby, MD, PhD Zélia M. Corrêa, MD, PhD, Andreas K. Lauer, MD Section Editor Contributing Writers Helena Prior Filipe, MD Prithvi Mruthyunjaya, MD, MHS Bennie H. Jeng, MD Dan S. Gombos, MD Kyoko Ohno-Matsui, MD Mark Mrvica, Kelly Miller Stephen D. McLeod, MD Tatyana Milman, MD Andrew P. Schachat, MD M.J. Mrvica Associates, Inc. 2 West Taunton Ave., Sonal S. Tuli, MD OPHTHALMIC PATHOLOGY Ingrid U. Scott, MD, MPH Berlin, NJ 08009 Deepak Paul Edward, MD Gaurav K. Shah, MD GLAUCOMA 856-768-9360 Sanjay G. Asrani, MD, David J. Wilson, MD UVEITIS [email protected] Section Editor OPHTHALMIC Gary N. Holland, MD, Advertising Sales Section Editor Iqbal K. Ahmed, MD PHOTOGRAPHY Lama Al-Aswad, MD, MPH Jason S. Calhoun Muge R. Kesen, MD Ahmad A. Aref, MD Michael P. Kelly, FOPS H. Nida Sen, MD Anne Louise Coleman, MD, PhD Steven Yeh, MD PEDIATRIC Steven J. Gedde, MD 655 Beach St. OPHTHALMOLOGY Catherine Green, MBChB San Francisco, CA 94109 David A. Plager, MD, 866-561-8558, 415-561-8500 Section Editor aao.org

Governmental Affairs Division 20 F Street NW, Suite 400 ACADEMY BOARD Washington, DC 20001 202-737-6662 PRESIDENT SR. SECRETARY FOR PUBLIC TRUSTEES

Keith D. Carter, MD, FACS CLINICAL EDUCATION Paul B. Ginsburg, PhD ARTICLE REVIEW PROCESS. Articles Louis B. Cantor, MD involving single-source medical and tech- PRESIDENT-ELECT TRUSTEES-AT-LARGE nical news are sent to quoted sources for George A. Williams, MD Michael F. Chiang, MD verification of accuracy prior to publication. SR. SECRETARY FOR Quotes and other information in multisource OPHTHALMIC PRACTICE William S. Clifford, MD articles are subject to confirmation by their PAST PRESIDENT respective sources. The chief medical editor Robert E. Wiggins Jr., MD, MHA Cynthia A. Bradford, MD Sanjay D. Goel, MD and the executive editor review all news and Cynthia Mattox, MD, FACS feature articles and have sole discretion as CHAIR, THE COUNCIL CEO to the acceptance and rejection of material Lynn K. Gordon, MD, PhD William F. Mieler, MD and final authority as to revisions deemed David W. Parke II, MD Andrew M. Prince, MD necessary for publication. VICE CHAIR, THE COUNCIL SR. SECRETARY FOR DISCLOSURE KEY. Financial interests Sarwat Salim, MD, FACS INTERNATIONAL TRUSTEES are indicated by the following abbrevia- ADVOCACY Kgaogelo Edward Legodi, MD tions: Daniel J. Briceland, MD OPHTHALMOLOGY EDITOR C = Consultant/Advisor Lihteh Wu, MD E = Employee Stephen D. McLeod, MD L = Speakers bureau SECRETARY O = Equity owner FOR ANNUAL MEETING CHAIR OF THE FOUNDATION P = Patents/Royalty S = Grant support Maria M. Aaron, MD ADVISORY BOARD Learn more about the Board For definitions of each category, see Christie L. Morse, MD at aao.org/bot. aao.org/eyenet/disclosures.

8 • JANUARY 2018 Letters

How to Shift Your advocacy to achieve a higher purpose (the pillar of fulfill- Perspective ment): service to others. The Academy, state and subspecialty EyeNetOCTOBER 2017 societies, and their advocacy groups exist to defend our In light of Dr. Williams’ professional autonomy, support our individual and collective column titled “Solo Practice efforts to achieve professional mastery, create vital bonds in Ophthalmology: Resist- with like-minded professionals, and ultimately fulfill our International Report The Lowdown ing the Tides?” (Opinion, purpose as healers. on High-Tech IOLs October), I want to encour- Alan E. Kimura, MD, MPH age physicians to shape their Denver futures despite the obstacles Unintended Consequences New Cancer Drugs, New Ocular Side Effects created by the following: More on Low Vision Bioptic Lenses for Driving? Counseling Low Vision Patients

OPINION The Enduring Appeal of Solo Practice Medicaid cost sharing with the federal government, I read with interest “Low Vision Drivers: The Ophthalmol- uncertainty around the fate ogist’s Role and Responsibility” (Clinical Update, October), of individual insurance markets, looming MACRA and MIPS which quite thoroughly discusses the benefit that bioptic regulations, and more. vision aids may offer to many individuals who would What happens when we take the reins. I invite you to otherwise be unable to acquire a driver’s license, with the imagine what is possible (and importantly, under our own independence that this certification offers. control) when we shift our perception of health care reform This remarkable visual/driving aid was brought to my and value-based care from externally imposed burdens to attention in 1996. At that time, I evaluated a then 8-year- internally driven improvements. By focusing on your indi- old boy who was found to have Stargardt disease, with his vidual practice, you can solve your own unique challenges. acuity eventually dropping to 20/200 in both eyes. With There is plenty to do to improve your practice for intrinsic subsequent evaluation by C.J. Reed, OD, COMS, at the reasons, and fortunately many of these changes can also help Judith A. Read Low Vision Services in Akron, Ohio, and fit you survive the transition from fee-for-service to value-based with the then-available Ocutech VES II/6 × magnification, payments—for example, inefficiencies are a threat like never he has been able to continue successfully through college before. and obtain ongoing driving privileges. The 3 elements of improvement. The foundation for phy- A debt of gratitude needs to be given to William Fein- sician-directed practice improvements rests upon 3 pillars: bloom, OD, PhD, the “father of low vision care” in the United autonomy, mastery, and purpose. Much has been written States, who introduced the concept of bioptic driving1 in this lately about these and “physician engagement with work”— country. In 1932, at age 28, he used an astronomer’s telescope and, yes, it is possible to use these concepts to find joy in our as a model to design a small 3 × power telescope that was work. For example, when you problem-solve to eliminate small enough to be mounted in a spectacle frame, restoring inefficiencies in your practice, you can find pleasure in this one individual’s functional vision.2 exercise of autonomy. As your practice improves due to the Later, in 1958, he introduced the concept of a bioptic tele- solutions you found, you experience the element of mastery. scopic system, which combined a prescription eyewear lens Finally, a higher-performing practice allows the individu- with a small mounted Galilean telescopic system. His system al and organization to more effectively fulfill its purpose allowed the patient to change view from the telescope to the of helping others. Conversely, actions that do not feature general prescription. these 3 principles lead to frustration and increase the risk of The website referenced below, with information from burnout. Richard L. Windsor, OD, is a most valuable resource, describ- Choose the best path for you. Both solo and group prac- ing a number of up-to-date options that ophthalmologists/ tice have their pros and cons; the choice boils down to how optometrists/low vision specialists may find useful, adding to strongly you value autonomy. For some ophthalmologists, EyeNet’s informative article. achieving mastery is found by working alone; for others, Stuart M. Terman, MD mastery can be facilitated through the advantages of a Cleveland group practice. At a minimum, we must continually evolve our clinical 1 www.biopticdrivingusa.com and surgical skills as well as basic business skills. At some 2 Feinbloom W. The training and after care of the partially blind patient. point, however, we realize the importance of community and Journal of the American Optometric Association. 1958:29:724.

EYENET MAGAZINE • 9 Opinion

RUTH D. WILLIAMS, MD Can You Practice Part Time?

uring the open microphone session at an Academy who reportedly want more work-life balance. This is an over- Young Ophthalmologist symposium, an ophthalmol- simplification of reality. For example, of the 15% of male Dogist newly in practice, who was also a new father, ophthalmologists who work part time, I wonder how many asked, “How do I manage the tension between the demands are older physicians who immensely enjoy practice but now of my job and the responsibility I feel to my son?” choose to work fewer hours and enjoy other activities. We I wanted to hug this young person. Finally, the well-known value these physicians for their experience and their wisdom, challenge of managing a young career and a young family has and they ground us in a tradition of providing quality care, become a nongendered issue. In response to this challenge, teaching colleagues, and continuing to learn. Likewise, we some young ophthalmologists—both men and women—now value the young ophthalmologists who might provide superb ask about the possibility of practicing part time. But while ophthalmic care and work fewer hours than their older they might wish to decrease work hours to accommodate peers did at the same career stage. And we recognize that other priorities, the concept of a part-time ophthalmologist many physicians who limit work hours early in their career is a flawed one. increase their time commitment in later decades. There is no such thing as a part-time ophthalmologist. Traditionally, full-time work has been Let me explain. A surprising number of physicians report measured by how many hours a person working part time. In a compensation survey of nearly works in the office. While this may 20,000 physicians across 26 specialties, 22% of the women be necessary for determining and 10% of the men report that they work fewer than 40 benefits, hours logged is hardly hours per week.1 In ophthalmology, 24% of female and 15% a meaningful measure of the of male ophthalmologists report working fewer than 40 hours value of a colleague. There each week. This trend might be increasing as dual professional are many metrics for valu- career families become commonplace. Furthermore, we’re ating work, including RVUs, told that today’s young physicians tend to protect family and productivity, papers written, leisure time more than their older peers have and might be leadership roles, and teaching bolder about requesting a day off or protecting their weekends. responsibilities. In my own Yet no survey can capture the commitment that is required practice, I’ve been impressed to be a physician. An ophthalmologist who chooses to work by the availability of my young fewer hours for a period of time is still a completely commit- colleagues to discuss a patient or ted physician. She might shorten her workday or compress provide advice at odd hours. Once, a the work week into fewer days, but she brings her training, colleague discussed a complex case with Ruth D. her expertise, her experience, her compassion, and her wisdom me, and at the end of the phone call I Williams, MD to work when seeing patients. The “part-time” physician often discovered that he was on a ski slope. Chief Medical maintains a regular call schedule and full malpractice cover- Some ophthalmologists who prac- Editor, EyeNet age, and he is committed to continuous learning. The “part- tice part time feel diminished by the time” ophthalmologist learns new techniques, innovates, and choice and don’t like the label. Let’s acknowledge the 100% attends educational meetings. The “part-time” ophthalmolo- commitment to patient care and stop counting the hours. gist is available for patients, emergencies, and advice to other An ophthalmologist is “all in,” even if it’s not all the time. physicians. In other words, the “part-time” ophthalmologist There is no such thing as a part-time ophthalmologist. has a 100% commitment to the practice of ophthalmology. Much has been written about Baby Boomers, for whom 1 Grisham S. Medscape physician compensation report 2017. April 5, 2017. work is a moral imperative, and Gen Xers and Millennials, www.medscape.com. Accessed Nov. 16, 2017.

10 • JANUARY 2018

Current Perspective

DAVID W. PARKE II, MD Sexual Harassment and Ophthalmology

exual harassment allegations know no workplace In the 30-plus years of the Academy’s Code of Ethics, boundaries. While most recent public cases involve there has never been an ethics challenge involving alleged Sthe media and entertainment industries or govern- sexual harassment or sexual misconduct involving patients, ment officials, other cases have touched nearly every type of colleagues, or staff. However, surveys of female physicians in organization and profession—including ophthalmology. This multiple specialties suggest that a large percentage of women should not be surprising because sexual harassment frequently ophthalmologists have personally experienced what they is driven by power differentials between the harasser and the perceived to be sexual harassment—verbal and/or physical— victim, leading to feelings of vulnerability. Medicine is replete from their physician colleagues. One study of 1,066 physicians with such power relationships—between physician and staff; revealed that 30% of women said they had directly experi- between professor and trainee; between senior and junior enced sexual harassment in their careers, versus 4% of men.1 colleagues; and between physician and patient. Members and Fellows also deserve to under- Harassment allegations run the gamut between single stand how the Academy addresses this verbal episodes to patterns of frank sexual assault. The issue, the seriousness with which it is U.S. Equal Employment Opportunity Commission defines taken, the organizational culture workplace sexual harassment in part as “unwelcome sexual we attempt to engender, and the advances or conduct of a sexual nature which … creates an processes we have in place to intimidating, hostile, or offensive work environment.” How protect our staff, our volun- many times in our professional lives have we been a witness teers, and our profession itself. (or a party) to a crude joke, comments of a highly personal Every Academy staff mem- or sexual nature—or worse? How often is such behavior ra- ber, without exception, must tionalized by statements like, “I’ve always been a big hugger” complete a sexual harassment or “I’ve always been like that and she has never complained.” training course every 2 years (Although I use “she,” sexual harassment may be male to and acknowledge in writing female, female to male, female to female, or male to male.) familiarity with the Academy’s As many gray zones as have been recently illuminated (for relevant policies. These policies example, “when is a hug appropriate?” and “what discussion acknowledge both organizational subjects cross the line?”), the #MeToo movement has created responsibility for compliance as well as David W. a valuable teaching moment, forcing all of us—men and individual responsibilities and report- Parke II, MD women—to rethink appropriateness and inclusiveness. ing obligations for every employee. Academy CEO Implicit in the trust and respect we receive as physicians is Any alleged incident is taken seriously, our responsibility to create a safe and respectful professional investigated thoroughly, and (if validated) is accompanied by environment. This includes zero tolerance for inappropriate disciplinary action—possibly including dismissal. Regardless behavior that might be interpreted as constituting harassment. of the investigation outcome, retaliation against an accuser is What is the Academy’s role? Every Academy member agrees forbidden not only by Academy policy but also under the law. to abide by the Code of Ethics and its Principles. The Princi- We owe it to ourselves, our patients, all members of our ples describe “model standards of exemplary professional professional team, and to ophthalmology itself to always conduct for all Fellows or Members of the Academy.” Principle exhibit exemplary behavior and to make all involved feel 2 states in part, “Ophthalmological services must be provided welcome, comfortable, and respected. The Academy as an with compassion, respect for human dignity, honesty, and organization similarly makes that pledge. integrity.” This applies to all involved in the care process— colleagues, staff, patients, and families. 1 Jagsi R et al. JAMA. 2016;315(19):2120-2121.

12 • JANUARY 2018 $80 Million Cumulative declared dividends 1987-2017 OMIC’s dividend returns averaged 20.8% the past 5 years vs. 6.6% for other carriers that have declared dividends.

OMIC consistently outperforms multispecialty malpractice insurance companies in almost all nancial results, benchmarks, and ratios used to evaluate performance in the industry.

OMIC’s coverage year loss and loss expense ratio was the best among our peer companies in 2016, and has averaged 45% lower than competitors’ for years 2012 to 2016.

Policyholders’ surplus surpassed $200 Million and OMIC’s premium to surplus ratio of 17.7% distiguishes us as one of the most scally sound insurance carriers in America.

Robert Wiggins, MD Chair, Finance Committee and Treasurer

800.562.6642 www.omic.com/request-a-quote

A Risk Retention Group President’s Statement

KEITH D. CARTER, MD The Value of Education, and the Satisfaction of Giving Back

hen I got the phone call from Dr. Parke inviting thinking, but efforts still must be made to change the profes- me to serve as Academy President-Elect in 2017 sional landscape. Wand Academy President in 2018, I was thrilled Giving back is vital—and a pleasure. As I progressed in and humbled. I am very honored to serve as your president. my own positions, I discovered the joy that comes from see- A member for 30 years, I value the Academy, and I have ing a student develop into a well-trained doctor, especially in worked on a great many projects and assumed many roles, terms of surgery. Another great pleasure about working with from writing for Focal Points to serving on the Ethics Com- young people is that they constantly challenge you and keep mittee. you thinking. They bring excellent ideas—and we need to For my presidential term, I have several goals. One is tech- listen to them. Some of the biggest achievements we’ve seen nical: to influence improvement of the ability of ophthalmic come from physicians in training. For example, EyeRounds, equipment to communicate with the electronic medical our department’s online education forum, was originally record. We see equipment with great promise at our meetings, presented by a resident who saw the vision of the Internet but, often, it can’t “talk” to the other systems that we use to while we were all worrying about the book chapters we’d care for patients. If we can promote a common language, as write. Now, EyeRounds is one of the most- radiology has done, it would be a great accomplishment. visited ophthalmology websites around The second goal stems from a core value of mine. One of the world. the mainstays of my career has been educating physicians While much practical training in training, both at the University of Iowa and through the and education is now online or Academy. This is because I would not be where I am without increasingly done in simula- very good teachers and mentors in my life. My first mentor tion labs, the art of medicine was the physician who delivered me! He wrote letters of can never be fully taught that recommendation in my support for my applications to way. Taking care of patients pharmacy school and medical school, and he influenced me is passed on from doctor to to choose academics. I would never have seen numerous doctor in real-life settings. trainees mature into successful physicians or had my gratify- Explaining how to alleviate a ing experiences at the Academy if it weren’t for the guidance, patient’s fears or how to deliver support, and encouragement of my mentors. bad news cannot easily be taught For this reason, I am excited about participating in a new from a book. It’s our role to be there collaborative program with the Association of University for young ophthalmologists and share Professors of Ophthalmology (AUPO) to attract underrepre- our experiences. Many practices recog- Keith D. sented minorities to the profession. We haven’t made signifi- nize this and are asking to have trainees Carter, MD cant gains in 30 years in recruiting professionals who reflect come to their offices for real-world Academy the populations that we serve. Part of the challenge is gaining exposure. That may be a bigger part of 2018 President the attention of these young students and securing mentors future training. to guide them through the process. Then, the student needs I am excited to step into this new role and hope to be to be prepared to be a competitive applicant. When compet- seen as a president who values education and diversity itive students with diverse experiences are in the classroom, and continually promotes the profession, but I can’t be this enhances everybody’s education. successful without you. The Academy is great because of its Enhancing diversity within ophthalmology is part of many volunteers. If you have interests in education, diversity, giving back to the generations that follow us. Many of the technology, or other areas, let us know. Your involvement is younger generation are less color- or gender-based in their welcome and necessary. Let’s get started!

14 • JANUARY 2018 MAKE XIIDRA YOUR FIIRST CHOICE When artiﬁ cial tears aren’t enough, consider prescribing Xiidra for symptomatic Dry Eye patients.

Proven to treat the signs of inferior corneal Indication Xiidra® (lifi tegrast ophthalmic solution) 5% is indicated for the treatment staining in 12 weeks and symptoms of eye of signs and symptoms of dry eye disease (DED). dryness in 12, 6, and as little as 2. Xiidra helped provide symptom relief from Important Safety Information In clinical trials, the most common adverse reactions reported in 5-25% eye dryness in some patients at week 2—and of patients were instillation site irritation, dysgeusia and reduced visual a measurable reduction in signs of inferior acuity. Other adverse reactions reported in 1% to 5% of the patients were corneal staining in just 12 weeks. Consider blurred vision, conjunctival hyperemia, eye irritation, headache, increased Xiidra to help your Dry Eye patients fi nd the lacrimation, eye discharge, eye discomfort, eye pruritus and sinusitis. relief they’ve been waiting for. To avoid the potential for eye injury or contamination of the solution, Check it out at Xiidra-ECP.com patients should not touch the tip of the single-use container to their eye or to any surface. Four randomized, double-masked, 12-week trials evaluated the effi cacy and safety of Xiidra versus Contact lenses should be removed prior to the administration of Xiidra vehicle as assessed by improvement in the signs and may be reinserted 15 minutes following administration. (measured by Inferior Corneal Staining Score) and symptoms (measured by Eye Dryness Score) of Dry Safety and effi cacy in pediatric patients below the age of 17 years have Eye Disease (N=2133). not been established.

For additional safety information, see accompanying Brief Summary of Safety Information and Full Prescribing Information on Xiidra-ECP.com.

Marks designated ® and ™ are owned by Shire or an afﬁ liated company. ©2017 Shire US Inc. Lexington, MA 02421 S28784 01/17 Animal Data Lifitegrast administered daily by intravenous (IV) injection to rats, from pre-mating through gestation day 17, caused an increase in mean preimplantation loss and an increased incidence of several minor skeletal anomalies at 30 mg /kg /day, representing 5,400-fold Rx Only the human plasma exposure at the RHOD of Xiidra, based on AUC. No teratogenicity was observed in the rat at BRIEF SUMMARY: Consult the Full Prescribing Information for complete 10 mg /kg /day (460-fold the human plasma exposure at product information. the RHOD, based on AUC ). In the rabbit, an increased incidence of omphalocele was observed at the lowest dose tested, 3 mg /kg /day (400-fold the human INDICATIONS AND USAGE plasma exposure at the RHOD, based on AUC), when ® Xiidra (lifitegrast ophthalmic solution) 5% is indicated administered by IV injection daily from gestation days 7 for the treatment of the signs and symptoms of dry eye through 19. A fetal No Observed Adverse Effect Level disease (DED). (NOAEL) was not identified in the rabbit.

DOSAGE AND ADMINISTRATION Lactation Instill one drop of Xiidra twice daily (approximately 12 There are no data on the presence of lifitegrast in human hours apart) into each eye using a single use container. milk, the effects on the breastfed infant, or the effects on Discard the single use container immediately after using milk production. However, systemic exposure to lifitegrast in each eye. Contact lenses should be removed prior to from ocular administration is low. The developmental and the administration of Xiidra and may be reinserted 15 health benefits of breastfeeding should be considered, minutes following administration. along with the mother’s clinical need for Xiidra and any potential adverse effects on the breastfed child from Xiidra. ADVERSE REACTIONS Clinical Trials Experience Because clinical studies are conducted under widely Pediatric Use Safety and efficacy in pediatric patients below the age of varying conditions, adverse reaction rates observed in 17 years have not been established. clinical studies of a drug cannot be directly compared to rates in the clinical trials of another drug and may Geriatric Use not reflect the rates observed in practice. In five clinical No overall differences in safety or effectiveness have been studies of dry eye disease conducted with lifitegrast observed between elderly and younger adult patients. ophthalmic solution, 1401 patients received at least 1 dose of lifitegrast (1287 of which received lifitegrast 5%). The majority of patients (84%) had ≤3 months of NONCLINICAL TOXICOLOGY treatment exposure. 170 patients were exposed to Carcinogenesis, Mutagenesis, Impairment of Fertility lifitegrast for approximately 12 months. The majority Carcinogenesis: Animal studies have not been conducted of the treated patients were female (77%). The most to determine the carcinogenic potential of lifitegrast. common adverse reactions reported in 5-25 % of patients Mutagenesis: Lifitegrast was not mutagenic in the in vitro were instillation site irritation, dysgeusia and reduced Ames assay. Lifitegrast was not clastogenic in the in vivo visual acuity. Other adverse reactions reported in 1% mouse micronucleus assay. In an in vitro chromosomal to 5% of the patients were blurred vision, conjunctival aberration assay using mammalian cells (Chinese hyperemia, eye irritation, headache, increased hamster ovary cells), lifitegrast was positive at the highest lacrimation, eye discharge, eye discomfort, eye pruritus concentration tested, without metabolic activation. and sinusitis. Impairment of fertility: Lifitegrast administered at intravenous (IV) doses of up to 30 mg/kg/day (5400-fold the human plasma exposure at the USE IN SPECIFIC POPULATIONS recommended human ophthalmic dose (RHOD) of Pregnancy lifitegrast ophthalmic solution, 5%) had no effect on There are no available data on Xiidra use in pregnant fertility and reproductive performance in male and women to inform any drug associated risks. Intravenous female treated rats. (IV) administration of lifitegrast to pregnant rats, from pre-mating through gestation day 17, did not produce teratogenicity at clinically relevant systemic exposures. Intravenous administration of lifitegrast to pregnant Manufactured for: Shire US Inc., 300 Shire Way, Lexington, MA 02421. rabbits during organogenesis produced an increased incidence of omphalocele at the lowest dose tested, For more information, go to www.Xiidra.com or call 1-800-828-2088. 3 mg/kg/day (400-fold the human plasma exposure at Marks designated ® and ™ are owned by Shire the recommended human ophthalmic dose [RHOD], or an affiliated company. based on the area under the curve [AUC] level). Since ©2016 Shire US Inc. human systemic exposure to lifitegrast following US Patents: 8367701; 9353088; 7314938; 7745460; 7790743; ocular administration of Xiidra at the RHOD is low, the 7928122; 9216174; 8168655; 8084047; 8592450; 9085553; 8927574; applicability of animal findings to the risk of Xiidra use in 9447077; 9353088 and pending patent applications. humans during pregnancy is unclear. Last Modified: 12/2016 S26218 News in Review COMMENTARY AND PERSPECTIVE

NEURO-OPHTHALMOLOGY investigation, especially because of the Using the Visual precision of clinical System to Treat tests available for assessment.” Multiple Sclerosis Possible remye lination? Patients in MULTIPLE SCLEROSIS (MS) IS A DE both groups experi- generative inflammatory disease of the enced a reduction in central nervous system (CNS) involving latency delay while destruction of myelin and progressive on the antihistamine neuroaxonal loss. Treatments capable of treatment, demon- remyelination are a major unmet need strating that the for patients with the disease. However, drug has a possible researchers at the University of Califor- remyelinating effect, nia, San Francisco (UCSF), may have even after prolonged taken a step toward filling that need damage to the CNS. using the visual system and the over- To Dr. Green, the-counter antihistamine clemastine this represents what fumarate (Claritin).1 he termed “a major OLIGODENDROCYTES. Clemastine fumarate can stimulate The study. For this double-blind breakthrough” differentiation of oligodendrocytes (shown here). From the randomized trial, known as ReBUILD, for drug-induced lab of Jonah R. Chan, PhD. investigators included 50 patients with repair in a chronic relapsing MS and chronic demyelin- neurodegenerative condition. “To our develop a more nuanced view acknowl- ating optic neuropathy. Patients were knowledge, this is the first time that a edging that there is some capacity for randomized into 2 groups: The first drug has reversed the deficits caused by regeneration,” he said. Thus, he said, received oral clemastine fumarate twice MS. We aren’t saying it’s a cure, but this as clinicians wait for other promising daily for 3 months and then placebo is a step toward that direction.” treatments, including stem cell therapy, for 2 months, while the second received Importance to ophthalmologists. to bear fruit, “we should harness the the placebo for 3 months and the active For Dr. Green, the ReBUILD study eye’s own natural regenerative abilities, treatment for 2 months. demonstrates the value of ophthal- utilizing the processes that biology The primary outcome measure mology in treating MS, as there’s also already provides us and manipulating was shortening of P100 latency delay preliminary evidence from the trial them via specific medications.” on full-field visual-evoked potentials. suggesting that drug-induced remy- —Mike Mott “Visual sensory dysfunction is the first elination might extend to improved symptom in up to 40% of patients low-contrast letter acuity in patients 1 Green AJ et al. Lancet. 2017;390(10111):2481- with MS, and injury to the optic nerve with MS. But that might only be the 2489. is extraordinarily common,” said Ari beginning. J. Green, MD, at the UCSF Multiple “We’ve been taught in the past that Relevant financial disclosures—Dr. Green: NIH: Sclerosis Center. “It made sense for the retina and optic nerve are incapa- S; National Multiple Sclerosis Society: S; Rachleff

Courtesy of Ari J. Green, MD Green, of Ari J. Courtesy us to choose the visual pathway for ble of self-repair; however, we need to Family: S; UCSF: S.

