Lean Practice Lessons Learned During the Pandemic

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42-47 Lean Practice: Lessons Learned During the Pandemic During the public health emergency, practices had to make some drastic changes. Which innovations are worth keeping, and how practices can stay nimble.

CLINICAL INSIGHTS 13-15 News in Review Cornea Graft survival in the time of COVID. Retina Ranibizumab biosimilar for treatment of AMD. 42 Cataract Outcomes in patients who’ve had anti-VEGF injections for DME. Glaucoma The worldwide impact of undetected disease.

19-23 Journal Highlights Key findings from Ophthalmology, Ophthal- mology Retina, AJO, JAMA Ophthalmology, and more.

25-31 Clinical Update 13 25 Cornea A look ahead to the Zoster Eye Disease Study and an update on the Herpetic Eye Disease Study. 29 32 Glaucoma Xen and Preserflo: Where these bleb-forming MIGS devices fit into the glau coma surgery landscape.

32-34 Ophthalmic Pearls Macular Hole Idiopathic and traumatic macular hole diagnosis, management, and outcomes—just in time for July 4.

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 to EyeNet, P.O. Box 7424, San Francisco, CA 94120-7424. American Academy of Ophthalmic Executives®, EyeSmart®, EyeWiki®, IRIS®, ONE®, the Focus logo, and Protecting Sight. Empowering Lives ® among other marks are trademarks of the American Academy of Ophthalmology®. All other trademarks are the property of their respective owners.

EYENET MAGAZINE • 5 Figure 1:

CLINICAL INSIGHTS 37-39 Morning Rounds Not Your Typical Headlight in the Fog The 11-year-old had experienced blurry vision for two months before she was referred to us for retinal inflammation. What’s your diagnosis?

IN PRACTICE 49-50 Savvy Coder 37 Coding for Ocular Trauma Tip: In the emergency department, the 1997 E/M rules still apply.

FROM THE AAO 53-56 Academy Notebook Dr. Parke to step down as Academy CEO. • Highlights of the second virtual Congressional Advocacy Day. • And more. 53 59-60 Destination AAO 2021 Celebrate 20 years of Spotlight on Cataract. • Members can register now for AAO 2021. • And more.

VIEWPOINTS 10 Opinion What will we do with our garbage? 12 Current Perspective 59 Industry-sponsored speaker programs.

MYSTERY IMAGE 62 Blink What do you see?

COVER IMAGE Beth Pelar, COA, and Mark Lucarelli, MD, FACS, at UW Health in Madison, Wisconsin. 62

® COPYRIGHT © 2021, 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 appr oved 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.

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1575725-01 BVI IPure Ad EyeNet 8.125 x 10.875 06-03-21 FINAL.indd 1 6/3/21 1:22 PM “The purpose of human life is to serve, and to show compassion and the will to help others.” – Albert Schweitzer

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Philadelphia, PA / www.willseye.org / 877.289.4557 EDITORIAL BOARD ®

MAGAZINE CATARACT LOW VISION REFRACTIVE SURGERY Kendall E. Donaldson, MD Joseph L. Fontenot, MD Soosan Jacob, FRCS David W. Parke II, MD Section Editor John D. Shepherd, MD Section Editor Editor-in-Chief William R. Barlow, MD John So-Min Chang, MD NEURO-OPHTHALMOLOGY Ruth D. Williams, MD John P. Berdahl, MD Damien Gatinel, MD Prem S. Subramanian, MD, PhD Chief Medical Editor Jeff H. Pettey, MD A. John Kanellopoulos, MD Section Editor Dale E. Fajardo, EdD, MBA Michael E. Snyder, MD Terry Kim, MD Rod Foroozan, MD Publisher Marie Jose Tassignon, MD Bradley J. Katz, MD Karolinne M. Rocha, MD Tim Schultz, MD Patty Ames COMPREHENSIVE Heather Moss, MD, PhD Executive Editor OPHTHALMOLOGY RETINA/VITREOUS OCULOPLASTICS Carey S. Ballard Linda M. Tsai, MD Femida Kherani, MD Janice C. Law, MD Section Editor Section Editor Art Director / Program Manager Section Editor Donna H. Kim, MD Chris McDonagh, Jean Shaw Elizabeth A. Bradley, MD Neil M. Bressler, MD April Y. Maa, MD Senior Editors Kasturi Bhattacharjee, MS, DNB, Albert O. Edwards, MD, PhD Suzann Pershing, MD FRCSEd, FRCS( Glasg) Mary Elizabeth Hartnett, MD, FACS Miranda Smith Gregg T. Kokame, MD Associate Editor / CORNEA AND EXTERNAL Laura A. Gadzala, MD Timothy Y. Lai, MD, FRCOphth, Advertising Manager DISEASE OPHTHALMIC ONCOLOGY Kathryn A. Colby, MD, PhD FRCS Lori Baker-Schena, MBA, EdD; Section Editor Dan S. Gombos, MD Prithvi Mruthyunjaya, MD, MHS Leslie Burling; Peggy Denny; Section Editor Deborah S. Jacobs, MD Andrew P. Schachat, MD Miriam Karmel; Mike Mott; Jesse L. Berry, MD Linda Roach; Lynda Seminara; Bennie H. Jeng, MD Lisa S. Schocket, MD Lauren A. Dalvin, MD Annie Stuart; Rebecca Taylor Carol L. Karp, MD TECHNOLOGY Contributing Writers Stephen D. McLeod, MD OPHTHALMIC PATHOLOGY Cecilia S. Lee, MD, MS Patricia Chévez-Barrios, MD Anuradha Khanna, MD Mark Mrvica, Kelly Miller GLAUCOMA Steffen Heegaard, MD, DMSc Jun Kong, MD M.J. Mrvica Associates, Inc. Ahmad A. Aref, MD, MBA 2 West Taunton Ave., Section Editor OPHTHALMIC UVEITIS Berlin, NJ 08009 Lama Al-Aswad, MD, MPH PHOTOGRAPHY Debra A. Goldstein, MD 856-768-9360 Sahar Bedrood, MD, PhD Jason S. Calhoun Section Editor [email protected] Henry D. Jampel, MD, MHS PEDIATRIC Muge R. Kesen, MD Advertising Sales Anthony P. Khawaja, MBBS OPHTHALMOLOGY Phoebe Lin, MD, PhD Ronit Nesher, MD Laura B. Enyedi, MD Marion Ronit Munk, MD, PhD Joseph F. Panarelli, MD Section Editor Richard K. Parrish II, MD Jane C. Edmond, MD Sarwat Salim, MD, FACS Kim Jiramongkolchai, MD 655 Beach St. Lucy Q. Shen, MD A. Melinda Rainey, MD San Francisco, CA 94109 Federico G. Velez, MD 866-561-8558, 415-561-8500 aao.org

Governmental Affairs Division ACADEMY BOARD 20 F Street NW, Suite 400 PRESIDENT SR. SECRETARY FOR PUBLIC TRUSTEES Washington, DC 20001 202-737-6662 Tamara R. Fountain, MD CLINICAL EDUCATION Paul B. Ginsburg, PhD Christopher J. Rapuano, MD David C. Herman, MD PRESIDENT-ELECT ARTICLE REVIEW PROCESS. Articles James A. Lawrence involving single-source medical and tech- Robert E. Wiggins Jr., MD, MHA SR. SECRETARY FOR nical news are sent to quoted sources for OPHTHALMIC PRACTICE TRUSTEES-AT-LARGE verification of accuracy prior to publication. PAST PRESIDENT Quotes and other information in multisource Ravi D. Goel, MD William S. Clifford, MD articles are subject to confirmation by their Anne L. Coleman, MD, PhD respective sources. The chief medical editor Mary Louise Z. Collins, MD CHAIR, THE COUNCIL and the executive editor review all news and CEO Anna Luisa Di Lorenzo, MD feature articles and have sole discretion as David W. Parke II, MD Sarwat Salim, MD, FACS to the acceptance and rejection of material Judy E. Kim, MD and final authority as to revisions deemed SR. SECRETARY FOR VICE CHAIR, THE COUNCIL Ron W. Pelton, MD, PhD necessary for publication. Thomas A. Graul, MD ADVOCACY Aaron P. Weingeist, MD DISCLOSURE KEY. Financial interests are indicated by the following abbrevia- George A. Williams, MD OPHTHALMOLOGY EDITOR INTERNATIONAL tions: Stephen D. McLeod, MD C = Consultant/Advisor SECRETARY TRUSTEES E = Employee FOR ANNUAL MEETING CHAIR OF THE FOUNDATION Alison Blake, MBBCH L = Speakers bureau O = Equity owner Maria M. Aaron, MD ADVISORY BOARD Donald Tan, MD, FRCS P = Patents/Royalty S = Grant support Gregory L. Skuta, MD Learn more about the Board at For definitions of each category, see aao.org/bot. aao.org/eyenet/disclosures.

8 • JULY 2021 Opinion

RUTH D. WILLIAMS, MD What Will We Do With Our Garbage?

he Mariana Trench is the deepest known place on cient protocols are implemented, a step that is necessary to planet Earth. The southern end of the trench, named convince regulatory agencies, health systems, and industry TChallenger Deep, is its lowest point. When Victor partners. The group is looking at three categories: single-use Vescovo, the American explorer and private equity investor, pharmaceuticals, reusable surgical supplies, and disposables. explored Challenger Deep in his submarine, he set the world Waste is so embedded in our surgical culture that change record for the deepest dive and identified three new species requires work at nearly every step. David Palmer, an oph of marine animals. He also found a plastic bag. thalmologist in Illinois, became increasingly frustrated that Some 150 metric tons of plastic circulates in marine eco medications used at the end of surgery are discarded. He systems, and we add 8 million metric tons of plastic waste pushed for the introduction of SB0579, every year,1 but plastic in the ocean is only one aspect of the which would allow patients to take global waste problem. Our health systems contribute an esti home topically applied medica mated 8% to 10% of the greenhouse gas emissions in the tions from surgery if needed for United States,2 and much of the waste is generated from post-op care. The bill passed in surgery. Think of the gloves and gowns, device packaging, the Illinois Senate and House single-use medications, tubing, and sheets that are thrown out and is now on the governor’s after every ophthalmic procedure. Because cataract surgery desk. Other ophthalmologists is the most commonly performed medical procedure world are interested in cellulose wide, addressing its waste is a great place to start. biodegradable surgical drapes, The good news: Among ophthalmologists, the interest in multidose labeling of phar tackling this challenge is growing. In a survey of 1,200 oph maceuticals, and decreasing thalmologists, 93% expressed concern about the amount of our dependence on single-use waste produced by cataract surgery and supported action to surgical supplies. reduce the garbage.3 In a Baltimore Sun editorial, published The shift to green surgery should on Earth Day, Sathvik Namburar and glaucoma specialist be anchored in evidence, driven by en Ruth D. Alan Robin argued that even those who are not convinced vironmental concerns, and motivated Williams, MD by the environmental argument should be concerned about by economic efficiencies. Each of us Chief Medical the economic implications of surgical waste.4 For instance: can become more aware of—and more Editor, EyeNet In one study, staff at one site threw out nearly $200,000 per uncomfortable with—the level of waste year of unused eyedrops after cataract surgery.5 generated by cataract surgery. Jeff Pettey, If ophthalmologists agree that the mountain of physical a member of the Academy’s Young Ophthalmologist Com waste is a problem, what can we do? The Ophthalmic Instru mittee, observes: “I’m witnessing a refreshing level of aware ment Cleaning and Sterilization (OICS) Task Force, chaired ness and concern among young physicians. As they become by David Chang and Cathleen McCabe and comprising the leaders of tomorrow, I predict green medicine will become representatives from several ophthalmology organizations, a core value for all of ophthalmology.” Let’s start now. is developing multipronged pragmatic strategies to decrease ophthalmic surgical waste. 1 www.worldwildlife.org/initiatives/oceans. Accessed May 11, 2021. We’ve all taken the oath primum non nocere (“First, do 2 Chung JW, Meltzer DO. JAMA. 2009;302(18):1970-1972. no harm”), and to promote safety, we’ve developed steril 3 Chang DF et al. J Cataract Refract Surg. 2020;46(7):933-940. ization and single-use standards that are not always evi 4 Namburar S, Robin A. U.S. health care sector combatting one crisis, but dence-based. The OICS Task Force is developing evidence that contributing to another: climate change. Baltimore Sun. April 23, 2021. endophthalmitis rates are not increased when resource-effi 5 Tauber J et al. JAMA Ophthalmol. 2019;137(10):1156-1163.

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DAVID W. PARKE II, MD Industry-Sponsored Speaker Programs

he relationship between pharmaceutical and medical Why is the OIG concerned? Because they deem this to be device companies and individual physicians is com a violation of the federal False Claims Act and anti-kickback Tplex. At one end of the spectrum, the three parties are statute by inducing physicians to differentially united by a desire to serve patients by developing, evaluating, prescribe drugs and devices to benefi and effectively disseminating new drugs and devices. Who ciaries in federal health programs, doesn’t want more effective therapeutic options for glaucoma costing the government billions of and diabetic retinopathy? At the other end, substantive (and dollars annually. opaque) financial entanglements can pollute the waters. KOLs have unique value Medical societies and academies also risk conflicts of in this setting. They are not interest given the interface between companies and large company employees. They meetings, journal and website advertisements, and contin are generally respected and uing medical education sponsorship. Fifteen to 20 years ago trusted. When they speak to this was a real problem, with some specialty societies deriving an audience of their peers large percentages of their revenue from industry. (That was at the behest of the company never the case for the Academy.) Fortunately, for all concerned, about a drug, device, or disease, a combination of government regulations, industry guide their opinion carries gravitas that lines, and accreditation agency policies have curtailed those might not attach to an employee of abuses. All organizations accredited to grant continuing CME the company itself. credits are regularly audited and subject to sanction if vio The OIG is particularly concerned David W. lations are detected. Most significantly, nearly a decade ago, about programs of suspect educational Parke II, MD the Academy was one of the first of more than 50 medical value—notably when “offered under Academy CEO societies to sign the landmark Council of Medical Specialty circumstances that are not conducive Societies policy “Code for Interactions with Companies.” This to learning.” Other red flags include speaker selection when detailed document and list of signatories is publicly available.1 influenced by company marketing divisions and reliance on I can confidently state that the Academy complies with the company-developed marketing materials for presentation. most stringent of applicable regulations and policies. Does this mean that all industry-sponsored speaker pro- But what about individual physicians who are recruited to grams are out of bounds? Absolutely not. Educationally- serve as paid speakers in industry-sponsored speaker pro sound, industry-sponsored programs will probably remain an grams? (They are sometimes referred to by the companies important component of CME—in legitimate educational as “key opinion leaders” or “KOLs.”) We’re not talking here programs with appropriate review and oversight. Companies about relationships as consultants, receiving research sup will endeavor to comply with this recent OIG Special Fraud port, or serving in clinical trials. This concerns being paid Alert as the economic sanctions and reputational risk are by a company to speak to other physicians to impact clinical prohibitive. Ophthalmologists, ophthalmic organizations, decision-making. The Office of the Inspector General (OIG) and ophthalmic industry must all continually self-monitor for the U.S. Department of Health and Human Services to retain the trust of those who depend upon us for indepen warns of “the fraud and abuse risks associated with the dent, science-based, and patient-centric clinical behavior. offer, payment, solicitation, or receipt of remuneration” in industry-sponsored speaking programs.2,3 How big an issue 1 https://cmss.org/code-signers-pdf/. is this? In recent years, aggregate payments have approached 2 https://oig.hhs.gov/fraud/docs/alertsandbulletins/2020/SpecialFraudAlert $1 billion. While oncology, cardiology, and orthopedics tend SpeakerPrograms.pdf. to top the list, ophthalmologists are represented as well. 3 Adashi EY, Cohen IG. JAMA. 2021;325:1835-1836.

12 • JULY 2021 News in Review COMMENTARY AND PERSPECTIVE

CORNEA nitely can occur— Corneal Graft and second, that early recognition Survival and COVID and early inten- Vaccines sive treatment are essential,” Dr. Phylactou said. AS MORE PATIENTS ARE VACCINATED Case exam- against COVID-19, cornea surgeons ples. The first are encountering a late postoperative affected patient complication that heretofore has been at Moorfields rare: postvaccination corneal allograft had a successful, ACUTE EARLY REJECTION. Endothelial rejection occurred rejection. unilateral kera- seven days after this patient received her COVID vaccination. The first publication of case reports toplasty with full came in April, from clinicians at Moor- graft attachment, a clear cornea, and corneal tissue, she said. fields Eye Hospital in London.1 Prior best-corrected visual acuity (BCVA) “In the first case, you could see to that, anecdotal reports of COVID of 6/6 (20/20) at postsurgical day 7. the rejection happen very quickly, at vaccine–associated rejection episodes Fourteen days after the transplant, the time when the immune system began surfacing during the first few she received the first injection of the would be responding to the vaccine. months of 2021, and some of these Pfizer-BioNTech vaccine. A week later, In the second case, the patient had a likely will be the subjects of additional her VA decreased, and she developed serious reaction bilaterally, which is peer-reviewed papers this year, said other signs of acute rejection. extremely rare, considering that she Bennie H. Jeng, MD, at the University The second patient had bilateral had a different donor for each eye. So of Maryland School of Medicine in grafts that had been functioning well that makes the probability of a causal Baltimore. for six years and three years. Three association with the vaccination even “This is an issue around the world,” weeks after her second dose of the higher,” she said. Dr. Jeng said. “On the Kera-net listserv Pfizer-BioNTech vaccine, she presented Dr. Jeng noted that in the cases that of the Cornea Society, more and more with acute graft rejection in both eyes. he has heard about anecdotally, rejec- cornea surgeons are reporting this with Treatment consisted of one week tion seems to occur one to two weeks the COVID vaccinations.” of hourly dosing with corticosteroid after the second vaccine dose, which Need for ongoing vigilance. Maria eyedrops (dexamethasone), followed suggests the body’s immune response Phylactou, MD, who coauthored the by judicious tapering. Both patients is the culprit. “That makes sense, right? Moorfields paper, and Dr. Jeng agreed recovered their previous visual acuity, Because the second shot is the one ex- that it is important for ophthalmologists the researchers reported. posing the patient to the antigens that in the COVID era to be vigilant for this. An issue of timing? Although a the body is seeing for the second time,” Even eyes that have been doing well causal link is not proven, the timing of he said. for years following a transplant can be vaccination and development of rejec- Not a brand-new issue. The litera- affected, so patients should be alerted tion signs suggested to Dr. Phylactou ture contains a few reports over the last to watch for rejection signs, they said. and her colleagues that the patients’ three decades of vaccine-related graft “What we’d like to highlight is, first, immune responses might have been rejection, Dr. Jeng said. He is a coau-

Maria Phylactou, MD Maria Phylactou, that this is a very rare event, but it defi- injuring the inner surface of the donor thor of a study slated to be published