EYENET MAGAZINE • 17 CATARACT these patients subsequently had phacoemulsification Assessing Retinal surgery. Up to 10 years after Redetachment the primary scleral buckling surgery, the cumulative rate Risk After Cataract of redetachment was 1%. Surgery The cumulative rate rose to 5% in the 10 years after cat- IN PATIENTS WHO HAVE HAD SCLERAL aract surgery, the researchers buckling surgery to repair a retinal said. (In eyes with no prior detachment (RD), the risk of a rede- detachment, the incidence of tachment remains low for up to 10 RD after cataract surgery is years after cataract surgery, a popula- REASSURANCE. A previous history of retinal de- estimated to range between tion-based Swedish study has found. tachment and scleral buckling surgery should not 0.6% and 1.7% in the first “One could easily think that these necessarily serve as a contraindication for cataract postoperative year, the re- patients would have a significant in- surgery, the study results indicate. searchers noted.) creased risk of redetachment, especially Three redetachments considering that they have had 1 RD ied records on all patients who under- (2.1%) occurred in the study cohort, already. This study found, in contrast to went surgery for primary repair of an taking place 2.4 years, 3.9 years, and that, a low risk of redetachment, 2.1%,” RD at Norrlands University Hospital in 6.9 years after the cataract surgery. In said Sara Forsell, MD, coauthor of the Umeå, Sweden, during a 10-year period all 3 cases, the retinas were successfully study.1 (N = 537). reattached with vitrectomy, and the Study details. The researchers stud- The records showed that 145 of final best-corrected visual acuity was

GLAUCOMA Building on earlier studies. Previously, the research- Gene Editing for POAG ers found that mutant myocilin is not secreted into the aqueous humor. Instead, it accumulates in the endo- Proves Successful in Mice plasmic reticulum (ER) of TM cells. ER stress leads to TM damage, resulting in increased outflow resistance RESEARCHERS HAVE DEMONSTRATED THE FEASI and IOP elevation, Dr. Zode said. “We also found that bility of directly targeting and editing a gene mutation normal myocilin is not required for regulation of IOP. in the trabecular meshwork to treat the leading genetic Therefore, deleting the gene completely works in this cause of primary open-angle glaucoma (POAG).1 This case.” novel approach delivers a one-two punch that both Proof of concept. In the murine portion of this rescues cell function and prevents further glaucoma- study, the researchers injected the MYOC gene intra tous damage—and it has implications for persons with vitreally with the virus Ad5-crMYOC to halt expression mutations in the myocilin gene (MYOC), which have of the mutant gene. In young asymptomatic mice, . been reported in some 4% of POAG patients, most gene deletion prevented IOP elevation compared with notably juveniles. controls. In older mice with MYOC ocular hypertension,

CRISPR to the rescue. “We found that reduction of treatment lowered pressure. aao.org/eyenet myocilin gene and protein lowered intraocular pressure Treatment also significantly increased outflow facility, [IOP] and prevented vision loss in a mouse model of demonstrating that disruption of mutant MYOC also myocilin glaucoma,” said cell biologist Gulab Zode, PhD, improves TM cell function in vivo. at North Texas Eye Research Institute in Fort Worth, who Beyond mice. Although the study also demonstrated conducted the study in collaboration with Val C. Shef- feasibility of human genome editing in cultured human field, MD, PhD, at the University of Iowa in Iowa City. eyes, additional research is needed before the treatment The rescue mission deployed CRISPR-Cas9 technol- can be taken to the clinic, Dr. Zode said. “We hope that ogy, a biological cut-and-paste method that homes in it translates in humans, but the main purpose was to on a gene defect, makes a double cut in the DNA, and demonstrate that genome editing is possible in vivo— then deletes, replaces, or repairs the damaged gene. and, especially, that human donor eyes can be used to For this study, the researchers used CRISPR (which study genome editing.” —Miriam Karmel stands for Clustered Regularly Interspaced Short Pal- indromic Repeats) to delete the MYOC gene in mice as 1 Jain A et al. PNAS. 2017;114(42):11199-11204. well as in cultured trabecular meshwork (TM) cells and human donor eyes. Relevant financial disclosures—Dr. Zode: NEI: S. The American Society of Retina Specialists. For full credit, see this article at see this article at full credit, For Specialists. American Society of Retina The

18 • JANUARY 2018 20/70, 20/25, and 20/30, the researchers [and am] more prone to do the cataract to seek prompt medical attention if reported. surgery earlier,” she said. “It is also of they experience symptoms of a rede- Reassuring cataract surgeons. The value to know that there is no need for tachment, even if several years have study’s results should reassure cataract extended postoperative care and that passed since the cataract procedure, surgeons who are considering surgery the risk of redetachment is not related Dr. Forsell said. —Linda Roach in patients with a history of RD and to the [length of] time after cataract scleral buckling, Dr. Forsell said. surgery.” 1 Forsell S, Mönestam E. Ophthalmol Retina. “Now that we know that the risk of Instead, pseudophakic patients who 2018;2(1):5-10. redetachment is low, I have changed my had a previous RD that was repaired view when counseling these patients with a scleral buckle should be advised Relevant financial disclosures—Dr. Forsell: None.

ONCOLOGY as early as possible and followed up asymptomatic children, no further appropriately to treat tumors when screening is recommended after this time First U.S. Guidelines they are very small and manageable unless they are known to carry an RB1 for Retinoblastoma with local therapies,” said coauthor Pa- mutation. These individuals should be tricia Chévez-Barrios, MD, at Houston followed indefinitely, every 1 to 2 years. Screening Methodist. “The treatment itself will • All decisions regarding examination A PANEL OF OPHTHALMIC ONCOLO vary depending on tumor size and loca- method should be discussed with the gists, pathologists, and geneticists has tion and other features in the eye, and child’s family. Anesthesia is strongly rec- published the first set of U.S. screen- it’s at the discretion of the treating team ommended for any child unable to par- ing guidelines for children at risk for to decide which approach is indicated ticipate in a thorough in-office exam. retinoblastoma—the most common eye once the diagnosis is made.” • Examiners should also be aware that tumor affecting children.1 The recommendations. Highlights tumor location can be age-specific. The goal. The team from the Ameri of the report include the following: Newborns may present with tumors in can Association of Ophthalmic Oncolo • All children with a family history of the posterior pole; however, in children gists and Pathologists met over the retinoblastoma should receive counsel- who are older at the time of disease course of 2 years to identify the key ing and testing to clarify disease risk. development, the tumor may present problems and clinical discrepancies in • The frequency of dilated fundus peripherally. approaching “at-risk” patients—that is, examination should be stratified on the Multispecialty support. The report children with a family history of retino- basis of age and risk. Newborns at high has been endorsed by the Academy’s blastoma in a parent, sibling, or first- or risk, for example, require more fre- Quality of Care Secretariat as well as second-degree relative. The published quent examination, every 2 to 4 weeks several medical organizations. consensus report is a consolidation of during their first 2 months of life. —Mike Mott how to proceed in different scenarios to Newborns at intermediate or low risk 1 Skalet AH et al. Ophthalmology. Published initially identify and stratify disease risk should undergo monthly examination. online Oct. 18, 2017. and then follow up with these patients. • Exam frequency declines as the child “The ultimate goal is that all children grows older, but screening for all at-risk Relevant financial disclosures—Dr. Chévez- at risk for retinoblastoma are diagnosed patients should occur up to age 7. For Barrios: None.

Management Guidelines for Childhood Screening for Retinoblastoma Families

Risk % risk Eye examination schedule based upon age of unaffected child Category

Birth to > 8 to 12 > 3 to 12 > 12 to 24 > 24 to 36 > 36 to 48 > 48 to 60 5-7 years 8 weeks* weeks months months months months months

Every 2-4 Every 2 Every 3 Every 4 Every 6 Every 6 High Risk > 7.5 Monthly weeks months months months months months

Intermediate Every 2 Every 6 1 - 7.5 Monthly Every 3 months Every 4-6 months Risk months months

Every 3 Every 4 Low Risk < 1 Monthly Every 6 months Annually months months

General 0.007 Screening with pediatrician Population

Nonsedated office examination Examination under anesthesia preferred by most centers preferred by most centers

@ 2018 American Academy of Ophthalmology American Academy @ 2018 See the financial disclosure key,page 8. For full disclosures, including category descriptions, view this News in Review at aao.org/eyenet.

EYENET MAGAZINE • 19 Ophthalmology Job Center Staff Your Practice Through the #1 Job Site in Ophthalmology

Access the most qualified and talented pool of physicians and ophthalmic staff professionals— or find a new position that’s right for you—on the Academy’s Ophthalmology Job Center.

Find the Right Candidate Today. aao.org/jobcenter Journal Highlights NEW FINDINGS FROM THE PEER-REVIEWED LITERATURE

Ophthalmology baseline reflected et al. studied the effect of Volume 125 | Number 1 pp. XXX–XXX Volume 125 | Number 1 | January 2018 Selected by Stephen D. McLeod, MD improvement of Elsevier | ISSN 0161-6420 formal training in visual arts 6.2 letters with on the observation skills of Treat-and-Extend for Wet AMD T&E and 8.1 medical students and found Garners More Support letters with the that just 6 sessions markedly January 2018 monthly regimen improved the students’ skills. (p < .001 for non- This study included 36

Monthly injections of ranibizumab can inferiority). Both OPHTHALMOLOGY first-year medical students improve best-corrected visual acuity groupsINSERT ADVERT had rapid who were assigned randomly (BCVA) outcomes in patients with neo gains in BCVA, (1:1) to receive either art vascular age-related macular degen- primarily during education at the Philadelphia

eration (AMD), but the frequency of the first 6 months, January 2018 Museum of Art or a free dosing can be inconvenient. Silva et al. which continued membership to the museum. compared monthly and treat-and-OPHTHA_v125_i1_COVER.indd 1 throughout the 21-09-2017 17:01:47 During a 3-month period, extend (T&E) protocols in patients study. Mean changes in CSFT were sim- the training group participated in 6 with wet AMD and concluded that ilar: 169.2 µm in the T&E group and customized 1.5-hour sessions. The art T&E was statistically noninferior and 173.3 µm in the monthly group. educators used the “Artful Thinking” clinically comparable to monthly treat- The mean number of ranibizumab approach, which emphasizes introspec- ment for improving visual acuity. injections was lower in the T&E group tion and observation before interpre- This 12-month phase 3 trial was (8.7, vs. 11.1 for those treated month- tation. conducted at 90 centers in 18 countries. ly), as was the mean number of post- Before and after the 3-month period, The main objective was to demonstrate baseline visits (8.9 and 11.2, respective- all participants underwent testing, which noninferiority of ranibizumab T&E, ly). Types and rates of adverse events entailed writing descriptions of works as measured by change in BCVA from were similar. of art, retinal pathology images, and baseline to study endpoint. The authors concluded that the T&E external photographs that depicted eye Secondary outcome measures were approach is not inferior to the monthly diseases. safety, treatment exposure, and changes regimen. Advantages of T&E include Reviewers graded each description in retinal central subfield thickness treatment individualization, fewer in- according to an a priori rubric for the (CSFT). jections, less-frequent visits, and lower type of image presented. Descriptions Patients ≥ 50 years of age (mean costs. of works of art were graded by museum age, 75.2 years; 55.4% women; 91.8% educators, while those of retinal and white) with newly diagnosed wet AMD Using Art Observation to external eye images were graded by 2 were assigned randomly to receive Improve Medical Students’ ophthalmologists and a fourth-year ranibizumab 0.5 mg either according to Ophthalmology Skills medical student. a T&E regimen (n = 323) or monthly January 2018 The assessments showed that overall (n = 327). Demographics and baseline observational skills improved signifi- ocular characteristics were similar for Although observation and description cantly in the training group, and results the study groups. are crucial for practicing ophthal- were similar for each image category. In Approximately 90% of each group mology and other medical specialties, a follow-up questionnaire, the students completed the study. At 12 months, the medical education does not include trained in art observation stated that least-squares mean BCVA change from specific training in these areas. Gurwin they were applying their new knowl-

EYENET MAGAZINE • 21 Clinical data edge in clinically meaningful ways. Layer segmentation Visual acuity Treatment The authors concluded that art assignment observation training can improve the observational skills of medical students. SD-OCT volume scans Motion artefact removal Such training may be vital for specialties Fluid segmentation Machine in which diagnosis and treatment are IRF Modelling database learning based mainly on direct observation, such as ophthalmology, dermatology, SRF and radiology. Additional research is warranted to document the durability of this effect PED and determine the impact on clinical care, the authors noted. (Also see related commentary by David Epstein and MACHINE LEARNING. This diagram of the computational image analysis image pipe- Malcom Gladwell in the same issue.) line illustrates the steps in data assessment. IRF = intraretinal fluid; SRF = subretinal fluid; PED = pigment epithelial detachment. Predicting Vision-Related Disability for Patients With with glaucoma were categorized as that currently used morphological fea- Glaucoma disabled and 169 (72%) as nondisabled tures were of limited value in predict- January 2018 based on NEI VFQ-25 results. Accord- ing BCVA outcome. ing to the LTA model, nondisabled For this post hoc analysis of a clinical The results of visual field assessments participants had a 14.2% likelihood trial database, the researchers evaluated and self-reported questionnaires can of transitioning to the disabled state data from 614 patients who partici- help physicians assess the overall degree during follow-up (mean, 4.3 years). pated in the HARBOR trial. (During of vision-related disability in patients Binocular MS data showed that visual HARBOR, patients received intravitreal with glaucoma. However, translating field loss occurred nearly 4 times faster injections of ranibizumab monthly or the findings from these tools into clini- in patients who became disabled. With on a pro re nata basis for 12 months; in cal practice can be challenging. To help adjustments for age, baseline visual addition, they were evaluated monthly classify and analyze changes that occur acuity, and follow-up duration, each via spectral-domain optical coherence with glaucoma, Abe et al. developed a 1-dB lower baseline binocular MS was tomography [SD-OCT] imaging.) The novel methodology, which demonstrat- associated with 34% higher odds of fu- researchers used AI algorithms to first ed that the risk of disability is associated ture disability. Each 0.5-dB/year faster correlate OCT parameters observed at with disease severity at baseline and rate of loss of binocular MS increased baseline to the corresponding visual the rate of deterioration over time. In the risk of developing disability more function at months 1, 2, and 3 and then addition, their method also may help than 3.5 times. to predict the patients’ final BCVA at 1 determine how aggressive the treatment —Summaries by Lynda Seminara year. must be to slow visual decline and They found that the correlation avoid disability. Ophthalmology Retina between predicted and final 12-month For this prospective observational Selected by Andrew P. Schachat, MD BCVA scores was loose at baseline—but study, vision-related quality of life (QoL) by month 3, individual BCVA levels was assessed at baseline and the end of Artificial Intelligence Predicts reached a solid predictive power for follow-up using portions of the 25-item Visual Outcomes in Neovascular month 12. National Eye Institute Visual Function AMD However, fluid-based morphological Questionnaire (NEI VFQ-25). A latent January 2018 features proved to be largely irrelevant transition analysis (LTA) model was for predicting therapeutic response, the used to characterize NEI VFQ-25 re- Schmidt-Erfurth et al. set out to eval- researchers said. sults and to evaluate the probability of uate the ability of machine learning to The latter finding implies that classic disability occurrence during follow-up. predict functional outcomes in patients exudative features—such as fluid with- Standard automated perimetry (SAP) treated with ranibizumab for neovas- in and underneath the retina—may be was conducted at 6-month intervals, cular age-related macular degeneration of limited value in explaining visual and mean sensitivity (MS) of the inte- (AMD). function in wet AMD and in providing grated binocular visual field was used They found that, according to their individual patients with a visual prog- to determine rates of change. Predictors artificial intelligence (AI) algorithms, nosis, the authors said, and they added of future disability that were investigat- best-corrected visual acuity (BCVA) at that this should prompt researchers to ed included baseline glaucoma severity month 3 was the strongest predictive search for additional markers, such as American Journal of Ophthalmology American Journal of and rate of visual field loss. factor of functional outcomes at the a disruption of the external limiting

22 • JANUARY 2018 American Journal of Corneal Changes in Pregnancy patients with hypothyroidism from Ophthalmology Linked to Fluctuating Thyroid the analysis). Moreover, differences in Hormone Levels corneal biomechanical and topographic Selected by Richard K. Parrish II, MD January 2018 parameters were found in relation to T3t and T4t as well as the T3t/T4t ratio. Do Normal Eyes Follow the Tabibian et al. documented corneal Further research is needed to deter- ISNT Rule? changes that occur during pregnancy mine the potential role of thyroid January 2018 and evaluated their association with diseases in the development and simultaneous hormonal changes. They progression of corneal disorders, Neuroretinal rim loss and thinning of found that the changes they observed the authors said. the retinal nerve fiber layer (RNFL) are correlated with fluctuating thyroid —Summaries by Lynda Seminara hallmark features of glaucoma. As a hormone levels rather than altered result, eyes that deviate from the ISNT estradiol levels. rule may need close monitoring for This prospective single-center ob- JAMA Ophthalmology Selected by Neil M. Bressler, MD, and glaucoma—but research findings on servational study involved 24 pregnant Deputy Editors the utility of this rule for establishing women (48 eyes). Biomechanical and glaucoma are conflicting. Poon et al. topographic properties of the cornea sought to determine the percentage of were measured with the Ocular Response Prevalence and Features of normal eyes that follow the ISNT rule Analyzer (ORA) and a Scheimpflug CPR-Type Diplopia in Epiretinal and found that, contrary to traditional imaging system at 4 time points: once Membrane teaching, the rule applies to less than during each trimester and 1 month December 2017 45% of rim assessments and RNFL after delivery. During the same 4 visits, measurements. the blood plasma level of estradiol Veverka et al. sought to determine the The authors’ cross-sectional study (E2) was determined, as were thyroid prevalence of central-peripheral rivalry included 110 normal eyes (110 partic- hormone levels (TSH, T3t, T4t). One- (CPR)–type diplopia among patients ipants). Neuroretinal rim assessments way multivariate analysis of covariance with epiretinal membrane (ERM) and were made from disc photographs, and was used to detect interactions between to describe the common clinical fea- measurements of RNFL thickness were hormonal plasma levels and changes tures. They found that CPR-type diplo- obtained from spectral-domain optical in corneal biomechanical/topographic pia is not uncommon in patients with coherence tomography. The main out- parameters. ERM and is linked to greater severity of comes were the percentages of eyes that Biomechanical and topographic data metamorphopsia. obeyed the ISNT rule and its variants. for the 4 time points were comparable. This study included 31 adults with The researchers found that the Although the level of E2 did not affect ERM treated at clinics specializing in ISNT rule was valid for only 37% of corneal parameters, TSH levels affected retinal disease in addition to a retro- rim assessments and 43.8% of RNFL the maximal keratometry and vertical spective cohort of 25 adults with ERM measurements. keratometry readings as well as the in- treated at strabismus clinics. Diplopia For both types of assessments, dex of height asymmetry (these results was established by patient history and variance of the nasal sector from the remained unchanged after excluding responses to questionnaires. CPR type expected ISNT pattern was a major rea- was defined as diplopia son for deviation. Nasal rims were wid- associated with evidence of er than inferior rims in 11% of subjects retinal misregistration in and wider than superior rims in 29%. the absence of other causes Nasal rims were narrower than tempo- of diplopia. Visual acuity ral rims in 15%. RNFL thickness was (VA) and ocular alignment greater in the nasal quadrant than the findings were document- temporal quadrant in 43%. Exclusion ed. Metamorphopsia was of the nasal quadrant from the ISNT assessed qualitatively and rule significantly increased validity of quantitatively. Aniseikonia the ISNT variants: 71% and 76% of was determined by sub- disc photographs followed the IST rule jective description and the and the IS rule, respectively. For RNFL Awaya new aniseikonia test. thickness, 71% and 72% coincided with EXCEPTION TO THE ISNT RULE. In this example, Testing for retinal misregis- IST and IS rules, respectively. the RNFL thickness (bottom left) in the nasal tration also was performed. As a result of these findings, the au- quadrant is thinner than the temporal quadrant. Clinical findings of patients thors advocate use of IST and IS rules This violates the ISNT rule, which holds that the with and without CPR-type American Journal of Ophthalmology American Journal of for distinguishing glaucomatous from inferior (I) rim is the widest, followed in turn by the diplopia were compared to

EYENET MAGAZINE • 23 Among the group of 31 patients, pigmentary abnormalities. edema received donor corneas pre- the prevalence of any type of diplopia The 5-year incidence of AMD, served for ≤ 7 days (675 eyes) or 8-14 was 23% (n = 7) and that of CPR-type adjusted for age and sex, was 8.8% for days (655 eyes). The median participant diplopia was 16% (n = 5). In the entire those born from 1901-1924, 3% for age was 70 years (range, 42-90 years), series of 56 patients, 12 (21%) had those born from 1925-1945, 1% for and 60.2% were female. Demographics CPR-type diplopia, and 37 (66%) had those born 1946-1964, and 0.3% for of the study groups were similar. no diplopia. The other 7 had another those born 1965-1984. The 3-year cumulative probability of type of diplopia and were excluded Each generation was > 60% less graft success was 95.3% for donor cor- from subsequent analyses. likely to experience AMD than the pre- neas preserved for ≤ 7 days and 92.1% Relative to patients who did not ceding generation, and this association for those preserved 8-14 days. The up- have CPR-type diplopia, those with the remained significant after adjusting per limit of the 1-sided 95% confidence disorder had better VA in their worse for age, sex, smoking status, education interval of this difference was 5.4%, eye (mean difference of –0.23; p = .003) level, amount of exercise, selected lipid which surpassed the noninferiority and more severe quantitative meta- levels, and high-sensitivity C-reactive limit of 4% and was attributed to more morphopsia (mean M-score difference protein levels, and use/nonuse of non primary donor failures in the group of 0.6; p = .01). Rates of aniseikonia steroidal anti-inflammatory drugs, with longer preservation time (condi- misregistration were similar for those statins, and multivitamins. tional probability of failure after the with and without the disorder. Although the 5-year risk of AMD first month: 3.1% vs. 2.4%). Although results indicate that pa- declined throughout the 20th century, A secondary analysis showed that tients with CPR-type diplopia generally factors responsible for the decline were the likelihood of graft success decreased have better worse-eye acuity and more not apparent from this study. However, as preservation time increased. The metamorphopsia than those without the results do suggest that modifiable success rate was lower for a period of the disorder, individual variability is factors contribute to the etiology of 12-14 days (89.3%) than for ≤ 4 days considerable. Coexistence of retinal AMD and that the current epidemic (96.5%), 5-7 days (94.9%), or 8-11 days misregistration and metamorphopsia of AMD among the oldest generation (93.8%). appears necessary for the development may diminish with time. Prospective The comparable success rates attained of CPR-type diplopia, but many patients epidemiologic studies are warranted for corneas that had been preserved for without this diplopia may exhibit those to confirm the findings. (Also see up to 11 days should reassure surgeons. features. related commentary in the same issue The high 3-year success rates with by Raphael R. Goldacre, MSc, and DSAEK for Fuchs dystrophy, regard- Generational Differences in AMD Tiaran D.L. Keenan, PhD.) less of preservation time, suggest that Incidence corneas that have been preserved for a December 2017 Does Cornea Preservation Time longer time period can be used when Affect DSAEK Success? necessary. Cruickshanks et al. set out to deter- December 2017 —Summaries by Lynda Seminara mine whether the 5-year risk of AMD is changing as longevity increases and Although donor corneas can be pre- Other Journals found that the risk has declined over served in FDA-approved solutions Selected by Deepak P. Edward, MD time. for up to 14 days, many surgeons will For their assessment, the authors not use cornea tissue that has been Spironolactone Effective for obtained longitudinal data from 2 preserved for more than 7 days. To Acute Central Serous Chorio Beaver Dam eye studies in which the examine the effect of preservation time retinopathy 5-year incidence of AMD was mea- on graft success, Rosenwasser et al. British Journal of Ophthalmology sured. A total of 4,819 participants compared 3-year outcomes of Descem- Published online Oct. 31, 2017 (baseline mean age, 54 years) were at et stripping automated endothelial risk for AMD based on findings from keratoplasty (DSAEK) among corneas Previous studies have shown the prom- the fundus images obtained at base- preserved for varying periods. They ise of mineralocorticoid-receptor an- line. Fundus images were graded for found that preservation time of < 12 tagonists in the treatment of chronic or AMD using the Wisconsin age-related days was linked to better success rates. recurrent central serous chorioretinop- maculopathy grading system, and AMD This double-masked randomized athy (CSC). Building on this premise, incidence was determined from 5-year trial was conducted at 40 U.S. clinical Sun et al. studied the efficacy of oral follow-up results. sites (70 surgeons) from April 2012 to spironolactone among patients with AMD was identified by the presence June 2017. acute CSC and found that, compared of pure geographic atrophy, exudative Eligible patients scheduled to under- with observation alone, the treatment macular degeneration, any type of go DSAEK for Fuchs endothelial corne- was much more effective and resulted drusen with pigmentary abnormali- al dystrophy (94.4% of participants) in fast absorption of subretinal fluid ties, or soft indistinct drusen without or pseudophakic or aphakic corneal (SRF).