EYENET MAGAZINE • 13 in Cornea; when he and his colleagues RETINA surveyed cornea surgeons before the Biosimilar Drug pandemic, they found that a fifth of the respondents had seen rejection asso- for AMD Shows ciated with herpes zoster or influenza Promise vaccines.2 Advice to patients. Neither Dr. Phylactou nor Dr. Jeng would discour- THE BIOSIMILAR OPHTHALMIC DRUG age patients from getting the COVID FYB201 (bioeq/Formycon) is clinically vaccine. equivalent to ranibizumab for treating However, postponing nonurgent neovascular age-related macular degen- keratoplasties until a few months after eration (AMD), an international team vaccination might be worthwhile, they of researchers has reported.1 HEADED TO MARKET? If approved, said. If this is not possible, patients “The study showed noninferiority biosimilars could lower the financial should be advised to seek treatment between the biosimilar FYB201 and the burden of AMD treatment. early if signs of rejection occur, they reference product, ranibizumab,” said said. And those with existing corneal coauthor Peter K. Kaiser, MD, at the patients with wet AMD were evaluated grafts also should be reminded of this, Cleveland Clinic’s Cole Eye Institute. at centers in 12 countries. Participants Dr. Jeng added. —Linda Roach He added, “Biosimilars are different were randomized to receive monthly from generic medications and require injections of either FYB201 (n = 238) 1 Phylactou M et al. Br J Ophthalmol. Published different regulatory hurdles. However, or 0.5 mg ranibizumab (n = 239). online April 28, 2021. the study did show noninferiority, At 48 weeks, data were available on 2 Lockington D et al. Cornea. 2021. In press. which would suggest similar efficacy.” 199 patients who had received FYB201 Relevant financial disclosures—Drs. Jeng and Study specifics.For the prospec- and 189 in the ranibizumab cohort. Phylactou: None. tive phase 3 study, treatment-naive Mean improvement in best-corrected

CATARACT ments before and after surgery. Outcomes After Cataract Worsening of DME. “Perhaps the most surprising result was that 46% of eyes developed worse DME Surgery in Patients With DME following cataract surgery,” said coauthor Sophie J. Bakri, MD. However, nearly all of these eyes did not PATIENTS WITH DIABETIC MACULAR EDEMA (DME) WHO have worse VA at any postoperative time point than are actively managed with anti-VEGF injections before did those eyes without new fluid. and after cataract surgery may experience mixed out- Active management required. Careful patient comes: While visual acuity (VA) may improve in these selection may account for the surgery’s success, patients, their DME may worsen and perhaps require the researchers said. additional treatment, report researchers at the Mayo “Our practice is conservative in choosing patients Clinic in Rochester, Minnesota.1 for cataract surgery, especially in those eyes with DME. Real-life outcomes. For this study, the researchers The cataracts were visually significant, which is likely retrospectively reviewed the charts of 30 patients (37 the reason patients saw a significant improvement in eyes) who underwent cataract surgery from Jan. 1, vision,” said lead author Matthew R. Starr, MD. 2012, to Dec. 31, 2017. All were actively managed with Dr. Starr added, “If a patient has a very dense cata- anti-VEGF injections for DME before and after cataract and can benefit from cataract surgery, the surgery ract surgery, with at least one injection within the six is certainly warranted. However, patients need to un- months preceding surgery. Most eyes (n = 22) received derstand they may need further intravitreal anti-VEGF injections of bevacizumab. injections and perhaps even more frequent follow-up” Visual acuity. Before surgery, mean VA for all eyes after surgery. was 20/107. This improved to 20/42 at post-op month Dr. Bakri advised clinicians to actively control the 1 and to 20/35 at post-op month 6. However, at the DME preoperatively with intravitreal anti-VEGF injec- six-month mark, the VA of three eyes was worse than tions. “Also, have a plan for postoperative management it had been before surgery. In one of these three eyes, rather than an as-needed approach.” —Miriam Karmel macular fluid also worsened following surgery. Retinal thickness. While 30 eyes (81.1%) had fluid on 1 Starr MR et al. Am J Ophthalmol. Published online April 11, the preoperative OCT, there were no statistically signif- 2021. icant differences in central subfield thickness measure- Relevant financial disclosures—Drs. Bakri and Starr: None. © American Academy of Ophthalmology. of Ophthalmology. © American Academy

14 • JULY 2021 visual acuity was 8.0 letters in both formycon-confirms-bla-submission-strat studies published between Jan. 1, 1990, groups (7.8 ± 11.7 vs. 7.1 ± 10.42 letters egy-and-timeline-for-its-lucentisr-biosim and June 1, 2020. The studies involved for the FYB201 and ranibizumab recip- ilar-candidate-fyb201-following-consulta 189,359 participants; of these, 6,949 ients, respectively). The frequency and tion-with-the-fda/. Accessed May 21, 2021. had manifest glaucoma, and 5,558 had type of adverse events were comparable 3 www.globenewswire.com/news-release/2020/ undetected disease prior to diagnosis in between the two groups, and most side 11/18/2129054/0/en/Samsung-Bioepis-and- the respective study. effects were mild or moderate. Biogen-Announce-FDA-Filing-Acceptance-of- A global problem. A meta-analysis Given these results, Formycon SB11-A-Proposed-Biosimilar-Referencing- of data by country of origin revealed announced in March that it will ask Lucentis-ranibizumab.html. Accessed May 21, 2021. that the average proportion of unde- this year for approval of FYB201 as a 4 Woo SJ et al. JAMA Ophthalmol. 2021;139(1): tected cases in each geographical region biosimilar to ranibizumab in the United 68-76. varies significantly. Africa, for example, States and Europe. The company, based Relevant financial disclosures—Dr. Kaiser: had the highest proportion (94%), in Germany, said it is prepared for Allergan: C; Bayer Healthcare Pharmaceuticals: whereas Oceania had the lowest (59%). quick commercialization of the drug.2 C,L; bioeq/Formycon: C; Boehringer Ingelheim: A second analysis, based on each Additional thoughts on biosimi- C; Genentech: C; Kanghong: C; Novartis: C,L; country’s human development index lars. FYB201 is not the only potential Regeneron: C,L. (HDI), found that the proportion of biosimilar for AMD treatment on the previously undetected cases was above regulatory horizon. A second possi- GLAUCOMA 90% in countries with a low HDI. That ble biosimilar to ranibizumab, SB11 proportion fell to the 70% range in (Samsung Bioepsis/Biogen), is under Global Burden countries with medium to very high review at the FDA and the European of Undetected socioeconomic development. Medicines Agency, based on positive The finding that 7 of 10 cases of outcomes reported last fall from a Glaucoma glaucoma were undetected on average smaller, shorter-term clinical trial.3,4 in developed countries was a surprise, Although follow-up remains to be DESPITE DECADES OF PROGRESS said Ching-Yu Cheng, MD, PhD, at done to show FYB201’s longer-term in glaucoma research as well as the the Singapore Eye Research Institute. safety, its approval as a biosimilar would advent of novel imaging technologies “Glaucoma detection is not just a have some potential advantages for and surgical interventions, undetected problem in countries with low develop- ophthalmologists who treat AMD, Dr. glaucoma remains highly prevalent ment.” Kaiser said. “Biosimilars in general worldwide. There were an estimated Regional variations. Africa and Asia have a much lower cost to obtain regu- 43 million cases of undetected prima- had higher odds of undetected glauco- latory approval and as such are cheaper ry open-angle glaucoma (POAG) in ma, compared to Europe. (Differences than the reference product. Moreover, 2020—and this number is projected to between other regions and Europe approval in one indication garners rise to 67 million by 2040.1 were insignificant.) By 2040, the largest approval for all the reference product’s To look more deeply into these increase (86.3%) is projected for Africa, indications, again lowering the cost.” statistics, researchers in Singapore although Asia, by sheer population (For more, see “Biosimilars in Ophthal- and Boston reviewed 61 articles from numbers, will account for 58.4% of all mology,” in the January 2021 EyeNet.) 55 population-based epidemiological undetected POAG. Finally, how might FYB201 affect Need for education. “We ended bevacizumab, the off-label alternative our paper with a call to action,” said for treating retinal diseases? It won’t. Dr. Cheng. He suggested a number “Bevacizumab is not a biosimilar,” Dr. of potential educational initiatives to Kaiser said. “It is a different medica- improve glaucoma awareness and de- tion with different binding coefficient, tection—and he encouraged clinicians different molecular structure, and to move ahead without waiting for different efficacy in some indications, formal initiatives. “Start advocating the such as diabetic macular edema.” More- importance of regular eye checks to the over, he added, “there is a biosimilar of general public. And start checking for bevacizumab that is currently in phase glaucoma in your next patient.” 3 clinical testing for ophthalmic use.” —Miriam Karmel —Linda Roach UNDETECTED? In every region of the 1 Soh ZD et al. Ophthalmology. Published online 1 Holz FG et al. Ophthalmology. Published online world, at least half of all POAG cases April 15, 2021. May 3, 2021. were undetected, the meta-analysis Relevant financial disclosures—Dr. Cheng: Sin- 2 www.formycon.com/en/press-release/ found. gapore National Medical Research Council: S.

Jason S. Calhoun, COA See the financial disclosure key, page 8. For full disclosures, including category descriptions, view this News in Review at aao.org/eyenet.

EYENET MAGAZINE • 15 STARTING EYLEA EARLIER MAY HELP PREVENT DR PROGRESSION Primary Endpoint Secondary Endpoint (Year 1) (Year 1) Proportion of patients with a Reduction in the risk of developing ≥2-step DRSS improvement1,2,* PDR or ASNV or CI-DME2,*,† EYLEA Q8 EYLEA Q16 EYLEA Q8 EYLEA Q16 (n=134) (n=135) (n=134) (n=135) 80% 65% 79% 82% vs 15% in the vs 15% in the Risk Reduction Risk Reduction sham group sham group Event rate: 11% vs 42% Event rate: 10% vs 42% (n=133) (n=133) in the sham group in the sham group (n=133) (n=133) Of 134 patients treated in a DR clinical trial P<0.01 vs sham. • The recommended dose for EYLEA in DR is 2 mg (0.05 mL) administered by intravitreal injection Q4 (≈every 28 days, monthly) for the first 5 injections, followed by 2 mg Q8 (every 2 months)1 • Although EYLEA may be dosed as frequently as 2 mg Q4 (≈every 25 days, monthly), additional efficacy was not demonstrated in most patients when EYLEA was dosed Q4 compared with Q8. Some patients may need Q4 (monthly) dosing after the first 20 weeks (5 months)1 *Full analysis set. †Event rate was estimated using the Kaplan-Meier method. Composite endpoint of developing PDR, ASNV was diagnosed by either the reading center or investigator.

Inspired by a real patient with DR. SEE WHAT EYLEA COULD DO FOR YOUR PATIENTS WITH DR AT HCP.EYLEA.US

anti-VEGF; anti–vascular endothelial growth factor; ASNV, anterior segment neovascularization; CI-DME, central-involved Diabetic Macular Edema; ETDRS-DRSS, Early Treatment Diabetic Retinopathy Study–Diabetic Retinopathy Severity Scale; PDR, proliferative diabetic retinopathy; Q4, every 4 weeks; Q8, every 8 weeks; Q16, every 16 weeks. WARNINGS AND PRECAUTIONS (continued) • There is a potential risk of arterial thromboembolic events (ATEs) following intravitreal use of VEGF inhibitors, including EYLEA. PANORAMA study design: Multicenter, double-masked, controlled clinical study in which patients with moderately severe to severe NPDR (ETDRS-DRSS: 47 or 53) without CI-DME (N=402; age range: 25-85 years, with a mean of 56 years) were randomized to receive 1 of 2 EYLEA dosing regimens or sham. Protocol-specified visits ATEs are defined as nonfatal stroke, nonfatal myocardial infarction, or vascular death (including deaths of unknown cause). The occurred every 28±7 days for the first 5 visits, then every 8 weeks (56±7 days). During Year 2 (Weeks 52-96), patients randomized to one of the EYLEA arms received a incidence of reported thromboembolic events in wet AMD studies during the first year was 1.8% (32 out of 1824) in the combined di¡ erent dosing regimen.1 group of patients treated with EYLEA compared with 1.5% (9 out of 595) in patients treated with ranibizumab; through 96 weeks, the incidence was 3.3% (60 out of 1824) in the EYLEA group compared with 3.2% (19 out of 595) in the ranibizumab group. The incidence in the DME studies from baseline to week 52 was 3.3% (19 out of 578) in the combined group of patients treated with EYLEA compared with 2.8% (8 out of 287) in the control group; from baseline to week 100, the incidence was 6.4% (37 out of 578) in the combined group of patients treated with EYLEA compared with 4.2% (12 out of 287) in the control group. There were no IMPORTANT SAFETY INFORMATION reported thromboembolic events in the patients treated with EYLEA in the first six months of the RVO studies. CONTRAINDICATIONS ADVERSE REACTIONS • EYLEA is contraindicated in patients with ocular or periocular infections, active intraocular inflammation, or known • Serious adverse reactions related to the injection procedure have occurred in <0.1% of intravitreal injections with EYLEA hypersensitivity to aflibercept or to any of the excipients in EYLEA. including endophthalmitis and retinal detachment. WARNINGS AND PRECAUTIONS • The most common adverse reactions (≥5%) reported in patients receiving EYLEA were conjunctival hemorrhage, eye pain, • Intravitreal injections, including those with EYLEA, have been associated with endophthalmitis and retinal detachments. cataract, vitreous detachment, vitreous floaters, and intraocular pressure increased. Proper aseptic injection technique must always be used when administering EYLEA. Patients should be instructed to report • Patients may experience temporary visual disturbances after an intravitreal injection with EYLEA and the associated eye any symptoms suggestive of endophthalmitis or retinal detachment without delay and should be managed appropriately. examinations. Advise patients not to drive or use machinery until visual function has recovered su¡ iciently. Intraocular inflammation has been reported with the use of EYLEA. INDICATIONS • Acute increases in intraocular pressure have been seen within 60 minutes of intravitreal injection, including with EYLEA. EYLEA® (aflibercept) Injection 2 mg (0.05 mL) is indicated for the treatment of patients with Neovascular (Wet) Age-related Sustained increases in intraocular pressure have also been reported after repeated intravitreal dosing with VEGF inhibitors. Macular Degeneration (AMD), Macular Edema following Retinal Vein Occlusion (RVO), Diabetic Macular Edema (DME), and Intraocular pressure and the perfusion of the optic nerve head should be monitored and managed appropriately. Diabetic Retinopathy (DR). References: 1. EYLEA® (aflibercept) Injection full U.S. Prescribing Information. Regeneron Pharmaceuticals, Inc. August 2019. 2. Wyko¡ CC. Intravitreal aflibercept EYLEA is a registered trademark of Regeneron Pharmaceuticals, Inc. for moderately severe to severe non-proliferative diabetic retinopathy (NPDR): 2-year outcomes of the phase 3 PANORAMA study. Data presented at: Angiogenesis, Exudation, and Degeneration Annual Meeting; February 8, 2020; Miami, FL. © 2021, Regeneron Pharmaceuticals, Inc. All rights reserved. 03/2021 777 Old Saw Mill River Road, Tarrytown, NY 10591 Please see Brief Summary of Prescribing Information on the following page. EYL.21.02.0049

EYL.21.02.0049_REEYR21348_Retina_DR Journal Ad_8.125x10.875_Final.indd 1-2 6/3/21 10:59 AM STARTING EYLEA EARLIER MAY HELP PREVENT DR PROGRESSION Primary Endpoint Secondary Endpoint (Year 1) (Year 1) Proportion of patients with a Reduction in the risk of developing ≥2-step DRSS improvement1,2,* PDR or ASNV or CI-DME2,*,† EYLEA Q8 EYLEA Q16 EYLEA Q8 EYLEA Q16 (n=134) (n=135) (n=134) (n=135) 80% 65% 79% 82% vs 15% in the vs 15% in the Risk Reduction Risk Reduction sham group sham group Event rate: 11% vs 42% Event rate: 10% vs 42% (n=133) (n=133) in the sham group in the sham group (n=133) (n=133) Of 134 patients treated in a DR clinical trial P<0.01 vs sham. • The recommended dose for EYLEA in DR is 2 mg (0.05 mL) administered by intravitreal injection Q4 (≈every 28 days, monthly) for the first 5 injections, followed by 2 mg Q8 (every 2 months)1 • Although EYLEA may be dosed as frequently as 2 mg Q4 (≈every 25 days, monthly), additional efficacy was not demonstrated in most patients when EYLEA was dosed Q4 compared with Q8. Some patients may need Q4 (monthly) dosing after the first 20 weeks (5 months)1 *Full analysis set. †Event rate was estimated using the Kaplan-Meier method. Composite endpoint of developing PDR, ASNV was diagnosed by either the reading center or investigator.

Inspired by a real patient with DR. SEE WHAT EYLEA COULD DO FOR YOUR PATIENTS WITH DR AT HCP.EYLEA.US

EYL.21.02.0049_REEYR21348_Retina_DR Journal Ad_8.125x10.875_Final.indd 1-2 6/3/21 10:59 AM BRIEF SUMMARY—Please see the EYLEA Table 2: Most Common Adverse Reactions (≥1%) in RVO Studies full Prescribing Information available CRVO BRVO on HCP.EYLEA.US for additional EYLEA Control EYLEA Control Adverse Reactions (N=218) (N=142) (N=91) (N=92) product information. Eye pain 13% 5% 4% 5% Conjunctival hemorrhage 12% 11% 20% 4% Intraocular pressure increased 8% 6% 2% 0% 1 INDICATIONS AND USAGE Corneal epithelium defect 5% 4% 2% 0% EYLEA is a vascular endothelial growth factor (VEGF) inhibitor indicated for the treatment of patients with: Vitreous floaters 5% 1% 1% 0% Neovascular (Wet) Age-Related Macular Degeneration (AMD), Macular Edema Following Retinal Vein Occlusion (RVO), Diabetic Ocular hyperemia 5% 3% 2% 2% Macular Edema (DME), Diabetic Retinopathy (DR). Foreign body sensation in eyes 3% 5% 3% 0% 4 CONTRAINDICATIONS Vitreous detachment 3% 4% 2% 0% 4.1 Ocular or Periocular Infections Lacrimation increased 3% 4% 3% 0% EYLEA is contraindicated in patients with ocular or periocular infections. Injection site pain 3% 1% 1% 0% 4.2 Active Intraocular Inflammation Vision blurred 1% <1% 1% 1% EYLEA is contraindicated in patients with active intraocular inflammation. Intraocular inflammation 1% 1% 0% 0% 4.3 Hypersensitivity Cataract <1% 1% 5% 0% EYLEA is contraindicated in patients with known hypersensitivity to aflibercept or any of the excipients in EYLEA. Hypersensitivity Eyelid edema <1% 1% 1% 0% reactions may manifest as rash, pruritus, urticaria, severe anaphylactic/anaphylactoid reactions, or severe intraocular inflammation. 5 WARNINGS AND PRECAUTIONS Less common adverse reactions reported in <1% of the patients treated with EYLEA in the CRVO studies were corneal edema, retinal 5.1 Endophthalmitis and Retinal Detachments tear, hypersensitivity, and endophthalmitis. Intravitreal injections, including those with EYLEA, have been associated with endophthalmitis and retinal detachments [see Adverse Diabetic Macular Edema (DME) and Diabetic Retinopathy (DR). The data described below reflect exposure to EYLEA in 578 patients Reactions (6.1)]. Proper aseptic injection technique must always be used when administering EYLEA. Patients should be instructed with DME treated with the 2-mg dose in 2 double-masked, controlled clinical studies (VIVID and VISTA) from baseline to week 52 and to report any symptoms suggestive of endophthalmitis or retinal detachment without delay and should be managed appropriately from baseline to week 100. [see Patient Counseling Information (17)]. Table 3: Most Common Adverse Reactions (≥1%) in DME Studies 5.2 Increase in Intraocular Pressure Acute increases in intraocular pressure have been seen within 60 minutes of intravitreal injection, including with EYLEA [see Adverse Baseline to Week 52 Baseline to Week 100 Reactions (6.1)]. Sustained increases in intraocular pressure have also been reported after repeated intravitreal dosing with vascular EYLEA Control EYLEA Control endothelial growth factor (VEGF) inhibitors. Intraocular pressure and the perfusion of the optic nerve head should be monitored and Adverse Reactions (N=578) (N=287) (N=578) (N=287) managed appropriately. Conjunctival hemorrhage 28% 17% 31% 21% 5.3 Thromboembolic Events There is a potential risk of arterial thromboembolic events (ATEs) following intravitreal use of VEGF inhibitors, including EYLEA. ATEs Eye pain 9% 6% 11% 9% are defined as nonfatal stroke, nonfatal myocardial infarction, or vascular death (including deaths of unknown cause). The incidence of Cataract 8% 9% 19% 17% reported thromboembolic events in wet AMD studies during the first year was 1.8% (32 out of 1824) in the combined group of patients Vitreous floaters 6% 3% 8% 6% treated with EYLEA compared with 1.5% (9 out of 595) in patients treated with ranibizumab; through 96 weeks, the incidence was Corneal epithelium defect 5% 3% 7% 5% 3.3% (60 out of 1824) in the EYLEA group compared with 3.2% (19 out of 595) in the ranibizumab group. The incidence in the DME Intraocular pressure increased 5% 3% 9% 5% studies from baseline to week 52 was 3.3% (19 out of 578) in the combined group of patients treated with EYLEA compared with 2.8% (8 out of 287) in the control group; from baseline to week 100, the incidence was 6.4% (37 out of 578) in the combined group of Ocular hyperemia 5% 6% 5% 6% patients treated with EYLEA compared with 4.2% (12 out of 287) in the control group. There were no reported thromboembolic events Vitreous detachment 3% 3% 8% 6% in the patients treated with EYLEA in the first six months of the RVO studies. Foreign body sensation in eyes 3% 3% 3% 3% 6 ADVERSE REACTIONS Lacrimation increased 3% 2% 4% 2% The following potentially serious adverse reactions are described elsewhere in the labeling: Vision blurred 2% 2% 3% 4% • Hypersensitivity [see Contraindications (4.3)] Intraocular inflammation 2% <1% 3% 1% • Endophthalmitis and retinal detachments [see Warnings and Precautions (5.1)] • Increase in intraocular pressure [see Warnings and Precautions (5.2)] Injection site pain 2% <1% 2% <1% Eyelid edema <1% 1% 2% 1% • Thromboembolic events [see Warnings and Precautions (5.3)] 6.1 Clinical Trials Experience Less common adverse reactions reported in <1% of the patients treated with EYLEA were hypersensitivity, retinal detachment, retinal Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug tear, corneal edema, and injection site hemorrhage. cannot be directly compared to rates in other clinical trials of the same or another drug and may not reflect the rates observed Safety data observed in 269 patients with nonproliferative diabetic retinopathy (NPDR) through week 52 in the PANORAMA trial were in practice. consistent with those seen in the phase 3 VIVID and VISTA trials (see Table 3 above). A total of 2980 patients treated with EYLEA constituted the safety population in eight phase 3 studies. Among those, 2379 patients 6.2 Immunogenicity were treated with the recommended dose of 2 mg. Serious adverse reactions related to the injection procedure have occurred in <0.1% As with all therapeutic proteins, there is a potential for an immune response in patients treated with EYLEA. The immunogenicity of intravitreal injections with EYLEA including endophthalmitis and retinal detachment. The most common adverse reactions (≥5%) of EYLEA was evaluated in serum samples. The immunogenicity data reflect the percentage of patients whose test results were reported in patients receiving EYLEA were conjunctival hemorrhage, eye pain, cataract, vitreous detachment, vitreous floaters, and considered positive for antibodies to EYLEA in immunoassays. The detection of an immune response is highly dependent on the intraocular pressure increased. sensitivity and specificity of the assays used, sample handling, timing of sample collection, concomitant medications, and underlying Neovascular (Wet) Age-Related Macular Degeneration (AMD). The data described below reflect exposure to EYLEA in 1824 patients disease. For these reasons, comparison of the incidence of antibodies to EYLEA with the incidence of antibodies to other products may with wet AMD, including 1223 patients treated with the 2-mg dose, in 2 double-masked, controlled clinical studies (VIEW1 and VIEW2) be misleading. for 24 months (with active control in year 1). In the wet AMD, RVO, and DME studies, the pre-treatment incidence of immunoreactivity to EYLEA was approximately 1% to 3% across Safety data observed in the EYLEA group in a 52-week, double-masked, Phase 2 study were consistent with these results. treatment groups. After dosing with EYLEA for 24-100 weeks, antibodies to EYLEA were detected in a similar percentage range of patients. There were no differences in efficacy or safety between patients with or without immunoreactivity. Table 1: Most Common Adverse Reactions (≥1%) in Wet AMD Studies Baseline to Week 52 Baseline to Week 96 8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy Active Control Control Risk Summary EYLEA (ranibizumab) EYLEA (ranibizumab) Adequate and well-controlled studies with EYLEA have not been conducted in pregnant women. Aflibercept produced adverse Adverse Reactions (N=1824) (N=595) (N=1824) (N=595) embryofetal effects in rabbits, including external, visceral, and skeletal malformations. A fetal No Observed Adverse Effect Level Conjunctival hemorrhage 25% 28% 27% 30% (NOAEL) was not identified. At the lowest dose shown to produce adverse embryofetal effects, systemic exposures (based on AUC for Eye pain 9% 9% 10% 10% free aflibercept) were approximately 6 times higher than AUC values observed in humans after a single intravitreal treatment at the Cataract 7% 7% 13% 10% recommended clinical dose [see Animal Data]. Animal reproduction studies are not always predictive of human response, and it is not known whether EYLEA can cause fetal harm Vitreous detachment 6% 6% 8% 8% when administered to a pregnant woman. Based on the anti-VEGF mechanism of action for aflibercept, treatment with EYLEA may Vitreous floaters 6% 7% 8% 10% pose a risk to human embryofetal development. EYLEA should be used during pregnancy only if the potential benefit justifies the Intraocular pressure increased 5% 7% 7% 11% potential risk to the fetus. Ocular hyperemia 4% 8% 5% 10% All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. The background risk of major birth defects Corneal epithelium defect 4% 5% 5% 6% and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. Detachment of the retinal pigment epithelium 3% 3% 5% 5% Injection site pain 3% 3% 3% 4% Data Foreign body sensation in eyes 3% 4% 4% 4% Animal Data In two embryofetal development studies, aflibercept produced adverse embryofetal effects when administered every three days Lacrimation increased 3% 1% 4% 2% during organogenesis to pregnant rabbits at intravenous doses ≥3 mg per kg, or every six days during organogenesis at subcutaneous Vision blurred 2% 2% 4% 3% doses ≥0.1 mg per kg. Intraocular inflammation 2% 3% 3% 4% Adverse embryofetal effects included increased incidences of postimplantation loss and fetal malformations, including anasarca, Retinal pigment epithelium tear 2% 1% 2% 2% umbilical hernia, diaphragmatic hernia, gastroschisis, cleft palate, ectrodactyly, intestinal atresia, spina bifida, encephalomeningocele, Injection site hemorrhage 1% 2% 2% 2% heart and major vessel defects, and skeletal malformations (fused vertebrae, sternebrae, and ribs; supernumerary vertebral arches and ribs; and incomplete ossification). The maternal No Observed Adverse Effect Level (NOAEL) in these studies was 3 mg per kg. Eyelid edema 1% 2% 2% 3% Aflibercept produced fetal malformations at all doses assessed in rabbits and the fetal NOAEL was not identified. At the lowest Corneal edema 1% 1% 1% 1% dose shown to produce adverse embryofetal effects in rabbits (0.1 mg per kg), systemic exposure (AUC) of free aflibercept was Retinal detachment <1% <1% 1% 1% approximately 6 times higher than systemic exposure (AUC) observed in humans after a single intravitreal dose of 2 mg. 8.2 Lactation Less common serious adverse reactions reported in <1% of the patients treated with EYLEA were hypersensitivity, retinal tear, and Risk Summary endophthalmitis. There is no information regarding the presence of aflibercept in human milk, the effects of the drug on the breastfed infant, or the Macular Edema Following Retinal Vein Occlusion (RVO). The data described below reflect 6 months exposure to EYLEA with a effects of the drug on milk production/excretion. Because many drugs are excreted in human milk, and because the potential for monthly 2 mg dose in 218 patients following central retinal vein occlusion (CRVO) in 2 clinical studies (COPERNICUS and GALILEO) absorption and harm to infant growth and development exists, EYLEA is not recommended during breastfeeding. and 91 patients following branch retinal vein occlusion (BRVO) in one clinical study (VIBRANT). The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for EYLEA and any potential adverse effects on the breastfed child from EYLEA. 8.3 Females and Males of Reproductive Potential Contraception Females of reproductive potential are advised to use effective contraception prior to the initial dose, during treatment, and for at least 3 months after the last intravitreal injection of EYLEA. Infertility There are no data regarding the effects of EYLEA on human fertility. Aflibercept adversely affected female and male reproductive systems in cynomolgus monkeys when administered by intravenous injection at a dose approximately 1500 times higher than the systemic level observed humans with an intravitreal dose of 2 mg. A No Observed Adverse Effect Level (NOAEL) was not identified. These findings were reversible within 20 weeks after cessation of treatment. 8.4 Pediatric Use The safety and effectiveness of EYLEA in pediatric patients have not been established. 8.5 Geriatric Use Manufactured by: In the clinical studies, approximately 76% (2049/2701) of patients randomized to treatment with EYLEA were ≥65 years of age and Regeneron Pharmaceuticals, Inc. Issue Date: 08/2019 approximately 46% (1250/2701) were ≥75 years of age. No significant differences in efficacy or safety were seen with increasing age 777 Old Saw Mill River Road Initial U.S. Approval: 2011 in these studies. Tarrytown, NY 10591 17 PATIENT COUNSELING INFORMATION Based on the August 2019 EYLEA is a registered trademark of Regeneron In the days following EYLEA administration, patients are at risk of developing endophthalmitis or retinal detachment. If the EYLEA® (aflibercept) Injection full eye becomes red, sensitive to light, painful, or develops a change in vision, advise patients to seek immediate care from an Pharmaceuticals, Inc. Prescribing Information. © 2020, Regeneron Pharmaceuticals, Inc. ophthalmologist [see Warnings and Precautions (5.1)]. All rights reserved. EYL.20.09.0052 Patients may experience temporary visual disturbances after an intravitreal injection with EYLEA and the associated eye examinations [see Adverse Reactions (6)]. Advise patients not to drive or use machinery until visual function has recovered sufficiently.

EYL.21.02.0049_REEYR21348_Retina_DR Journal Ad_8.125x10.875_Final.indd 3 6/3/21 11:00 AM Journal Highlights NEW FINDINGS FROM THE PEER-REVIEWED LITERATURE Volume 128 Volume 128 | Number 7 | July 2021 Ophthalmology patients on abicipar Q8, Elsevier | ISSN 0161-6420 received by the drug’s | Selected by Stephen D. McLeod, MD 442 on abicipar Q12, and Number 7 manufacturer indi- | 520 on ranibizumab Q4. pp. XXXX–XXXX cating that retinal Abicipar for Neovascular AMD: At week 104, vision was vasculitis or retinal Two-Year Results stable in 93.0%, 89.8%, vascular occlusion July 2021 and 94.4% of those in occurred in up to

each cohort, respectively. OPHTHALMOLOGY 4.71 of every 10,000

Khurana et al. pooled two-year data Mean BCVAINSERT gains ADVERT from injections of brolu- for the CEDAR and SEQUOIA trials baseline were 7.8, 6.1, and cizumab. The safety and found that abicipar was effective 8.5 letters, respectively. committee reported when given every eight or 12 weeks (Q8 Mean CRT reductions signs of retinal vas- or Q12) for neovascular age-related from baseline were 147 July 2021 culitis, with or with-

macular degeneration (AMD). This OPHTHA_v128_i7_COVER.inddμm, 1 146 μm, and 142 μm, 3/18/2021 9:52:20 PM out retinal vascular longer duration of effect, when com respectively. occlusion, which pared to ranibizumab, translates to With regard to intraocular in- were linked to greater risk of visual fewer overall injections and lower costs flammation, the overall incidence of acuity (VA) decline. This knowledge for patients with neovascular AMD. inflammation from baseline through should help physicians weigh the risks However, a higher incidence of intra week 52 was 15.4% for the abicipar Q8 and benefits of brolucizumab for their ocular inflammation was noted in patients, 15.3% for those who received patients with neovascular age-related abicipar-treated eyes than in those abicipar Q12, and 0.3% of those who macular degeneration (AMD), said the that received ranibizumab. received ranibizumab Q4. From base- authors. The CEDAR and SEQUOIA trials line through week 104, those percent- Patients enrolled in HAWK and were designed to test whether abicipar ages were 16.2%, 17.6%, and 1.3%, HARRIER had untreated active cho- is noninferior to ranibizumab through respectively. The overall percentage of roidal neovascularization due to AMD 52 weeks in patients with active cho- enrolled patients who completed the and were assigned randomly to receive roidal neovascularization secondary two-year study was 70.8% for the ab- brolucizumab or aflibercept. The inde- to AMD. One eye per patient was icipar Q8 cohort, 70.7% for those who pendent safety review committee stud- enrolled; best-corrected visual acuity received abicipar Q12, and 82.7% for ied the subset of cases of intraocular (BCVA) ranged from 24 to 73 ETDRS those who received ranibizumab Q4. inflammation that occurred (60/1,088 letters. Favorable results led to treat- with brolucizumab, vs. 8/729 with ment continuity through week 104 to Risk of Adverse Ocular Events aflibercept) by looking at patient data determine if the benefits persisted for With Brolucizumab and imaging studies. Main outcome another year. In year 2, each patient re- July 2021 measures were signs and incidence of ceived four or six injections of abicipar VA loss and vasculitis and/or retinal or 11 injections of ranibizumab. Effi- Monés et al. conducted an independent vascular occlusion; time from the initial cacy measures included stable vision (a safety review of HAWK and HARRIER brolucizumab injection to onset of in- loss of <15 letters from initial baseline data to learn more about investigator- traocular inflammation; and frequency values) and changes in central retinal reported cases of intraocular inflam- of VA loss after brolucizumab injection thickness (CRT). Adverse events were mation, endophthalmitis, and retinal by time of inflammation onset. recorded to assess safety. arterial occlusion. This analysis was In 50 brolucizumab-treated eyes, the The final analysis set included 443 prompted by postmarketing evidence intraocular inflammation was definitely

EYENET MAGAZINE • 19 or probably related to the study drug, < .001) and thinner CCT (p = .004) in ers, using the average interval between the safety review committee confirmed. the follow-up period, which averaged treatments (low: ≥10 weeks; high: ≤5 The combined rate of definite/proba- 4.2 years. Eyes with higher SP-A1 and weeks; moderate: all other eyes). They ble inflammation was 4.6%, and eight thinner CCT showed accelerated RNFL then trained two random forest models eyes treated with brolucizumab (0.74% thinning (0.72 μm/year) relative to eyes to predict the long-term treatment overall) had moderate or severe VA loss. with lower values for these metrics. demand of a new patient. Both models In contrast, the incidence of intraocular They also were nearly three times more used patient demographic information inflammation among aflibercept-treat- likely to have RNFL decline exceeding and morphological features automated eyes was 1.1%, and moderate or 1 μm/year. Findings for GCIPL thinning ically extracted from OCT volumes at severe VA loss occurred in 0.14%. were similar. High SP-A1 values also baseline and after two consecutive vis- The authors encourage close sur- were linked to greater risk of visual its. Mean area under the curve (AUC) veillance of patients on brolucizumab field progression (p = .002) and thinner of both models was measured. therapy to ensure prompt recognition CCT (p = .010). The risk of visual field In the cohort of patients with AMD, of intraocular inflammation, retinal decline was 3.7 times greater for eyes the researchers identified 127 low-, 42 vasculitis, or retinal occlusion. They with worse SP-A1 and CCT data. high-, and 208 moderate-treatment de- recommend adding slit-lamp exam- These findings augment the body manders. Of those with RVO or DME, inations, ophthalmoscopy, and fundus of evidence denoting the importance 61 patients were low-, 50 were high-, imaging to the monitoring protocol. of considering corneal biomechanics and 222 were moderate-treatment when estimating progression for eyes demanders. For patients with AMD, Corneal Stiffness Metrics Signal with suspected glaucoma. the mean AUC was 0.79 for both low Glaucoma Progression —Summaries by Lynda Seminara and high demanders. For those with July 2021 retinal vascular disease, the mean AUC Ophthalmology Retina was 0.76 and 0.78 for low and high Qassim et al. assessed whether corneal Selected by Andrew P. Schachat, MD demanders, respectively. To predict low stiffness metrics could signal risk of treatment demand, only the informa- progression in eyes suspected of having Machine Learning Predicts tion derived at baseline was necessary. glaucoma. They found that progression Anti-VEGF Treatment Demand In contrast, accurate prediction of high risk was greatest for eyes with relatively July 2021 treatment demand required additional high corneal stiffness and low central information from follow-up visits. corneal thickness (CCT). Hence, corneal Gallardo et al. assessed the potential of —Summary by Jean Shaw stiffness parameters (SPs) and CCT machine learning to predict low and may contribute synergistically to pro- high treatment demand in patients American Journal of gression, they concluded. with neovascular age-related macular Ophthalmology For this prospective longitudinal degeneration (AMD) or retinal vascular Selected by Richard K. Parrish II, MD study, the researchers included 371 disease who received treat-and-extend eyes (228 patients) whose optic disc injections in a routine clinical setting. Social Work Program Boosts appearance suggested glaucoma—but They found that machine learning Adherence to Follow-Up Care whose Humphrey visual field (HVF) can predict treatment demand and July 2021 results were normal. The researchers potentially could be used to establish obtained corneal SPs at baseline and patient-specific treatment plans. Can social outreach programs bring then assessed patients every six months For this retrospective cohort study, effective—and low-cost—vision care to with clinical examinations, OCT scans, the researchers evaluated 340 patients children? In a previous study, Chung et and HVF testing. The baseline SP at (377 eyes) with neovascular AMD and al. explored costs and outcomes of the first applanation (SP-A1) and highest 285 patients (333 eyes) with retinal Children’s Eye Care Adherence Pro- concavity point predicted the out- vascular disease. The latter group com- gram (CECAP1), a social work inter- come measures. Structural progression prised 150 patients with retinal vascular vention shown to improve adherence was determined by OCT-measured occlusion (RVO) and 135 patients with to eye care for underserved children thinning of the retinal nerve fiber diabetic macular edema (DME). All in Philadelphia. After analysis of the layer (RNFL) and ganglion cell–inner eyes were treated with either afliber- flagship program, the authors modified plexiform layer (GCIPL). Functional cept or ranibizumab according to a it to reduce costs. In their subsequent progression was established by per- predefined treat-and-extend protocol study, they investigated the effectiveness mutation analysis of pointwise linear at the University of Bern, Switzerland. of the reduced-cost model (CECAP2) regression criteria on HVF testing. The study period ran from 2014 to and found that, even when costs were The authors found a strong correla- 2018, and patients received anti-VEGF lowered by more than 50%, the pro- tion between SPs and CCT. A higher injections for at least one year. gram was just as successful. SP-A1 value (suggesting a stiffer cor- The researchers defined eyes as low-, For this CECAP2 study, the authors nea) signaled faster RNFL thinning (p moderate-, or high-treatment demand- gathered data from records of children