24 • JANUARY 2018 For this prospective trial, the authors strated that such evidence also exists in evaluated 30 patients (30 eyes) with the retinas of living patients. According acute CSC. The patients were assigned to the retinal amyloid index (RAI) randomly either to the treatment group developed by the investigators, index (spironolactone 40 mg orally, twice scores were more than twice as high for daily for 2 months; n = 18) or to the patients with AD than in cognitively EyeNet control group (observation alone; n normal controls. = 12). Main outcome measures were The authors first examined the Gives You the proportion of eyes with complete burden, distribution, cellular layer, and resolution of SRF by 2 months and the structure of retinal Aβ plaques in do- changes in central macular thickness nor tissue (eyes and brain) of patients the Full (CMT), SRF height, best-corrected with definitive AD (n = 23) and cog- visual acuity (BCVA), and subfoveal nitively normal controls (n = 14). An Picture choroidal thickness (SFCT) during the amyloid probe curcumin formulation same period. was derived from histologic findings, By 2 months, complete resolution of and a protocol for retinal amyloid Get Extra Insights at SRF had occurred in 10 of the 18 treat- imaging was established and applied to aao.org/eyenet ed eyes and in only 1 of the 12 control living patients (10 with AD, 6 healthy eyes. Both groups experienced a signif- controls). icant decline in mean CMT and mean Histologic examination showed that SRF height (p < .05), with significant patients with AD had classic and neu- between-group differences apparent at ritic-like Aβ deposits, with increased 2 months (p < .05 and p < .05, respec- retinal Aβ42 plaques (4.7-fold; p = .0063) tively). Mean BCVA improved in both and neuronal loss (p = .0023) relative groups by 2 months (p < .05). In the to matched controls. The retinal Aβ treatment group, mean SFCT decreased plaque presentation mirrored brain significantly, from 502.50 ± 87.38 μm pathology, particularly in the primary at baseline to 427.44 ± 74.37 μm at 2 visual cortex. Retinal deposits often months (p < .01), whereas the change were associated with blood vessels and from baseline in the control group was occurred in hot-spot peripheral regions not significant. Spironolactone did of the superior quadrant and inner- not produce any adverse effects in this most layer of the retina. Transmission study, perhaps because of the short electron microscopy showed the assem- duration of treatment. blage of retinal Aβ into protofibrils and Due to the multifactorial nature of fibrils. CSC, the mineralocorticoid receptor The authors then demonstrated the may play a role in some patients but ability to image retinal amyloid deposits Enrich your EyeNet® Magazine not others. Findings of this study may with solid-lipid curcumin and a mod- reading experience—go online each month for material that help to guide early intervention for ified scanning laser ophthalmoscope supplements the print issue. acute CSC. In addition, the authors in living patients. A fully automated View Web Extras, which can suggested that patients with CSC be calculation of the RAI, a quantitative include text, photos, videos, given a medication guide to treatment measure of increased curcumin fluo- graphs and slideshows that of the disease. rescence, was devised. Analysis of RAI provide further detail and insight. scores showed that scores for patients Comment on articles to voice your Retinal Scanning May Help with AD were 2.1 times higher than opinion or discuss research and Detect Alzheimer Disease in those of controls. techniques with your peers. Living Patients The geometric distribution and Explore the archives for more JCI Insight increased burden of retinal amyloid articles that can enhance your patient care. 2017;2(16):e93621 pathology in AD, coupled with the feasibility to noninvasively detect retinal Retinal examination may be a nonin- amyloid deposits in living patients, may Visit Us Online aao.org/eyenet vasive method of detecting Alzheimer lead to a practical approach for large- disease (AD). The retinas of deceased scale diagnosis and monitoring of AD. Write to Us patients with AD exhibit myriad retinal Such imaging technology may prove to [email protected] pathologies, including the hallmark be sensitive and inexpensive for screen- amyloid-β (Aβ) protein. Koronyo et al., ing people at risk for AD. in a proof-of-concept study, demon- —Summaries by Lynda Seminara

EYENET MAGAZINE • 25 Exclusively for Academy Members Ophthalmologists Business Summit March 24-25, 2018 | Dallas, TX

The Academy’s first physician-oriented business summit will address the key financial and operational challenges your practice is facing right now. Gain valuable insights and actionable strategies that positively impact the revenue and growth of your practice. Register today: aao.org/business-summit

American Academy of Ophthalmic Executives® ANTERIOR SEGMENT CLINICAL UPDATE

Identifying and Managing Iris Cysts

rimary iris cysts originate in the 1 2 iris pigment epithelium or iris Pstroma, and secondary iris cysts are stimulated by outside factors. Most of these cysts are quite rare, but some can cause visual problems, requiring treatment. In addition, differential diagnosis is crucial to rule out more se rious problems, mainly malignancies.1 3 4 Types of Iris Cysts Although iris cysts are relatively rare, the following are more commonly seen. Iris pigment epithelium cysts. The most common type of iris cyst, iris pig ment epithelium cysts tend to show up on routine examinations because they TYPES OF CYSTS. (1) Iris pigment epithelium cyst. (2 and 3) Iris stromal cysts. (4) are asymptomatic and rarely cause vi Epithelial inclusion cyst, or epithelial “downgrowth.” sual problems, said Prithvi Mruthyun jaya, MD, MHS, at Stanford University or vitreous. They are translucent with said Michael E. Snyder, MD, at Cincin in Palo Alto, California. Although these speckles of light brown and are usually nati Eye Institute. cysts are typically referred to the ocular benign, said Dr. Mruthyunjaya. “When surface epithelial cells get in oncologist as a single iris mass of un Stromal cysts. Arising from the side the eye, they do not behave nicely,” known origin, he said, they are often front part of the iris, stromal cysts tend he said. “If they start forming an iris multifocal and bilateral. to be translucent-white and can more cyst, they are unlikely to cause imme Located underneath the iris, these readily deform the structure of the iris diate sight-impairing complications as cysts push the iris forward, creating itself than iris pigment epithelium cysts long as they remain encased. But if they a dome-shaped surface, said Zélia M. do, said Dr. Mruthyunjaya. “This cyst break or start growing into important Corrêa, MD, PhD, at the University of can be confused for an iris melanoma, structures of the eye, they can, rarely, Cincinnati. They may be midzonal, especially if it is strongly pigmented, cause fairly profound vision loss and right in the middle of the iris leaflet, making it look like a nodule.” sometimes loss of the eyeball itself.” In but also can be located at the inner or Epithelial downgrowth cysts. Fol children younger than age 10, he added, outer edges of the iris, near the pupil or lowing trauma—from either surgery or these cysts can cover the pupil space, ciliary body, potentially making them injury—epithelial cells may be trans leading to amblyopia. a diagnostic challenge. In some cases, mitted from the outside of the eye to Because they grow toward the inside these cysts may also detach from the iris the inside, or cells inside the eye may of the eye, Dr. Corrêa prefers to call and float freely in the anterior chamber transdifferentiate into epithelial cells, them epithelial ingrowth—rather than downgrowth—cysts. “Although they may start developing years after the BY ANNIE STUART, CONTRIBUTING WRITER, INTERVIEWING ZÉLIA M. CORRÊA, initial trauma,” she said, “they are very MD, PHD, PRITHVI MRUTHYUNJAYA, MD, MHS, AND MICHAEL E. SNYDER, MD. aggressive and can grow quickly, almost

EYENET MAGAZINE • 27 like a tumor, acquiring a surprising size.” Another interesting feature of these cysts, said Dr. Mruthyunjaya, is the When Cancer Is a Concern proteinaceous reflectivity of the cystic “Although it is easier to assume that small lumps or bumps in the iris are fluid—they are not completely clear. benign,” said Dr. Corrêa, “in the back of your mind, you need to consider other

more serious differential diagnoses. Always remember that tumors can be Confirming a Cyst Diagnosis occasionally associated with cysts or have a cystic component.” “I want to be able to properly identify Most worrisome. In her practice, Dr. Corrêa has seen a number of iridocil- the location and origins of a cyst,” said iary melanomas with a cystic component located right at the root of the iris. Dr. Mruthyunjaya. “That will involve “I’ve also seen patients with medulloepithelioma, a rare type of neuroectoder- a thorough history; complete exam mal tumor that can be aggressive and have a prominent cystic component, ination, including a gonioscopy and especially ones in the ciliary body.” Most worrisome, she said, are tumors in the examination of the anterior segment; transition between the iris and ciliary body. They are usually hidden, harder to and imaging. Sometimes looking at diagnose, and trickier to treat. “You must rely on imaging such as high-resolu- both eyes also provides clues about the tion ultrasound because it’s hard to visualize them directly or indirectly,” she said. etiology of the cyst.” Other serious signs. “Any time you see an iris lesion associated with prom- In the case of a suspected downgrowth inent episcleral blood vessels, unexplained acute increase in intraocular pres- cyst, he added, confirming etiology sure, or iris heterochromia,” she said, “a neoplasm should be in the differential might also involve looking for surgical diagnosis.” Also, patients with localized graying or darkening of the sclera wounds or previous operative notes. should be cautiously evaluated to rule out a melanocytic tumor, she said. Don’t overlook history. “Curious Using transillumination, it is possible to identify a melanocytic lesion, which and peculiar stories have underscored almost always will cast a dark shadow. the importance of history-taking for me,” said Dr. Corrêa. She recounted the story of a civil engineer who felt “a slight snag” in his eye while overseeing the doctor in charge of monitoring OCT helpful in imaging peripheral the paving of a road. A tiny piece of grav the eyedrops, especially if the cyst has cysts, Dr. Corrêa warned that it may el had lodged in his iris, but it didn’t become quite large. not be possible to see the full extent of raise red flags until months later when Imaging. To rule out other problems these cysts with OCT, especially if they his vision became blurry from a devel and diagnose an iris cyst, ophthalmol are large. oping cyst. Complicating matters, said ogists may use either anterior segment Advantages of ultrasound. Dr. Corrêa, the cyst looked like a tumor OCT or high-resolution ultrasound High-resolution ultrasound of the because the gravel was dark in color. biomicroscopy (UBM), said Dr. Corrêa. anterior segment provides a very good Dr. Snyder mentioned another “As long as you scan the whole cyst view, allowing you to visualize thin instance in which history-taking is and have a good enough image of the walls and hollow cavities, indicating a critical: Ask patients if they have trav lesion, you’re in great shape,” she said, fluid-filled cyst, versus the solid nature eled to other parts of the world where adding that each diagnostic modality of a malignancy, said Dr. Snyder. In parasites are endemic; they may have has its advantages. addition to looking at the quadrant of experienced a parasitic infection. “Par Advantages of OCT. Anterior seg the suspected cyst, Dr. Mruthyunjaya’s asites that travel to the eye, such as Cys- ment OCT may identify small cystic initial evaluation involves a scanning ticercus cellulosae, can cause cysts that structures, giving early confirmation protocol around the peripheral part of can be quite dangerous. If you inad of diagnosis. However, it does have the iris and ciliary body—as well as the vertently open the cyst and expose the limitations. For example, in patients other eye. “It’s striking how often you parasite to the eye, it can die, causing a with dark irides, the OCT signal may will find tiny cysts in multiple locations significant inflammatory response.” become attenuated, said Dr. Mruthyun that weren’t detected clinically.” Other questions to ask. Dr. Corrêa jaya. Also, the pigmentation or size of Dr. Corrêa also uses UBM for surg counsels colleagues to take time to talk the cyst may prevent ideal resolution, ical planning. “It’s easier to turn the with the patient and ask questions like he said. “But I’ve been impressed with probe around and get a feel for the these: How long have you been aware the ability to penetrate even small cysts,” extent of the cyst and consistency of the of the cyst? How long has it been since he said, adding that repeatedly scan tissue.” Those who lack experience with your last ophthalmology visit? What ning the same area also provides a use UBM should consider referring this kind of exam did you receive? Did you ful way to follow up on a cyst’s growth out, she said. have your pupils dilated? over time. OCT also has the advantage What’s next? If you see a lesion with If a cyst appears suddenly, said of no contact with the patient’s eye, a solid component, you might confirm Dr. Mruthyunjaya, it’s worth asking said Dr. Corrêa, which can be especially this with magnetic resonance imaging, whether the patient is on prostaglandin helpful for younger patients. said Dr. Corrêa, and even biopsy for analogs, which can affect cyst size. Alert Although Dr. Mruthyunjaya finds confirmation of malignancy.

28 • JANUARY 2018 When Treatment Is Needed Drainage and injection. Dr. Corrêa In most cases, Dr. Corrêa simply also likes to treat ingrowth cysts by Coming in the next observes iris pigment epithelial and using a needle to drain the cyst, inject stromal cysts. alcohol inside it, and then deflate the ® Conditions dictate choices. How cyst. “In case there is any sign of residu ever, said Dr. Corrêa, treatment may al epithelium on the surface of the iris, be needed if there are other problems I use an endolaser probe to treat the such as increasing eye pressure or area and make sure any epithelial cells Feature multiple cysts occluding the angle. Con are destroyed.” MIGS Moves Forward sider other conditions as well, said Dr. To minimize the chances of leaving An overview of the Mruthyunjaya: Is there an incomplete cells behind, Dr. Mruthyunjaya rec latest developments in wound involved in epithelial down ommended avoiding going through microinvasive surgery growth that you need to address? What the open aqueous humor and anterior and devices, and how is the size of the cyst and its velocity of chamber. “Try to go through the back they are expanding growth? Is it intermittently leaking and or more peripheral part of the cyst. causing inflammation? Is it rubbing Consequently, if there’s anything that’s treatment options for against ocular structures such as the being released when you pull in and glaucoma patients. lens or the cornea, causing secondary out of the eye, it’s coming right out of problems? the eye with your needle.” Clinical Update Treat it like a tumor? Dr. Snyder said Dr. Mruthyunjaya also uses fluores Cornea Acceptance of it is most effective to treat epithelial cein eye stain to make sure the alcohol DMEK is growing. An over- downgrowth cysts as though they are is contained within the cyst and not view of the procedure’s tumors, as they cause unrestricted accidentally instilled into the anterior pros and cons, plus new growth of cells where they don’t belong. chamber, where it can be very toxic. research. “Sometimes, treatment’s one and done,” Filling the eye with Healon viscoelastic Oculoplastics What’s said Dr. Mruthyunjaya, “but some also acts as a diffusion barrier for the involved in facial recon- times it requires multiple attempts at alcohol, he said, but the viscoelastic struction? Three experts controlling the cyst. In other cases, must be thoroughly removed after the discuss this challenging reduction is good enough. Regardless, procedure. procedure. you need to watch them closely.” Cryotherapy. Following drainage What to consider beforehand. You and injection, Dr. Mruthyunjaya then Pearls can use a variety of options to treat uses cryotherapy at the edge of the Submacular Hemorrhage epithelial downgrowth cysts. “But track by the limbus to sterilize any cells How to treat this uncommon whatever you do with these cysts,” said that may be remaining. Sometimes it but serious complication. Dr. Corrêa, “you must remove every is possible to freeze an entire cyst if it little bit of abnormal epithelium from is tiny and located peripherally, right the anterior chamber, or the cyst may at the edge of the cornea at the limbus, Practice Perfect recur, proliferate rapidly, and cause a added Dr. Snyder. Benchmarking Know the lot of damage inside the eye.” Before “vital signs” of your practice. any procedure, ensure that imaging 1 Shields JA, Shields CL. Asia Pac J Ophthalmol. has revealed the full extent, size, and 2017;6(1):64-69. Blink location of the cyst, she said, so you can Take a guess at the next approach it the right way. Dr. Corrêa is professor of ophthalmology at the issue’s mystery image. Excision. To cause less collateral University of Cincinnati in Ohio and director of damage, Dr. Mruthyunjaya prefers the Ocular Oncology Program. Relevant financial excising these cysts when they are small. disclosures: None. For Your Convenience Dr. Snyder recommends a partial lamellar Dr. Mruthyunjaya is associate professor of oph These stories also will be iridocorneal trabeculectomy—removing thalmology at Stanford University and director of available online at the internal eye wall and the areas the ocular oncology at the Byers Eye Institute in Palo aao.org/eyenet. cyst is touching—to avoid rupturing Alto, Calif. Relevant financial disclosures: None. or breaking the wall of the cyst. “If Dr. Snyder is chair of clinical research and on FOR ADVERTISING INFORMATION this procedure creates a serious iris the board of directors at Cincinnati Eye Institute Mark Mrvica or Kelly Miller defect,” he said, “it often causes glare and is associate professor of ophthalmology–af M. J. Mrvica Associates Inc. or light sensitivity. If it is not possi filiated, at the University of Cincinnati in Ohio. 856-768-9360 ble to surgically close the area that’s Relevant financial disclosures: HumanOptics: C. [email protected] been removed, an artificial iris may be See the disclosure key, page 8. For full disclo- needed.” sures, view this article at aao.org/eyenet.

EYENET MAGAZINE • 29 Ace Your MOC Exams with the Ultimate Ophthalmic Study Guide

Practicing Ophthalmologists Learning System, 2017-2019 is an innovative program that will help you successfully prepare for maintenance of certification exams with more than 4,000 self-assessment questions covering 1,400 topics. It’s also perfect for lifelong learning and self-assessment.

Order today aao.org/learningsystem RETINA CLINICAL UPDATE

Outer Retinal Tubulation: Sign of Neurodegeneration

f you use high-resolution imaging to 1A 1B guide treatment of retinal diseases, Ithe most important thing to know about outer retinal tubulation (ORT) structures is that they commonly appear in cross-sectional images as features that look somewhat like intraretinal cysts—but aren’t. The tubular structures in ORT- affected eyes appear on high-resolution, spectral-domain ocular coherence ORT ON OCT. (1A) Representative SD-OCT B-scan of 3 ORT cross-sections (yellow tomography (SD-OCT) B-scans as arrowheads) in an 81-year-old woman with neovascular AMD. Two closed ORT well-defined circular or ovoid areas structures are evident on the left, and a branching tubulation can be seen on the of hyporeflectivity, surrounded by a right. A hyporeflective wedge (pink arrowhead) and Bruch membrane (cyan arrow- hyperreflective band, said K. Bailey head) are also evident. (1B) High-resolution histology section of degenerate cones Freund, MD, who coauthored the first in ORT, at 1.5 mm from the fovea, in a different 81-year-old woman with neovas- clinical description of ORT.1 cular AMD. Cone lipofuscin (green arrowheads), mitochondria in outer fiber (red “If you did not know that these arrowheads), Müller cell body (white arrowhead), and ORT cross-sections (yellow lesions existed, particularly if you were arrowheads) are indicated. BLamD = basal laminar deposit; Ch = choroid; fv.s = using the older time-domain OCT fibrovascular scar; INL and ONL = inner and outer nuclear layer; M = lipid-containing devices, you could easily confuse them macrophage; RPE = entombed and melanotic retinal pigment epithelium. with cysts or subretinal fluid,” said Dr. Freund, who practices in New York City. vascular age-related macular degener- visual function,” he said. “And if you were using a treatment ation (AMD); geographic atrophy (GA) A better understanding of the ORT regimen that was guided by presence secondary to AMD and other disorders; process eventually might yield clues or absence of fluid, you could end up inherited retinal diseases, particularly about how to stop photoreceptors from giving intravitreal injections to an eye choroideremia; and mitochondrial dying, said Glenn J. Jaffe, MD, at Duke that really didn’t need them.” diseases.2 Eye Center in Durham, North Carolina. Prognostic value. In all of these In treatment trials, a biomarker like Many Roads Lead to ORT conditions, the presence of ORT ORT might prove valuable for exclud-

. Despite this narrow clinical utility, ORT structures indicates disorganized outer ing prospective participants unlikely to has garnered increasing attention over retinal layers, irreversible photoreceptor regain vision, he said. the last several years because of the damage, and a worse visual prognosis, “The hope would be that we could

aao.org/eyenet realization that tubulations in the outer Dr. Freund said. “Most people would help preserve people’s vision if we can nuclear layer represent a common consider ORT a sign that, at least in prevent the degeneration of the photo- neurodegenerative pathway in a variety that one particular area of the macula, receptors,” Dr. Jaffe said. “Whether it’s of retinal diseases. These include neo- you’re not going to be able to recover with a neurotrophic agent or some other type of treatment, we are becoming more aware that we need to be able to BY LINDA ROACH, CONTRIBUTING WRITER, INTERVIEWING CHRISTINE A. prevent the loss of the photoreceptors

For full credit, see this article at see this article at full credit, For CURCIO, PHD, K. BAILEY FREUND, MD, AND GLENN J. JAFFE, MD. in these diseases.”

EYENET MAGAZINE • 31 Clues from CATT. Dr. Jaffe said he cells that are driving this process, and What about GA? In a subgroup of became interested in ORT because of in the very late stage of tubulation you affected patients in the Geographic what he observed during the Compari- only have Müller cells and no surviving Atrophy Treatment Evaluation (GATE) son Age-related Macular Degeneration cones,” he said. trial, ORT was present in 65% of eyes Treatment Trials (CATT).3 “We were Rolling up the photoreceptors. As in the atrophic region and in 26% of the OCT reading center for CATT, and described recently by Dolz-Marco et eyes in the junctional zone.7 But there is while we were looking at the images I al.,2 ORT occurs when the external disagreement over what this means, Dr. started to notice that ORT [structures] limiting membrane (ELM), which Jaffe said. were becoming more frequent as the is normally a thin horizontal reflec- “It’s a little bit unclear” as to how study went on. So we looked at the tive line made by Müller cells and well the presence of ORT predicts GA percentages and found that by 5 years, photoreceptors, begins “circling the progression, he said. “In one of the about 1 in 5 patients had this character- wagons.” The ELM descends toward publications that we’ve done, we found istic appearance,” Dr. Jaffe said. Bruch membrane and gradually begins that it was associated with more rapid scrolling the at-risk photoreceptors progression. But at least one other Genesis of Tubulation into a tubular structure. Depending group [led by SriniVas Sadda, MD, at The tubules characteristic of ORT are on the stage of development, the outer the University of Southern California] the retina’s heroic yet last-ditch attempt band can appear in cross-section as flat, has reported not seeing that.”8 to protect localized areas of macular J-shaped, or partially (or fully) curved Attention to the different stages of cone photoreceptors from the failure of back on itself. ORT, which were not appreciated at the the underlying retinal pigment epithe- Both the inner and outer segments time of these prior studies, might help lium (RPE), said Christine A. Curcio, of the scrolled photoreceptors initially solve this discrepancy in future studies, PhD, at the University of Alabama at point radially into the lumen delineated Dr. Freund’s group suggested.2 Birmingham. by the ELM,2 and these can be seen “What ORT lesions have in com- clinically as a reflective fringe around 1 Zweifel SA et al. Arch Ophthalmol. 2009;127(12): mon with each other is that the RPE is the hyporeflective lumen (dark on the 1596-1602. dying or is gone. These are responses of OCT). 2 Dolz-Marco R et al. Ophthalmology. 2017;124(9): retina cells to the extreme stress of this As ORT progresses, the lumen be- 1353-1367. detachment,” Dr. Curcio said. comes uniformly hyporeflective as the 3 Lee JY et al. Ophthalmology. 2014;121(12):2423- In 1996, her research group pub- outer segments degenerate and the in- 2431. lished the first histological descriptions ner segments are pulled back across the 4 Curcio CA et al. Invest Ophthalmol Vis Sci. 1996; of photoreceptors surviving in myste- ELM. Remnants of the numerous mito- 37(7):1236-1249. rious interconnected tubes in the mac- chondria in the inner segments migrate 5 Litts KM et al. Invest Ophthalmol Vis Sci. 2016; ulas of eyes with neovascular AMD.4 It into the cell body of the degenerating 57(6):2647-2656. wasn’t until 2009 that Dr. Freund and cells, accounting for the reflectivity of 6 Jung JJ, Freund KB. Arch Ophthalmol. 2012; his colleagues, using SD-OCT images, the outer band of ORT. 130(12):1618-1619. published the first clinically oriented In their study of 38 eyes with pre- 7 Moussa K et al. Retina. 2013;33(8):1590-1599. paper about “a peculiar outer retinal existing ORT, Dolz-Marco et al. found 8 Hariri A et al. Ophthalmology. 2015;122(2):407- morphologic change occurring in a that the mean time for new tubules to 413. variety of advanced degenerative retinal form was 14.9 months.2 It is unknown disorders.”1 how long the end-stage ORT lesions Dr. Curcio is professor of ophthalmology and Since those publications, Drs. Curcio persist in the retina, but in clinical director of the AMD Histopathology Lab at the and Freund have worked together to experience they commonly are stable University of Alabama at Birmingham. Relevant correlate high-resolution histopathol- through at least 3 years of follow-up.6 financial disclosures: Heidelberg Engineering: S. ogy in donor eyes with eye-tracked Serpentine patterns on OCT. En face Dr. Freund practices at Vitreous Retina Macula OCT images of living eyes, in order to OCT scans of ORT-affected maculas Consultants of New York and is clinical professor understand the ORT process.2,5 reveal the tubules snaking in various of ophthalmology at the New York Universi- Gliosis implicated. Their overall patterns across the retina. “A branching ty School of Medicine in New York City. Relevant conclusion: Tubulation is a protective or pseudodendritic pattern is observed financial disclosures: Heidelberg Engineering: C; gliotic response—ultimately futile— mainly in association with neovas- Optovue: C; Spark Therapeutics: C. triggered by activated Müller cells, Dr. cularization, whereas a singular tube Dr. Jaffe is the Robert Machemer Professor of Curcio said. “The Müller cells are trying may line the border of GA. Interest- Ophthalmology and chief of the Vitreoretinal to take care of the remaining photore- ingly, analysis of ORT over time has Division at Duke University and director of the ceptor cells. They are protecting them shown fluctuations in ORT volume in Duke Reading Center at the Duke Eye Center from the failure of the RPE and all the cross-sectional SD-OCT scans, even in Durham, N.C. Relevant financial disclosures: problems in the RPE/Bruch membrane while the ORT footprint seen with Heidelberg Engineering: C. complex.” en face imaging remains constant,” See the disclosure key, page 8. For full disclo- Dr. Freund agreed. “It’s the Müller Dolz-Marco et al. wrote.2 sures, view this article at aao.org/eyenet.

32 • JANUARY 2018 RETINA OPHTHALMIC PEARLS

Diagnosis and Management of Central Retinal Vein Occlusion

etinal vein occlusion (RVO) has Ocular conditions. Open-angle glau- 1 a prevalence of 0.5%, making coma is a major ocular risk factor for Rit the second most-common CRVO. retinal vascular disorder after diabetic In addition, individuals with CRVO retinopathy.1 RVO is classified accord- in 1 eye are at higher risk of developing ing to the anatomic level of the occlu- CRVO in the fellow eye.2 In the Central sion, with 3 major distinct entities: Vein Occlusion Study (CVOS), 4% of • Central retinal vein occlusion patients presented with bilateral CRVO (CRVO): occlusion of the central reti- at study enrollment, and a further 5% nal vein at the level of, or posterior to, had evidence of previous CRVO in the the lamina cribrosa (Fig. 1) fellow eye at baseline. In the remaining • Hemiretinal vein occlusion (HRVO): subjects, 1.4% developed CRVO in the occlusion at the disc, involving either fellow eye during 3 years of follow-up. ACUTE CRVO. Classic “blood and thun- the superior or inferior hemiretina Other ocular risk factors include der” fundus appearance of a patient • Branch retinal vein occlusion retrobulbar external compression of the presenting acutely with central retinal (BRVO): occlusion of a tributary vein, central retinal vein, as occurs in thyroid vein occlusion of the right eye. typically at the site of an arteriovenous orbitopathy, or compression by intra crossing; thought to be caused by com- orbital space-occupying lesions. may be absent. In subacute or late pression from an overlying atheroscle- presentations in which disc swelling rotic arteriole Clinical Presentation has resolved (with or without collateral This article will focus on diagnosis Patients with CRVO typically present vessel formation), the flame-shaped and management of the first entity, with a history of unilateral acute, pain hemorrhages clear first, leaving deeper CRVO. less visual loss. Visual impairment may dot/blot hemorrhages that may be be severe, ranging from better than difficult to distinguish from a severe Risk Factors 20/40 to worse than 20/200. A relative microangiopathic retinopathy such as Systemic disorders. Systemic risk factors afferent pupillary defect may be present diabetic retinopathy (Fig. 2). Fluores- for CRVO include increasing age, diabetes in the affected eye. cein angiography (FA) may help to mellitus, and hypertension. In selected Fundus findings.Dilated fundus confirm the diagnosis of CRVO. cases, hypercoagulable states, including examination reveals unilateral disc Other key aspects. As part of the hyperhomocysteinemia and factor V swelling with peripapillary intraretinal examination, the clinician should note Leiden mutation, or local vessel factors hemorrhages, dilated tortuous veins, the intraocular pressure and cup-to-disc such as vasculitis are also associated and intraretinal dot, blot, and flame ratio, which may suggest concurrent with increased risk of CRVO. The hemorrhages in all quadrants, result- glaucoma, as well as any sequelae, such literature also contains case reports of ing in the classic “blood and thunder” as rubeosis iridis. Undilated gonioscopic many other systemic conditions possi- fundus appearance (Fig. 1). The macula examination is important to rule out bly associated with the development of may be edematous. neovascularization of the angles. CRVO. In less severe cases, disc swelling Types of CRVO Clinically, CRVO may be divided into 2 BY SIEHYEAN KIEW, MD, AND DANIEL S.W. TING, MD, PHD. EDITED BY SHA- major subtypes: ischemic and nonisch-

Kasi Sandhanam and Joseph Ho, Singapore National Eye Centre Eye National Singapore Sandhanam and Joseph Ho, Kasi RON FEKRAT, MD, AND INGRID U. SCOTT, MD, MPH. emic.