20 • JULY 2021 who needed ophthalmic follow-up or epithelial defect at presentation, and after participating in community-based greater maximum depth of stromal ne- JAMA Ophthalmology Selected and reviewed by Neil M. vision screening programs. They mod- crosis. Stromal necrosis required more Bressler, MD, and Deputy Editors ified CECAP1 to prioritize the children than conservative treatment in nearly who, based on that earlier study, were half of non-CLWs but in less than 14% more likely to complete a follow-up of CLWs. Ethnic Disparities in Clinical visit. Efforts were made to decrease For this retrospective study, the Trials of Ophthalmic Drugs phone calls and scheduling attempts authors evaluated 214 eyes with PAK. June 2021 and to constrict the geographic catch- Of these, 163 were in the CLW cohort. ment area for better accessibility. Costs For both groups, the authors assessed Berkowitz et al. evaluated the ethnic were based on the social workers’ time patients’ clinical features, microbiologic representation, trends, and disparities in devoted to the program. Effectiveness findings, and treatment course. They clinical trials leading to FDA ophthal- was expressed as the percentage of also conducted analyses based on ma- mology drug approvals from 2000 to patients who completed at least one chine learning to determine predictors 2020. They found that Black, Hispanic, follow-up visit within the recommend- of poor final VA. and other non-White populations were ed time frame. Patients’ average age was 39.2 years underrepresented in these studies, Altogether, 462 children were referred for CLWs and 71.9 for non-CLWs. At although some improvement occurred to CECAP2 from the vision-screening presentation, mean logMAR VA was during the 20-year time frame. programs. Of these, 242 (52.4%) com- 1.39 and 2.17, respectively (p < .0001). For this cohort study, the research- pleted a recommended follow-up exam. The mean final VA was 0.76 in CLWs ers used data from participants in 31 The proportion was nearly identical and 1.82 in non-CLWs (p < .0001). clinical trials of drugs for neovascular to that for CECAP1 (52.3%). Children Throughout treatment, PAK was age-related macular degeneration who spoke English at home were more more severe in non-CLWs. In addition, (AMD; n = 10), open-angle glaucoma likely to return for follow-up than were the hospitalization rate was signifi- (OAG; n = 16), and expanded indica- children who spoke another language cantly higher for this group (58.8% tions for diabetic retinopathy (DR; (60.8% vs. 46.8%). In CECAP2, the vs. 19.6%): The mean hospital stay n = 5). All told, 13 drugs were studied. social workers’ time averaged 0.8 hours was 9.29 days for non-CLWs, versus National expected ethnic propor- per patient—significantly less than 5.44 days for CLWs. Stromal necrosis tions were sourced from U.S. Census previously (2.6 hours per patient). required surgical or procedural inter- Bureau and NEI data. The primary out- The cost per patient was reduced from vention in 13.5% of CLWs and 49.0% come measures were the distribution $77.20 to $32.73. of non-CLWs (p < .0001). According of and change over time in the ethnic To the authors’ knowledge, this is the to machine learning analyses, strong proportion of participants in clinical first publication of efforts to minimize predictors of poor VA outcomes (i.e., trials leading to FDA approval of drugs costs of a social work program aimed worse than 20/40) were older age, worse for the three disease categories. at increasing follow-up adherence. initial VA, larger infiltrate or epitheli- The 31 clinical trials involved 18,410 Although CECAP2 is more sustainable al defect at presentation, and greater participants. With regard to overall than CECAP1, the authors do not wish depth of stromal necrosis. par ticipation, disparity analyses showed to overlook children who are “lost to In most published cases of PAK, the overrepresentation of White partici- follow-up.” Rather, they hope other condition is linked to contact lens wear pants and underrepresentation of Black interventions can be developed to because P. aeruginosa is the most fre- and Hispanic participants compared reach those children. quently isolated pathogen from corneal with the expected disease burden and scrapings of patients with infectious ethnic distribution in the United States. PAK Outcomes Are Better for keratitis who wear contacts. Although These disparities did begin to narrow Contact Lens Wearers this relationship certainly deserves over time, with increased enrollment July 2021 attention, the authors emphasized that of Asian participants in AMD and DR PAK also is a common cause of keratitis studies, increased participation of His Pseudomonas aeruginosa is a common in non-CLWs, as shown by their find- panics in AMD and OAG trials, and cause of bacterial keratitis among ings. They recommend further study increased enrollment of Black patients patients who wear contact lenses. Enzor of PAK, particularly to explore reasons in OAG studies. However, there was no et al. compared risk factors and out- for the major differences in outcomes change in enrollment of Black partici- comes for P. aeruginosa keratitis (PAK) between CLWs and non-CLWs. Al- pants in AMD studies and a decrease in between contact lens wearers (CLWs) though P. aeruginosa is more prevalent Black participants in DR trials. and those who do not wear contacts. in CLWs, the related damage seems The researchers noted that category They observed better outcomes among more severe for non-CLWs, leading to reporting by ethnicity was inconsistent CLWs. Strong predictors of poor visual more challenging treatment courses and variable across the studies evaluat- acuity (VA) in both groups were worse and poorer VA outcomes. ed, and they called for comprehensive initial VA, advanced age, larger infiltrate —Summaries by Lynda Seminara and standardized reporting of demo-

EYENET MAGAZINE • 21 graphic characteristics in clinical trials. A total of 26 at-fault crashes and 55 • Data on ocular alignment were Above all, they said, investigators at-fault near crashes occurred during available for 64 participants; strabismus should focus on diverse, representative the six-month study period. Of these, was reported in 23 of the 64. enrollment in pivotal studies. (Also see 55 (67.9%) involved other vehicles. • Glaucoma was infrequent and related commentary by Päivi H. Miskala, Participants who had deficits in their diagnosed in four of the 74 eyes (all MSPH, PhD, and Senaka A. Peter, MPH, visual processing speed, contrast sen- four were pseudophakic). No cases of in the same issue.) sitivity, and motion perception were glaucoma suspect were reported. more likely to be involved in an at-fault Based on these findings, the PEDIG Older Drivers and Accidents collision or near collision. (Also see researchers recommended ongoing June 2021 related commentary by Sheila K. West, monitoring of these children, partic- PhD, in the same issue.) ularly with regard to the development Swain et al. set out to examine the of strabismus and visual axis opacifica- visual risk factors associated with at- PEDIG Report: Lensectomy for tion. —Summaries by Jean Shaw fault crashes and near crashes among Traumatic Cataract older drivers, using data acquired from June 2021 OTHER JOURNALS sensors placed in the drivers’ cars. They Selected by Prem S. Subramanian, MD, identified three visual factors likely to The Pediatric Eye Disease Investigator PhD increase a driver’s risk of accidents and Group (PEDIG) set out to assess visual near accidents. acuity (VA) outcomes and adverse Stroke Risk Soars After RAO For this study, the researchers events in children who undergo surgery Eye evaluated 154 participants 70 years of for traumatic cataracts. Bothun et al. Published online April 28, 2021 age or older who reported driving at found that, within 15 months after len- least four days a week. An unobtrusive sectomy in these children, substantial Based on mounting evidence of a data acquisition system, which cap- ocular morbidity was common. relationship between stroke and retinal tured information on roadway envi- This cohort study was drawn from artery occlusion (RAO), the American ronment, accelerator position, brake a larger study of 994 children younger Heart Association recommends imme- actuation, and speed, was installed than 13 years who underwent lensecto- diate assessment for any patient with in each participant’s car. The partici- my from June 2012 to July 2015. Trau- RAO or amaurosis fugax. Although the pants were instructed to continue their matic cataract was reported in 84 of Academy has adopted these guidelines, normal driving patterns for six months. the 994 children, and an office visit fewer ophthalmologists than neurol- The primary outcome was the rate of was documented for 72 of the 84 with- ogists are likely to recommend urgent combined incident at-fault crashes and in 15 months following surgery. workup for patients with RAO. Scoles near crashes, defined by the number of Main outcomes were best-corrected et al. assessed the near-term risk of events and the number of miles driven. VA (BCVA) from nine to 15 months stroke after RAO and found that stroke Of the drivers, 85 were in their 70s, after lensectomy for traumatic cataract risk was highest in the days following 66 were in their 80s, and three were in and the cumulative proportion with central or branch RAO. their 90s. Cognitive status was normal strabismus, glaucoma, and other ocular For this matched-case series, the in 152 of the participants. Information complications by 15 months. authors used a large health care claims was available on the eye health of 151 For the 72 children (74 eyes), the database and estimated stroke risk for participants; of these, 14 had no eye median age at time of surgery was 7.3 two cohorts: 1) a self-controlled case disease, while the remainder had such years (range, 0.1-12.6 years), and an series (SCCS; n = 16,193) and 2) a co- conditions as cataract (n = 63; 41.7%), intraoperative complication was iden- hort matched by propensity score (PS; primary open-angle glaucoma (n = 43; tified in 10 of the eyes (14%). An IOL n = 18,213 with RAO but no previous 28.5%), age-related macular degen- was placed in 57 of the 74 eyes (77%). stroke matched with 18,213 patients eration (n = 28; 18.5%), and diabetic Other results included the following: with hip fracture). All participants were retinopathy or macular edema (n = 10; • Visual loss was common. In children 55 years of age or older. The date of 6.6%). who were 3 years or older at follow-up, RAO diagnosis was considered the in- With regard to visual acuity (VA), median BCVA was 20/63 for pseu- dex date. In the SCCS, stroke incidence 151 participants had VA of 20/40 or dophakic eyes (n = 26; range, 20/20 was compared for periods before and better, while three had a VA of 20/40 to 20/200) and 20/250 for eyes with after the index date. Primary outcome or worse. Seventeen had impaired aphakia (n = 6; range, 20/20 to worse measures were the occurrence of stroke contrast sensitivity (worse than 1.5 log than 20/800). and its timing relative to the index sensitivity). Visual processing speed was • Visual axis opacification also was date. Cox proportional regression was measured in 125 participants; of these, common, with a cumulative proportion applied to determine the hazard ratios 62 had slowed visual processing speed. of 42% among children with IOLs. for stroke. Other factors measured included visual Most of these patients subsequently RAO raised the risk of stroke in both field sensitivity and motion perception. underwent laser capsulotomy. groups. In the SCCS, the incidence rate

22 • JULY 2021 ratio of stroke was significantly higher not exist, in part because the value of 15-minute period, both before correc- within 30 days after RAO diagnosis providing correction in this population tion of hyperopia and one week after than in periods more than two months has not been demonstrated. Although full correction. The displayed font and before RAO (p < .012). In the PS- some children can exert adequate font size remained uniform for all read- matched cohort, the hazard ratio for accom mo dation to focus for near work, ing work. Reading speed was assessed stroke was nearly 3 times greater after doing so may be uncomfortable. Ntodie with and without correction. The effect central or branch RAO than after hip et al. looked at the effect of refractive of optical correction on accommoda- fracture (p < .001). correction on the accommodative tive response was considered “positive” An unexpected finding of this study responses in children during sustained if the correction either improved accu- was the large number of first strokes near tasks and found that correcting racy of the mean response when there occurring shortly before RAO diag- low and moderate hyperopia substan- was accommodative lag or reduced the nosis. A possible explanation, said the tially relieved the compensatory efforts. mean response when the accommoda- authors, is that a danger period exists The authors recruited 134 children tive lead was 0.50 D or greater. in which any embolic phenomenon can between 5 and 10 years of age with Of the 63 qualified enrollees, 62 occur. Whether or not this proves to be varying levels of hyperopia from three completed the reading evaluation, the case, they stressed the importance settings in the United Kingdom: a local and 61 completed the movie portion. of promptly referring patients with primary school, a community optomet- After refractive correction, the accuracy RAO for a full workup to include stroke ric practice, and a university optometry of accommodative responses improved evaluation. clinic. Of these children, 63 met the for the reading task (p = .001) and the inclusion criteria; their spherical equiv- movie task (p < .001). Reading speed Correcting Hyperopia Improves alent refraction ranged from +1 D to also increased (p < .001). Accommodative Function +4.38 D in the less hyperopic eye. The effects of refractive correction TearCareInvestigative EyeNet OphthalmologyPrint (JULY) & Visual The authors recorded binocular in this study were independent of age Trim 7x4.75Science” accommodation measures while the or the degree of hyperopia. The authors 2021;62(4):6 children were engaged in reading small recommend exploring the longer-term print on a Kindle device and watching clinical and academic outcomes of Guidelines for optical correction of low an animated movie7 ”on an LCD screen. hyperopia correction. to moderate hyperopia in children do The children performed6” each task for a —Summaries by Lynda Seminara

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EYENET MAGAZINE • 23

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Keep accurate info on hand: aao.org/techs CORNEA CLINICAL UPDATE

Key Cornea Trials: The Legacy of HEDS, the Promise of ZEDS

erpesviruses cause a multitude demonstrating what mea- of miseries for the eye, affecting sures do not work as in con- Hnot only the cornea but also the firming those that do. But ocular adnexa, uvea, and retina. For the the following two questions cornea in particular, the herpes simplex have had the strongest con- virus (HSV) is the most common cause tinuing effect on practice, of epithelial keratitis, and the virus can said Sonal S. Tuli, MD, at also produce more serious consquences, the University of Florida in including stromal keratitis and corneal Gainesville. perforation. The varicella-zoster virus Question: Are topical (VZV)—another member of the her- steroids beneficial in treat- pesvirus group—is the causative agent ing HSV stromal keratitis? for herpes zoster ophthalmicus (HZO), Before HEDS, the use of cor- HERPETIC EPITHELIAL DISEASE. A dendrite with which includes neurotrophic keratitis ticosteroids for HSV keratitis dichotomous branching and terminal bulbs. among its many manifestations. was controversial, with some The Herpetic Eye Disease Study authors arguing that the availability resolution of stromal keratitis,” said (HEDS), a series of randomized placebo- of ophthalmic topical steroids had led Dr. Tuli. “In fact, a 68% reduction in controlled clinical trials initiated in to more frequent and severe keratitis. disease persistence and progression was 1989, assessed the optimal treatment Prior studies were hampered by lack of observed during this study,” she added. and prophylaxis for HSV keratitis or effective antiviral drugs and the inclu- However, six months after the study, no iridocyclitis, as well as factors in disease sion of cases of epithelial keratitis.3 significant difference was seen between recurrence. HEDS changed treatment To resolve this question, HEDS the groups, “but this may be related to a paradigms and is still considered the enrolled 106 patients with active HSV much more rapid taper of steroids than gold standard in the management of stromal keratitis who had not received is currently the practice,” said Dr. Tuli.4 anterior segment HSV disease.1,2 The corticosteroids within 10 days before Question: Does prophylaxis with Zoster Eye Disease Study (ZEDS), now enrollment. They were randomized to oral acyclovir reduce recurrence of underway, has the potential to make a receive placebo or a tapering regimen HSV? The virus is known to persist in similar impact on management of VZV of topical prednisolone phosphate for a latent form, often in the trigeminal eye disease, notably HZO. 10 weeks, and all participants also re- nerve, which can lead to repeated reac- ceived antiviral eye drops (trifluridine). tivation of ocular disease. Prophylactic HEDS: Important Questions They were followed every other week use of antivirals had been shown to Each of the studies within HEDS for six weeks and again at six months reduce recurrence in orofacial HSV but focused on a key clinical question (see after randomization.4 had not been tested in a randomized “HEDS Key Clinical Questions and Answer: Yes. HEDS investigators controlled trial of HSV keratitis.5 Studies,” page 27). The answers to found that patients who received pred- The HEDS investigators enrolled all of these questions have helped to nisolone phosphate drops experienced 703 participants who had experienced guide treatment—as important in “fewer treatment failures and faster an episode of anterior segment HSV in the prior 12 months but not within 30 days before the study. Participants were BY LESLIE BURLING, CONTRIBUTING WRITER, INTERVIEWING PENNY A. randomized to placebo or 400 mg of

Sonal S. Tuli, MD Sonal S. Tuli, ASBELL, MD, MBA, ELISABETH J. COHEN, MD, AND SONAL S. TULI, MD. oral acyclovir twice daily for 12 months

EYENET MAGAZINE • 25 and remained on the assigned treatment However, she said, the optimal regimen steroids to the lowest dose possible to regardless of recurrence (those who had for ocular HSV keratitis has not been maintain quiescence, knowing that some a recurrence were treated with topical established for these drugs. patients with stromal HSV will require antivirals at the physician’s discretion).5 Tailoring HSV treatment. For epithe- indefinite use of topical steroids. Answer: Yes. The researchers found lial keratitis, antiviral treatment alone Duration of steroid treatment. that recurrence was decreased by 45% is recommended, and topical steroids During the 10-week study period in in the acyclovir group compared with should be avoided.1 Dr. Tuli said that HEDS, the steroid-treated group did the placebo group.5 They considered cornea specialists are split on whether significantly better than the placebo this reduction of greatest benefit in to use topical or oral antiviral agents. group; but in the six-week observation stromal keratitis, which causes the most “You need to play it by ear. There is not period after treatment cessation, failure severe visual problems. The magnitude a one-size-fits-all solution.” rates rose dramatically.4 Thus, a longer of absolute benefit was the greatest For example, oral agents may be steroid regimen is now recommended, among patients with the highest num- preferable for patients with preexist- and “the treatment course should be ber of prior episodes of ocular HSV ing ocular surface disease, those who titrated empirically depending on clini- disease.2 However, in the six-month have hand tremors or arthritis, people cal response.”1 observation phase after treatment who wear contact lenses, or children Reducing recurrence. “The more ceased, there was no significant differ- who flinch at eye drops. Topicals are episodes of HSV you have, the more ence in recurrence between the groups,5 preferred for patients with renal im- likely you are to have another—the suggesting that there is no rebound pairment, individuals taking systemic odds are about 50%,” said Dr. Tuli. in HSV infections when acyclovir is immunosuppressants, and women who “There is also evidence suggesting that stopped, said Penny A. Asbell, MD, are pregnant or breastfeeding.1 short intervals between attacks tend MBA, at the University of Tennessee Stromal HSV: combined therapy. to be correlated with short intervals Health Science Center in Memphis. The HEDS trial of corticosteroids for between future attacks.” She noted that Dr. Tuli said that it also indicates that stromal keratitis used topical formula- those who are immunocompromised the protection only lasts as long as the tions for both the steroid and antiviral or who have atopy, atopic dermatitis, prophylaxis is continued. components.4 However, the Academy’s or asthma are also more likely to expe- 2014 clinical guidelines recommend rience recurrences. Treatment Updates oral antivirals for most patients because “One of the most valuable lessons In the quarter-century since these two of concerns over ocular surface tox- from HEDS is that an oral antiviral HEDS trials were published, new drugs icity with trifluridine and inadequate prevents recurrences when taken long- have become available, and additional corneal penetration with both triflu- term,” Dr. Tuli said. “HEDS showed that research has revealed some nuances for ridine and topical ganciclovir (topical if you treat patients for a year, there better tailoring the treatment regimens. acyclovir is not FDA approved).1 “Oral are fewer recurrences during that year. New therapeutic options. “At the antivirals are also preferred since stro- But the moment you stop, the risk goes time of HEDS, trifluridine was the most mal keratitis is an immune-mediated back exactly to where it was before you widely prescribed topical antiviral agent response, and the goal of antivirals is started prophylactic treatment. for treatment of HSV keratitis in the to prevent recurrence in the trigeminal “Some of my patients have been United States,” said Dr. Asbell. “How ganglion while on topical steroids rath- taking oral acyclovir for 20 or more ever, side effects such as punctate kera- er than to treat active viral keratitis,” years,” said Dr. Tuli. “They have tol- topathy, allergic conjunctivitis, and said Dr. Tuli. erated it well, and it has significantly ocular surface toxicity have led to de- As with epithelial keratitis treatment, reduced their number of HSV recur- cline in its use as new topical antivirals however, cornea experts differ in their rences.” She noted a few caveats: “Since have become available.” Dr. Asbell noted choice of topical versus oral antiviral valacyclovir is metabolized in the liver, that these newer antivirals—ganciclovir therapy for stromal keratitis. Dr. Asbell I recommend checking liver function 0.15% gel and acyclovir 3% ointment said she “generally recommends starting tests yearly. Also, since antivirals are [not available in the United States]— a combination of topical steroid (for excreted through the kidney, a basic are highly specific to virus-infected cells instance, prednisolone 1% or diflu metabolic panel is recommended yearly and thus less likely to harm host cells. prednate 0.05%) used about four times to prevent toxicity in case of decreased Topical acyclovir and ganciclovir are re- a day together with topical ganciclovir renal function.” ported to have similar efficacy, although gel 0.15% five times a day.” She added Corneal procedures in HSV patients. ganciclovir was better tolerated.2 that she tapers the topical steroid and Surgical trauma coupled with local Newer oral antiviral agents have also antiviral together, ideally maintaining immunosuppression by perioperative been introduced since HEDS. According the antiviral coverage until the steroid corticosteroids increases the likelihood to Dr. Asbell, famciclovir and valacyclo- is discontinued. In contrast, Dr. Tuli of HSV recurrence. Thus, performing vir (a prodrug of acyclovir) have better uses oral antiviral instead of topical elective eye surgery on a patient with bioavailability and less burdensome agents to reduce ocular surface toxicity, a history of HSV ocular disease is dosing regimens than oral acyclovir. and she tries to gradually reduce topical typically contraindicated.2 “All patients

26 • JULY 2021 with a history of ocular HSV infection ZEDS: Seeking Evidence Dr. Asbell, who is on the ZEDS should be well informed regarding the As with HSV, after initial infection, steering committee, said that “HZO risk of HSV reactivation following VZV lurks in the nerves and can reac- and HSV keratitis are analogous in LASIK or PRK,” Dr. Asbell emphasized. tivate after a period of latency due to many ways” and that the classification However, if surgery is performed, she declining cell mediated immunity. In of keratitis in the HSV guidelines1 is said, “perioperative and postoperative addition to HZO, VZV can cause the applicable to HZO as well. Dr. Cohen antiviral therapy should be given.” systemic manifestations of shingles and said, “These similarities are the ratio- Dr. Asbell added that “two proce- postherpetic neuralgia.6 nale for why we believe that prolonged dures developed since HEDS—corneal A survey conducted among ZEDS low-dose suppressive antiviral treat- cross-linking and excimer refractive investigators showed that about half ment may have similar benefits in HZO.” surgery—may also put patients at risk of them treat HZO with prolonged Primary objective. The primary for ocular HSV disease resulting from oral antivirals, in addition to topical aim of ZEDS is to determine whether exposure to the ultraviolet light.” steroids, and two-thirds believe that suppressive antiviral treatment with Dr. Tuli said that some of her patients approach is effective—despite a lack oral valacyclovir for 12 months delays have had phototherapeutic keratectomy of good evidence.6 “ZEDS is a unique the occurrence of specific forms of for HSV scarring. “I usually put such opportunity to find out if that’s true or HZO keratitis and iritis. The researchers patients on therapeutic doses of oral anti not. If it’s true we will have evidence- are enrolling patients who have had virals starting three to five days before based standards of care to reduce com HZO at any time in the past and an the surgery and continuing for at least plications,” said Elisabeth J. Cohen, episode of active keratitis or iritis in the two to three weeks afterward, followed MD, at NYU Langone Health in New year prior to enrollment. They will be by prophylactic doses long-term.” York City, and chair of the ZEDS study. assessed at 12 months as the primary

HEDS Key Clinical Questions and Studies QUESTION FINDINGS REFERENCE Are topical steroids Yes. Topical steroid significantly Wilhelmus KR et al., for the Herpetic Eye Dis- beneficial in treating reduced stromal inflammation and ease Study Group. Herpetic eye disease study: HSV stromal keratitis? duration of keratitis. A controlled trial of topical corticosteroids for herpes simplex stromal keratitis. Ophthalmology. 1994;101(12):1883-1895; discussion 1895-1896. Does the addition of oral No treatment benefit was seen in Barron BA et al., for the Herpetic Eye Disease acyclovir to a regimen nonnecrotizing stromal keratitis; too Study Group. Herpetic eye disease study: A of topical steroid and few patients with necrotizing stromal controlled trial of oral acyclovir for herpes trifluridine improve the keratitis to assess benefit. simplex stromal keratitis. Ophthalmology. clinical outcome in 1994;101(12):1871-1882. stromal keratitis? Is oral acyclovir helpful Too few patients to attain statistical A controlled trial of oral acyclovir for iridocycli- in treating iridocyclitis? significance, although the trend fa- tis caused by herpes simplex virus. The Herpetic vored treatment with oral acyclovir. Eye Disease Study Group. Arch Ophthalmol. 1996;114(9):1065-1072. Does oral acyclovir No difference was apparent between A controlled trial of oral acyclovir for the preven- prevent development the acyclovir and placebo groups. tion of stromal keratitis or iritis in patients with of stromal keratitis in herpes simplex virus epithelial keratitis. The Her- patients with epithelial petic Eye Disease Study Group. Arch Ophthalmol. keratitis? 1997;115(6):703-712.

Does prophylaxis with Yes. Recurrence was reduced by 45% Wilhelmus KR et al., for the Herpetic Eye Disease oral acyclovir reduce in the acyclovir group compared Study Group. Acyclovir for the prevention of re- recurrence of HSV? with placebo. current herpes simplex virus eye disease. N Engl J Med. 1998;339(5):300-306.

What triggers HSV None of the factors studied were Psychological stress and other potential triggers recurrence? confirmed as triggers as recorded by for recurrences of herpes simplex virus eye patients in weekly logs. infections. The Herpetic Eye Disease Study Group. Arch Ophthalmol. 2000;118(12):1617-1625. Adapted from: BCSC Section 8, External Disease and Cornea, 2020-2021, Table 9-6.

EYENET MAGAZINE • 27 endpoint and at 18 months as the sec- study participants to know that— 29(4):340-346. ondary endpoint.7 regardless of study arm assignment 3 Chodosh J. Ophthalmology. 2020;127(Suppl 4): “The results could be huge,” said Dr. —open-label treatment is available S3-S4. Cohen. “We have seen that HSV oph if new or worsening HZO occurs. 4 Wilhelmus KR et al. Ophthalmology. 1994; 101 thalmic outcomes have really been im- (12):1883-1896. proved with prolonged suppressive an- A Strong Recommendation 5 Herpetic Eye Disease Study Group. N Engl J tiviral treatment, and we have the same Until the ZEDS results are available, Med. 1998;339(5):300-306. potential to achieve that with HZO.” there is something that all doctors can 6 Lo DM et al. Cornea. 2019; 38(1):13-17. Implications beyond the eye. As a do to reduce the burden of HZO: advo- 7 clinicaltrials.gov, NCT03134196. secondary objective, the ZEDS inves- cate for vaccination against VZV, Drs. tigators will assess whether the study Asbell and Cohen agreed. Dr. Asbell is the Barrett G. Haik Endowed Chair drug reduces the incidence or severity Dr. Cohen said, “It is very important for Ophthalmology and Director of the Hamilton of postherpetic neuralgia. If so, said Dr. for ophthalmologists to take a history Eye Institute at the University of Tennessee Cohen, “then our findings would be about vaccination against zoster and Health Science Center, in Memphis. Financial dis- relevant to HZ in other locations where encourage all of their patients ages 50 closures: Alcon: C; Allakos: C; Axero: C; BlephEx: people, particularly the elderly, develop and over to get vaccinated with the C; Contact Lens Association of Ophthalmologists: chronic pain that can ruin the quality two-dose series of Shingrix,” even if C; Dompé: C; EyePoint: C; Kala: C; MC2: S; Mio- of life for the rest of their lives.” they already received the earlier Zos- tech: S; NIH: S; Novaliq: C; Regeneron: C; Sanofi: Help needed. Dr. Cohen said that tavax. “It is readily available at chain C; Santen: C; Senju Pharmaceuticals: C; Shire: C; the investigators need support from pharmacies, where pharmacists are well Sun: C; TopiVert: C. ophthalmologists in the United States trained to administer the vaccine.” Dr. Cohen is professor of ophthalmology at NYU and Canada to refer their HZO patients Langone Health, in New York City. Financial to one of the 70 centers in the United 1 White ML, Chodosh J. Herpes Simplex Virus disclosures: None. States or to the nine centers in Canada. Keratitis: A Treatment Guideline. 2014. aao.org/ Dr. Tuli is professor and chair in the department Addressing a possible source of hesitan- clinical-statement/herpes-simplex-virus-keratitis- of ophthalmology at the University of Florida, cy, she emphasized that it is important treatment-guideline. Accessed March 15, 2021. Gainesville. Financial disclosures: None. for ophthalmologists and potential 2 Kalezic T et al. Curr Opin Ophthalmol. 2018; See disclosure key, page 8.

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28 • JULY 2021 GLAUCOMA CLINICAL UPDATE

Xen and Preserflo: Their Places in the Glaucoma Toolkit

sed for lowering eye pressure clear that Xen and Preserflo occupy a 1 when medication, laser, or other unique position along the continuum Usurgery has failed or has a high of glaucoma care, but how do they stack risk of failure, glaucoma tube shunts up against the traditional glaucoma have enjoyed a decades-long spot in drainage device? the traditional glaucoma toolkit. Then along came microinvasive glaucoma Surgical Niches surgeries (MIGS). “These interventional From their physical aspects to their ap- glaucoma procedures are minimally plications, glaucoma drainage devices, disruptive to the structures of the eye, Xen, and Preserflo each have distinctions. causing few intra- or postoperative Physical aspects. Tube shunts are complications,” said Sahar Bedrood, composed of silicone, and the physics MD, PhD, a glaucoma and cataract of their relatively large lumen size often 2 specialist in Pasadena, California. allows for a good reduction in intraoc- Of the many MIGS devices, the Xen ular pressure (IOP), said Dr. Bedrood. Gel Stent and the Preserflo MicroShunt By contrast, the Xen is a hydrophilic (not yet FDA approved) come closest to tube composed of porcine dermis, with approximating glaucoma drainage de- a lumen of 45 μm.1 Approved by the vices. Although the definition of MIGS FDA in 2016, the Xen is 6 mm long keeps evolving, these two devices are and just the thickness of an eyelash, slightly more invasive than classic MIGS Dr. Bedrood said. approaches, said Michele C. Lim, MD, Approved in Canada and Europe, at the University of California Davis the Preserflo MicroShunt is 8.5 mm Eye Center in Sacramento. “They are long with a 70-μm lumen, and it is THE DEVICES AT POST-OP MONTH 1. like a hybrid technology—able to treat made of poly(styrene-block-isobuty- (1) Xen implant, red arrow, with a glaucoma along the spectrum of mod lene-block-styrene), known as SIBS, well-formed bleb, blue arrow, and a erate to severe disease.” Lauren S. Blieden, said Dr. Bedrood. Its biocompatible, (2) Preserflo implant, red arrow, and MD, at the Cullen Eye Institute, Baylor thermoplastic elastomer was first used its bleb, blue arrow. College of Medicine in Houston, agreed. successfully in cardiac stents.2 This led “I think of Xen and Preserflo as rela- to its proposed use in glaucoma filter- been reserved for advanced glaucoma,” tively microinvasive, conjunctival-based ing surgery, said Dr. Lim, who describes said Dr. Bedrood. “The larger lumen surgeries that create new drains for the the device as a tiny flute with fins. size, more extensive surgical time, and eye—a bit of a different animal than Time will tell if it’s inert enough to not possibility of postoperative complica- the angle-based MIGS such as iStent produce a fibrotic reaction in the eye, tions are not ideal in early glaucoma.” inject and Hydrus Microstent, which added Dr. Bedrood. Additionally, Dr. Bedrood will use tubes improve outflow.” Candidates for glaucoma drainage in patients at risk for inflammation, As bleb-forming MIGS devices, it’s devices. “Historically, tube shunts have such as those with uveitis or neovascular glaucoma. “These eyes will have a tendency to be more inflamed and scar BY ANNIE STUART, CONTRIBUTING WRITER, INTERVIEWING SAHAR down smaller tubes,” like the Xen or

(1) Courtesy of Lauren S. Blieden, MD. (2) Courtesy of Laura Baker. of Laura (2) Courtesy S. Blieden, MD. of Lauren (1) Courtesy BEDROOD, MD, PHD, LAUREN S. BLIEDEN, MD, AND MICHELE C. LIM, MD. Preserflo, she said.

EYENET MAGAZINE • 29 Challenges of tube shunts. Because On the upside, both devices are I know the needle is skimming along a tube shunt is larger than Xen or made of material that limits postsur- sclera as I move forward. Then I use a Preserflo and its plate must be inserted gical inflammation, and they have a Weck-Cel sponge to gently move the 8 to 9 mm behind the limbus, said Dr. valveless, flow-limiting design that tissue across the needle as it advances Bedrood, it requires more dissection of decreases the risk of hypotony.3 “I tell toward the limbus to avoid causing any tissue and more manipulation of the all of my patients that the most com- microperforations. Once at the marked conjunctiva, turning it into a longer mon “risk” of these (or any) glaucoma entry point, I enter the sclera with the procedure. surgeries is that they may need another injector needle, confirm position of the Candidates for Xen and Preserflo. intervention later to control their dis needle tip in the anterior chamber, and Although adults of any age may be ease—whether drops, laser, or more deploy the device.” After deployment of good candidates for either a glaucoma surgery,” said Dr. Blieden. the device and confirming the position drainage device or a MIGS device by bleb formation, Dr. Blieden occludes such as Xen or Preserflo, patients with The Xen Procedure the distal tip with gentle pressure from significant disease who are in their 40s, “I find Xen to be a really robust step a Weck-Cel sponge prior to injecting 50s, or 60s and in the workforce may before doing a trabeculectomy, and it MMC into the sub-Tenon space of the benefit greatly from the MIGS devices doesn’t preclude me from doing either superior quadrant. because of the potential for a quicker a trab or a tube shunt later on,” said Postsurgical results. Studies with recovery, which could get them back to Dr. Blieden. Xen generally show a decrease in IOP to work faster, said Dr. Lim. She said that Ab interno versus ab externo. the low- or mid-teens and a decreased suitable candidates “may have more For Xen, the on-label approach is ab need for medications afterward,5 said advanced disease than a less-invasive interno. Surgeons may perform the Dr. Bedrood. “It may not get the patient MIGS (such as iStent or Hydrus) could procedure alone or at the same time as off all medications, but even eliminating help them with, but you don’t want to a cataract surgery.4 “You go through the one or two is a success.” subject them to a long recovery or the anterior chamber using the same type If needed, a postoperative revision of potential for serious adverse events that of incision as you would for cataract the implant can free it from scar tissue they might experience with a glaucoma surgery, and then insert the device and get fluid flowing again. In a vari- drainage device.” through the angle and out underneath ety of Xen studies, needling has been Patients with early-stage glaucoma the conjunctiva,” said Dr. Bedrood. required in 22% to 49% of patients.1 tend to have good central vision, said Many ophthalmologists are now adopt- Because it’s a small implant, it is prone Dr. Bedrood, so performing a less- ing off-label ab externo technique, she to clogging, said Dr. Blieden. “I recently invasive surgery that helps maintain said. (See “More Online” for video of had a couple of cases where this oc- their good refractive status is easier for each technique.) curred. One was a uveitic patient who these patient to tolerate. The Xen and “I had a hate-love relationship with flared after surgery, which caused the Preserflo devices may also help reduce Xen when it first came out,” said Dr. Xen to fail.” Another patient had excel- glaucoma drops in patients who have Blieden. “I disliked the ergonomics lent results initially. “She’d previously developed an allergy or intolerance to of the injector with the ab interno had a corneal transplant, her inflamma- their topical medications. approach. But when Won Kim, MD, tion was controlled, and we didn’t want In addition, Dr. Blieden defines a popularized the ab externo approach, to put in a huge tube shunt. But after a good Xen patient as one who in earlier I decided to try it and now do all Xens cataract surgery, the Xen clogged.” One days would have undergone a trabe- this way.” This type of placement can be patient required a tube and the other a culectomy with minimal or no mito performed with or without conjuncti- trabeculectomy to control their disease. mycin-C (MMC). “I would choose val dissection.1 Dr. Bedrood said that postoperative Xen for people whose goal is minimal The procedure. Surgeons perform management of the bleb includes surgery, sedation, and time in the OR,” the ab externo procedure under local “examination for bleb failure, cystic she said. anesthesia.4 changes, erosions, or leaks.” These Challenges of Xen and Preserflo. Using a superior peripheral corneal postoperative issues are not common Despite being microinvasive, both Xen traction suture to infraduct the eye, and often can be managed by either and Preserflo may pose a risk for con- Dr. Blieden marks off 2 mm and then the comprehensive ophthalmologist junctival scarring and should be used 4 mm from the limbus using calipers or the glaucoma physician, she said. with antifibrotic agents like MMC, said to gauge the entry and length of the Dr. Blieden. She cautions against using implant after deployment. The Preserflo Procedure Xen or Preserflo in patients who scar “I make absolutely certain the Xen is Dr. Blieden was an investigator in easily, have active lifestyles like swim- lying flat against the sclera, away from Preserflo clinical trials, and she sees the mers or other athletes, or have to wear Tenon’s,” said Dr. Blieden. “With the device as having a role similar to Xen. contact lenses. “These are cases where eye rotated down and marked, I take a However, she said that the Preserflo you may not want a conjunctival bleb,” tissue forceps way back at the fornix, may be a little more broadly applicable she said. pick up Tenon’s and conjunctiva, so because it is a bigger implant—the