EYENET MAGAZINE • 33 2A 2B 2C

Ischemic. The CVOS investigators CHANGES OVER TIME. Same eye as shown in Fig. 1 at (2A) 1 month, (2B) 4 months, defined ischemic CRVO as evidence and (2C) 1 year following initial presentation, demonstrating evolution of the clinical of more than 10 disc areas of capillary picture. Disc edema resolves first, then the flame hemorrhages, and finally the dot nonperfusion on 7-field fundus FA (al- and blot hemorrhages, with development of collateral vessels at the optic disc. though investigators are reassessing this definition in light of recent advances in in a patient with existing nonischemic often performed in patients with CRVO widefield angiography). CRVO should, therefore, prompt further and is directed by the patient’s age, Ischemic CRVO may be identified by assessment for development of ischemic coexisting risk factors, and medical his- the following characteristics: CRVO. tory. Assessment should be performed • Poor visual acuity (>90% had VA of Of the eyes that remained nonin conjunction with an internist, as <20/200) ischemic, approximately 30% showed patients with RVO may be at higher • Presence of a relative afferent pupil- resolution of macular edema within risk of cardiovascular disease and cere- lary defect in the affected eye 15 months. Occurrence of subsequent brovascular accidents. • Presence of extensive dark, deep neovascular complications is rare in There are no clear guidelines on intraretinal hemorrhages nonischemic eyes. systemic testing, but it generally begins • Presence of multiple cotton-wool with a dilated funduscopic examination spots Workup in clinic, along with a detailed medical • Greater than 10 disc areas of retinal A thorough initial workup can provide history to identify risk factors; further capillary nonperfusion on 7-field FA useful information to guide clinical assessment includes blood pressure and • Reduced b-wave amplitude, reduced decision making. serum glucose, complete blood count, b:a ratio, and prolonged b-wave implic- Optical coherence tomography. and erythrocyte sedimentation rate. it time on electroretinography OCT is useful to confirm and quantify In young patients without clear risk In ischemic CRVO, visual acuity the severity of macular edema, assess factors, additional testing should be remains poor, often decreasing further the integrity of the ellipsoid zone/ considered to exclude a hematologic over time. Causes of visual loss include photoreceptor layers, and monitor or vasculitic etiology. chronic macular edema, macular isch- response to treatment. In clinical prac- emia, peripheral/global ischemia with tice, OCT measurements often guide Treatment secondary vitreous hemorrhage, and treatment decisions. All patients should optimize control neovascular glaucoma. Fluorescein angiography. Fea- of systemic risk factors, with the help Approximately 23% of eyes with tures of CRVO on FA include delayed of their internist. Management of the ischemic CRVO develop iris neovas- arm-to-retina time, prolonged arterio ocular manifestations may be divided cularization over 15 months; in the venous transit time (markedly so in into the following areas. CVOS, 44% of eyes that presented with ischemic CRVO), late staining along Macular edema. Both laser and vision worse than 20/200 subsequently vessel walls, capillary dropout with medical therapies have been used in the developed iris neovascularization.2 pruning of the vessels in areas of treatment of macular edema. Some patients may develop retinal ischemia, and late leakage in a petal- Laser. Studies assessing grid-pattern neovascularization. loid pattern in the presence of macular laser photocoagulation for treatment of Nonischemic. In the CVOS, 34% of edema (Fig. 3). macular edema in CRVO showed ana- eyes that initially presented with non- Clinically, FA allows evaluation of tomic improvement without improve- ischemic CRVO underwent conversion the extent of capillary nonperfusion ment in visual acuity.2 to an ischemic perfusion status over 3 and the degree of macular ischemia and Anti–vascular endothelial growth years2; conversion is heralded by rapid enables differentiation between collater- factor. Intravitreal anti-VEGF therapy visual deterioration in the affected al vessels and new vessels. is currently the gold standard of treat-

eye. Sudden decrease in visual acuity Systemic. Systemic evaluation is ment for macular edema associated Centre Eye National Singapore Sandhanam and Joseph Ho, Kasi

34 • JANUARY 2018 (mean improve- Anti-VEGF agents are antiangiogen- 3A 3B ment of 18.6 ic and may be useful adjuncts to PRP vs. 18.9 ETDRS in the management of patients with letters, respec- CRVO and associated anterior segment tively).3 neovascularization, particularly when Corticoste- the view of the fundus is not sufficient- roids. Cortico- ly clear to permit adequate PRP. steroids reduce Venous outflow.A number of alter- retinal capillary native therapies focused on improving permeability retinal blood flow have been described. 3C 3D and inhibit the These include the use of antiplatelet expression and agents (e.g., ticlopidine),4 hemodilu- metabolic path- tion,5 and thrombolytic agents de- way of VEGF. The livered systemically, intravitreally, or SCORE-CRVO directly into a retinal vein during pars trial demonstrat- plana vitrectomy. ed that intravitre- Techniques to alleviate a possible al triamcinolone compartment syndrome, with optic acetonide was nerve sheath decompression through FLUORESCEIN FINDINGS. FA at 4 time points shows (3A) superior to obser- an orbital approach or radial optic masking from intraretinal hemorrhages, (3B) delayed arte- vation for visual neurotomy via a pars plana approach, riovenous transit time, (3C) leakage at the swollen optic disc, loss associated have been tried. However, these are no and (3D) late staining of the vessel walls. with CRVO-relat- longer used because of their limited ed macular ede- benefit and significant risks. with CRVO. There is increasing evi- ma. The GENEVA trial evaluated the Creation of a laser chorioretinal dence that anti-VEGF therapy results use of a sustained-release intravitreal venous anastomosis (L-CRA) to by- in lower risk of visual loss, higher rates dexamethasone implant (Ozurdex) and pass the occluded central retinal vein of visual gains, greater reduction in demonstrated improvements in visual has been reported to be beneficial in central retinal thickness, and reduced acuity and macular thickness compared nonischemic CRVO, with improvement risk of progression to iris neovascular- with both sham and laser-treated groups. in visual acuity and reduced rates of ization. More recently, the Clinical Efficacy ischemic progression,6 but less so in For example, the CRUISE study and Safety of Ranibizumab Versus eyes with the ischemic type of disease. reported that intravitreal ranibizumab Dexamethasone for Central Retinal The failure of anastomosis was most significantly improved best-corrected Vein Occlusion (COMRADE C) trial likely due to endothelial cell damage visual acuity (BCVA) at 6 and 12 compared intravitreal ranibizumab secondary to ischemia.7 months compared with sham injec- 0.5 mg (monthly for at least 3 months, tions. In the open-label extension followed by as-needed dosing) to 1 Klein R et al. Arch Ophthalmol. 2008;126(4): HORIZON trial, the eyes initially a single injection of Ozurdex. This 513-518. treated with sham and subsequently trial reported similar efficacy between 2 Central Vein Occlusion Study Group. Arch Oph- treated with ranibizumab showed im- ranibizumab and Ozurdex but found thalmol. 1997;115(4):486-491. [Erratum in Arch provement in BCVA but did not catch a higher incidence of adverse effects in Ophthalmol. 1997;115(10):1275.] up to the visual outcomes attained by the group receiving Ozurdex. 3 Scott IU et al. JAMA. 2017;317(20):2072-2087. the group that received ranibizumab at Retinal ischemia. Current evidence 4 Yamamoto T et al. Am J Ophthalmol. 2004;138(5): enrollment. This finding suggests that recommends regular monitoring of 809-817. delaying treatment for macular edema patients with ischemic CRVO for 5 Wolf S et al. Graefes Arch Clin Exp Ophthalmol. has adverse effects on visual outcomes. development of iris or angle neovas- 1994;232(1):33-39. Aflibercept, a VEGF-trap mole- cularization, for which panretinal laser 6 McAllister IL et al. Ophthalmology. 2010;117(5): cule, has also been shown to improve photocoagulation (PRP) remains the 954-965. BCVA compared with sham and laser mainstay of treatment. 7 Kwok AK et al. Br J Ophthalmol. 2003;87(8): treatment in the COPERNICUS and There is currently no evidence to 1043-1044. GALILEO trials. recommend prophylactic treatment More recently, SCORE2, a random- prior to the development of new ves- Dr. Kiew is an ophthalmology resident at the ized noninferiority trial including eyes sels. However, in circumstances where Singapore National Eye Centre. Dr. Ting is an with CRVO or HRVO, demonstrated regular follow-up is impractical and the associate consultant at the Singapore National that bevacizumab was noninferior to degree of ischemia is severe (high risk Eye Centre and assistant professor at Duke-Na- aflibercept in terms of visual acuity of progression to neovascularization), tional University Singapore. Relevant financial

Kasi Sandhanam and Joseph Ho, Singapore National Eye Centre Eye National Singapore Sandhanam and Joseph Ho, Kasi gain at month 6 compared to baseline prophylactic PRP may be appropriate. disclosures: None.

EYENET MAGAZINE • 35 Enhance your clinical knowledge and connect with leading experts in refractive and anterior segment surgery with your ISRS membership.

Join now or learn more at www.isrs.org.

EyeNet and JRS ad: 8.125x10.875” WHAT’S YOUR DIAGNOSIS? MORNING ROUNDS

The Case of Aches and Pains and Blurry Vision

ecky Brown*, a 28-year-old 1A 1B Caucasian woman, was doing Bwell until about 2 weeks prior to presentation, when she felt as if she had the flu, complete with headaches and joint pain. A few days later, she noted that her eyes were red, painful, and highly sensitive to light. Her vision was also becoming blurred. Very wor- ried about her symptoms, Ms. Brown sought medical help. 2A We Get a Look Prior to evaluation by our vitreoretinal service, Ms. Brown had been treated by a primary care provider with oral methylprednisolone. By the time she came to our clinic, her arthralgia had resolved with steroid treatment, but her headaches and blurred vision persisted. 2B She did not have any other significant ocular or medical history. Exam findings.On presentation, Ms. Brown’s visual acuity was 20/40 in the right eye and 20/80 in the left eye. Intraocular pressure was 13 mm Hg in each eye. Her pupils were equal, round, and reactive, with no afferent pupillary defect. She had full ocular motility AT PRESENTATION. Fundus photos of the patient’s right (1A) and left (1B) eyes. bilaterally. OCT images of central macula in the right (2A) and left (2B) eyes. We observed conjunctival injection in both eyes. Slit-lamp exam showed exam revealed optic disc hyperemia macula. The lesions appeared to be at fine, diffuse keratic precipitates, as well with obscured borders. Multiple the level of deep retina and the retinal as 2+ cells and fibrin in the anterior creamy, yellow-white placoid lesions pigment epithelium (Fig. 1). The chamber. Trace anterior vitreous cells were visible in the posterior pole peripheral retina appeared normal. were also noted. adjacent to the superior and inferior Imaging. To augment the exam Fundus lesions. Dilated fundus arcades, with extension into the central findings, we obtained the following imaging studies. Optical coherence tomography. BY ALEC CHALEFF, MD, MBA, HERSHEL PATEL, MD, MS, AND SWETANGI OCT demonstrated multiple hyper

Swetangi Bhaleeya, MD Bhaleeya, Swetangi BHALEEYA, MD. EDITED BY STEVEN J. GEDDE, MD. reflective discrete areas at the level of

EYENET MAGAZINE • 37 the outer nuclear layer and ellipsoid 3A 3B band, with attenuation of the normal retinal architecture (Fig. 2; see also online Figs. 2A-2D). Fundus autofluorescence.FAF showed diffuse areas of hyperfluores- cence corresponding to the lesions in the posterior pole and some mottled areas of hypofluorescence (see online Fig. 3). Fluorescein angiography. FA revealed hypofluorescence or blockage corresponding to areas of the lesions in the early phase, followed by hyper- fluorescence in the late phase consistent FA VS. ICGA. Left eye at presentation as seen on early-phase FA (3A) and ICGA (3B). with staining (Fig. 3A; see also online Fig. 4). considered to be rare, and the true inci- ed urgent neurology consultation. Indocyanine green angiography. dence and prevalence are unknown.1 She underwent extensive testing with ICGA disclosed confluent areas of Pathogenesis. Although the etiology neuroimaging, including conventional hypofluorescence in the posterior pole of APMPPE is unclear, up to one-third and computed tomography angiogra- and midperiphery in both the early and of patients experience a viral prodrome phy, which did not demonstrate any late stages. On ICGA, the lesions were before the onset of ocular symptoms. evidence of cerebral vasculitis. found to be more numerous than what The pathogenesis is thought to be Further studies. Examination of was apparent on examination or FA, obstruction of choriocapillary lobules, her cerebrospinal fluid (CSF) showed especially in the midperiphery (Fig. 3B; possibly as an inflammatory reaction to nonspecific lymphocytic pleocytosis see also online Fig. 4). a viral infection. Alternatively, APMPPE with normal protein and glucose levels. may be a primary disease of the retinal Polymerase chain reaction studies of Making the Diagnosis pigment epithelium itself.2 the CSF found no evidence of herpes Based on the history, exam, and im- Systemic symptoms and complica- simplex virus, varicella-zoster virus, or aging findings, our working diagnosis tions. APMPPE is a vasculitis that is cytomegalovirus infection. was acute posterior multifocal placoid often accompanied by a viral pro- Direct antigen testing of the CSF pigment epitheliopathy (APMPPE). drome, and systemic manifestations was also performed, and the results The creamy, yellow-white placoid reti- may include headaches, flulike symp- were negative for Haemophilus influ- nal lesions we noted in Ms. Brown are toms, erythema nodosum, arthralgias, enzae, Streptococcus pneumoniae, and characteristic funduscopic findings1; and myalgias.1 Neisseria meningitidis. similarly, the early-phase blockage or Neurologic symptoms such as head In addition, the following laboratory hypofluorescence followed by diffuse aches, transient aphasia, paresthesias, studies were ordered as part of her late staining in the same areas are typi- and muscular weakness may be associ- neurology evaluation: rapid plasma cal of APMPPE.2,3 ated with cerebral vasculitis and require reagin (RPR) and fluorescent trepone- However, her fundus appearance further evaluation.1 Thomas et al. mal antibody absorption (FTA-ABS) also raised the possibility of serpiginous reviewed 18 patients diagnosed with tests for syphilis, Quantiferon-TB Gold, choroiditis or serpiginous-like choroi- APMPPE; of these, 11 patients (61%) and Lyme disease antibody testing. All dopathy associated with tuberculosis. had neurologic symptoms, with the were negative. Thus, we ordered a Quantiferon-TB most common being headache (9 pa- Gold test, which was negative, ruling tients).5 Stroke due to cerebral vasculi- Treatment out the alternative diagnosis. tis was the most severe complication.5 APMPPE is typically a self-limited Although there is no sexual predilec- condition. No particular therapy has Discussion tion for APMPPE per se, the majority proved to be beneficial, although some APMPPE, one of the white dot syn- of cerebral vasculitis cases occur in patients with severe ocular inflamma- dromes, was first described by Gass men.6 tion or signs and symptoms of cerebral in 1968.4 It is an acute-onset bilateral vasculitis are treated with systemic disease with characteristic findings of What About Our Patient’s corticosteroids. multiple yellow-white patches of cho- Headaches? The chorioretinal lesions may begin rioretinal inflammation in the posterior Ms. Brown’s symptoms of headaches to resolve in 1 to 2 weeks even without pole. The mean age of onset is 27 years, along with ocular findings consistent treatment.4 Visual prognosis is usually with 85% of cases occurring in patients with APMPPE were concerning for good, and patients can expect improve 1 16 to 40 years of age. APMPPE is cerebral vasculitis, and we recommend- ment in visual acuity in the long term; MD Bhaleeya, Swetangi

38 • JANUARY 2018 however, visual recovery is often incomplete.3 Our patient’s course. Ms. Brown was started on topical prednisolone acetate 6 times per day and atropine twice a day in both eyes for the anterior chamber inflammation. Treatment with systemic corticosteroids was deferred until she completed evaluation for cerebral vasculitis, which was negative. We decided to initiate treatment with systemic steroids because of Ms. Brown’s persistent ocular inflammation and lack of visual improvement. She was treated with a course of 60 mg of oral prednisone daily for 10 High-quality days, which was then tapered weekly over 4 weeks. research from the world’s leading Follow-up After 1 month of treatment, Ms. Brown’s ophthalmic journal visual acuity had improved to 20/20 in the right eye and 20/40 in the left eye. Fundus exam showed pigmentary changes in area of the yellow-white placoid lesions (see online Fig. 5), which were better seen by FAF. The lesions, as seen on OCT, improved with restoration of near-normal retinal architecture (see online Fig. 6).

*Patient name is fictitious.

1 Kooragayala LM. http://emedicine.medscape. com/article/1225531-overview. Updated May 3, The Academy’s newest scientific 2017. Accessed November 21, 2017. 2 American Academy of Ophthalmology. Basic publication, Ophthalmology® and Clinical Science Course: Section 12, Retina and Retina, focuses on advances in Vitreous. 2013-2014: pp 185-187. 3 Fiore T et al. Retina. 2009;29(7):994-1001. medical drug treatment, surgery 4 Gass JD. Arch Ophthalmol. 1968;80(2):177-185. and technology for retina-related 5 Thomas B et al. J Ophthalmic Inflamm Infect. disesases and conditions. 2012;2(3):125-131. 6 Case D et al. J Stroke Cerebrovasc Dis. 2012;2(3): 125-131. Subscribe at aao.org/store.

Dr. Chaleff is a first-year transitional resident,Dr. Patel is a second-year ophthalmology resident, and Dr. Bhaleeya is a professor of ophthalmology; all are at the University of South Florida Eye Institute, Morsani College of Medicine, in Tampa. Relevant financial disclosures: None.

MORE ONLINE. See this article at aao.org/eyenet for additional OCT, FAF, FA, and ICGA images before and after treatment.

EYENET MAGAZINE • 39 40 • JANUARY 2018 Global Ophthalmology

Volunteer ophthalmologists are ramping up the fight against eye disease by building capacity in communities around the world. Here’s how you can help.

By Mike Mott, Contributing Writer

OLUNTEERING ABROAD IS UNDERGOING A SEA CHANGE. GONE are the days of simply flying overseas to an under-resourced community, Vperforming hundreds of cataract surgeries, and returning home to your practice. Most communities now have their own health systems in place with local physicians who can perform procedures at a lower cost than in the past.

Rethinking the Rationale Instead of “delivering care,” the buzzword in medical volunteerism is now “building capacity.” Magnify your impact. “Given the cataract backlog in the world today, we are more than 100 years from eradicating this cause of blindness if we simply rely on delivery of care,” said Jeff H. Pettey, MD, at the University of Utah in Salt Lake City. “Yes, performing cataract surgeries will impact individuals, but it pales in comparison to the overall impact you’ll have if you build capacity in an individual, a practice, and a country.” Build local partnerships. How is this done? By partnering with individuals and groups to improve education and training. By procuring equipment and connect- ing communities to local resources. By bringing local physicians to international meetings and uniting them with their ophthalmic societies. “It’s about substitut- ing single-episode surgical care with impact that functions 365 days a year,” said Dr. Pettey. “We as volunteers transfer our skills to a community and empower a population because it’s the members of that community who are best able to care for one another.” And the more boots on the ground the better. Here’s how you can play a role in the leading edge of global ophthalmology.

Why They Do It Volunteering is a uniquely individual experience, as each community has distinct needs with its own rewards and challenges. At the same time, each volunteer brings his or her own motivations.

STRABISMUS. Dr. Safran, shown with a young boy who had strabismus surgery that was provided via Healing the Children in Guayaquil, Ecuador. Courtesy of Marc Safran, MD Safran, of Marc Courtesy

EYENET MAGAZINE • 41 Marc Safran, MD, who practices in Liverpool, N.Y., easily corrected if eyeglasses were available. “Seeing the has volunteered in Bolivia, Ecuador, India, and Viet- natural path of uncorrected disease gives you a genuine nam. Doing work overseas allows him to reconnect appreciation of its true nature and severity,” he said. with the core of why he originally went into medicine. “Whether it’s amblyopia, congenital cataract, or ptosis, “It’s a throwback to providing medical care to needy I’ve gained a better appreciation for biology in a way people in a free and unencumbered way,” said Dr. that’s not possible in the normal U.S. clinic, where we Safran, “without elec- have more early interventions [available].” tronic health records, Deepen connections with patients. Not only can MIPS, MACRA, and volunteering abroad make you a better surgeon, but it all of the bureaucratic also will teach you how to build better physician-pa- hassles we now face at tient relationships. “By having the opportunity to work home.” with people from different cultures and backgrounds, For Mitchell V. I’m building a skill set that translates to a lot of differ- Brinks, MD, MPH, ent scenarios domestically,” said resident Travis Redd, the motivation to MD, MPH, at the Casey Eye Institute. volunteer overseas Andreas K. Lauer, MD, also at the Casey Eye Insti- in areas like Cambo- tute, agreed. “In my experience, it’s been really helpful dia, Guatemala, and to learn more about other cultures firsthand so that Myanmar stems from when I return home, I can interact more meaningfully the power of human with patients from diverse backgrounds. If I can tell connection. “It’s a a patient, ‘Hey, I recently visited your country,’ there’s BUILDING CAPACITY. Today’s pretty special feeling to automatically a better connection.” No. 1 goal is to help build know you have friends Gain greater perspective. In addition to giving you programs that will continue and a sense of home a broader and deeper perspective on another culture, long after the volunteer in another part of the working abroad can also give you a new perspective on returns home. Friendships— world,” said Dr. Brinks, your own practice. “Volunteering gives you a window as the one between Dr. at Oregon Health & like no other into how commercialized and money Brinks (left) and Benjamin Science University’s -oriented medicine has become here in the United D. Siatu’u, MD, who practices Casey Eye Institute in States,” said Dr. Brinks. “Many times, we as physicians in Pago Pago, American Portland. “Cataract buy into the earnings and the patient volume as our Samoa—are a bonus. surgery, for example, metrics of success. We can take it too seriously. Getting can open the door to out of the clinic and setting foot in another world can do so much good in so little time. And to have that help you build another model of professional satis- access to the inside of a community? That’s pretty rare. faction. It can make ophthalmology a truly enjoyable, But we as ophthalmologists have the key—it’s sitting long-term endeavor.” there right in our hands.” For Dr. Redd, his mission work as a resident has made him rethink the role of public health in the prac- Become a Better Clinician tice of ophthalmology. “Going overseas to places like Volunteering might mean different things to different Uganda and Ethiopia reminds me to think about med- ophthalmologists, but all agree on one thing: Whether icine in a different way when I return home. It’s more you are a resident, a young ophthalmologist new to than just, how am I going to treat someone? It’s, how practice, or a seasoned vet, the skills you learn doing are my patients getting to the exam room? What hoops mission work will have a significant impact on your do they have to jump through? How can I better recruit practice at home. my patients and better serve my local community?” Sharpen your skills. “There might not be a better way to hone your skills as an ophthalmologist,” said Dr. Getting Started Pettey. “You’ll be faced with the most complicated cases There are several ways to approach volunteering and forced to make important decisions in incredibly abroad, depending on your career stage. difficult environments. Afterwards, little will faze you. Residents. For ophthalmologists still in training, You return more focused and more capable of making many U.S. residency programs have integrated overseas difficult decisions on the fly. When done right, you experiences into their educational program. And some return a better surgeon.” of them will help subsidize a resident’s travel expenses You’ll also see the natural progression of diseases and other costs. For example, the International Oph- in a way that’s just not part of most ophthalmologists’ thalmology Program at the Casey Eye Institute allows day-to-day experience in the United States. During ophthalmology residents to travel internationally to his travels, Dr. Safran has witnessed child after child areas like Fiji to learn low-cost alternative surgical skills,

with advanced strabismus, which could have been such as manual small-incision cataract surgery, for MPH MD, Brinks, V. Mitchell

42 • JANUARY 2018 treating patients in underserved communities. Fellows. A small but growing number of institutions around the United States have also created global ophthalmology fellowships to help young ophthalmologists put their training at home into practice abroad. These include the following: • Dean McGee Eye Institute’s Global Eye Care Fellow- ship (University of Oklahoma) • Emory Eye Center’s Global Ophthalmology Fellow- ship (Emory University) • Moran Eye Center’s Moran International Ophthal- mology Fellowship (University of Utah) • Truhlsen Eye Institute’s Prevention of Global Blind- ness Fellowship (University of Nebraska) • Wills Eye Center for Academic Global Ophthalmolo- TEAM EFFORT. Patients, their family members, and gy Fellowship (Wills Eye Hospital) members of the team from Healing the Children. The Midcareer and older physicians. More established group of 5 ophthalmologists and 20 staff performed 125 ophthalmologists may want to consider volunteer- general strabismus cases during a week-long mission in ing through a charitable or nonprofit organization. Guayaquil, Ecuador. Groups like Orbis International (www.orbis.org), the Seva Foundation (www.seva.org), and the Himalayan Start at home. After a decade of local volunteering, Cataract Project (www.cureblindness.org), for exam- Linda M. Lawrence, MD, who practices in Salina, Kan- ple, serve close to 100 countries and train thousands of sas, began collaborating with more than 30 nonprofit medical professionals a year in how to build self-sus- organizations everywhere from Nigeria to Vietnam. Her taining programs for preserving and restoring vision. advice for prospective global ophthalmologists? Don’t For such a trip, most ophthalmologists can expect to just jump on a plane. Start by doing work around your take a hit on the income they’d normally bring in from local community. their own practices, but some of these organizations She said, “When a new volunteer asks me how they might be able to offset a portion of the costs, including can get involved in international work, I ask them, travel and lodging. ‘What are you doing at home?’ Home is your training ground. Home is where you learn about people and Developing a Plan different health care systems. It’s where you learn how Regardless of the route you take to get involved, to network and really how to volunteer.” prospective volunteers will want to heed the following EyeCare America. You can do mission work with- expert advice when exploring their opportunities. out ever leaving your office, thanks to the Academy’s

Before You Go

Once the path is clear and you’ve decided on your become acutely ill and stranded in a foreign country journey, you’ll want to make sure you follow a stan- that lacks proper resources. In addition to purchas- dard to-do list: ing health insurance when traveling abroad, you • Get your passport ready. The minute you decide should obtain evacuation insurance. This service will you are going somewhere, check the official country provide a jet or helicopter to extricate you from the website and figure out what you need (e.g., passport direst of circumstances. and visa) to enter the country. Plan ahead; the mate- • Register with the appropriate U.S. consulate. You rials can take months to acquire. shouldn’t expect any danger when you are working • Make sure you’re licensed. You’ll head out over- overseas, but you’ll want to make sure the U.S. State seas with the best of intentions. But if you aren’t Department knows where you are in case of ca- legally approved by the host country’s government tastrophe, natural disaster, or political unrest. to perform surgery in your host country, you’ll be • Learn the language. Doing your homework about heading back home sooner than expected. the local language and cultural makeup will be tre- • Get your vaccines. This is essential. Some coun- mendously helpful down the road. You don’t need to tries may even require proof of immunization prior be fluent, but learning simple terms like “thank you” to entry. and “good evening” will ingratiate you with hosts

Mitchell V. Brinks, MD, MPH MD, Brinks, V. Mitchell MD Safran, of Marc Courtesy • Purchase evacuation insurance. You don’t want to and patients.