30 • JULY 2021 length is longer and the lumen is bigger. tomy or glaucoma drainage device. (2):132-183. In her experience, she said, “It’s easier And Dr. Blieden added, “Many patients 4 Buffault J et al. J Fr Ophtalmol. 2019;42(2): to needle because the material is more end up on just one drop, which is very e37-e46. robust in my hands.” As with the Xen, reasonable.” Study results presented at 5 Poelman H et al. J Clin Med. 2021;10:1118. this may be a standalone procedure or AAO 2020 showed that compared with 6 Sadruddin O et al. Eye Vis (Lond). 2019;6:36. combined with cataract surgery.6 71% of trabeculectomy patients about 7 Scheres LMJ et al. Acta Ophthalmol. Published Use of MMC. The phase 2 Preserflo half the Preserflo patients achieved a online Sep. 10, 2020. study used sponges with a fairly high 20% reduction in mean diurnal pres- 8 Panarelli et al. Poster #189, One-year safety and concentration of MMC: 4 μg per mL sure from baseline without increasing effectiveness of microshunt vs. trabeculectomy for 4 minutes, said Dr. Blieden. “In the glaucoma medications.8 However, in sites in the USA and Europe in a randomized phase 3 study, we used a half-dose for said Dr. Lim, trabeculectomy resulted study. Presented at: AAO 2020 Virtual; Friday, 2 minutes, also on sponges.” However, in a higher percent of patients with Nov. 13, 2020. a Canadian study showed that a higher hypotony, early bleb leaks, and post-op 9 Moster M et al. Poster #193, Safety outcomes dose of MMC gave better pressure- interventions. “The value of Preserflo, of microshunt implantation vs. trabeculectomy lowering results, said Dr. Lim, who was therefore, may be its superior safety in patients with POAG. Presented at: AAO 2020 also an investigator in the Preserflo profile over trabeculectomy,” she said. Virtual; Friday, Nov. 13, 2020. trials. Assuming that the FDA approves The need for needling. Another Preserflo, she said, surgeons will learn poster presented at AAO 20209 showed Dr. Bedrood is a glaucoma and cataract specialist what works best for certain patients that about 19% of patients required with Acuity Eye Group, Pasadena, Calif. Relevant and will titrate the dosing of MMC. “In needling within the first two or three financial disclosures: Allergan: C,L; Santen: C. addition, injecting mitomycin-C may months and then do very well, said Dr. Blieden is a glaucoma and cataract specialist, allow surgeons to perform surgery with Dr. Blieden, adding that this parallels associate professor, Baylor College of Medicine in smaller incisions in the conjunctiva, her own experience. “I’ve also found Houston. Relevant financial disclosures: Allergan: C. which can help with the healing pro- needling of the Preserflo to be easier Dr. Lim is a glaucoma specialist, professor, cess,” she said. In the future, Dr. Blieden than with the Xen, which is a bit more vice chair and medical director, University of anticipates injecting MMC as she does fragile.” California, Davis Department of Ophthalmology for all her conjunctival procedures. Special cases. Although patients & Vision Sciences, Sacramento, Calif. Relevant The procedure. The Preserflo in- with neovascular glaucoma or uveitic financial disclosures: Santen: C. volves a quick, straightforward open glaucoma have done well with glauco- See disclosure key, page 8. For full disclosures, ab externo procedure, said Dr. Blieden. ma drainage devices, it remains to be see this article at aao.org/eyenet. “A specialized blade comes with the seen how well they will do with Preser device to help create an anterior wound. flo, said Dr. Blieden. MORE ONLINE. View “Ab Interno Xen The surgeon can easily slide the device Implantation” at aao.org/master-class- directly into the scleral pocket, and Physician Adoption? video/ab-interno-xen-implantation- then ensure that the device is clear of Dr. Blieden noted that Xen and Preserflo classic-approach, and “Ab Externo Xen Tenon’s when closing the peritomy.” could be a natural fit for many glaucoma Implantation” at aao.org/master-class- (See “More Online” for a Preserflo surgeons, as the surgeries may translate video/ab-externo-xen-implantation. video recommendation.) relatively easily into their algorithms View “The Perfect PreserFlo Bleb” at A unique bleb. “The Preserflo bleb is and management styles. She added that aao.org/annual-meeting-video/perfect- different in morphology than anything Xen and Preserflo may also serve as preserflo-bleb. else I’ve seen,” said Dr. Blieden. “It tends a great procedure for comprehensive to be flat and form more posteriorly physicians when a glaucoma surgeon and out of the way, whereas the Xen is is not available. SUBSPECIALTY DAY more anterior. A low and posterior bleb “It’s a big decision to take someone Subspecialty Day is makes it possible to resume contact lens from medications to a tube or trab,” Friday, Nov. 12, and wear in some patients.” Dr. Lim added said Dr. Blieden. The traditional devices Saturday, Nov. 13. that the Preserflo bleb’s low profile and easily take three or four times longer Friday: Retina more posterior position may reduce the in the OR than a Xen or Preserflo, and (day 1), Glaucoma, risk of bleb breakdown and bleb leak clinicians lose more real estate in the Neuro-Ophthalmology, over time. process, she said. “It’s really exciting to Ocular Oncology and Pathology, Postsurgical results. The Preserflo have new options available.” Pediatric Ophthalmology, and has achieved results comparable to Xen Refractive Surgery. Saturday: in terms of surgical success, IOP lower- 1 Fea AM et al. Clin Ophthalmol. 2020;14:1805- Retina (day 2), Cornea, Oculofa- 7 ing, and safety profile. In the Preserflo 1832. cial Plastic Surgery. patients whom Dr. Lim has followed, 2 Pinchuk L et al. Biomaterials. 2008;29(4):448- Learn more at aao.org/ she’s noticed a faster recovery and re- 460. registration. turn to comfort than with a trabeculec- 3 Do AT et al. Curr Opin Ophthalmol. 2020;32

EYENET MAGAZINE • 31 NOTE: This article has been updated since print publication. In the original article, EyeNet incorrectly stated that Fig. 3A shows a detached posterior vitreous cortex. In fact, the patient had an attached posterior vitreous during the surgery. This version of the article corrects the mistake.

RETINA OPHTHALMIC PEARLS

Diagnosis and Management of Macular Holes

acular holes (MH) result in are also a common cause 1 central vision loss, metamor of TMH. Mphopsia, and a central scotoma. Idiopathic macular holes (IMHs) ac Diagnosis and count for 83% of cases; they are found Classification more commonly in females and are MH is diagnosed by means associated with increased age. Trauma is of a thorough history and another cause, with traumatic macular clinical examination includ holes (TMHs) comprising 5% to 8% of ing slit-lamp biomicroscopy total cases.1 It is important to consider of the fundus with a dilated TMH as a cause of vision loss following pupil. Symptoms usually in trauma, as it will inform medical and clude blurred central vision, surgical management. inability to read or watch television, and distortion MACULAR HOLE. Fundus photograph shows a Pathophysiology of the central vision with full-thickness MH in an elderly woman. Idiopathic. IMHs are most common metamorphopsia. Visual in women over the age of 65, and they acuity is decreased, and Amsler grid on OCT. The Watzke-Allen sign is are due to tangential traction by the testing shows the central scotoma and negative. cortical vitreous on the fovea. The metamorphopsia. At the slit lamp, a Macular pseudoholes associated retina is thinnest at the foveal floor, and Watzke-Allen sign shows a break noted with epiretinal membranes appear as a progressive traction results in elevation by the patient when a thin slit-lamp central reddish spot in the fovea with of the fovea—and, subsequently, an beam is focused across the MH. OCT a surrounding epiretinal membrane. opening in the foveal tissue, which then provides the detailed imaging to make On OCT, the outer retina is intact, and results in a full-thickness MH (Fig. 1). the diagnosis of full-thickness MH, the inner retinal defect often has steep Traumatic. A TMH has a different which shows a break involving all the edges. The Watze-Allen sign is negative. aao.org/eyenet. etiology from IMH. TMH occurs when different layers of the retina. Vitreomacular traction syndrome an acute blunt force on the globe results Differential diagnosis.OCT can be can result in tractional macular cystic in a contrecoup injury on the macula. used to differentiate between true MH changes but often is associated with MH develops due to a contusion on the and conditions that may appear similar many areas of traction on the retina retina with secondary necrosis, subfo on clinical examination, including outside the fovea. veal hemorrhage, and acute vitreous lamellar macular hole and pseudohole, Other less common causes of traction resulting from the acute flat among others.2 diagnoses simulating a macular hole, tening of the posterior globe. Trauma Lamellar macular holes have an especially in its early stages, include can occur with sports injuries, work-re irregular contour with a break in the subfoveal drusen, central serous chorio lated accidents, lightning strikes, and inner fovea without a break in the retinopathy, cystoid macular edema, electrical shock. With the 4th of July outer retina. There are often overhang and vitelliform lesions resulting in a celebrations, fireworks-related injuries ing edges over the inner foveal defect central yellow spot typical of stage I macular holes (see “Classification,” next page) with traction on the fovea result BY MAHERA HUSAIN, BS, STEVE GERBER, MD, AND AMIR HAJRASOULIHA, ing in increased visualization of the

MD. EDITED BY GREGG T. KOKAME, MD, AND BENNIE H. JENG, MD. xanthophyl pigment. see this article at full credit, For Specialists. @ American Society of Retina

32 • JULY 2021 Classification. There are two main 2 systems for classifying MHs. The Gass system (1988; updated in 1995) divides MHs into various stages based on fundus biomicroscopy. The IMH progresses through stages as ini tially described by Gass in his biomi LAMELLAR HOLE. OCT shows a partial-thickness hole and a large subfoveal druse. croscopic examinations.3 The patient had 20/25 visual acuity. • Stage I is a foveal elevation without a break. surgery utilized for IMHs.6 the internal limiting membrane (ILM) • Stage II is foveal elevation with a Surgery. Surgical technique for MHs is performed by many vitreoretinal break either in the central fovea or at has evolved since the initial description surgeons. This step often utilizes agents the peripheral edge of the elevated by Kelly and Wendel in 1991.7 Vitrecto to assist in peeling including brilliant fovea. my, membrane peeling, and the use of blue dye, indocyanine green dye, and

• Stage III is a full-thickness macular an intraocular tamponade, such as SF6 triamcinolone.

hole. gas, C3F8 gas, or silicone oil, are utilized Recently for larger or recurrent MHs, • Stage IV is a full-thickness macular to relieve traction on the MH and to different substrates have been put into hole with complete posterior vitreous stimulate closure of the MH. Peeling of the MH to facilitate closure by provid detachment. The International Vitreomacular Traction Study (IVTS) classification (2013) is based on OCT appearance. Case Study: Firecracker Trauma It considers size (horizontal diameter at narrowest point) and status of the A 12-year-old boy was 3A vitreomacular interface. Full-thickness playing with firecrackers MHs are categorized by size as small when he threw one down (≤250 μm), medium (>250 μm to and a rock shot up, striking ≤400 μm), or large (>400 μm). They him in the eye, causing im- are further characterized by vitreous mediate pain and blurred status (with or without vitreomacular vision. When seen in the traction) and by cause (primary or sec office the next day, he had 3B ondary).4 Full-thickness macular hole is a VA of counting fingers primary if caused by vitreous traction, and extreme photophobia and secondary if the macular hole is in that eye. He also had 2+ caused by pathologic characteristics anterior chamber cells, a TRAUMA AND TREATMENT. (3A) Macular OCT other than vitreomacular traction superficial central corneal taken two days after injury shows a MH (>1,500 abrasion, and no hyphe- µm). (3B) Image taken six months postoperatively Management ma. He was put on topical shows repaired MH with overall thinning centrally Management of MH depends on the prednisolone acetate every due to photoreceptor loss. etiology, the size of the hole, and, in the 2 hours. case of trauma, the presence of associ He was feeling much better when he returned the next day, but his vision ated ocular complications such as vit had not improved, despite a clear cornea and much-reduced inflammation. reous hemorrhage, choroidal ruptures, An OCT was ordered because of the unexplained vision loss. The OCT showed and commotio retinae. a MH (>1,500 µm) with attached posterior vitreous, which was confirmed Observation. Small idiopathic holes intraoperatively (Fig. 3A). (≤250 μm) may close spontaneously, Surgery. The decision was made to perform surgery because of the large and this may be facilitated by the use size of the hole. A 25-gauge pars plana vitrectomy was performed. The ILM of topical medications to decrease mac was stained with brilliant blue dye, and ILM peel was performed from arcade ular edema. TMHs appear to have to arcade with a retractable Tano scraper and ILM forceps. A retinal break was a higher rate of spontaneous closure noted at the 7-o’clock position, as well as lattice degeneration. Endolaser was than do IMHs. Because of the high used to seal both the break and the lattice degeneration. The final step was

er chance of spontaneous closure of air-fluid exchange with 15% perfluoropropane 3(C F8). TMHs, which can occur most com Follow-up. At the six-week postoperative follow-up, the patient still had 15%

monly over two to six months, initial C3F8 gas in the eye with the closed MH, and vision had improved to 20/100+2. management is often observation.5 At the six-month postoperative appointment, the patient’s VA was 20/200. However, if TMHs persist, these holes Although the hole was anatomically closed, vision was decreased as a result

Steve Gerber, MD; Indiana University Department of Ophthalmology, Amir Hajrasouliha, MD; Steve Gerber, MD. MD. Gerber, MD; Steve Amir Hajrasouliha, Department of Ophthalmology, MD; Indiana University Gerber, Steve can be managed by the same type of of photoreceptor loss (Fig. 3B).

EYENET MAGAZINE • 33 ing a scaffold for glial proliferation. An Coming in the next inverted flap technique involves peeling of the ILM and inverting the ILM flap Fireworks Trauma ® into the MH or over the MH.8 One ran Prevention domized trial compared the inverted flap technique to conventional peeling 1. Fireworks are dangerous explo- in holes larger than 600 μm and found sives and often result in trauma Feature significantly higher rates of anatomic not only to the person lighting the Diversity, Equity, and success (90% vs. 70%, respectively) and fireworks but also to bystanders. Inclusion What are the visual recovery (2.1 lines vs. 1.4 lines, It is important to be aware of your changes that practices respectively) with the inverted flap surroundings and where fireworks are 9 and organizations should method. ILM transplantation from being lit. make—and how can they other parts of the macular region may 2. Use protective eyewear. 10 best be implemented? also facilitate closure. In very large 3. Keep unused fireworks in a safe MHs, retinal transplantation into the place away from children. Clinical Update hole is used by an autologous retinal 4. Never return to a lit firework and, 11 Cornea Experts discuss graft from the retinal periphery. especially, do not look down over a lit cataract surgery in patients Postoperative positioning has tradi firework. Do not relight a dud. with compromised corneas. tionally been face down, which floats Part 1 of 3. the bubble directly to the macular Oculoplastics Reducing region. However, many surgeons feel risk of periorbital hemor- comfortable not putting their patients closure, so observation is often recom rhage in patients on anti face down and feel that the gas bubble mended. However, the most important thrombotics. Plus: New contact even in the sitting-up position recommendation is to prevent ocular medications in development. allows for adequate tamponade. trauma, especially with fireworks that may be used to celebrate the 4th of July. Pearls Outcomes Bell Palsy What you need Visual outcomes are best for patients 1 Gao M et al. Curr Eye Res. 2017;42(2):287-296. to know about Bell palsy who were symptomatic for less than 2 Chen JC, Lee LR. Br J Ophthalmol. 2008;92(10): and its medical and surgical six months before surgery. MHs that 1342-1346. management. Plus, an up- are larger than 1,200 μm have a greater 3 Gass JDM. Am J Ophthalmol. 1995;119:752-759. date on facial reanimation. chance of failing to close after surgery. 4 Duker JS et al. Ophthalmology. 2013;120:2611- Chronic MHs, which have persisted for 2619. Savvy Coder longer than two to three years, have a 5 Kusaka S et al. Am J Ophthalmol. 1997;123:937- E/M Update Clarifications poorer visual prognosis even when the 839. on using the new evaluation MH closes. However, closure of MHs 6 Johnson RN et al. Ophthalmology. 2001;108: and management rules. in the majority of cases has resulted in 853-857. improved visual acuity and decrease 7 Kelly NE, Wendel RT. Arch Ophthalmol. 1991; Blink in metamorphopsia. There is a small 109:654-659. Take a guess at the next chance of MHs reopening, but vision 8 Michalewska Z et al. Ophthalmology. 2010;117: issue’s mystery image. Then improvement remains long-term in 2018-2025. report your diagnosis at most patients. 9 Baumann C et al. Retina. 2020;40:1955-1963. aao.org/eyenet. 10 Morizane Y et at. Am J Ophthalmol. 2014;861- Conclusion 869. Surgery for MHs has developed over 11 Grewal DS et al. Ophthalmology. 2019; 125: For Your Convenience the past 30 years into a very successful 1399-1408. These stories also will be procedure to improve vision by closure available online at of the MHs. Symptoms of MHs include Ms. Husain is a third-year medical student at the aao.org/eyenet. blurred vision, a central scotoma, and Indiana University School of Medicine in South metamorphopsia. Fundus examina Bend. Dr. Gerber is in practice at Advanced Oph FOR ADVERTISING INFORMATION tion shows a defect in the fovea and is thalmology in Michiana, Ind., and is a clinical confirmed with OCT showing a defect professor of ophthalmology at Indiana University Mark Mrvica or Kelly Miller in all layers of the retina. Surgical School of Medicine in South Bend. Dr. Hajrasou- M. J. Mrvica Associates Inc. techniques have developed to increase liha is a vitreoretinal specialist and assistant 856-768-9360 closure rates in larger MHs. TMHs have professor of ophthalmology at Indiana University [email protected] a different etiology than IMHs and School of Medicine in Indianapolis. Financial have a higher chance of spontaneous disclosures: None.

34 • JULY 2021 FROM BRAIN SCIENCE TO FULL VISION

American Medical Association (AMA) Assigns CPT Code to Software Clinically Proven to Treat Adult Amblyopia (Lazy Eye) AMA Approval of Reimbursement Code Offers Access to Neuro-Vision-Based Therapy for Millions of U.S. Adults with Amblyopia

MODI’IN, Israel – July 1, 2021 – RevitalVision announced that its standalone therapeutic vision training software, the only FDA-approved product for market, and clinically proven to improve vision in adult amblyopia (age nine-plus), received a unique Current Procedural Terminology (CPT) reimbursement code from the American Medical Association (AMA).

BRAND“Innovation BOOK is important to advance patient vision care, and it is vital to look at clinical evidence and creating a reimbursement environment so that health professionals can make a difference for people with eye and vision conditions,” said Yair Yahav, chief executive ofﬁcer, RevitalVision. “Securing a CPT reimbursement code for this FDA-cleared Vision Training Software Program enables healthcare professionals to offer it to their patients. Given the success of our clinical studies, we will work to make RevitalVision the new standard of care for treating adult amblyopia.”

"RevitalVision is a great advance for adults and older children with amblyopia, who we previously could not treat. I hope that this new code will push insurance companies to pay for this valuable treatment." said David Silbert MD FAAP a pediatric ophthalmologist and CEO of Conestoga Eye.

Based on Nobel Prize recipient Dennis Gabor’s science, this approach resulted from more than two decades research by Prof. Uri Polat, head of Bar Ilan University’s School of Optometry and Vision Science. RevitalVi- sion neural training program improves vision by 2.5 lines on average on the visual acuity chart, and 100% in contrast sensitivity. Most amblyopic patients also improve stereo acuity and binocular function.

RevitalVision user friendly and easy to use web app vision training technology platform is performed from the comfort of the patient’s home computer for three to four 30-minute home training sessions per week, for a period of three months. Through repetitive practice of defined visual tasks, the brain is trained to be more efficient in processing visual information. RevitalVision specialized algorithms analyze performance and continuously adjust training sessions to improve vision, customized to patients’ specific needs.

A physician is able to closely monitor patient progress through an in-person ofﬁce visit to measure actual vision improvement after 20 and 40 sessions, remote monitoring of patient’s training activity by actively accessing the management portal, and by receiving automated reports from the system.

About RevitalVision

RevitalVision, developers of a unique therapeutic vision training software that improves vision in patients suffering from different eye diseases & visual impairments, when no other alternative treatment is available or effective. In addition to adult amblyopia, RevitalVision is clinically proven to improve vision after cataract & laser refractive surgery and in various pathologies, such as retinal and corneal disease as well as congenital nystagmus.

Clinicians who wish to use RevitalVision products can easily self-register as Provider's on Company's website and have immediate access to prescribe the therapy to patients.

www.revitalvision.com [email protected] Foundation Give Back to Ophthalmology With Your Donor Advised Fund

A donor advised fund is an effective way to invest and give back to philanthropic organizations like the American Academy of Ophthalmology Foundation. Now is a great time to recommend a grant or recurring grants that will make an immediate impact on the success of academy programs.

Discover the ease of opening a donor advised fund—plus the advantages you’ll enjoy—with our guide at aao.org/daf.

“We established our donor advised fund several years ago and have benefited by its investment growth. Nonprofit organizations such as the Academy Foundation need our support, and they need it now. Join us in donating generously to the Foundation.”

DR. GEORGE B. AND LYNN BARTLEY WHAT’S YOUR DIAGNOSIS? MORNING ROUNDS

Not Your Typical Headlight in the Fog

Figure 1:

essica Taylor,* an otherwise 1 FIRST WEEKS OF TREAT- healthy 11-year-old girl, had MENT. When we first saw Jstarted experiencing blurred Jessica, (1) a fundus photo vision in her right eye, as well as a of the right eye showed that shadow over the top of her right field a yellow cream–colored cho- of vision. After two months, her parents rioretinal lesion was present took her to see an optometrist who inferotemporal to the macula stated that there was retinal inflamma- with overlying vitreous haze. tion in Jessica’s right eye and referred On the same day, (2) an OCT

her to us. Figure 2 scan through that lesion showed that a large sub-RPE We Get a Look and intraretinal hyperreflec- When we first saw Jessica, she didn’t tive lesion was present with mention the shadow, but she may associated choroidal thicken- 2 have been nervous and hesitant to say ing. Multiple hyperreflective much. She did tell us that there hadn’t spots were present within been any curtains over her vision and the vitreous, indicating vitri- Figure 5: that she hadn’t noticed any floaters or tis. At a later exam, we saw flashes of light. improvement in the retino- While talking with Jessica and her choroiditis and vitritis (to see parents, we learned that they are avid images from that exam, view meat-eaters and, on occasion, eat 3 this article online). However, medium-rare venison. Jessica also several weeks after the initial told us that she loves to spend time presentation, (3) OCT imag- playing with their five cats. ing revealed a new finding On exam, her vision was 20/40 in of subretinal fluid and a her right eye and 20/20 in the left. hyperreflective lesion in In her right eye, she had no anterior the subretinal space. segment keratic precipitates (KPs) but did have 1+ vitreous cells and haze. central scotoma in her right eye. in the vitreous consistent with vitritis. Also in her right eye, the fundus exam- An OCT image (Fig. 2) through the Our initial differential. Clinically, the ination (Fig. 1) showed a yellow chorio- inferior macular lesion demonstrated a focal yellow retinal lesion with associat- retinal lesion inferior to the fovea. Of large hyperreflective intraretinal lesion ed vitritis immediately pointed toward note, there were no chorioretinal scars corresponding to an area of retinocho- an infectious or inflammatory etiology, and no evidence of previous inflamma- roiditis and significant choroidal thick- with toxoplasmosis high on the differ- tion in either eye. ening that was seen on the exam. There ential. This was supported by Jessica’s Visual field testing revealed a large were also multiple hyperreflective spots history of close contact with cats and eating undercooked meat. We considered white dot syndromes, BY GUNEET S. SODHI, MD, JOHN D. SHEPPARD, MD, AND ROHIT S. trauma, and malignancy to be lower

Virginia Eye Consultants, Norfolk, Virginia. Norfolk, Consultants, Eye Virginia ADYANTHAYA, MD. EDITED BY AHMAD A. AREF, MD, MBA. on the differential, based on Jessica’s

EYENET MAGAZINE • 37 Figure 7

Figure 7

presentation and history. Jessica received intravitreal aflibercept 4 What we did. We started Jessica on (Eylea) as an off-label indication and topical steroids and ordered uveitis labs, experienced complete resolution of the which included a complete blood count subretinal fluid (for an OCT image, see (CBC), erythrocyte sedimentation rate “More Online”). Her final visual acuity (ESR), toxoplasmosis IgM and IgG, was 20/20 in the right eye. syphilis labs (rapid plasma reagin [RPR] and FTA-Abs), TB Quantiferon Gold, Our Diagnosis and a chest x-ray. With the combination of a positive Figure 6: The toxoplasmosis IgG titer was 221 toxoplasmosis titer, pertinent clinical IU/mL (reference range, 0-7 IU/mL), history, posterior segment inflammation but the IgM antibodies were within that was responding to fourth-line anti normal limits. All the other labs were toxoplasmosis therapy, and no prior unremarkable. We referred her to a 5 evidence of chorioretinal scarring, we pediatric infectious disease specialist diagnosed primary ocular toxoplasmo- who started her on oral pyrimethamine sis in an adolescent patient. Jessica pre- 25 mg (daily), oral sulfadiazine 2 g sented with only macular involvement, (twice a day), and leucovorin 15 mg complicated by a CNVM, which is rare (daily), followed by oral prednisone 40 in the literature. mg (daily) three days after initiating anti-toxoplasmosis therapy. Discussion The next visit. When we saw Jessica Ocular toxoplasmosis is a progressive a few days later, her retinal exam and PINNING DOWN THE DIAGNOSIS. After and recurring necrotizing retinitis vitritis had imp roved. a further change in medications, (4) caused by infection with Toxoplasma Allergic reaction. However, she had OCTA through the area of subretinal gondii, a ubiquitous obligate intracellu- developed an allergic reaction to the fluid showed an obvious neovascular lar parasite. sulfadiazine (fever, rash, and headaches) membrane. (5) The fundus exam of the Can be congenital or acquired. and, three days later, to pyrimethamine right eye revealed a new hemorrhage During a congenital infection, the fetus (rash). Because of her reaction to the in the temporal parafovea, adjacent to is infected via the placental blood- sulfadiazine, she was admitted as an the retinochoroidal lesion. stream. During an acquired infection, inpatient. Both sulfadiazine and pyri- parasite transfer is typically mediated methamine were discontinued. She was As we were under the impression that through the gastrointestinal tract. The started on azithromycin 250 mg (twice this was an active toxoplasmosis infec- main routes of acquired infection are a day) and oral clindamycin 150 mg tion refractory to the current regimen, thought to be from ingestion of oocysts (four times a day) and continued on she was given an intravitreal injection from cat feces in soil (via, for example, the oral steroid course. of clindamycin in her right eye. She was hand-to-mouth transmission), un- Vision worsens. Two weeks after remarkably cooperative for an 11-year- washed fruits and vegetables, and raw starting on azithromycin and clin- old. However, her subretinal fluid not or undercooked meat. damycin, a fundus exam and OCT only persisted but also increased by the A clinical diagnosis. T. gondii is imaging (see “More Online”) showed time we saw her the next week. Despite prevalent in nature, and the presence improvement in the retinochoroiditis a reduction in the choroidal thickening of antibodies to T. gondii is useful only and vitritis. However, after finishing and vitritis at this visit, the volume of to confirm previous exposures to the a three-week course of clindamycin, retinal fluid continued to increase. She parasite. Absence of IgG titers virtually a one-month course of azithromycin, was started on atovaquone therapy in rules out the infection. The combina- and an oral prednisone taper, Jessica’s addition to the other medications. tion of high titers of toxoplasmosis IgG vision worsened to 20/50 in the right Pinning it down. A few days later, and IgM antibodies is usually consistent eye. Furthermore, OCT imaging (Fig. OCT angiography (OCTA; Fig. 4) with recent infection. 3) showed increasing hyperreflectivity showed a definitive secondary choroi- Nonetheless, the diagnosis is usually in the subretinal space. dal neovascular membrane (CNVM). made clinically.1 This, along with a hemorrhage on Impacts the retina and choroid. The Mystery Fluid fundus exam (Fig. 5), clinched the Once the parasites reach the eye, they We restarted Jessica on oral clindamycin diagnosis. will create a focus of retinal inflamma- (three times a day), oral azithromycin, The CNVM diagnosis was support- tion, involving the choroid secondarily. oral prednisone, and topical steroids. ed by the fact that the vitritis and cho- Immune responses of the host induce No improvement in vision. One roidal thickening were actually improv- conversion of the parasitic forms, the week later, we saw no improvement in ing, indicating that the systemic therapy tachyzoites, into the dormant bradyzoites

her vision or macular subretinal fluid. was adequately treating the infection. and cyst forms, which remain inactive Virginia. Norfolk, Consultants, Eye Virginia

38 • JUNE 2021 in scars. A reactivation of retinitis from Increased expression of VEGF and RPE pump in adults with age-related rupture of the cysts can develop near Bruch membrane compromise second- macular degeneration. Given that the the preexisting scars. ary to inflammation from T. gondii has adverse ocular and systemic side effects Clinically, the focal necrotizing been posited to contribute to neovas- of anti-VEGF therapy in children have retinitis is associated with vitritis and, cular disease in ocular toxoplasmosis not been as extensively studied as in often, with an anterior uveitis, either and provides a rationale for intravitreal adults, a reduced number of intravit- granulomatous or nongranulomatous. anti-VEGF therapy. real anti-VEGF agents administered as Vitritis is usually intense near the lesion Furthermore, intravitreal anti-VEGF needed in pediatric patients is strongly of active chorioretinitis, creating the therapy minimizes the destruction of advised.5 classic “headlight in the fog” presenta- the retina and choroid and provides a Long-term studies will be required tion.1 favorable visual outcome.3 Therefore, to establish the safety of these injec- Management. Since ocular toxoplas- a number of cases of macular CNVM tions in this age group. mosis is a self-limiting disease, some secondary to ocular toxoplasmosis have clinicians will not treat small peripheral improved with anti-VEGF therapy.3-5 * Patient name is fictitious. lesions. However, if treatment is war- With the exception of one case, all of 1 Park YH, Nam HW. Korean J Parasitol. 2013; ranted, numerous therapies have been these patients presented with a macular 51(4):393-399. used, with no consensus as to the most CNVM near a healed, inactive lesion 2 Stanford MR et al. Ophthalmology. 2003;110(5): efficacious regimen. after having had a primary episode of 926-932. The classic treatment regimen toxoplasmosis. Only one case presented 3 Benevento JD et al. Arch Ophthalmol. 2008; consists of triple therapy: oral pyri- with a macular CNVM at the time of 126(8):1152-1156. methamine, sulfadiazine, and predni- primary acquired Toxoplasma retino- 4 Kohly RP et al. Can J Ophthalmol. 2011;46(1): sone, with folinic acid usually added to choroiditis.6 Our case is unique to the 46-50. prevent the leukopenia and thrombo- aforementioned case because Jessica 5 Mathur G et al. Oman J Ophthalmol. 2014;7(3): cytopenia associated with pyrimeth- presented with a primary toxoplasmo- 141-143. amine therapy. Some clinicians add oral sis lesion without a CNVM and then 6 Mushtaq F et al. Cureus. 2019;11(2):400. clindamycin as quadruple therapy. later developed a CNVM, possibly as 7 Cotliar AM, Friedman AH. Br J Ophthalmol. Clindamycin, either alone or in an indicator of a poor response to first- 1982;66(8):524-529. combination with other agents, has and second-line antitoxoplasmosis been shown to be effective in manag- therapy due to a sulfa and pyrimeth- Dr. Sodhi has just completed an ophthalmic on- ing acute lesions and can be used in amine allergy. This underscores the fact cology fellowship at the Cleveland Clinic’s Cole patients who experience sulfa allergies. that macular toxoplasmosis should be Eye Institute and starts a vitreoretinal surgery This was demonstrated in our patient followed particularly carefully for the fellowship at VitreoRetinal Surgery (VRS), based who had allergic reactions to both sul- development of choroidal neovascular- in the Minneapolis region, this month. Dr. Ady- fadiazine and pyrimethamine. ization, especially in younger patients anthaya is a vitreoretinal surgeon and assistant For patients who do not have sulfa as hypothesized in an analysis by Cot- professor of ophthalmology, and Dr. Sheppard is allergies, some physicians prefer tri- liar and Friedman.7 a cornea and uveitis specialist and assistant methoprim-sulfamethoxazole due to its Last, our pediatric patient only professor of ophthalmology; both are at the low cost and the frequent unavailability required one intravitreal injection of Eastern Virginia School of Medicine in Norfolk, of sulfadiazine in pharmacies and po- aflibercept, supporting other studies Virginia. Financial disclosures: None. tential cost issues with pyrimethamine. that hypothesize toxoplasmosis mac- For lesions threatening the macula, ular CNVMs are exquisitely sensitive MORE ONLINE. For additional imag- intravitreal clindamycin has also been to anti-VEGF therapy, particularly in es, including OCT images showing im- suggested, as it bypasses blood-ocular the pediatric population. This reduced provement in the chorioretinal lesion barriers. number of treatments to achieve invo- three weeks after the initial presenta- Other agents that have been used lution of CNVMs may be explained by tion and complete resolution of the include doxycycline, minocycline, and the relative good health of the retinal subretinal fluid following anti-VEGF atovaquone.2 pigment epithelium (RPE) pump in therapy, view this article at aao.org/ younger patients, compared with the eyenet. A Twist in the Story CNVM rarely complicates toxoplasmic chorioretinitis. A few cases in the literature report this finding, which has been Further Retina-Related Cases managed with observation, anti-VEGF See this article at aao.org/eyenet for links to a selection of retina-related cases therapy, antiparasitic and anti-inflam- from the Morning Rounds archives. These include a teenager with nyctalopia, matory medications, laser photocoag- a 75-year-old with a diagnosis of presumed ocular histoplasmosis syndrome, ulation, or photodynamic therapy, all a 38-year-old with a freckle at the back of her eye, and a 34-year-old with a with variable outcomes. growing spot in his vision.

EYENET MAGAZINE • 39 Join Us in New Orleans!

AAO 2021 Fri–Mon, Nov 12–15 Subspecialty Day Fri–Sat, Nov 12–13 Register and Book Your Hotel AAOE® Program Fri–Mon, Nov 12–15 Academy and AAOE members Open now ASORN Nursing Program Fri–Sat, Nov 12–13 Nonmembers and ASORN members July 7

Where All of Celebrate Laureate Excellence Ophthalmology Meets® Join us for the Opening Session — now on Friday, Nov. 12, at 5 p.m. We will present aao.org/2021 the Laureate Award, the Academy’s highest honor, to two outstanding Re/create With Us in New Orleans individuals for their extraordinary Scan this code with your smart contributions to our profession. phone to get a video preview of the sights, tastes, sounds and community feel you’ll find at AAO 2021 in New Orleans!

All Aboard! George B. Bartley, MD (2020), left Michael T. Trese, MD (2021) Of all the riverboats that cruise the mighty Mississippi, the steamboat Natchez holds a special place in the hearts of New Orleans Plan Ahead for Subspecialty Day locals. On board there’s creole food, Friday Meetings: Glaucoma, drinks, live jazz, and a famous calliope, Neuro-Ophthalmology, whose music is said to be an auditory Ocular Oncology/Pathology, Pediatric, symbol of the city’s resilience. Refractive Surgery, Retina (Day 1) Saturday Meetings: Cornea, Oculofacial Plastic Surgery, Retina (Day 2) re/c reate Join Us in New Orleans!

Last year’s public health emergency forced practices to make drastic changes. Learn how a lean approach helped, which innovations are worth keeping, and how organizations can stay nimble beyond the pandemic.