EYENET MAGAZINE • 43 EyeCare America program (aao. said. “Unless you have someone org/eyecare-america/volunteer- alongside you who’s gone through ophthalmologists). The program it before, you’ll have to relearn helps medically underserved their same mistakes on patients seniors and those who are at who are in dire need. So even for increased risk for glaucoma the smartest ophthalmologist out receive eye care through dedicat- there who has the best of inten- ed volunteer ophthalmologists. tions, there’s just too much to Once an ophthalmologist enrolls learn on the ground to think you as a volunteer, eligible patients can do it by yourself the first try.” are matched online to the nearest ZIKA OUTREACH. Dr. Lawrence with Go with a group that has ex- volunteer by zip code. a mother and infant in Brazil, both of perience. Your first impressions of Find a mentor. Dr. Pettey’s whom were affected by the Zika virus. your mission site will be vital, so experience echoes that of Dr. find an experienced organization Lawrence. Before taking his experience overseas, he to join. “Inspiration is your fuel when you’re volunteer- started volunteering locally in a homeless clinic in Salt ing abroad,” said Dr. Brinks. “And it’s delicate. You don’t Lake City. And he is adamant about the importance of want a traumatic experience to destroy it. So, research mentors. Under the guidance of Drs. Randy Olson, Alan the location and go with a group that reflects your own Crandall, and Geoff Tabin at the Moran Eye Center, he values, because once you go overseas, the regulations learned how to translate the skills he was developing and standards of care that you are accustomed to are at home into the ability to provide high-quality care all gone. The only things you have to guide you are abroad. the values and principles of the people you surround “Good mentors really are the doorway to involve- yourself with.” ment,” Dr. Pettey said. “As a young ophthalmologist, Consider long-term impact. Finally, be sure the you don’t have a clinical skill set that translates to the organization has a plan for long-term follow-up care, developing world. The cataracts you’ll encounter, for Dr. Redd added. “Many new volunteers think they’ll example, are the most difficult cases you’ve seen. It just pop into an outreach camp, work for a few days, takes mentors who can build that clinical capacity in and then return home. That might sound appealing, you before you can really get to work in a different but you can do more harm than good in the long run if country.” the organization has no plan for follow-up care and has Even for the most seasoned physician, a good no foundation built up for referral networks to help pa- mentor can prevent you from becoming a burden, tients after you leave.” You have a duty to these patients

added Dr. Brinks. “You’re not sleeping well, you have to volunteer with a responsible organization, he said. MD Linda M. Lawrence, jet lag, you might have a bug, everything is difficult,” he

The Academy’s GO Guide

“Familiarizing yourself with global ophthalmology is one of the best ways to get started,” said Dr. Pettey. “And to really prep my residents, I send them to the Academy’s Global Ophthalmology (GO) Guide.” The guide provides members-in-training with a listing of fellowships and observerships available Prospective volunteers will also want to check as well as online CME courses for all physicians who out the Academy’s “Advisory Opinion on Ethical want to work overseas. Topics include the following: Issues in Global Ophthalmology.” It covers the • “Starting in Global Ophthalmology: Mentorship, challenges involved in international ophthalmic Funding, and the Work-Home Balance” care, including how ophthalmologists can maintain • “Assessing Outcomes in Global Health Programs” professionalism and high clinical standards while • “So You Want to Work Overseas?” practicing abroad. You can use the GO Guide to find region-based For more information about the GO Guide, visit treatment and management information on a variety aao.org/global-ophthalmology-guide. To read the of disease topics; multimedia clips pertaining to Academy’s Advisory Opinion as well as other ethics- global ophthalmology; and an Academy pamphlet, related material, visit aao.org/clinical-education/ “Before You Go,” in which veteran physicians discuss redmond-ethics-center and click on “Global Oph- how to make lasting changes around the world. thalmology.”

44 • JANUARY 2018 On the Ground overseas might be saving up the most difficult cases for No matter how long you prepare for your work overseas, someone like you. But if it involves something that you there are certain things that only experience can teach wouldn’t normally do or involves compromising on your when you touch down on the ground. own safety or the safety of your patients, you should Don’t be the hero. “As a resident or new volunteer know when to say “no” and defer to someone else. in a foreign country, keep in mind that you are first “Most of the patients you’ll see are going to be a guest,” said Dr. Lauer. “So be respectful of the host blind, and they will need a lot of care,” said Dr. Brinks. because the host has a lot of responsibility. There’s a Arriving at your destination “with an undefined desire cost to them to ensure that the visit achieves the aim. If to help isn’t a sophisticated strategy. People try to work you go over there thinking that you’re going to run the themselves to death. They’ll do things they’re not ready show, you won’t be welcomed back.” to do, and then there’s nobody to help fix the problem It’s also important to remember that your surgical afterwards. So be safe, be calm, and be humble.” skills or station in life should never dictate how you interact with the people you meet on the ground. An Unmet Need “Fifteen years ago, physicians in the developing world According to the World Health Organization, almost didn’t have great access to the internet,” Dr. Safran said. 90% of the world’s visually impaired live in low-income “Times have changed, and now an ophthalmologist countries. And in these areas, treatable cataracts are the from the furthest reaches of the globe might very likely leading cause of blindness.1 It’s therefore no surprise be a better surgeon than you. So, treat every person you that mission work to provide cataract surgery is the meet—physicians, nurses, patients, community mem- leading intervention for ophthalmologists. But there are bers—as a fellow human citizen.” also millions of others suffering from other diseases, Don’t undercut the local economy. “This is some- such as glaucoma, who require ophthalmology’s atten- thing very important that I’ve learned from decades of tion. And this is where new recruits play a vital role. volunteering abroad,” said Dr. Lawrence. “Where I work “Manual small-incision cataract surgery is definitely in Peru, for example, I used to bring donated [glasses] an amazing type of intervention to prevent blindness,” frames to a local school. But a mother of one of the said Dr. Lauer. “It has the ‘wow’ factor. But as we get students is an optician in the community. Why would I more sophisticated about doing international missions, want to compete with her and take away her livelihood? building capacity, and investing in public health, we In the end, you want to transfer your skills and promote need to expand our focus and find new volunteers to the local economy and infrastructure.” tackle these other conditions. It’s going to be a chal- Understand your limits. Perhaps the most important lenge, but if we can help these patients collectively, we caveat is to set realistic expectations of yourself, the really will be making the world a better place.”

Linda M. Lawrence, MD Linda M. Lawrence, experts said. For a resident, this might mean that you simply go as a student rather than a practitioner. But 1 World Health Organization. Global Data on Visual Impairments even the most experienced ophthalmologist will still 2010. www.who.int/blindness/GLOBALDATAFINALforweb.pdf. want to be cognizant of his or her comfort zone. Clinics Accessed Oct. 25, 2017.

Meet the Experts

Mitchell V. Brinks, MD, MPH Assistant Jeff H. Pettey, MD Associate professor of professor of ophthalmology and codirec- ophthalmology and visual sciences, residen- tor of the International Ophthalmology cy program director, and medical director of Program at Oregon Health & Science Uni- global outreach at the University of Utah in versity’s Casey Eye Institute in Portland. Salt Lake City. Relevant financial disclosures: Relevant financial disclosures: None. None. Andreas K. Lauer, MD Professor of oph- Marc Safran, MD In practice at the Clay Eye thalmology, vice-chair for education, and Center in Liverpool, N.Y., and associate fac- chief of the Retina-Vitreous Division at ulty professor at Upstate Medical Center in Oregon Health & Science University’s Ca- Syracuse, N.Y. Relevant financial disclosures: sey Eye Institute. Relevant financial disclo- None. sures: None. Travis Redd, MD, MPH Second-year ophthal- Linda M. Lawrence, MD In private prac- mology resident at Oregon Health & Science tice in Salina, Kansas. Relevant financial University’s Casey Eye Institute. Relevant disclosures: None. financial disclosures: None.

For full disclosures, view this article at aao.org/eyenet.

EYENET MAGAZINE • 45 B:16.5” T:16.25” S:15.75”

NOW APPROVED FOR GIANT CELL ARTERITIS (GCA) IN ADULT PATIENTS1 PrimaryIn the Endpoint: ACTEMRA Sustained + Steroid* Remission Taper Arms, More Patients Experienced AchievedSustained in 4x MoreRemission Patients at 52 Weeks vs Placebo + Steroid Taper Arms2

Sustained Remission at 52 Weeks: ITT Population2

Primary Endpoint Key Secondary Endpoint 100 Most patients in the 90 p<0.0001 p<0.0001 ACTEMRA arms were 80 steroid free from Week 26 p<0.0001 p=0.0002 through Week 522 WHEN IS THE 70 60 56% 53.1% 56% 53.1% TIME TO START 50 The most commonly 40 ACTEMRA? reported adverse reactions 30 were nasopharyngitis, headache, and 20 17.6% 14% peripheral edema2 Sustained remission (% of patients) Sustained remission 10

0 ACTEMRA ACTEMRA placebo ACTEMRA ACTEMRA placebo QW + 26w Q2W + 26w + 26w QW + 26w Q2W + 26w + 52w steroid taper steroid taper steroid taper steroid taper steroid taper steroid taper n=100 n=49 n=50 n=100 n=49 n=51

GiACTA was a randomized, double-blind, multicenter study in patients with active GCA. Patients (N=251) were randomized to one of four treatment arms. 1 Two SC doses of ACTEMRA (162 mg QW and 162 mg Q2W) were compared to two different placebo control groups (pre-specified prednisone-taper regimen SUPERIOR EFFICACY AND STEROID-SPARING SUSTAINED REMISSION over 26 weeks and 52 weeks) randomized 2:1:1:1.

INDICATION neutrophils, platelets, lipids, and liver function tests. Dosage modi cations of ACTEMRA in patients with preexisting or recent-onset The most common types of infections across all treatment groups were B:11.125” T:10.875” ACTEMRA is indicated for the treatment of giant cell arteritis (GCA) in may be required. demyelinating disorders. nasopharyngitis, upper respiratory tract infection, bronchitis, and urinary S:10.375” adult patients. Neutropenia: Treatment with ACTEMRA was associated with a higher Active Hepatic Disease and Hepatic Impairment: Treatment with tract infection. IMPORTANT SAFETY INFORMATION incidence of neutropenia. It is not recommended to initiate ACTEMRA ACTEMRA is not recommended in patients with active hepatic disease or Injection-Site Reactions: The frequency of injection-site reactions was treatment in patients with a low neutrophil count i.e., absolute neutrophil hepatic impairment. 6% (6/100) in the ACTEMRA SC weekly group, and 14% (7/49) in the BOXED WARNING: RISK OF SERIOUS INFECTIONS 3 count (ANC) less than 2000 per mm . In patients who develop an ANC less Avoid use of live vaccines concurrently with ACTEMRA. ACTEMRA SC every other week group, as compared to 10% (5/50) in the Patients treated with ACTEMRA are at increased risk for developing 3 Vaccinations: than 500 per mm treatment is not recommended. No data are available on the secondary transmission of infection from placebo + 26 week prednisone taper and 2% (1/51) in the placebo + 52 serious infections that may lead to hospitalization or death, Thrombocytopenia: Treatment with ACTEMRA was associated with a week taper groups. No injection site reaction was reported as a serious including tuberculosis (TB), bacterial, invasive fungal, viral, or other persons receiving live vaccines to patients receiving ACTEMRA or on the reduction in platelet counts. It is not recommended to initiate ACTEMRA effectiveness of vaccination in patients receiving ACTEMRA. Patients adverse event or required treatment discontinuation. opportunistic infections. If a serious infection develops, interrupt 3 in patients with a platelet count below 100,000 per mm . In patients should be brought up to date on all recommended vaccinations prior to DRUG INTERACTIONS ACTEMRA until the infection is controlled. 3 who develop a platelet count less than 50,000 per mm , treatment is initiation of ACTEMRA therapy. Reported infections include: In GCA patients, no effect of concomitant corticosteroid on ACTEMRA not recommended. ADVERSE REACTIONS exposure was observed. • Active tuberculosis, which may present with pulmonary or Elevated Liver Enzymes: Treatment with ACTEMRA was associated extrapulmonary disease. Patients should be tested for latent GIANT CELL ARTERITIS (GCA) Cytochrome P450s in the liver are down-regulated by infection and with a higher incidence of transaminase elevations. These elevations did in ammation stimuli including cytokines such as IL-6. Exercise caution tuberculosis before ACTEMRA use and during therapy. Treatment not result in apparent permanent or clinically evident hepatic injury in In the Phase III clinical trial, the most common adverse events (>20% of for latent infection should be initiated prior to ACTEMRA use. patients treated with ACTEMRA-SC) during the 52-week study were: when coadministering ACTEMRA with CYP3A4 substrate drugs where clinical trials. Increased frequency and magnitude of these elevations was decrease in effectiveness is undesirable, e.g., oral contraceptives, observed when potentially hepatotoxic drugs (e.g., methotrexate) were • Invasive fungal infections, including candidiasis, aspergillosis, PBO + 26 weeks PBO + 52 weeks TCZ 162mg SC QW TCZ 162 mg SC Q2W lovastatin, atorvastatin, etc. and pneumocystis. Patients with invasive fungal infections may used in combination with ACTEMRA. prednisone taper prednisone taper + 26 weeks + 26 weeks USE IN PREGNANCY present with disseminated, rather than localized, disease. – It is not recommended to initiate ACTEMRA treatment in patients with prednisone taper prednisone taper (%) (%) (%) (%) • Bacterial, viral and other infections due to elevated transaminases ALT or AST >1.5x ULN. In patients who develop There is a pregnancy exposure registry that monitors pregnancy opportunistic pathogens. elevated ALT or AST >5x ULN, treatment is not recommended. Headache 32.0 23.5 27.0 20.4 outcomes in women exposed to ACTEMRA during pregnancy. Physicians are encouraged to register patients and pregnant women are encouraged Lipid Abnormalities: Treatment with ACTEMRA was associated with Nasopharyngitis 18.0 25.5 29.0 24.5 The risks and bene ts of treatment with ACTEMRA should be Peripheral Edema 16.0 11.8 16.0 24.5 to register themselves by calling 1-877-311-8972. carefully considered prior to initiating therapy in patients with increases in lipid parameters such as total cholesterol, triglycerides, LDL chronic or recurrent infection. cholesterols, and/or HDL cholesterol. Dizziness 12.0 15.7 6.0 20.4 The limited available data with ACTEMRA in pregnant women are not The overall safety pro le observed in the ACTEMRA treatment groups was suf cient to determine whether there is a drug-associated risk for major Patients should be closely monitored for the development of Immunosuppression: The impact of treatment with ACTEMRA on birth defects and miscarriage. signs and symptoms of infection during and after treatment with the development of malignancies is not known, but malignancies generally consistent with the known safety pro le of ACTEMRA. There ACTEMRA, including the possible development of tuberculosis in were observed in clinical studies with ACTEMRA. ACTEMRA is an was an overall higher incidence of infections in GCA patients relative to You may report side effects to the FDA at (800) FDA- 1088 or patients who tested negative for latent tuberculosis infection prior to immunosuppressant, and treatment with immunosuppressants may result RA patients. www.fda.gov/medwatch. You may also report side effects to initiating therapy. in an increased risk of malignancies. Infections: The rate of infections was 200.2 per 100 patient-years in Genentech at (888) 835- 2555. CONTRAINDICATION Hypersensitivity Reactions: Hypersensitivity reactions, including the ACTEMRA SC weekly group and 160.2 per 100 patient-years in the Please see following brief summary of Prescribing Information, including anaphylaxis, have been reported in association with ACTEMRA. For ACTEMRA SC every other week group, as compared to 156.0 per 100 Boxed WARNING, for additional important safety information. ACTEMRA is contraindicated in patients with known hypersensitivity patient-years in the placebo + 26 week prednisone taper and 210.2 per to ACTEMRA. ACTEMRA subcutaneous injection, advise patients to seek immediate medical attention if they experience any symptoms of a hypersensitivity 100 patient-years in the placebo + 52 week taper groups. References: 1. ACTEMRA [package insert]. South San Francisco, CA: WARNINGS AND PRECAUTIONS reaction. If anaphylaxis or other hypersensitivity reaction occurs, stop The rate of serious infections was 9.7 per 100 patient-years in the Genentech, Inc. 2. Data on le, GiACTA CSR, Genentech, Inc. South Gastrointestinal Perforations: Events of gastrointestinal (GI) perforation administration of ACTEMRA immediately and discontinue ACTEMRA ACTEMRA SC weekly group and 4.4 per 100 patient-years in the San Francisco, CA. have been reported in clinical trials, primarily as complications of permanently. Do not administer ACTEMRA to patients with known ACTEMRA SC every other week group, as compared to 4.2 per 100 Q2W=every-other-week dose; QW=every-week dose. diverticulitis in RA patients. Use ACTEMRA with caution in patients who hypersensitivity to ACTEMRA. patient-years in the placebo + 26 week prednisone taper and 12.5 per *Prednisone. may be at increased risk for GI perforation. Promptly evaluate patients Demyelinating Disorders: The impact of treatment with ACTEMRA on 100 patient-years in the placebo + 52 week prednisone taper groups. presenting with new-onset abdominal symptoms for early identi cation demyelinating disorders is not known, but multiple sclerosis and chronic of GI perforation. in ammatory demyelinating polyneuropathy were reported rarely in Laboratory Parameters: Laboratory monitoring is recommended due to clinical studies. Monitor patients for signs and symptoms of demyelinating potential consequences of treatment-related laboratory abnormalities in disorders. Prescribers should exercise caution in considering the use © 2017 Genentech USA, Inc. All rights reserved. ACT/071217/0075 08/17

FS:7.375” FS:7.375” F:8.125” F:8.125” 10751079_GCA_NOW_JA_EYE_M1.indd 1 8/14/17 5:19 PM

PREPARED BY FCB Releasing as: PDFx1A Production: Maria Abreu x3124 Job #: 10751079 Colors: 4/1 (4C Process/Black) AD: Trent Orvis x2492 Client: Genentech Flat Size: 16.25”w X 10.875”h AE: Katie Majewski x7927 Product: Actemra Bleed: 16.5”w X 11.125”h Producer: Karisa Williams x3721 Client Code: ACT/071217/0075 Trim: 16.25”w X 10.875”h QC: L.Powell Date: August 14, 2017 5:19 PM Safety: 15.75”w X 10.375”h Digital Artist: VA, Add’l Size Info: PI Page Dimensions - Trim 8.125”w X 10.875”h; Live 7.875”w Proof: M1 X 10.625”h; Bleed 8.375”w X 11.125”h Fonts: Helvetica Neue LT Std, Avenir M1 Spellcheck: Jacob Albrecht FR Spellcheck: Path: PrePress:Genentech:10751079:10751079_GCA_NOW_JA_EYE_M1 4C GCA 2017 Journal Ad: Eyenet B:16.5” T:16.25” S:15.75”

Sustained Remission at 52 Weeks: ITT Population2

INDICATION neutrophils, platelets, lipids, and liver function tests. Dosage modi cations of ACTEMRA in patients with preexisting or recent-onset The most common types of infections across all treatment groups were B:11.125” T:10.875” ACTEMRA is indicated for the treatment of giant cell arteritis (GCA) in may be required. demyelinating disorders. nasopharyngitis, upper respiratory tract infection, bronchitis, and urinary S:10.375” adult patients. Neutropenia: Treatment with ACTEMRA was associated with a higher Active Hepatic Disease and Hepatic Impairment: Treatment with tract infection. IMPORTANT SAFETY INFORMATION incidence of neutropenia. It is not recommended to initiate ACTEMRA ACTEMRA is not recommended in patients with active hepatic disease or Injection-Site Reactions: The frequency of injection-site reactions was treatment in patients with a low neutrophil count i.e., absolute neutrophil hepatic impairment. 6% (6/100) in the ACTEMRA SC weekly group, and 14% (7/49) in the BOXED WARNING: RISK OF SERIOUS INFECTIONS 3 count (ANC) less than 2000 per mm . In patients who develop an ANC less Avoid use of live vaccines concurrently with ACTEMRA. ACTEMRA SC every other week group, as compared to 10% (5/50) in the Patients treated with ACTEMRA are at increased risk for developing 3 Vaccinations: than 500 per mm treatment is not recommended. No data are available on the secondary transmission of infection from placebo + 26 week prednisone taper and 2% (1/51) in the placebo + 52 serious infections that may lead to hospitalization or death, Thrombocytopenia: Treatment with ACTEMRA was associated with a week taper groups. No injection site reaction was reported as a serious including tuberculosis (TB), bacterial, invasive fungal, viral, or other persons receiving live vaccines to patients receiving ACTEMRA or on the reduction in platelet counts. It is not recommended to initiate ACTEMRA effectiveness of vaccination in patients receiving ACTEMRA. Patients adverse event or required treatment discontinuation. opportunistic infections. If a serious infection develops, interrupt 3 in patients with a platelet count below 100,000 per mm . In patients should be brought up to date on all recommended vaccinations prior to DRUG INTERACTIONS ACTEMRA until the infection is controlled. 3 who develop a platelet count less than 50,000 per mm , treatment is initiation of ACTEMRA therapy. Reported infections include: In GCA patients, no effect of concomitant corticosteroid on ACTEMRA not recommended. ADVERSE REACTIONS exposure was observed. • Active tuberculosis, which may present with pulmonary or Elevated Liver Enzymes: Treatment with ACTEMRA was associated extrapulmonary disease. Patients should be tested for latent GIANT CELL ARTERITIS (GCA) Cytochrome P450s in the liver are down-regulated by infection and with a higher incidence of transaminase elevations. These elevations did in ammation stimuli including cytokines such as IL-6. Exercise caution tuberculosis before ACTEMRA use and during therapy. Treatment not result in apparent permanent or clinically evident hepatic injury in In the Phase III clinical trial, the most common adverse events (>20% of for latent infection should be initiated prior to ACTEMRA use. patients treated with ACTEMRA-SC) during the 52-week study were: when coadministering ACTEMRA with CYP3A4 substrate drugs where clinical trials. Increased frequency and magnitude of these elevations was decrease in effectiveness is undesirable, e.g., oral contraceptives, observed when potentially hepatotoxic drugs (e.g., methotrexate) were • Invasive fungal infections, including candidiasis, aspergillosis, PBO + 26 weeks PBO + 52 weeks TCZ 162mg SC QW TCZ 162 mg SC Q2W lovastatin, atorvastatin, etc. and pneumocystis. Patients with invasive fungal infections may used in combination with ACTEMRA. prednisone taper prednisone taper + 26 weeks + 26 weeks USE IN PREGNANCY present with disseminated, rather than localized, disease. – It is not recommended to initiate ACTEMRA treatment in patients with prednisone taper prednisone taper (%) (%) (%) (%) • Bacterial, viral and other infections due to elevated transaminases ALT or AST >1.5x ULN. In patients who develop There is a pregnancy exposure registry that monitors pregnancy opportunistic pathogens. elevated ALT or AST >5x ULN, treatment is not recommended. Headache 32.0 23.5 27.0 20.4 outcomes in women exposed to ACTEMRA during pregnancy. Physicians are encouraged to register patients and pregnant women are encouraged Lipid Abnormalities: Treatment with ACTEMRA was associated with Nasopharyngitis 18.0 25.5 29.0 24.5 The risks and bene ts of treatment with ACTEMRA should be Peripheral Edema 16.0 11.8 16.0 24.5 to register themselves by calling 1-877-311-8972. carefully considered prior to initiating therapy in patients with increases in lipid parameters such as total cholesterol, triglycerides, LDL chronic or recurrent infection. cholesterols, and/or HDL cholesterol. Dizziness 12.0 15.7 6.0 20.4 The limited available data with ACTEMRA in pregnant women are not The overall safety pro le observed in the ACTEMRA treatment groups was suf cient to determine whether there is a drug-associated risk for major Patients should be closely monitored for the development of Immunosuppression: The impact of treatment with ACTEMRA on birth defects and miscarriage. signs and symptoms of infection during and after treatment with the development of malignancies is not known, but malignancies generally consistent with the known safety pro le of ACTEMRA. There ACTEMRA, including the possible development of tuberculosis in were observed in clinical studies with ACTEMRA. ACTEMRA is an was an overall higher incidence of infections in GCA patients relative to You may report side effects to the FDA at (800) FDA- 1088 or patients who tested negative for latent tuberculosis infection prior to immunosuppressant, and treatment with immunosuppressants may result RA patients. www.fda.gov/medwatch. You may also report side effects to initiating therapy. in an increased risk of malignancies. Infections: The rate of infections was 200.2 per 100 patient-years in Genentech at (888) 835-2555. CONTRAINDICATION Hypersensitivity Reactions: Hypersensitivity reactions, including the ACTEMRA SC weekly group and 160.2 per 100 patient-years in the Please see following brief summary of Prescribing Information, including anaphylaxis, have been reported in association with ACTEMRA. For ACTEMRA SC every other week group, as compared to 156.0 per 100 Boxed WARNING, for additional important safety information. ACTEMRA is contraindicated in patients with known hypersensitivity patient-years in the placebo + 26 week prednisone taper and 210.2 per to ACTEMRA. ACTEMRA subcutaneous injection, advise patients to seek immediate medical attention if they experience any symptoms of a hypersensitivity 100 patient-years in the placebo + 52 week taper groups. References: 1. ACTEMRA [package insert]. South San Francisco, CA: WARNINGS AND PRECAUTIONS reaction. If anaphylaxis or other hypersensitivity reaction occurs, stop The rate of serious infections was 9.7 per 100 patient-years in the Genentech, Inc. 2. Data on le, GiACTA CSR, Genentech, Inc. South Gastrointestinal Perforations: Events of gastrointestinal (GI) perforation administration of ACTEMRA immediately and discontinue ACTEMRA ACTEMRA SC weekly group and 4.4 per 100 patient-years in the San Francisco, CA. have been reported in clinical trials, primarily as complications of permanently. Do not administer ACTEMRA to patients with known ACTEMRA SC every other week group, as compared to 4.2 per 100 Q2W=every-other-week dose; QW=every-week dose. diverticulitis in RA patients. Use ACTEMRA with caution in patients who hypersensitivity to ACTEMRA. patient-years in the placebo + 26 week prednisone taper and 12.5 per *Prednisone. may be at increased risk for GI perforation. Promptly evaluate patients Demyelinating Disorders: The impact of treatment with ACTEMRA on 100 patient-years in the placebo + 52 week prednisone taper groups. presenting with new-onset abdominal symptoms for early identi cation demyelinating disorders is not known, but multiple sclerosis and chronic of GI perforation. in ammatory demyelinating polyneuropathy were reported rarely in Laboratory Parameters: Laboratory monitoring is recommended due to clinical studies. Monitor patients for signs and symptoms of demyelinating potential consequences of treatment-related laboratory abnormalities in disorders. Prescribers should exercise caution in considering the use © 2017 Genentech USA, Inc. All rights reserved. ACT/071217/0075 08/17

FS:7.375” FS:7.375” F:8.125” F:8.125” 10751079_GCA_NOW_JA_EYE_M1.indd 1 8/14/17 5:19 PM

ACTEMRA® (tocilizumab) Treatment-related reduction in platelets was not associated with serious bleeding events in Injection, for intravenous use clinical trials [see Adverse Reactions (6.1, 6.2)]. Injection, for subcutaneous use – It is not recommended to initiate ACTEMRA treatment in patients with a platelet count below This is a brief summary. Before prescribing, please refer to the full Prescribing 100,000 per mm3. In patients who develop a platelet count less than 50,000 per mm3 treatment Information. is not recommended. – Monitor platelets 4 to 8 weeks after start of therapy and every 3 months thereafter. WARNING: RISK OF SERIOUS INFECTIONS For recommended modifications based on platelet counts see [Dosage and Patients treated with ACTEMRA are at increased risk for developing serious infections Administration (2.8)]. that may lead to hospitalization or death [see Warnings and Precautions (5.1), Adverse Elevated Liver Enzymes Treatment with ACTEMRA was associated with a higher incidence of Reactions (6.1)] . Most patients who developed these infections were taking concomitant transaminase elevations. These elevations did not result in apparent permanent or clinically immunosuppressants such as methotrexate or corticosteroids. If a serious infection evident hepatic injury in clinical trials [see Adverse Reactions (6.1, 6.2)]. Increased frequency and develops, interrupt ACTEMRA until the infection is controlled. magnitude of these elevations was observed when potentially hepatotoxic drugs (e.g., MTX) were Reported infections include: used in combination with ACTEMRA. • Active tuberculosis, which may present with pulmonary or extrapulmonary disease. In one case, a patient who had received ACTEMRA 8 mg per kg monotherapy without Patients should be tested for latent tuberculosis before ACTEMRA use and during elevations in transaminases experienced elevation in AST to above 10x ULN and elevation in therapy. Treatment for latent infection should be initiated prior to ACTEMRA use. ALT to above 16x ULN when MTX was initiated in combination with ACTEMRA. Transaminases • Invasive fungal infections, including candidiasis, aspergillosis, and pneumocystis. normalized when both treatments were held, but elevations recurred when MTX and Patients with invasive fungal infections may present with disseminated, rather than ACTEMRA were restarted at lower doses. Elevations resolved when MTX and ACTEMRA localized, disease. were discontinued. • Bacterial, viral and other infections due to opportunistic pathogens. – It is not recommended to initiate ACTEMRA treatment in patients with elevated transaminases The risks and benefits of treatment with ACTEMRA should be carefully considered prior ALT or AST greater than 1.5x ULN. In patients who develop elevated ALT or AST greater than to initiating therapy in patients with chronic or recurrent infection. Patients should be 5x ULN treatment is not recommended. closely monitored for the development of signs and symptoms of infection during and – Monitor ALT and AST levels 4 to 8 weeks after start of therapy and every 3 months thereafter. after treatment with ACTEMRA, including the possible development of tuberculosis in When clinically indicated, other liver function tests such as bilirubin should be considered. For patients who tested negative for latent tuberculosis infection prior to initiating therapy recommended modifications based on transaminases see [Dosage and Administration (2.8)]. [see Warnings and Precautions (5.1)]. Lipid Abnormalities Treatment with ACTEMRA was associated with increases in lipid parameters 1 INDICATIONS AND USAGE such as total cholesterol, triglycerides, LDL cholesterol, and/or HDL cholesterol [see Adverse 1.1 Rheumatoid Arthritis (RA) Reactions (6.1, 6.2)]. ACTEMRA® (tocilizumab) is indicated for the treatment of adult patients with moderately to – Assess lipid parameters approximately 4 to 8 weeks following initiation of ACTEMRA therapy, severely active rheumatoid arthritis (RA) who have had an inadequate response to one or more then at approximately 24 week intervals. Disease-Modifying Anti-Rheumatic Drugs (DMARDs). – Manage patients according to clinical guidelines [e.g., National Cholesterol Educational Program (NCEP)] for the management of hyperlipidemia. 1.2 Giant Cell Arteritis (GCA) 5.4 Immunosuppression ® ACTEMRA (tocilizumab) is indicated for the treatment of giant cell arteritis (GCA) in adult The impact of treatment with ACTEMRA on the development of malignancies is not known but patients. malignancies were observed in clinical studies [see Adverse Reactions (6.1)]. ACTEMRA is an 4 CONTRAINDICATIONS immunosuppressant, and treatment with immunosuppressants may result in an increased risk ACTEMRA is contraindicated in patients with known hypersensitivity to ACTEMRA [see Warnings of malignancies. and Precautions (5.5)]. 5.5 Hypersensitivity Reactions, Including Anaphylaxis Hypersensitivity reactions, including anaphylaxis, have been reported in association with 5 WARNINGS AND PRECAUTIONS ACTEMRA [see Adverse Reactions (6)] and anaphylactic events with a fatal outcome have 5.1 Serious Infections been reported with intravenous infusion of ACTEMRA. Anaphylaxis and other hypersensitivity Serious and sometimes fatal infections due to bacterial, mycobacterial, invasive fungal, reactions that required treatment discontinuation were reported in 0.1% (3 out of 2644) of viral, protozoal, or other opportunistic pathogens have been reported in patients receiving patients in the 6-month controlled trials of intravenous ACTEMRA, 0.2% (8 out of 4009) of immunosuppressive agents including ACTEMRA. The most common serious infections included patients in the intravenous all-exposure RA population, 0.7% (8 out of 1068) in the subcutaneous pneumonia, urinary tract infection, cellulitis, herpes zoster, gastroenteritis, diverticulitis, sepsis 6-month controlled RA trials, and in 0.7% (10 out of 1465) of patients in the subcutaneous all- and bacterial arthritis [see Adverse Reactions (6.1)]. Among opportunistic infections, tuberculosis, exposure population. Reactions that required treatment discontinuation included generalized cryptococcus, aspergillosis, candidiasis, and pneumocystosis were reported with ACTEMRA. erythema, rash, and uticaria. Injection site reactions were categorized separately [see Adverse Other serious infections, not reported in clinical studies, may also occur (e.g., histoplasmosis, Reactions (6) ]. coccidioidomycosis, listeriosis). Patients have presented with disseminated rather than localized B:11.125” T:10.875” In the postmarketing setting, events of hypersensitivity reactions, including anaphylaxis and S:10.625” disease, and were often taking concomitant immunosuppressants such as methotrexate or death have occurred in patients treated with a range of doses of intravenous ACTEMRA, corticosteroids which in addition to rheumatoid arthritis may predispose them to infections. with or without concomitant therapies. Events have occurred in patients who received Do not administer ACTEMRA in patients with an active infection, including localized infections. premedication. Hypersensitivity, including anaphylaxis events, have occurred both with and The risks and benefits of treatment should be considered prior to initiating ACTEMRA in patients: without previous hypersensitivity reactions and as early as the first infusion of ACTEMRA • with chronic or recurrent infection; • who have resided or traveled in areas of [see Adverse Reactions (6.5)]. ACTEMRA for intravenous use should only be infused • who have been exposed to tuberculosis; endemic tuberculosis or endemic mycoses; or by a healthcare professional with appropriate medical support to manage anaphylaxis. • with a history of serious or an • with underlying conditions that may For ACTEMRA subcutaneous injection, advise patients to seek immediate medical attention opportunistic infection; predispose them to infection. if they experience any symptoms of a hypersensitivity reaction. If anaphylaxis or other Closely monitor patients for the development of signs and symptoms of infection during and hypersensitivity reaction occurs, stop administration of ACTEMRA immediately and discontinue after treatment with ACTEMRA, as signs and symptoms of acute inflammation may be lessened ACTEMRA permanently. Do not administer ACTEMRA to patients with known hypersensitivity to due to suppression of the acute phase reactants [see Dosage and Administration (2.5), Adverse ACTEMRA [see Contraindications (4) and Adverse Reactions (6)]. Reactions (6.1), and Patient Counseling Information (17)]. 5.6 Demyelinating Disorders Hold ACTEMRA if a patient develops a serious infection, an opportunistic infection, or sepsis. A The impact of treatment with ACTEMRA on demyelinating disorders is not known, but multiple patient who develops a new infection during treatment with ACTEMRA should undergo a prompt sclerosis and chronic inflammatory demyelinating polyneuropathy were reported rarely in RA and complete diagnostic workup appropriate for an immunocompromised patient, initiate clinical studies. Monitor patients for signs and symptoms potentially indicative of demyelinating appropriate antimicrobial therapy, and closely monitor the patient. disorders. Prescribers should exercise caution in considering the use of ACTEMRA in patients Tuberculosis Evaluate patients for tuberculosis risk factors and test for latent infection prior to with preexisting or recent onset demyelinating disorders. initiating ACTEMRA. 5.7 Active Hepatic Disease and Hepatic Impairment Consider anti-tuberculosis therapy prior to initiation of ACTEMRA in patients with a past history Treatment with ACTEMRA is not recommended in patients with active hepatic disease or hepatic of latent or active tuberculosis in whom an adequate course of treatment cannot be confirmed, impairment [see Adverse Reactions (6.1), Use in Specific Populations (8.6)]. and for patients with a negative test for latent tuberculosis but having risk factors for tuberculosis 5.8 Vaccinations infection. Consultation with a physician with expertise in the treatment of tuberculosis is Avoid use of live vaccines concurrently with ACTEMRA as clinical safety has not been established. recommended to aid in the decision whether initiating anti-tuberculosis therapy is appropriate No data are available on the secondary transmission of infection from persons receiving live for an individual patient. vaccines to patients receiving ACTEMRA. Closely monitor patients for the development of signs and symptoms of tuberculosis including No data are available on the effectiveness of vaccination in patients receiving ACTEMRA. patients who tested negative for latent tuberculosis infection prior to initiating therapy. Because IL-6 inhibition may interfere with the normal immune response to new antigens, it is It is recommended that patients be screened for latent tuberculosis infection prior to starting recommended that all patients, particularly pediatric or elderly patients, if possible, be brought up ACTEMRA. The incidence of tuberculosis in worldwide clinical development programs is 0.1%. to date with all immunizations in agreement with current immunization guidelines prior to initiating Patients with latent tuberculosis should be treated with standard antimycobacterial therapy ACTEMRA therapy. The interval between live vaccinations and initiation of ACTEMRA therapy before initiating ACTEMRA. should be in accordance with current vaccination guidelines regarding immunosuppressive Viral Reactivation Viral reactivation has been reported with immunosuppressive biologic therapies agents. and cases of herpes zoster exacerbation were observed in clinical studies with ACTEMRA. No cases of Hepatitis B reactivation were observed in the trials; however patients who screened 6 ADVERSE REACTIONS positive for hepatitis were excluded. Because clinical studies are conducted under widely varying conditions, adverse reaction rates 5.2 Gastrointestinal Perforations observed in the clinical studies of a drug cannot be directly compared to rates in the clinical Events of gastrointestinal perforation have been reported in clinical trials, primarily as studies of another drug and may not predict the rates observed in a broader patient population complications of diverticulitis in patients treated with ACTEMRA. Use ACTEMRA with caution in in clinical practice. patients who may be at increased risk for gastrointestinal perforation. Promptly evaluate patients 6.1 Clinical Trials Experience in Rheumatoid Arthritis Patients Treated with Intravenous presenting with new onset abdominal symptoms for early identification of gastrointestinal ACTEMRA (ACTEMRA-IV) perforation [see Adverse Reactions (6.1)]. The ACTEMRA-IV data in rheumatoid arthritis (RA) includes 5 double-blind, controlled, multicenter 5.3 Laboratory Parameters studies. In these studies, patients received doses of ACTEMRA-IV 8 mg per kg monotherapy (288 Approved Adult Indications patients), ACTEMRA-IV 8 mg per kg in combination with DMARDs (including methotrexate) (1582 Neutropenia Treatment with ACTEMRA was associated with a higher incidence of neutropenia. patients), or ACTEMRA-IV 4 mg per kg in combination with methotrexate (774 patients). Infections have been uncommonly reported in association with treatment-related neutropenia in The all exposure population includes all patients in registration studies who received at least one long-term extension studies and postmarketing clinical experience. dose of ACTEMRA-IV. Of the 4009 patients in this population, 3577 received treatment for at least 6 – It is not recommended to initiate ACTEMRA treatment in patients with a low neutrophil count, months, 3309 for at least one year; 2954 received treatment for at least 2 years and 2189 for 3 years. i.e., absolute neutrophil count (ANC) less than 2000 per mm3. In patients who develop an All patients in these studies had moderately to severely active rheumatoid arthritis. The absolute neutrophil count less than 500 per mm3 treatment is not recommended. study population had a mean age of 52 years, 82% were female and 74% were Caucasian. – Monitor neutrophils 4 to 8 weeks after start of therapy and every 3 months thereafter [see The most common serious adverse reactions were serious infections [see Warnings and Clinical Pharmacology (12.2)]. For recommended modifications based on ANC results, [see Precautions (5.1)]. Dosage and Administration (2.8)]. The most commonly reported adverse reactions in controlled studies up to 24 weeks (occurring Thrombocytopenia Treatment with ACTEMRA was associated with a reduction in platelet counts. in at least 5% of patients treated with ACTEMRA-IV monotherapy or in combination with

10751079_GCA_NOW_JA_EYE_M1.indd 2 8/14/17 5:19 PM PREPARED BY FCB Releasing as: PDFx1A Production: Maria Abreu x3124 Job #: 10751079 Colors: 4/1 (4C Process/Black) AD: Trent Orvis x2492 Client: Genentech Flat Size: 16.25”w X 10.875”h AE: Katie Majewski x7927 Product: Actemra Bleed: 16.5”w X 11.125”h Producer: Karisa Williams x3721 Client Code: ACT/071217/0075 Trim: 16.25”w X 10.875”h QC: L.Powell Date: August 14, 2017 5:19 PM Safety: 15.75”w X 10.375”h Digital Artist: VA, Add’l Size Info: PI Page Dimensions - Trim 8.125”w X 10.875”h; Live 7.875”w Proof: M1 X 10.625”h; Bleed 8.375”w X 11.125”h Fonts: Helvetica Neue LT Std, Avenir M1 Spellcheck: Jacob Albrecht FR Spellcheck: Path: PrePress:Genentech:10751079:10751079_GCA_NOW_JA_EYE_M1 4C GCA 2017 Journal Ad: Eyenet B:8.375” T:8.125” S:7.875”

DMARDs) were upper respiratory tract infections, nasopharyngitis, headache, hypertension and *For a description of these studies, see Section 14, Clinical Studies. increased ALT. In the all-exposure population, the elevations in ALT and AST remained consistent with what was The proportion of patients who discontinued treatment due to any adverse reactions during the seen in the 24 week, controlled clinical trials. double-blind, placebo-controlled studies was 5% for patients taking ACTEMRA-IV and 3% for Lipids Elevations in lipid parameters (total cholesterol, LDL, HDL, triglycerides) were first assessed placebo-treated patients. The most common adverse reactions that required discontinuation at 6 weeks following initiation of ACTEMRA-IV in the controlled 24 week clinical trials. Increases of ACTEMRA-IV were increased hepatic transaminase values (per protocol requirement) and were observed at this time point and remained stable thereafter. Increases in triglycerides to serious infections. levels above 500 mg per dL were rarely observed. Changes in other lipid parameters from Overall Infections In the 24 week, controlled clinical studies, the rate of infections in the baseline to week 24 were evaluated and are summarized below: ACTEMRA-IV monotherapy group was 119 events per 100 patient-years and was similar in the – Mean LDL increased by 13 mg per dL in the ACTEMRA 4 mg per kg+DMARD arm, 20 mg methotrexate monotherapy group. The rate of infections in the 4 mg per kg and 8 mg per kg per dL in the ACTEMRA 8 mg per kg+DMARD, and 25 mg per dL in ACTEMRA 8 mg per kg ACTEMRA-IV plus DMARD group was 133 and 127 events per 100 patient-years, respectively, monotherapy. compared to 112 events per 100 patient-years in the placebo plus DMARD group. The most – Mean HDL increased by 3 mg per dL in the ACTEMRA 4 mg per kg+DMARD arm, 5 mg per dL in commonly reported infections (5% to 8% of patients) were upper respiratory tract infections and the ACTEMRA 8 mg per kg+DMARD, and 4 mg per dL in ACTEMRA 8 mg per kg monotherapy. nasopharyngitis. – Mean LDL/HDL ratio increased by an average of 0.14 in the ACTEMRA 4 mg per kg+DMARD The overall rate of infections with ACTEMRA-IV in the all exposure population remained arm, 0.15 in the ACTEMRA 8 mg per kg+DMARD, and 0.26 in ACTEMRA 8 mg per kg consistent with rates in the controlled periods of the studies. monotherapy. Serious Infections In the 24 week, controlled clinical studies, the rate of serious infections in – ApoB/ApoA1 ratios were essentially unchanged in ACTEMRA-treated patients. the ACTEMRA-IV monotherapy group was 3.6 per 100 patient-years compared to 1.5 per 100 Elevated lipids responded to lipid lowering agents. patient-years in the methotrexate group. The rate of serious infections in the 4 mg per kg and In the all-exposure population, the elevations in lipid parameters remained consistent with what 8 mg per kg ACTEMRA-IV plus DMARD group was 4.4 and 5.3 events per 100 patient-years, was seen in the 24 week, controlled clinical trials. respectively, compared to 3.9 events per 100 patient-years in the placebo plus DMARD group. Immunogenicity In the 24 week, controlled clinical studies, a total of 2876 patients have been In the all-exposure population, the overall rate of serious infections remained consistent with tested for anti-tocilizumab antibodies. Forty-six patients (2%) developed positive anti-tocilizumab rates in the controlled periods of the studies. The most common serious infections included antibodies, of whom 5 had an associated, medically significant, hypersensitivity reaction leading pneumonia, urinary tract infection, cellulitis, herpes zoster, gastroenteritis, diverticulitis, sepsis to withdrawal. Thirty patients (1%) developed neutralizing antibodies. and bacterial arthritis. Cases of opportunistic infections have been reported [see Warnings and The data reflect the percentage of patients whose test results were positive for antibodies to Precautions (5.1)]. tocilizumab in specific assays. The observed incidence of antibody positivity in an assay is highly Gastrointestinal Perforations During the 24 week, controlled clinical trials, the overall rate of dependent on several factors, including assay sensitivity and specificity, assay methodology, gastrointestinal perforation was 0.26 events per 100 patient-years with ACTEMRA-IV therapy. sample handling, timing of sample collection, concomitant medication, and underlying disease. In the all-exposure population, the overall rate of gastrointestinal perforation remained consistent For these reasons, comparison of the incidence of antibodies to tocilizumab with the incidence with rates in the controlled periods of the studies. Reports of gastrointestinal perforation were of antibodies to other products may be misleading. primarily reported as complications of diverticulitis including generalized purulent peritonitis, Malignancies During the 24 week, controlled period of the studies, 15 malignancies were lower GI perforation, fistula and abscess. Most patients who developed gastrointestinal diagnosed in patients receiving ACTEMRA-IV, compared to 8 malignancies in patients in the perforations were taking concomitant nonsteroidal anti-inflammatory medications (NSAIDs), control groups. Exposure-adjusted incidence was similar in the ACTEMRA-IV groups (1.32 events corticosteroids, or methotrexate [see Warnings and Precautions (5.2)]. The relative contribution per 100 patient-years) and in the placebo plus DMARD group (1.37 events per 100 patient-years). of these concomitant medications versus ACTEMRA-IV to the development of GI perforations In the all-exposure population, the rate of malignancies remained consistent with the rate is not known. observed in the 24 week, controlled period [see Warnings and Precautions (5.4)]. Infusion Reactions In the 24 week, controlled clinical studies, adverse events associated with the Other Adverse Reactions Adverse reactions occurring in 2% or more of patients on 4 or 8 mg per infusion (occurring during or within 24 hours of the start of infusion) were reported in 8% and 7% kg ACTEMRA-IV plus DMARD and at least 1% greater than that observed in patients on placebo of patients in the 4 mg per kg and 8 mg per kg ACTEMRA-IV plus DMARD group, respectively, plus DMARD are summarized in Table 2. compared to 5% of patients in the placebo plus DMARD group. The most frequently reported event on the 4 mg per kg and 8 mg per kg dose during the infusion was hypertension (1% for Table 2 Adverse Reactions Occurring in at Least 2% or More of Patients on 4 or 8 mg per both doses), while the most frequently reported event occurring within 24 hours of finishing an kg ACTEMRA plus DMARD and at Least 1% Greater Than That Observed in Patients on infusion were headache (1% for both doses) and skin reactions (1% for both doses), including Placebo plus DMARD rash, pruritus and urticaria. These events were not treatment limiting. 24 Week Phase 3 Controlled Study Population Anaphylaxis Hypersensitivity reactions requiring treatment discontinuation, including anaphylaxis, ACTEMRA Metho- ACTEMRA ACTEMRA Placebo + associated with ACTEMRA-IV were reported in 0.1% (3 out of 2644) in the 24 week, controlled 8 mg per trexate 4 mg per 8 mg per DMARDs trials and in 0.2% (8 out of 4009) in the all-exposure population. These reactions were generally kg kg + kg + observed during the second to fourth infusion of ACTEMRA-IV. Appropriate medical treatment MONO- DMARDs DMARDs B:11.125” T:10.875” should be available for immediate use in the event of a serious hypersensitivity reaction [see THERAPY S:10.625” Warnings and Precautions (5.5)]. Laboratory Abnormalities N = 288 N = 284 N = 774 N = 1582 N = 1170 Neutropenia In the 24 week, controlled clinical studies, decreases in neutrophil counts below Preferred Term (%) (%) (%) (%) (%) 1000 per mm3 occurred in 1.8% and 3.4% of patients in the 4 mg per kg and 8 mg per kg Upper Respiratory 7 5 6 8 6 ACTEMRA-IV plus DMARD group, respectively, compared to 0.1% of patients in the placebo Tract Infection plus DMARD group. Approximately half of the instances of ANC below 1000 per mm3 occurred Nasopharyngitis 7 6 4 6 4 within 8 weeks of starting therapy. Decreases in neutrophil counts below 500 per mm3 occurred Headache 7 2 6 5 3 in 0.4% and 0.3% of patients in the 4 mg per kg and 8 mg per kg ACTEMRA-IV plus DMARD, Hypertension 6 2 4 4 3 respectively, compared to 0.1% of patients in the placebo plus DMARD group. There was no ALT increased 6 4 3 3 1 clear relationship between decreases in neutrophils below 1000 per mm3 and the occurrence of Dizziness 3 1 2 3 2 serious infections. Bronchitis 3 2 4 3 3 In the all-exposure population, the pattern and incidence of decreases in neutrophil counts Rash 2 1 4 3 1 remained consistent with what was seen in the 24 week controlled clinical studies [see Warnings Mouth Ulceration 2 2 1 2 1 and Precautions (5.3)]. Abdominal Pain 2 2 3 3 2 Thrombocytopenia In the 24 week, controlled clinical studies, decreases in platelet counts Upper below 100,000 per mm3 occurred in 1.3% and 1.7% of patients on 4 mg per kg and 8 mg Gastritis 1 2 1 2 1 per kg ACTEMRA-IV plus DMARD, respectively, compared to 0.5% of patients on placebo plus Transaminase 1 5 2 2 1 DMARD, without associated bleeding events. increased In the all-exposure population, the pattern and incidence of decreases in platelet counts Other infrequent and medically relevant adverse reactions occurring at an incidence less than 2% remained consistent with what was seen in the 24 week controlled clinical studies [see Warnings in rheumatoid arthritis patients treated with ACTEMRA-IV in controlled trials were: and Precautions (5.3)]. Infections and Infestations: oral herpes simplex Elevated Liver Enzymes Liver enzyme abnormalities are summarized in Table 1. In patients Gastrointestinal disorders: stomatitis, gastric ulcer experiencing liver enzyme elevation, modification of treatment regimen, such as reduction in Investigations: weight increased, total bilirubin increased the dose of concomitant DMARD, interruption of ACTEMRA-IV, or reduction in ACTEMRA-IV Blood and lymphatic system disorders: leukopenia dose, resulted in decrease or normalization of liver enzymes [see Dosage and Administration General disorders and administration site conditions: edema peripheral (2.6)]. These elevations were not associated with clinically relevant increases in direct bilirubin, Respiratory, thoracic, and mediastinal disorders: dyspnea, cough nor were they associated with clinical evidence of hepatitis or hepatic insufficiency [see Warnings Eye disorders: conjunctivitis and Precautions (5.3)]. Renal disorders: nephrolithiasis Table 1 Incidence of Liver Enzyme Abnormalities in the 24 Week Controlled Period of Endocrine disorders: hypothyroidism Studies I to V* 6.2 Clinical Trials Experience in Rheumatoid Arthritis Patients Treated with Subcutaneous ACTEMRA Metho- ACTEMRA ACTEMRA Placebo + ACTEMRA (ACTEMRA-SC) 8 mg per trexate 4 mg per 8 mg per DMARDs The ACTEMRA-SC data in rheumatoid arthritis (RA) includes 2 double-blind, controlled, kg kg + kg + multicenter studies. Study SC-I was a non-inferiority study that compared the efficacy and MONO- DMARDs DMARDs safety of tocilizumab 162 mg administered every week subcutaneously (SC) and 8 mg/kg THERAPY intravenously (IV) every four weeks in 1262 adult subjects with rheumatoid arthritis. Study SC-II was a placebo controlled superiority study that evaluated the safety and efficacy of tocilizumab N = 288 N = 284 N = 774 N = 1582 N = 1170 162 mg administered every other week SC or placebo in 656 patients. All patients in both studies (%) (%) (%) (%) (%) received background non-biologic DMARDs. AST (U/L) The safety observed for ACTEMRA administered subcutaneously was consistent with the known > ULN to 3x ULN 22 26 34 41 17 safety profile of intravenous ACTEMRA, with the exception of injection site reactions, which were > 3x ULN to 5x ULN 0.3 2 1 2 0.3 more common with ACTEMRA-SC compared with placebo SC injections (IV arm). Injection Site Reactions In the 6-month control period, in SC-I, the frequency of injection site > 5x ULN 0.7 0.4 0.1 0.2 <0.1 reactions was 10.1% (64/631) and 2.4% (15/631) for the weekly ACTEMRA-SC and placebo SC ALT (U/L) (IV-arm) groups, respectively. In SC-II, the frequency of injection site reactions was 7.1% (31/437) and 4.1% (9/218) for the every other week SC ACTEMRA and placebo groups, respectively. > ULN to 3x ULN 36 33 45 48 23 These injection site reactions (including erythema, pruritus, pain and hematoma) were mild to > 3x ULN to 5x ULN 1 4 5 5 1 moderate in severity. The majority resolved without any treatment and none necessitated drug discontinuation. > 5x ULN 0.7 1 1.3 1.5 0.3 Immunogenicity In the 6-month control period in SC-I, 0.8% (5/625) in the ACTEMRA-SC arm and 0.8% (5/627) in the IV arm developed anti-tocilizumab antibodies; of these, all developed ULN = Upper Limit of Normal

PREPARED BY FCB 10751079_GCA_NOW_JA_EYE_M1.indd 3 8/14/17 5:19 PM Releasing as: PDFx1A Production: Maria Abreu x3124 Job #: 10751079 Colors: 4/1 (4C Process/Black) AD: Trent Orvis x2492 Client: Genentech Flat Size: 16.25”w X 10.875”h AE: Katie Majewski x7927 Product: Actemra Bleed: 16.5”w X 11.125”h Producer: Karisa Williams x3721 Client Code: ACT/071217/0075 Trim: 16.25”w X 10.875”h QC: L.Powell Date: August 14, 2017 5:19 PM Safety: 15.75”w X 10.375”h Digital Artist: VA, Add’l Size Info: PI Page Dimensions - Trim 8.125”w X 10.875”h; Live 7.875”w Proof: M1 X 10.625”h; Bleed 8.375”w X 11.125”h Fonts: Helvetica Neue LT Std, Avenir M1 Spellcheck: Jacob Albrecht FR Spellcheck: Path: PrePress:Genentech:10751079:10751079_GCA_NOW_JA_EYE_M1 4C GCA 2017 Journal Ad: Eyenet B:8.375” T:8.125” S:7.875”

neutralizing antibodies. In SC-II, 1.6% (7/434) in the ACTEMRA-SC arm compared with 1.4% Data (3/217) in the placebo arm developed anti- tocilizumab antibodies; of these, 1.4% (6/434) in the Animal Data An embryo-fetal developmental toxicity study was performed in which pregnant ACTEMRA-SC arm and 0.5% (1/217) in the placebo arm also developed neutralizing antibodies. Cynomolgus monkeys were treated intravenously with tocilizumab at daily doses of 2, 10, or 50 A total of 1454 (>99%) patients who received ACTEMRA-SC in the all exposure group have mg/ kg during organogenesis from gestation day (GD) 20-50. Although there was no evidence been tested for anti-tocilizumab antibodies. Thirteen patients (0.9%) developed anti-tocilizumab for a teratogenic/dysmorphogenic effect at any dose, tocilizumab produced an increase in antibodies, and, of these, 12 patients (0.8%) developed neutralizing antibodies. the incidence of abortion/embryo-fetal death at doses 1.25 times and higher the MRHD by The rate is consistent with previous intravenous experience. No correlation of antibody the intravenous route at maternal intravenous doses of 10 and 50 mg/ kg. Testing of a murine development to adverse events or loss of clinical response was observed. analogue of tocilizumab in mice did not yield any evidence of harm to offspring during the Laboratory Abnormalities pre- and postnatal development phase when dosed at 50 mg/kg intravenously with treatment Neutropenia During routine laboratory monitoring in the 6-month controlled clinical trials, a every three days from implantation (GD 6) until post-partum day 21 (weaning). There was no decrease in neutrophil count below 1 × 109/L occurred in 2.9% and 3.7% of patients receiving evidence for any functional impairment of the development and behavior, learning ability, immune ACTEMRA-SC weekly and every other week, respectively. competence and fertility of the offspring. There was no clear relationship between decreases in neutrophils below 1 x 109/L and the Parturition is associated with significant increases of IL-6 in the cervix and myometrium. The occurrence of serious infections. literature suggests that inhibition of IL-6 signaling may interfere with cervical ripening and Thrombocytopenia During routine laboratory monitoring in the ACTEMRA-SC 6-month controlled dilatation and myometrial contractile activity leading to potential delays of parturition. For clinical trials, none of the patients had a decrease in platelet count to ≤50,000/mm3. mice deficient in IL-6 (ll6-/- null mice), parturition was delayed relative to wild-type (ll6+/+) mice. Elevated Liver Enzymes During routine laboratory monitoring in the 6-month controlled clinical Administration of recombinant IL-6 to ll6-/- null mice restored the normal timing of delivery. trials, elevation in ALT or AST ≥3 x ULN occurred in 6.5% and 1.4% of patients, respectively, 8.2 Lactation receiving ACTEMRA-SC weekly and 3.4% and 0.7% receiving ACTEMRA SC every other week. Risk Summary Lipid Parameters Elevations During routine laboratory monitoring in the ACTEMRA-SC 6-month No information is available on the presence of tocilizumab in human milk, the effects of the drug clinical trials, 19% of patients dosed weekly and 19.6% of patients dosed every other week and on the breastfed infant, or the effects of the drug on milk production. Maternal immunoglobulin 10.2% of patients on placebo experienced sustained elevations in total cholesterol > 6.2 mmol/l G (IgG) is present in human milk. If tocilizumab is transferred into human milk, the effects of local (240 mg/dL), with 9%, 10.4% and 5.1% experiencing a sustained increase in LDL to 4.1 mmol/l exposure in the gastrointestinal tract and potential limited systemic exposure in the infant to (160 mg/dL) receiving ACTEMRA-SC weekly, every other week and placebo, respectively. tocilizumab are unknown. The lack of clinical data during lactation precludes clear determination 6.3 Clinical Trials Experience in Giant Cell Arteritis Patients Treated with Subcutaneous of the risk of ACTEMRA to an infant during lactation; therefore the developmental and health ACTEMRA (ACTEMRA-SC) benefits of breastfeeding should be considered along with the mother’s clinical need for The safety of subcutaneous ACTEMRA (tocilizumab) has been studied in one Phase III study ACTEMRA and the potential adverse effects on the breastfed child from tocilizumab or from the (WA28119) with 251 GCA patients. The total patient years duration in the ACTEMRA GCA underlying maternal condition. all exposure population was 138.5 patient years during the 12-month double blind, placebo- 8.5 Geriatric Use controlled phase of the study. The overall safety profile observed in the ACTEMRA treatment Of the 2644 patients who received ACTEMRA in Studies I to V [see Clinical Studies (14)], a total of groups was generally consistent with the known safety profile of ACTEMRA. There was an overall 435 rheumatoid arthritis patients were 65 years of age and older, including 50 patients 75 years higher incidence of infections in GCA patients relative to RA patients. The rate of infection/serious and older. Of the 1069 patients who received ACTEMRA-SC in studies SC-I and SC-II there were infection events was 200.2/9.7 events per 100 patient years in the ACTEMRA weekly group and 295 patients 65 years of age and older, including 41 patients 75 years and older. The frequency 160.2/4.4 events per 100 patient years in the ACTEMRA every other week group as compared to of serious infection among ACTEMRA treated subjects 65 years of age and older was higher than 156.0/4.2 events per 100 patient years in the placebo + 26 week prednisone taper and 210.2/12.5 those under the age of 65. As there is a higher incidence of infections in the elderly population in events per 100 patient years in the placebo + 52 week taper groups. general, caution should be used when treating the elderly. 8.6 Hepatic Impairment 7 DRUG INTERACTIONS The safety and efficacy of ACTEMRA have not been studied in patients with hepatic impairment, 7.1 Concomitant Drugs for Treatment of Adult Indications including patients with positive HBV and HCV serology [see Warnings and Precautions (5.7)]. In RA patients, population pharmacokinetic analyses did not detect any effect of methotrexate (MTX), non-steroidal anti-inflammatory drugs or corticosteroids on tocilizumab clearance. 8.7 Renal Impairment No dose adjustment is required in patients with mild or moderate renal impairment. ACTEMRA Concomitant administration of a single intravenous dose of 10 mg/kg ACTEMRA with 10-25 has not been studied in patients with severe renal impairment [see Clinical Pharmacology (12.3)]. mg MTX once weekly had no clinically significant effect on MTX exposure. ACTEMRA has not been studied in combination with biological DMARDs such as TNF antagonists [see Dosage and 10 OVERDOSAGE Administration (2.1)]. There are limited data available on overdoses with ACTEMRA. One case of accidental overdose In GCA patients, no effect of concomitant corticosteroid on tocilizumab exposure was observed. was reported with intravenous ACTEMRA in which a patient with multiple myeloma received 7.2 Interactions with CYP450 Substrates a dose of 40 mg per kg. No adverse drug reactions were observed. No serious adverse drug Cytochrome P450s in the liver are down-regulated by infection and inflammation stimuli including reactions were observed in healthy volunteers who received single doses of up to 28 mg per kg, B:11.125” T:10.875” cytokines such as IL-6. Inhibition of IL-6 signaling in RA patients treated with tocilizumab may although all 5 patients at the highest dose of 28 mg per kg developed dose-limiting neutropenia. S:10.625” restore CYP450 activities to higher levels than those in the absence of tocilizumab leading In case of an overdose, it is recommended that the patient be monitored for signs and symptoms to increased metabolism of drugs that are CYP450 substrates. In vitro studies showed that of adverse reactions. Patients who develop adverse reactions should receive appropriate tocilizumab has the potential to affect expression of multiple CYP enzymes including CYP1A2, symptomatic treatment. CYP2B6, CYP2C9, CYP2C19, CYP2D6 and CYP3A4. Its effect on CYP2C8 or transporters is unknown. In vivo studies with omeprazole, metabolized by CYP2C19 and CYP3A4, and 17 PATIENT COUNSELING INFORMATION simvastatin, metabolized by CYP3A4, showed up to a 28% and 57% decrease in exposure See FDA-approved patient labeling (Medication Guide) one week following a single dose of ACTEMRA, respectively. The effect of tocilizumab on CYP Patient Counseling enzymes may be clinically relevant for CYP450 substrates with narrow therapeutic index, where Advise patients of the potential benefits and risks of ACTEMRA. Physicians should instruct their the dose is individually adjusted. Upon initiation or discontinuation of ACTEMRA, in patients patients to read the Medication Guide before starting ACTEMRA therapy. being treated with these types of medicinal products, perform therapeutic monitoring of effect • Infections: (e.g., warfarin) or drug concentration (e.g., cyclosporine or theophylline) and the individual Inform patients that ACTEMRA may lower their resistance to infections. Instruct the patient of the dose of the medicinal product adjusted as needed. Exercise caution when coadministering importance of contacting their doctor immediately when symptoms suggesting infection appear ACTEMRA with CYP3A4 substrate drugs where decrease in effectiveness is undesirable, e.g., in order to assure rapid evaluation and appropriate treatment. oral contraceptives, lovastatin, atorvastatin, etc. The effect of tocilizumab on CYP450 enzyme • Gastrointestinal Perforation: activity may persist for several weeks after stopping therapy [see Clinical Pharmacology (12.3)]. Inform patients that some patients who have been treated with ACTEMRA have had serious side 7.3 Live Vaccines effects in the stomach and intestines. Instruct the patient of the importance of contacting their Avoid use of live vaccines concurrently with ACTEMRA [see Warnings and Precautions (5.8)]. doctor immediately when symptoms of severe, persistent abdominal pain appear to assure rapid evaluation and appropriate treatment. 8 USE IN SPECIFIC POPULATIONS • Hypersensitivity and Serious Allergic Reactions: 8.1 Pregnancy Assess patient suitability for home use for SC injection. Inform patients that some patients Pregnancy Exposure Registry who have been treated with ACTEMRA have developed serious allergic reactions, including There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed anaphylaxis. Advise patients to seek immediate medical attention if they experience any to ACTEMRA during pregnancy. Physicians are encouraged to register patients and pregnant symptom of serious allergic reactions. women are encouraged to register themselves by calling 1-877-311-8972. Instruction on Injection Technique Risk Summary Perform the first injection under the supervision of a qualified healthcare professional. If a The limited available data with ACTEMRA in pregnant women are not sufficient to determine patient or caregiver is to administer subcutaneous ACTEMRA, instruct him/her in injection whether there is a drug-associated risk for major birth defects and miscarriage. Monoclonal techniques and assess his/her ability to inject subcutaneously to ensure proper administration antibodies, such as tocilizumab, are actively transported across the placenta during the third of subcutaneous ACTEMRA and the suitability for home use [see Patient Instructions for Use]. trimester of pregnancy and may affect immune response in the in utero exposed infant [see Prior to use, remove the prefilled syringe from the refrigerator and allow to sit at room temperature Clinical Considerations]. In animal reproduction studies, intravenous administration of tocilizumab outside of the carton for 30 minutes, out of the reach of children. Do not warm ACTEMRA in any to Cynomolgus monkeys during organogenesis caused abortion/embryo-fetal death at doses other way. 1.25 times and higher than the maximum recommended human dose by the intravenous route of Advise patients to consult their healthcare provider if the full dose is not received. 8 mg per kg every 2 to 4 weeks. The literature in animals suggests that inhibition of IL-6 signaling A puncture-resistant container for disposal of needles and syringes should be used and should may interfere with cervical ripening and dilatation and myometrial contractile activity leading to be kept out of the reach of children. Instruct patients or caregivers in the technique as well as potential delays of parturition [see Data]. Based on the animal data, there may be a potential risk proper syringe and needle disposal, and caution against reuse of these items. to the fetus. Pregnancy Exposure Registry The estimated background risk of major birth defects and miscarriage for the indicated population Inform patients that there is a pregnancy registry to monitor fetal outcomes of is unknown. All pregnancies have a background risk of birth defect, loss or other adverse pregnant women exposed to ACTEMRA [see Use in Specific Populations (8.1)]. outcomes. In the U.S. general population, the estimated background risk of major birth defects Pregnancy and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Inform female patients of reproductive potential that ACTEMRA may cause fetal harm Clinical Considerations and to inform their prescriber of a known or suspected pregnancy [see Use in Specific Fetal/Neonatal adverse reactions Monoclonal antibodies are increasingly transported across the Populations (8.1)]. placenta as pregnancy progresses, with the largest amount transferred during the third trimester. Risks and benefits should be considered prior to administering live or live-attenuated vaccines to infants exposed to ACTEMRA in utero [see Warnings and Precautions (5.8)].

10751079_GCA_NOW_JA_EYE_M1.indd 4 PREPARED BY FCB 8/14/17 5:19 PM Releasing as: PDFx1A Production: Maria Abreu x3124 Job #: 10751079 Colors: 4/1 (4C Process/Black) AD: Trent Orvis x2492 Client: Genentech Flat Size: 16.25”w X 10.875”h AE: Katie Majewski x7927 Product: Actemra Bleed: 16.5”w X 11.125”h Producer: Karisa Williams x3721 Client Code: ACT/071217/0075 Trim: 16.25”w X 10.875”h QC: L.Powell Date: August 14, 2017 5:19 PM Safety: 15.75”w X 10.375”h Digital Artist: VA, Add’l Size Info: PI Page Dimensions - Trim 8.125”w X 10.875”h; Live 7.875”w Proof: M1 X 10.625”h; Bleed 8.375”w X 11.125”h Fonts: Helvetica Neue LT Std, Avenir M1 Spellcheck: Jacob Albrecht FR Spellcheck: Path: PrePress:Genentech:10751079:10751079_GCA_NOW_JA_EYE_M1 4C GCA 2017 Journal Ad: Eyenet CODING & REIMBURSEMENT SAVVY CODER

Put on Your Audit Armor, Part 1

t’s not a matter of if but when a third-party payer sends you a request Two Real-Life Scenarios Ifor records. And when that day ar- rives, having a written protocol in place Scenario 1: The dutiful but ill-informed staff member. A staff member opens will help to ease your angst. Here’s how the mail and finds an audit request for 40 charts. In an effort to be helpful, he to get started. compiles what he perceives to be the appropriate documentation. He submits it without telling the physician. Be Audit Ready: Create The audit results are not favorable, and a substantial refund is requested. Written Protocol Now the employee needs to plan for an appeal or a refund and must tell the Use the protocol below as a starting physician. If the refund is not made within the allotted time frame, future pay- point, and customize it to fit your ments will be withheld until the recoupment is paid in full. This can have some practice. awkward repercussions. Suppose, for instance, the physician’s partner submits You receive a request for records. the next few claims to this payer. It will be the partner who is impacted when What do you do next? the payer withholds payment for those claims. Patients may also be affected, 1. Do not toss the envelope. It shows as the practice won’t be able to post a payment to a patient’s account if actual the postmark date. The letter inside funds aren’t available for deposit. may be dated much earlier than the Scenario 2: Kicking the can down the road. A request for 30 records is re- date when you received the request. ceived. Rather than putting her best foot forward and making sure all the doc- 2. Determine the type of audit or umentation that the auditor requested is submitted, the practice administrator investigation. The government has determines that the practice will just send in records and hope for the best, assigned auditing duties to several types knowing that the practice can always appeal. While appealing denied claims of organization, each with its own type is always an option, it is a costly one. Best practice is to review the request of audit. These include the following: and carefully compile the documentation. When you send the documentation, • CERT: Comprehensive Error Rate include a cover letter that can provide further explanation and can help set Testing the tone for the audit. • OIG: Office of Inspector General investigation • RA and RAC: Recovery Audit (RA) 3. Identify the due date for sending volume surgery? Is it a single date and Recovery Audit Contractor (RAC) records. Respond within the time limits of service versus a series of encounters? • SMRC: Supplemental Medical Re- provided, or immediately request an 5. Note the date of service request- view Contractor extension. Make sure you document ed. Make sure that you are gathering • TPE: Targeted Probe and Educate written confirmation of new due date. documentation for the correct date of • ZPIC: Zone Program Integrity 4. Look for the common theme. service. Contractor Does the auditor seem to be zeroing 6. Check the records for signatures. The mechanics of the audit may in on a particular level of E&M or For paper charts, is the physician signa- vary, depending on which type of audit Eye visit code? A consistent modifier? ture present and identifiable? If signatures is performed. A particular testing service? A high- are illegible, immediately prepare a signature log. Include the names of all who document in the medical record BY SUE VICCHRILLI, COT, OCS, ACADEMY DIRECTOR OF CODING AND and identify their title (i.e., MD, DO, REIMBURSEMENT. OD, technician, scribe, receptionist,

EYENET MAGAZINE • 51 etc.). If the signature is missing from chart note plus the dictation. After all, the medical documentation, it is only that which can be read can be acceptable for the author of the medical audited. record entry to add a signed attestation With EHR, check whether all fields that he or she had entered the original are populated. For example, if doc- information into the record. umentation shows only those body If you use electronic health records systems that have a problem and (EHRs), provide documentation that not those that are normal, you won’t the physician signature is “secure” and receive credit for reviewing 10 or more nobody else has or uses the physician systems. Work with the vendor to make password. Most audits also request sure all fields show when the record is EHR signature protocol. Without an printed. identifiable, secure physician signature, 12. Remember that the Academy is the auditors do not have to complete here for you. Email [email protected]. the actual audit—they can just deny payment. 7. Provide a list of abbreviations Codequest 2018 used. Don’t assume that the auditor will understand the abbreviations used Strengthen your audit armor. Stay up in your records. to date with shifting regulations by 8. Check whether LCD(s) apply. If attending Codequest 2018, a half- the payer has a Local Coverage Deter- day event that will be tailored to the mination (LCD) on a test or surgery region where you practice. performed, quote chapter and verse New for Codequest’s 2018 program. from that LCD. Be sure to use the LCD Audit-proof your documentation with that was in place at the time the test or payer-specific checklists for the top surgery took place. surgical procedures for each subspe- 9. Make sure tests are fully docu- cialty. Learn about new CPT, HCPCS, mented. If testing services are part of and ICD-10 codes as well as new CCI Ace Your MOC the audit, make sure there is a written edits. Get tips on coding for telemedi- order that identifies by name what test cine, blepharoplasty, and much more. Exams with and which eye(s). Furthermore, the When is Codequest coming to the Ultimate medical necessity for the test should be your state? Codequest will have vis- obvious in the medical record; the phy- ited 15 states by the end of April and Ophthalmic Study sician should provide the interpretation several more by the end of the year. Guide and report as soon as possible; and if Here are the first 16 Codequests: the delegated test falls under direct su- • Columbia, S.C. (Friday, Jan. 12) Practicing pervision, make sure the payer is aware • Nashville, Tenn. (Saturday, Jan. 13) Ophthalmologists that one of the practice’s physicians was • Southern California (Friday, Jan. 19) Learning System, 2017-2019 on site during the test. • Little Rock, Ark. (Thursday, Jan. 25) is an innovative program 10. Self-audit. If the auditor is • Northern California (Friday, Jan. 26) that will help you looking at E&M or Eye visit codes, • Lubbock, Texas (Friday, Feb. 2) successfully prepare for audit internally before submitting the • San Marcos, Texas (Saturday, Feb. 3) maintenance of certification documentation, so you can gauge your • Greensboro, N.C. (Saturday, Feb. 3) exams with more than worst-case scenario. Next, you can • St. Paul, Minn. (Saturday, Feb. 17) 4,000 self-assessment estimate how much money the auditor • Salt Lake City, Utah (Saturday, questions covering 1,400 might seek to recoup and plan accord- March 3) topics. It’s also perfect for ingly. • Manhattan, N.Y. (Thursday, March 15) lifelong learning and self- 11. Make sure that a physician re- • Long Island, N.Y. (Friday, March 16) assessment. views the documentation. Physicians • Detroit, Mich. (Saturday, March 17) should have the opportunity to review • Rochester, N.Y. (Thursday, March 22) Order today all records before that documentation • Albany, N.Y. (Friday, March 23) aao.org/learningsystem is sent to the auditor. • Dallas, Texas (Saturday, March 24) With paper charts, if the handwrit- For the full schedule, plus informa- ing is not readily legible, physicians tion on educational credits (including should take the time to dictate (not CME for physicians), visit aao.org/ embellish) the notes. Include the actual codequest.

52 • JANUARY 2018 LOW VISION PRACTICE PERFECT

Help Low Vision Patients Avoid Depression: Get Them Started on Social Media

e all derive support from family and friends. But af- Depression—Who Is at Risk? Wter patients develop visual impairment, that network of support “Individuals who might be having significant trouble participating in favorite can start to unravel. This is because activities include those who have a chronic eye condition, visual acuity of less new impediments—such as the inabil- than 20/40, or a central or paracentral scotoma,” said Dr. Shepherd. ity to recognize an acquaintance’s face Ask a few basic questions. “When you encounter any of those scenarios, or the inability to drive—can prevent you should simply ask your patient if he/she is having difficulty participating patients from maintaining social ties. in activities—particularly reading or using the computer,” said Dr. Shepherd. One potential remedy: online social “If your patient responds with a lengthy list of deficits, there is a much greater networks. “I believe that this oppor- likelihood for depression.” tunity for social interaction can bring Provide solutions. “Many of our patients with vision loss do not realize that hope to our patients,” said Rahul N. participating in social media is possible,” said Dr. Khurana. “It is therefore im- Khurana, MD, a retina specialist in portant for us to raise awareness and educate them about the available social Mountain View, California. media accessibility options.”

Feeling Isolated and Miserable Recognize the risk of depression. “As Look for cues and ask questions. Urge Patients to Go Online ophthalmologists, we often give all of Because patients are prone to report the Keeping patients engaged is thought our attention to disease management physical symptoms that they are expe- to reduce feelings of isolation and and overlook the importance of man- riencing rather than identifying tasks depression that frequently accompany aging the impairment caused by the that they are unable to accomplish, it vision loss. And for many people, social disease. But it is essential to recognize may be necessary to delve a little deeper media platforms—Facebook, Insta- that individuals with low vision are up to determine the level of impact that gram, and Twitter, for example—are a to 3 times more likely to develop de- vision loss may be having on an indi- good option for maintaining social ties. pression than are those without a visual vidual’s activity participation. “These and other platforms have made impairment,” said low vision specialist Vision loss is on the rise. A study tremendous strides to make the inter- John D. Shepherd, MD. “Furthermore, published in JAMA Ophthalmology net, and specifically social media, more the degree of depression directly cor- found that the number of new cases of accessible to individuals with low vision relates with the level of disability. This low vision and blindness is projected and vision loss,” said Dr. Khurana, who essentially means that the more difficult to double during the next 30 years.1 has observed patients socially withdraw it is for our patients to participate in According to the authors, however, this and become depressed once they lose their favorite activities, such as so- estimate may be low due to the limited vision. “It is important for us to inform cializing, the greater the likelihood of sample size of particular populations them about the various options that depression,” said Dr. Shepherd, at the (e.g., certain racial/ethnic groups). In can help them connect or remain con- Weigel Williamson Center for Visual any event, the number of your patients nected with others,” he said. Rehabilitation in Omaha, Nebraska. at risk for depression is set to rise. Support networks are important. Although there is currently no empiri- cal evidence to suggest that starting to BY LESLIE BURLING-PHILLIPS, CONTRIBUTING WRITER, INTERVIEWING use social media will help prevent or RAHUL N. KHURANA, MD, JOHN D. SHEPHERD, MD, AND JEFF WIELAND. reduce depression, it is likely that this

EYENET MAGAZINE • 53 social interaction could minimize the element to gain context,” he explained. image-based Facebook posts. “Auto sense of loneliness that often accompa- Facebook utilizes shortcut keys matic Alt Text uses Facebook’s propri- nies visual impairment. that enable individuals who only use etary object recognition service that Patients can exchange tips with their their keyboards for online navigation currently detects approximately 120 peers. Patients can connect with others to “Friend,” “Like,” “Comment,” and distinct objects and concepts within who are experiencing the challenges “Share,” just as sighted users can. This is the hundreds of millions of photo- of low vision and blindness; ideas and particularly relevant to those with low graphs that are uploaded and shared on suggestions can be exchanged. vision because research indicates that Facebook daily,” said Mr. Wieland. “The patients with a strong desire for social service runs instantaneously at the The Tools interaction use online social groups time of an upload and is supported in Usage patterns are similar. More to make one-to-one connections with 20 languages.” The result is a brief but than 100 million people use the zoom other users by friending.2 descriptive narrative of what is depict- feature in a desktop browser, and 1 in Font size and screen readers. All ed in the photograph. Now, when the 5 increase the text size on their mo- computer operating systems have capa- screen reader encounters a photograph bile device for a more readable online bility features that enable the end-user on Facebook, rather than simply stating experience, according to Jeff Wieland, to increase the font size or change the “image,” Automatic Alt Text enables director of accessibility at Facebook. text and background colors for im- screen readers to read aloud a descrip- His department is responsible for edu- proved readability. When this is not tion of the photo (e.g., “Image may cating Facebook’s product teams about sufficient, screen readers enable even contain: Two people, smiling, beach”). accessibility so that they can build those who have extremely low vision or products for people with disabilities. are completely blind to access the inter- Refer Patients When Necessary “We have found that people with vision net and social media. This technology Patients who struggle with using the loss and blindness use social media in converts text to speech and reads aloud computer, navigating the internet, and the same ways as everyone else,” said what is displayed on the screen. other day-to-day activities due to their Mr. Wieland. “The only difference is the What about images? Now that visual impairments should be referred mechanism employed for interacting every smartphone includes a camera, to a low vision specialist. with Facebook. For instance, someone photographs often play a starring role “The goal of the low vision specialist who is blind will use a screen reader to in social media posts. And the text that is first to identify all of the functional access Facebook and, therefore, navi- accompanies these image-based posts difficulties that an individual is having gation patterns change. This individual might not make much sense without and then to minimize the disability is likely to navigate by page headings the context that the image provides. through the use of optical devices, or landmarks and, in some cases, from Automated Alt Text technology accessibility options, skill training, user-interface element to user-interface can help unlock the meaning of environmental adaptations, and counseling,” said Dr. Shepherd. For those in areas without a low vision specialist, state and local services for the blind Additional Resources and visually impaired are a good starting point for helpful information. American Foundation for the Blind has a social media overview: www.afb. org/info/living-with-vision-loss/using-technology/using-social-media-with- 1 Chan T et al. JAMA Ophthalmol. Published a-visual-impairment-or-blindness-facebook-twitter-and-linkedin/123. online Nov. 2, 2017. Facebook offers some basic resources to get started: 2 Chung JE. J Health Commun. 2014;19(6):639- • The Facebook Accessibility Help Center: www.facebook.com/help/ 659. • The Facebook Accessibility Page for news and updates: www.facebook. com/accessibility Dr. Khurana is a retina specialist at Northern More than 100 iOS apps designed for blind and low vision users can be California Retina Vitreous Associates, which has found at www.applevis.com/apps/ios-apps-for-blind-and-vision-impaired. 6 locations in the San Francisco area. Relevant The Academy initiative in vision rehabilitation will help you to refer low financial disclosures: None. vision patients or provide them with vision rehabilitation. To learn more, visit Dr. Shepherd is the director of the Weigel aao.org/low-vision-and-vision-rehab. Williamson Center for Visual Rehabilitation at Related reading. Visit aao.org/eyenet and click “Archive” for the following the University of Nebraska Medical Center in articles: Low Vision Drivers: The Ophthalmologist’s Role and Responsibility Omaha. Relevant financial disclosures: None. (Clinical Update, October 2017); Boost Website Accessibility for Those With Mr. Wieland is head of accessibility engineering No Vision and Low Vision (Practice Perfect, October 2017); A Guide to Vision and operations at Facebook. Relevant financial Aid Apps for Apple and Android Smartphones (Practice Perfect, April 2016); disclosures: Facebook: E. Make Your Office Safer for Patients With Low Vision (Practice Perfect, Novem- See the disclosure key, page 8. For full disclo- ber 2014). sures, view this article at aao.org/eyenet.

54 • JANUARY 2018 QUALITY REPORTING PRACTICE PERFECT

From PQRS to MIPS, the IRIS Registry Is a Winning Tool for Quality Reporting

he IRIS Registry (aao.org/iris- $10,801 per ophthalmologist in 2018. the practice (in some cases the physi- registry) helped ophthalmology Most ophthalmologists reported cian had joined the practice partway Tsucceed at Physician Quality PQRS via IRIS Registry–EHR integra- through the year; there also were cases Reporting System (PQRS) and is now tion. For the 2016 performance year, in which the physician worked in the the specialty’s tool of choice for the the IRIS Registry sent CMS 11,612 files practice part time or only occasionally) Merit-Based Incentive Payment System for eligible clinicians and group prac- • not reporting for a TIN that is used (MIPS). Indeed, CMS chief Seema tices. Of these, 9,177 files were from just now and again Verma, MPH, has said that although practices that had integrated their EHR • not reporting and instead relying on quality reporting is too burdensome, system with the IRIS Registry. an Accountable Care Organization that “one bright spot” is the IRIS Registry. Closing in on 100% success for IRIS failed PQRS The IRIS Registry has 2 reporting Registry–EHR integrated practices. options. Use a web portal to manually Through Dec. 1, 2017, the IRIS Registry MIPS: Beat the Jan. 15 Deadline report up to 3 MIPS performance cate- had not been notified of any participat- First, see if you’re exempt from MIPS gories; if you integrate your electronic ing practice’s fully completed EHR (https://qpp.cms.gov/participation- health record (EHR) system with the submission receiving the penalty adjust- lookup). Next, if you signed up to IRIS Registry, an automated process ment due to unsuccessful reporting use the IRIS Registry for 2017 MIPS extracts data for quality reporting. of quality measures. However, there reporting, make sure you meet the Jan. were a handful of cases with incorrect 15 deadline for (1) providing the TIN/ PQRS—Widespread Success, combinations of the 2 identifiers: the NPI combinations, (2) submitting Data Plus Some Lessons Learned National Provider Identifier (NPI), Release Consent Forms, (3) attesting to In fall of 2017, practices learned wheth- which is used to identify individual improvement activities and advancing er they had successfully reported PQRS clinicians, and the Tax Identification care information measures, and, if re- for the 2016 performance year. Number (TIN), which is used to iden- porting quality measures manually via What was at stake. What happens to tify the practice. These were corrected the web portal, (4) entering quality mea- those who failed to successfully report upon appeal to CMS. sure data. (For consent form instruc- PQRS measures for the 2016 reporting Most manual reporters were suc- tions, see aao.org/consent-form.) period? In 2018, their Medicare Part cessful. Practices could manually re- If your practice is one in which eli B service payments will be adjusted port PQRS measures through the IRIS gible clinicians are reporting MIPS as downward. This penalty will be 2% Registry web portal and were respon- individuals, ensure that the correct TIN/ plus an additional value-based mod- sible for their own data entry. While NPI combination(s) is entered for each ifier penalty of 1% or 2% for smaller it seems that most of these manual one. Also be sure that every eligible (no more than 10 eligible clinicians) reporters were successful, several prac- clinician expected to remain in the and larger practices, respectively. Based tices did receive penalty notification practice in 2019 is included and signs on an average Medicare Fee Sched- letters for the following reasons: a Data Release Consent Form. If your ule of $270,036 for all PQRS-eligible • incorrect TIN, NPI, or TIN/NPI practice is group reporting, ensure that ophthalmologists, this would translate combination all the applicable TINs used in Medicare into a penalty adjustment of $8,101 to • not reporting for a physician in billing are correct in their Data Release Consent Forms. For more on 2017 MIPS reporting, BY FLORA LUM, MD, VICE PRESIDENT OF THE ACADEMY QUALITY AND see EyeNet’s MIPS Manual at aao.org/ DATA SCIENCE DIVISION. mips-manual-2017.

EYENET MAGAZINE • 55 PATIENT EDUCATION TOOLS Turn Your Patients into Informed Partners

Solve the challenge of informing your patients about their conditions and treatment options. The American Academy of Ophthalmology makes educating patients easy with the most complete suite of patient education tools available.

Brochures

Print-on-Demand Handouts

Video Education

Booklets

Order Today aao.org/store 866.561.8558 Academy Notebook NEWS ● TIPS ● RESOURCES

WHAT’S HAPPENING

State Societies Honored On Nov. 13 during AAO 2017, the Academy’s Secretariat for State Affairs recognized 2 societies with its 2017 Star Award. The Star Award program provides special recognition to state ophthalmology societies for outstanding efforts on programs or projects they STAR AWARDS. From left to right: Alan L. Wagner, MD, FACS, (VSEPS Past Pres- have implemented in the previous year. ident), Michael R. Keverline, MD (VSEPS Membership Chair), Anthony J. Viti, MD The winning societies are as follows. (VSEPS President-Elect and Academy Councilor for Virginia), Geoffrey G. Cooper, North Carolina Society of Eye Phy- MD, FACS (VSEPS Past President), and Kurt F. Heitman, MD (Academy Secretary sicians and Surgeons (NCSEPS)—for for State Affairs). its Ocular Melanoma Cluster Response project, which focused on investigating ogy societies may apply for this award Society of Eye Physicians and Surgeons and increasing patient awareness about by responding to the Secretariat for (www.nceyemed.org). an increased rate of diagnosis of ocular State Affairs’ annual organizational The Academy Secretary for State melanoma among younger people in survey of state societies. Affairs, Kurt F. Heitman, MD, applaud- the Huntersville, North Carolina area. ed the dedication and professionalism With other health care organizations, State Societies’ Outstanding of all executive directors on behalf of NCSEPS encouraged citizens to get Executive Directors state societies and ophthalmologists eye examinations to screen for ocular Each year, the Academy Secretariat for across the country. “State society exec- melanoma and other eye diseases. State Affairs publicly acknowledges utive directors are crucial members of Virginia Society of Eye Physicians state ophthalmology society executive ophthalmology’s team, and we in State and Surgeons (VSEPS)—for its Pro- directors for their outstanding con- Affairs value their expertise and their tecting Patients’ Access to Emerging tributions to their state societies and commitment to preserving quality eye Technologies effort, which worked to for their partnership and collabora- care in their states.” pass legislation that protects physicians’ tion with the Academy on its national right to evaluate and adopt new tech- efforts. During AAO 2017 in New TAKE NOTICE nologies that may improve patient care. Orleans, the Secretariat recognized To date, the Secretariat for State executive staff of 2 state ophthalmology Nominate a Colleague for Affairs has recognized 64 state ophthal- societies for their work. the Laureate Award mology society programs and projects 2017 Outstanding Executive Direc- The Academy is accepting nominations with the Star Award. State ophthalmol- tor: Organizational Development— through Jan. 31 for the 2018 Laureate Debra Alderman, Executive Director, Recognition Award. This award honors Washington Academy of Eye Physicians an outstanding ophthalmologist whose and Surgeons (www.waeps.org). scientific contribution to the field has 2017 Outstanding Executive Direc- shaped modern ophthalmology. tor: Political Action—Alan Skipper, To submit a nomination, visit aao. Executive Director, North Carolina org/about/awards/laureate#nominations.

EYENET MAGAZINE • 57 Don’t Miss the Jan. 15 itarian efforts, such as participation Deadline for MIPS in charitable activities, care of the If you are using the IRIS Registry to indigent, and community service. It ac- report the Merit-Based Incentive Pay- knowledges those who have performed ment System (MIPS), Jan. 15 is a key above and beyond the normal duties of date on 2 counts. an ophthalmologist. Finish manually entering your MIPS To obtain a nomination form, information by Jan. 15. This deadline please contact Member Services by applies if you are using the IRIS Regis- phone, 866-561-8558 (toll-free) or 415- try web portal to manually report qual- 561-8581; by fax, 415-561-8575; or by ity measures, advancing care information email, [email protected]. You (ACI) measures, or improvement activ- can also complete a nomination form ities. If you successfully integrated your at aao.org/about/awards/humanitarian. electronic health record (EHR) system with the IRIS Registry, your MIPS Follow @AAOjournal for quality data is automatically extracted the Latest Academy Journal from your EHRs, but you can only Articles LEADERSHIP DEVELOPMENT ACROSS report ACI measures and improvement Stay up-to-date on research from THE WORLD. Drs. Dissanayake and activities manually. Ophthalmology and Ophthalmology Brennan during the Asia Pacific Submit a signed data-release con- Retina via the @AAOjournal Twitter Academy of Ophthalmology’s (APAO) sent form for each provider by Jan. handle. New content is posted every Leadership Development Program 15. The IRIS Registry won’t submit a day, including new articles in press, (LDP) master class session held Sept. provider’s MIPS data to Centers for fascinating “Pictures and Perspectives,” 29 through Oct. 1 in Sri Lanka. Medicare & Medicaid Services (CMS) thought-provoking editorials, and new unless it has received the signed con- issue alerts. sent form by Jan 15. You must submit collection of poems in honor of teachers a new consent form each year and can MEMBERS AT LARGE who were instrumental in steering her do so via the IRIS Registry dashboard. career, including a poem for the faculty For instructions, visit aao.org/consent- ACS Election at the APAO LDP. Dr. Dissanayake wrote form. Sarwat Salim, MD, has been elected to that the APAO LDP was “a unique To learn more about the IRIS Regis- the Board of Governors of the American experience during a period of 2 years try and MIPS, visit aao.org/iris-registry College of Surgeons (ACS), expanding into 3 countries. The jour- and aao.org/medicare. the largest organization ney started in Japan, was followed by of surgeons in the world the APAO LDP Masterclass in Vietnam, International Blindness with over 80,000 and then wound up in China.” The Prevention Award members. Dr. Salim Academy’s 20th LDP class meets in Established in 1992, the said, “I am honored San Francisco Jan. 12-14. The Academy International Blindness Pre- to represent ophthal- continues to collaborate with its coun- vention Award is presented at mology and look for- terpart LDPs from the supranational the Academy’s annual meeting ward to working with societies, including APAO, European to honor individuals who have Dr. Salim ACS leadership in Society of Ophthalmology, Pan-Ameri- made significant contributions raising the standards can Association of Ophthalmology, to the prevention of blindness or resto- of surgical practice across the board and the African Council of Ophthal- ration of sight. The deadline through education, quality, advocacy, mology. for 2019 nominations is Feb. 20. and health policy.” To submit a nomination, visit aao. OWL Awards org/about/awards/blindness-prevention. LDP in Sri Lanka Ophthalmic World Leaders (OWL) is a Madhuwanthi Dissanayake, MBBS, U.S. not-for-profit organization dedi- Seeking Outstanding MD, a graduate of the Asia Pacific cated to driving ophthalmic innovation Ophthalmologists Academy of Ophthalmology’s (APAO) and patient care by advancing diversity Would you like to nominate a colleague Leadership Development Program in leadership. On Nov. 12 during OWL’s for next year’s Outstanding Human- (LDP) and now president of the signature event at AAO 2017, OWL’s itarian Service Award? The Academy College of Ophthalmologists of Sri president, Heather Ready, presented must receive your nomination by Lanka (COSL), presented LDP faculty Cynthia Matossian, MD, FACS, with March 16, 2018. This award recognizes and Academy past president Michael the Visionary Award. The OWL Awards Academy fellows and members for W. Brennan, MD, with “A Tribute” are given to those who best exemplify outstanding contributions to human- booklet. It highlights Dr. Dissanayake’s OWL’s core values and vision.

58 • JANUARY 2018 Who’s in the News D.C. REPORT Brian Boxer Wachler, MD, was featured on Great Day Washington Morning Major Quality Program Changes and Show (WUSA9) with hosts Chris Leary, Markette Sheppard, and Meaghan Stable Payments Mooney to discuss his new book, Per- The 2018 Medicare fee schedule will provide some relief for ophthal- ceptual Intelligence: The Secret Behind mologists. The policy, unveiled by the Centers for Medicare & Medic- Perception Revealed. Via concrete exam- aid Services (CMS) in November, adopts much of what it proposed ples and case studies, the book explains in the summer of 2017, including several major Academy wins. High- why senses do not always match reality lights of the CMS policy include the following: and describes how we can influence the • All proposed, retroactive changes to the Physician Quality Report- world through perceptions. ing System (PQRS) have been finalized. This reduced the number of For more information, visit www. required quality measures physicians must report on. This change perceptualintelligence.com. stemmed from the Academy spearheading a months-long regulatory ACADEMY STORE relief campaign, and it is a significant win for ophthalmology. • All proposed, retroactive changes to meaningful use were finalized. • All changes to the value-based modifier, including a 50% cut in Jan. 10 Webinar on New Cat- value-based modifier penalties, were finalized. aract Surgery Technologies • There was a zero net change, overall, for ophthalmology during Join experts Sonia H. Yoo, MD, Eric D. 2017—CMS generally spared us from major reductions. Donnenfeld, MD, Douglas D. Koch, • All revised work values proposed by the Academy and the AMA/ MD, Rachel A. Lieberman, MD, and Specialty Society RVS Update Committee were accepted. Bruna V. Ventura, MD, on Jan. 10 for Changes to legacy quality programs stick. CMS will adopt changes a live, interactive webinar that will to legacy quality programs, including PQRS, meaningful use, and the expand your repertoire of techniques value-based modifier. In doing so, the agency reduces the require- for achieving improved refractive ments on which you’ll be scored. It will not, however, reopen PQRS outcomes. New Technology in Cataract submissions for 2016. The Academy devoted many hours to convincing Surgery and Multifocal Implants will CMS that these were necessary changes to the existing policy, as they deepen your understanding of both provide significant relief for affected physicians. manual and femtosecond laser-assisted Slight uptick in physicians’ conversion factor. CMS increased the techniques for limbal-relaxing inci- physician conversion factor to 35.99. This is an increase from 2017’s sions and multifocal toric intraocular 35.8887. lenses (IOLs). Presenters will also share CMS limits what the public will see on Physician Compare. The pearls in patient selection and surgical Physician Compare website will not share your value-based modifier planning. results. This is significant because the public lacks the necessary con- Visit aao.org/store to sign up for the text to understand this program. webinear or purchase the recording. No overall reduction in payments. There are some reductions to the low-volume services. These stem from the time for these procedures, Help Your Patients Remem- which has changed significantly over the years. Overall, though, pay- ber What You Tell Them ments for ophthalmic services will remain stable for 2018. Nearly half of American adults find it challenging to comprehend basic medical information, and many immediately forget the information and instruc- coding products are now available for the most significant coding and reim- tions provided by physicians. To save shipping. These updated coding tools bursement changes impacting ophthal- time, improve recall, and mitigate your developed by coding experts ensure mology. If you can’t attend, you can risk, give your patients the Academy’s you’re coding correctly so you can max- purchase a recording. easy-to-understand, ophthalmologist- imize your reimbursements and avoid To register, visit store.aao.org/ reviewed brochures and handouts. audit triggers. Save 10% when you buy webinar-2018-ophthalmology-coding- To order brochures, visit aao.org/ 4 or more. updates.html. patientbrochures. Visit aao.org/codingproducts. To subscribe to handouts, visit aao. Codequest 2018 Is Coming org/patienthandouts. Jan. 5 Webinar on 2018 to a City Near You Coding Updates Get expert instruction from the rec- Now Shipping: Ophthalmol- Make sure you’re up to date by attend ognized leader of ophthalmic coding ogy’s Leading Coding Tools ing the 2018 Coding Update on Jan. 5. programs at the Academy’s Codequest The Academy’s complete suite of 2018 The 60-minute webinar will spotlight 2018 course, a 4-hour course presented

EYENET MAGAZINE • 59 with the ophthalmic state societies. ing and assessment, and educational participation in this process. Member- Stay up-to-date on changing regula- publications. ship participation is vital, not only for tions, get strategies for maintaining Trustee-at-large (4-year term). This the Academy but also for our collective compliance with federal and commer- individual should be an Academy Fellow goals of being able to provide appropri- cial payers’ rules, and learn the latest who demonstrates strong leadership ate, accessible, and affordable eye care tactics to maximize your reimburse- potential and would be able to rep- to the public. On behalf of the Nom- ments. resent and articulate the needs and inating Committee, I look forward to For a list of 2018’s first 16 Code- concerns of the membership to the receiving your suggestions as we seek to quest events, see page 52. Academy board. identify our profession’s future leaders. To learn more and sign up, visit aao. International trustee-at-large (3- Send your confidential suggestions org/codequest. year term). This individual should by Jan. 31 to Cynthia A. Bradford, be an Academy International Fellow MD; Nominating Committee Chair, FOR THE RECORD or Member who practices exclusively American Academy of Ophthalmolo- outside of the United States. He or she gy, P.O. Box 7424, San Francisco, CA Nominations for the should have a strong affinity for the 94120-7424. Suggestions can also be Academy Board Academy and broad experience and e-mailed to [email protected] or faxed By Cynthia A. Bradford, MD understanding of his or her region. This to 415-561-8526. As past president of the Academy, it is individual should be able to represent For more information, go to aao.org/ my privilege to serve as chairman of the and articulate to the Academy board about/governance/board-nominations. Academy’s Nominating Committee in the perspective of international mem- 2018. This committee represents a vari- bers. Election Results ety of interests within the Academy and Public trustee (a renewable 3-year On Nov. 13, voting opened for 5 po- is charged with identifying appropriate appointment; an advisor to and mem- sitions on the 2018 Board of Trustees. candidates for the open positions on ber of the Board of Trustees). The by- The results are as follows: the 2019 Board of Trustees. laws allow the board to appoint up to 3 President-Elect: George A. Williams, We are interested in identifying public trustees. We currently are served MD leaders in our profession with experi- by Paul B. Ginsburg, PhD. Public trust- Senior Secretary for Advocacy: Daniel ence in confronting the critical issues ees provide insight on how ophthal- J. Briceland, MD facing organized medicine and who mology can better work with the rest of Trustee-at-Large: William S. Clifford, reflect the strength and diversity of medicine, the public, government, and MD our members. The Academy’s leaders industry. The nominating committee Chair, the Council: Lynn K. Gordon, should be knowledgeable, experienced, will be pleased to receive suggestions MD, PhD and prepared to devote the time and for individuals, who may include physi- Vice Chair, the Council: Sarwat Salim, energy required by a large organization cians from other medical specialties or MD, FACS in these challenging times. This work leaders in industry, government, public For more information about the is both demanding and rewarding for policy, or advocacy. elections, visit aao.org/about/gover those interested in helping to assure the Thank you for your interest and nance/elections. Academy’s success and responsiveness to members. With these characteristics in mind, I ask you to assist the ABOUT THE NOMINATING COMMITTEE committee by suggesting appropriate The Academy nominating process has been carefully crafted to be inclu- candidates for the following positions sive, fair, and efficient. This process encourages a broad base of nomina- in 2019: tions from the entire Academy membership. The Nominating Committee President-elect (to serve as presi- composition is delineated by the bylaws, and it considers a number of dent in 2020). Nominees should have factors when screening potential candidates. These include integrity, leadership experience within the Acad- ophthalmology leadership ability, special expertise, past committee and emy as well as demonstrated leadership leadership experience and performance, and knowledge and interest in qualities in clinical practice, in their the multitude of issues currently facing ophthalmology. In addition to own ophthalmic communities, and nominations from the current year, the committee reviews prior-year in other medical or ophthalmological nominations to ensure a wide range of potential candidates for each organizations. position. Following months of confidential deliberations, the committee Senior Secretary for Clinical presents final recommendations to the Board of Trustees for approval. Education (3-year term). This senior This single-candidate method avoids the loss of valuable future leaders, secretary coordinates the programs and as there are no public “losers” in the election. Often, those considered activities of the Academy’s education but not selected for an open position one year become the nominee of division including curriculum develop- choice in a future year. ment, online education, lifelong learn-

60 • JANUARY 2018 Save the Date Mid-Year Forum 2018 Politics. Policy. Practice Management.

April 18 – 21 Washington, DC

Registration Opens Help Make a Positive Impact in January 2018. on Ophthalmology’s Future aao.org/myf #myf2018 Mid-Year Forum is one of the Academy’s most significant yearly meetings, bringing the ophthalmology community together to drive change and shape our profession’s future.

• Meet with federal lawmakers during Congressional Advocacy Day.

• Directly advocate for your profession and patients.

• Learn about changes that impact how you practice.

• Develop key strategies for successfully implementing new programs into your patient-care approach.

• Hear from expert panels on the future of our profession.

• Play a key role in driving the highest quality of care for your patients. MYSTERY IMAGE BLINK Patrick A. Coady, MD, MBA, West Haven Veterans Affairs Eye Clinic, Clinic, Eye Affairs Veterans Haven West MBA, MD, A. Coady, Patrick Conn. Haven, West

WHAT IS THIS MONTH’S MYSTERY CONDITION? Visit aao.org/ eyenet to make your diagnosis in the comments.

LAST MONTH’S BLINK 1A 1B Traumatic Aniridia

77-year-old woman, 2 weeks after under going uncomplicated laser-assisted phaco emulsification of her right eye, presented A 1C 1D 2 hours after falling onto the right side of her face. Her vision was hand motion with 2+ corneal folds, total hyphema, and IOP of 40 mm Hg. There was no evidence of corneal or scleral laceration. Upon emergent anterior chamber washout (1A; note residual blood), absence of the iris was observed (1B). No vitreous hemorrhage or retinal detach intact. Thus, it is possible that the IOL may have ment was evident. The recently implanted IOL acted to absorb the impact and block disruption was centered and intact within the capsular bag. of surrounding tissue.5 An additional theory is The patient was placed on topical glaucoma that the traumatized iris may have remained with- medications, bed rest, and a short course of oral in the eye, only to undergo rapid phagocytosis by prednisone. Over 1 month, her corneal edema macrophages and trabecular meshwork cells.3 and hyphema cleared (1C). A year later, with total aniridia and a centered, intact IOL (1D), she 1 Gencer B et al. Turk J Ophthalmol. 2014;44:80-82. denies complaints of glare and has maintained 2 Kim KH, Kim WS. Arq Bras Oftalmol. 2016;79(1):44-45. 20/30 uncorrected VA. 3 Parmeggiani F et al. J Ultrasound Med. 2007;26:1795-1797. There are few reports of isolated aniridia in 4 Muzaffar W, O’Duffy D. J Cataract Refract Surg. 2006;32(2): pseudophakic eyes after nonperforating blunt 361-362. trauma, without dehiscence/extension of the 5 Khemka S et al. The Internet Journal of Ophthalmology and cataract incision.1-6 Small self-sealing modern Visual Science. 2005;4(1):1-4. cataract incisions appear to be protective against 6 Mikhail M et al. Clin Ophthalmol. 2012;6:237-241. expulsion of intraocular contents, which has led to several theories regarding the mechanism of traumatic aniridia.2-6 Acute rise in IOP from blunt WRITTEN BY ALANNA S. NATTIS, DO, LINDENHURST trauma may allow the corneal incision to act as a EYE PHYSICIANS AND SURGEONS, BABYLON, N.Y.; “release valve,” promoting rapid progression of an HENRY D. PERRY, MD, NASSAU UNIVERSITY MEDICAL iridodialysis to complete avulsion and subsequent CENTER, EAST MEADOW, N.Y.; ERIC D. DONNENFELD, expulsion due to the high-velocity injury.3,4 In our MD, NEW YORK UNIVERSITY, NEW YORK, N.Y.; ERIC D. case, there was total iris loss, but the remainder ROSENBERG, DO, NEW YORK MEDICAL COLLEGE, of the intraocular contents remained stable and VALHALLA, N.Y.

62 • JANUARY 2018 Amplifying your voice in Washington, D.C. — Make Your Voice The Academy leads ophthalmology’s efforts to prevent new administrative burdens and Heard on Key minimize the effect of penalties on your practice. No other ophthalmic organization Issues That Impact has our deep relationships with leaders who shape guidelines for Medicare, the Patient Care Department of Veterans Affairs and the F.D.A.

Renew your Academy Protecting surgery by medically and membership to support sound surgically trained physicians — The Academy is actively fighting in every U.S. healthcare policy. state and territory to ensure that eye surgery is the exclusive responsibility of surgeons.

Providing expert insight into the policies that affect your practice and patients — The Academy’s experts provide leading analysis to help you understand how your practice is affected when federal agencies change and evolve the nation’s myriad health policies.

Activate your benefits and renew your valuable membership today. aao.org/benefits

Rep. Dave Loebsack (D-Iowa), left, met with Academy Advocacy Ambassador Philip I. Niles, MD, MBA, during Mid-Year Forum 2016’s Congressional Advocacy Day. This in-person advocacy allows attendees to directly interface with federal lawmakers on behalf of ophthalmology’s patients, discussing topics such as fair Medicare physician reimbursements, relief from administrative burdens, and preserving access to sight- saving compounded drugs. azasite new master ad.pdf 1 12/12/17 11:08 AM

ONLY

Combines Azithromycin ®

C with DuraSite

M Y Now included in the CM ® MY RxDirect Service CY • Eye patients save significantly CMY on their prescription and it can be K delivered to their home for free

Visit azasite.com to learn more