By Leslie Burling, Contributing Writer

he COVID-19 pandemic was a defining metrics to see whether the revised procedures are event “that revealed the strengths and a success, or if further changes are needed. Tweaknesses of ophthalmic practices,” said A team-based approach to iterative change. Alan E. Kimura, MD, MPH. “It acted as a magnifi- “We were able to transition and respond to the er and an accelerant. It exposed both the oppor- global health crisis due to our understanding tunities and the threats that existed within every of lean processes,” said Dr. Kimura. “Staff was entity pre-COVID.” already accustomed to altering our procedures How to survive and thrive. At Dr. Kimura’s expeditiously, sharing input, and working closely practice—Colorado Retina Associates, in Denver with our management team. We were therefore —physicians and staff used the principles of lean able to refine, as needed, the adjustments made practice management to adapt to the exigencies during the days and weeks following the initial of the emergency. Below, several practice leaders shutdown.” explain how the lean approach helped them to Lean habits make it easier to respond to a navigate the crisis, and they describe the chang- crisis. Staff and physicians at Austin Retina Asso- es that they plan to keep in place beyond the ciates had a similar experience, said the practice’s pandemic. They are joined in their discussion by CEO, Stephanie Collins Mangham, MBA, COA, Aneesh Suneja, MBA, the consultant who helped OCSR, who emphasized their focus on metrics to initiate the lean transformation in each of their evaluate the effectiveness of change. “Because our practices. organization had been conducting [lean] trials for many years, and we were constantly looking How Lean Helps in a Crisis for ways to improve, we were more agilely able to The lean approach provides a framework for respond to the pandemic. Even though it was a experimenting with change: Staff members con- stressful situation, we were ready,” she said. Kelsey Pulkrabek, COA Pulkrabek, Kelsey tinually look for ways to improve processes, are Turning crisis into opportunity. “None of us empowered to make modifications, and gather will ever forget this pandemic,” said Mark Lucarelli,

COVID PROMPTED A RETHINK ON SCHEDULING. In Dr. Lucarelli’s clinic, new scheduling procedures, remote scribing, in-room photography, and an electronic patient tracker were among the lean factors that reduced the average duration of patient visits by almost 40%. At right, Beth Pelar, COA, reviews the schedule with Dr. Lucarelli.

42 • JULY 2021 EYENET MAGAZINE • 43 MD, FACS, an oculoplastic surgeon at University improvement are both valued and expected. They of Wisconsin (UW) Health in Madison. “The are your frontline change agents who should be COVID-19 pandemic confronted us with unprec- constantly looking for ways to enhance clinic flow. edented logistical challenges, but it also provided Ultimately, the feeling of continual improvement big opportunities for us to reexamine our process- snowballs and it can be a powerful experience for es and become more efficient.” Dr. Lucarelli is an the entire organization,” said Dr. Lucarelli. oculoplastic surgeon who serves as the medical Don’t stall before you get started: Get out of director of UW Health’s University Station Eye the staff’s way!When organizations first try to Clinic, where they began the implementation of adopt lean principles, one of the biggest obstacles lean principles in 2018. to progress can be posed by leadership. “Some struggle mightily with relinquishing control and You Need to Empower Staff, and encouraging staff input,” said Dr. Kimura. “But They Need a Lean Champion they must get out of the way for the lean process The lean approach will work only if it is a team to work.” effort. Who will champion the lean approach in your Why you should empower your staff. “We were practice? At the heart of successful lean implemen- once a very top-down organization in that the ad- tation is a clinic administrator and/or a physician ministrators and physicians made all the decisions —preferably both—who will lean into lean and and then pushed them downstream to our staff,” fully embrace the philosophy. This should be said Ms. Mangham. “Now we are a very horizontal “someone in a leadership role who is visionary organization that empowers our employees. and will buy into the ideology in such a way that it Through lean, we recognized that those on the initiates a cultural shift in the organization,” said front lines are the first to encounter problems and Ms. Mangham. probably know better than most of us how to fix them. They have the clearest perspective of which Reimagining Patient Flow process modifications will work and which will Social distancing prompted a reimagining of not.” patient flow.When the pandemic struck, every Build momentum: Success begets success. clinic faced the challenge of keeping patients, staff, With lean, your staff “knows that their ideas for and physicians safe. As practices adopted a strate-

What Is Lean?

The lean health care approach can be broken Gain a deeper understanding of your prac- down as follows: tice. In a lean transformation, a practice should • Identify what it is that the patient values study “every clinical task, remove waste, and (e.g., reduced wait time). optimize workflows,” according to Mr. Suneja. • Review the processes that are used to pro- He emphasized that doing so “results in a deep vide those values and break each process down under standing of clinical operations and en- into its constituent steps. (This is known as ables both staff and leaders to quickly adjust to value stream mapping.) any emergency.” • Review each step to look for waste. Lean can work for any practice, no matter • Eliminate that waste. its size. The lean approach to practice management can be effective with any organization, How do you make a lean transformation? no matter what size it is. “Whether you are Lean is not a one-size-fits-all solution or a managing a regional medical center or an one-and-done endeavor. It is an ever-evolving academic medical center, or are operating as process, as exemplified by Ms. Mangham’s prac- a solo practitioner, the fundamental premise tice, which continually tests ways to improve of treating patients is immutable: It involves efficiency. a team that focuses its efforts on caring for Use metrics to evaluate any changes. When patients. Regardless of the various details, the Austin Retina tests a change in its processes, the fundamental challenges are the same, and the evaluation will be based on metrics. Under the principles of lean can be effectively applied to lean approach, tracking metrics is an integral efficiently improve your clinical processes and part of perpetuating continued growth—after transform your practice,” said Dr. Lucarelli. all, what can be measured, can be managed. For more on lean, visit aao.org/lean.

44 • JULY 2021 gy of social distancing, they were forced to reengineer patient flow. This resulted EXAM EXAM Physicians & Scribes g HIGH RISK OF COVID EXPOSURE in a “eureka” moment for some practices, a. Check In Staff #7 b. Other Waiting Patients c. Tech, Other Patients (3’ Hallways) as their new procedures resulted in sig- d. Other Waiting Patients e. OCT Staff f. Other Waiting Patients nificantly reduced patient wait times g. MD and Scribe RETHINKING h. Check Out Staff and increased satisfaction among both SPACE EXAM EXAM Patient Motion In the Clinic patients and staff. Under the lean Check In/Out, Tech, OCT, MD approach, said Dr. Lucarelli, with its emphasis on minimizing waste and c #3 monitoring results, practices can set f TYPICAL CHALLENGES Check Out Check h TECH TECH TECH Sub

goals of maintaining and capitalizing - #8 #6 Wait Long walking distances (up to 300 steps) Poor patient satisfaction on these improvements in efficiency Check In Visit lengths of 1-3 hours Long patient wait times post-pandemic. d Loss of productivity a #1 Before the visit, prescreen patients. b e #4 #5 You can significantly reduce the amount #2 OCT of time patients spend at your clinic by FlowOne Lean Consulting, LLC All Rights Reserved www.flowone.com gathering as much relevant informa- ANALYZING PATIENT FLOW. In this analysis of patient flow tion (such as their medical history and at the start of the pandemic, steps #1 through #8 represent medication list) before they arrive at patient motion in the clinic. The red stars represent points your office. in the patient flow where there could be high risk of COVID During the pandemic, Ms. Mangham exposure: a) check-in staff; b) other waiting patients; c) tech, decided to give prescreening a try at other patients (3-foot hallways); d) other waiting patients; Austin Retina. It worked so well that e) OCT staff; f) other waiting patients; g) MD and scribe; the practice now has two full-time staff and h) check-out staff. members devoted to the task. Working See this article at aao.org/eyenet for the revised patient remotely, they call new patients to flow, which reduced the patient’s walking distance by 50% capture as much data as possible ahead and increased patient satisfaction by 15%. of time. They also tell patients what to bring and what to expect during the visit. When ination and discuss the options, making my time, the patients arrive at the clinic, a staff member and my patient’s time, in the clinic considerably will verify that nothing has changed since the more efficient,” he said. prescreening. Similarly, the UW Health’s oculoplastics service Patients have been positive about being now conducts the majority of all pre- and post-op screened ahead of their visit. “Patients have been photography in the exam room, rather than having very receptive because they do not feel rushed to patients travel upstairs to another location in the complete the required forms, and they appreciate clinic for this portion of the visit. “The old proce- knowing ahead of time what will occur during dure was extremely wasteful and inefficient,” said their visit,” said Ms. Mangham. “We will continue Dr. Lucarelli. “Now the photos can be immediately this practice post-COVID and are striving to take uploaded into our electronic health record [EHR], it further with our established patients in the where they can be reviewed, which saves our pa- future.” tients and care team a lot of time and steps.” During the visit, reduce the number of stops How the duration of a patient visit was cut by patients have to make. When Sanjay D. Goel, almost 40%. Before COVID-19 vaccinations be- MD, opened his solo practice in January 2020, came available, practices put considerable thought he could not have anticipated the quick impact into reducing (or eliminating) the amount of time COVID would have or the challenges it would that patients spent in the waiting room. For exam- present. With a firm understanding of lean, how- ple, said Dr. Lucarelli, “we now schedule patients ever, he was able to quickly reconfigure patient with complicated cases later in the clinic, so the visits from seven stops in his clinic to three by entire clinic session does not fall behind due to a cutting out unnecessary steps in the process. patient taking longer than expected.” Patients now enter the office, receive a tempera- His practice also instituted “buffering,” which ture check, and are taken to the technician lane involves scheduling a more straightforward type for testing and, when necessary, dilation. Then of encounter, such as a post-op visit, before and the patient is taken to the exam lane and seen by after less predictable encounters, such as a new pa- Dr. Goel. “Prior to entering the room, I can look tient exam. By implementing a multipronged lean at all the scans and analyze the data on my iPad, overhaul, Dr. Lucarelli has decreased his average so when I’m engaged, I perform a slit-lamp exam- total visit time for patients by nearly 40%.

EYENET MAGAZINE • 45 Can More Staff Work From Home? Permitting staff to work remotely not only supports social distancing, it also saves space in the clinic Four Lean Efficiencies and eliminates some of the operational costs that When practices embark on a lean transforma- would be incurred by having them work onsite. tion, it helps to start with the low-hanging fruit. Before the pandemic, Ms. Mangham said that The four suggestions below, for example, could 10 of her staff were already working from home, be implemented relatively easily. so practice policies and the technical infrastructure were already in place when the decision was made 1. Send and receive documents electronically. to make more positions remote. “The moment This saves paper and time. we had to clear out our call center and billing 2. Make electronic payments touch-free. Con- department—because they were working in a sider taking credit card payments through elec- tight, shared collaborative space—we were able tronic devices such as Swipesimple or Square to do so. Now we have approximately 20 people to expedite the checkout process. working from home, and I do not plan to have 3. Standardize spaces. Arrange every exam these individuals return to the clinic post-COVID. room so that equipment is stocked identically, It is unnecessary,” she said. enabling technicians and physicians to quick- How scribes can work remotely. UW Health ly find what they need during an exam. Use was one of the first academic centers to incorpo- screening and exam rooms interchangeably, if rate virtual scribes, which was a remarkable “game possible, to avoid moving patients in and out of changer,” said Dr. Lucarelli. His scribe is located sub-waiting rooms to minimize exposure and in Florida and is connected by a secure, HIPAA- reduce steps. compliant audio link. The scribe has access to the 4. Clearly and concisely communicate proce- patient chart and updates the EHR—from tran- dural changes within your clinic. Patients need scribing pertinent patient history and examina- to understand your current processes and visit tion information to entering orders and complet- expectations to prevent confusion, which can ing after-visit summaries—while Dr. Lucarelli lead to bottlenecks. Convey these messages on conducts the patient encounter. “This enables your website, via social media, inside the clinic, me to maintain a more personal and energized, and at every opportunity available. face-to-face encounter with each patient, rather than disengaging while I enter information into the EHR. I preview each visit of the clinic session ahead of time and establish a game plan. This has “light bulb” moment occurred when a patient with helped us to become more efficient. Patients have flashes and floaters came to the clinic with her noticed these improvements and have expressed daughter early on in the pandemic. “All three of us great appreciation,” he said. were wearing masks, and I realized how imper- At Austin Retina, remote scribing was one of sonal the experience had become, so I decided to the most helpful of last year’s changes. Austin offer telehealth visits when it is unnecessary for Retina has also found virtual scribing to be a boon me to see my patients in person—predominantly for efficiency and safety. “Some of our physicians for consultations and preoperative visits with my wanted to decrease the number of people in the laser refractive patients.” He said that he does not exam room, so they implemented remote scrib- charge for this service, and he makes himself avail- ing,” said Ms. Mangham. “The scribe can be at able after hours and on weekends to accommodate home, in another office, or in the hallway instead his patients’ schedules. of being in the room with the physician and the Dr. Lucarelli also incorporated telemedicine patient. The physician simply tells the patient that into his routine for counseling-type visits, pri- the scribe is listening to their encounter, and the marily, because they are a good fit for this type of scribe performs the same duties as if they were interaction. “In oculoplastics, we are often able to present in the room. Making this change was one observe and assess external conditions remotely as of the most beneficial adaptations we made in well as gather information and provide education,” response to the pandemic.” he said. “Patients now understand that some of their postoperative care can be conducted remotely. Incorporating Telemedicine They like the efficiency it provides because they no During the pandemic, telemedicine became an longer have to travel to the clinic for every visit. important bridge to patient care for many physi- I plan to continue to offer this service post-pan- cians, even if ophthalmology wasn’t able to utilize demic.” (For tips on telehealth payment, see aao. it as much as other specialties did. Dr. Goel’s org/practice-management/telehealth.)

46 • JULY 2021 Create Efficient Physician Flow As a physician’s available time ultimately de- MORE AT AAO 2021 termines how many patients can be seen in the At this year’s annual meeting, clinic, it should never be wasted, said Mr. Suneja. make time in your schedule “Constant management, awareness, and commun for one or more of these lean ication between the physician and the staff results events. in efficient use of everyone’s time and talents,” he SATURDAY, NOV. 13: said. “Staff should ensure that when a physician • Lean Unexpectedly Proves Its Value enters an exam room everything that he or she During the COVID-19 Pandemic (Event needs to conduct the exam is easily accessible. code: 216; senior instructor: Alan E. Kimura, When the physician exits the exam room, any MD, MPH; when: 9:45–11:00 a.m) pending needs should be passed on before • Boost Physician Efficiencies: Creating a moving on to the next patient.” Lean Culture With Technology (Event code: He added, “Preventing wasted time for the phy- 229; senior instructor: Aneesh Suneja, MBA; sician, in between exams, results in less wait time when: 11:30 a.m.–12:45 p.m.) for the next ready patient. This prevents over- SUNDAY, NOV. 14: crowding in the waiting rooms, and it improves • Successful Lean Implementation: The flow through the exam lanes.” Clinical Manager’s Perspective (Event code: 409; senior instructor: Alan E. Kimura, MD, Beyond the Pandemic—How to MPH; when: 9:45–11:00 a.m.) Maintain a Culture of Innovation • Lean for Pediatric Ophthalmology Prac- To grow, look beyond the status quo. It is much tices (Event code: 424; senior instructor: too easy to become complacent and revert to Yasmin Bradfield, MD; when: 11:30 a.m.–12:45 old habits when things appear to be running p.m.) smoothly in the clinic. Practices should evaluate • Lean Healthcare Design for Ophthalmol- their procedures on an ongoing basis and actively ogy (Event code: 444; senior instructor: seek out areas where improvements can be made. Samuel C. Spalding, MD; when: 2:00–3:15 “Choose changes that will be most impactful and p.m.) are easily achievable by everyone involved, then maintain and build upon your successes,” advised MONDAY, NOV. 15: Ms. Mangham, who requires her teams to perform • Boost Positive Employee and Patient Ex- at least four lean trials per year to ensure that they periences Through Lean Process Improve- are proactively pursuing more efficient ways of ment (Event code: 642; senior instructor: performing their duties. Stephanie Collins Mangham, COA, MBA, OCSR; when: 2:00–3:15 p.m.)

MORE ONLINE. For further reading, see this arti- For more information, visit aao.org/program cle at aao.org/eyenet. search.

Meet the Experts

SANJAY D. GOEL, MD A solo director of its University Station Eye Clinic, practitioner at Goel Vision, which and Dortzbach Professor of Oculofacial Plastic has two locations near Baltimore. Surgery at UW–Madison. Financial disclosures: Financial disclosures: Carl Zeiss None. Meditec: C. STEPHANIE COLLINS MANGHAM, ALAN E. KIMURA, MD, MPH MBA, COA, OCSR CEO at Austin President of Colorado Retina Retina Associates in Austin, Texas. Associates and Clinical Associate Financial disclosures: Regeneron: Professor of Ophthalmology at C,L. the University of Colorado Health ANEESH SUNEJA, MBA Lead con- Sciences Center, both in Denver. sultant at FlowOne Lean Consult- Financial disclosures: None. ing, based in Wisconsin. Financial MARK LUCARELLI, MD, FACS An disclosures: FlowOne Lean Con- oculoplastic surgeon at UW Health sulting: C. in Madison, Wis., and medical See the disclosure key on page 8.

EYENET MAGAZINE • 47 We are Here for you

You can rely on OMIC to provide the best patient New Resources education resources available. We continually analyze closed claims and monitor changes in medicine Several new sample informed consent templates including announcements and alerts by the FDA and Forms to comply with FTC Contact Lens Rule and other organizations. We then use this data to ensure Contact Lens Prescriptions that our forms are up-to-date and comprehensive. Guidance and sample consent for observers of We know many ophthalmologists count on us for ophthalmic procedures procedure/drug guidance, recommendations, and Tips on managing the disruptive patient sample forms and documents so that you may carefully inform patients of the risks and bene ts of Sample checklist for idiopathic intracranial ophthalmic medicine and procedures. hypertension/Pseudotumor cerebri

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Coding for Ocular Trauma (Tip: In the ED, the 1997 E/M Rules Still Apply)

he pandemic’s home improve- POS is 23. For an exam in the ED, eye—CPT code 65285 Repair of lacera- ment boom did not go unno- submit 23 as the place of service (POS) tion; cornea and/or sclera, perforating, Tticed in emergency departments value. with reposition or resection of uveal (EDs) around the country. If you need tissue. to code for trauma, use the two cases Case 1: Nail Splinter • Posterior segment intraocular (mag- presented as a refresher, and also visit An open globe injury repair requiring netic) foreign body removal—CPT the AAOE’s resources (aao.org/practice- removal of cataract without insertion code 65260 Removal of foreign body, management/coding/coding-ocular- of IOL. A 55-year-old man had been intraocular; from posterior segment, trauma). hammering a nail when a piece of the magnetic extraction, anterior or poste- nail’s shaft flew into his left eye. rior route. The ED Has Its Own E/M Codes Pre-op diagnosis. The pre-op diag- • Pars plana lensectomy—CPT code E/M codes 99281-99285 are specifically nosis included these elements: 66852 Removal of lens material; pars for exams that take place in the ED. If • Posterior segment intraocular for- plana approach, with or without vitrec- you use these codes, the new stream- eign body tomy. lined 2021 E/M documentation guide- • Zone 2 globe rupture with uveal Coding the case. Follow the nine lines do not apply. Instead, you must prolapse steps for coding multiple procedures meet the requirements of the 1997 E/M • Traumatic cataract during the same surgical session (see guidelines. • Rhegmatogenous retinal detach- “Take Nine Steps,” next page). This dis- 99285 is the highest level of E/M ment with 270-degree giant retinal tear cussion highlights a few of those steps. code in the ED. In both of this month’s Title of operation. The patient un- Can you bill for all four procedures? cases, there is an immediate threat to derwent the following procedures: Although you performed four pro- vision. This means that you can use • Complex retinal detachment repair cedures, and each of those has a CPT E/M code 99285, provided that your with 23-gauge pars plana vitrectomy— code, you need to check whether you documentation shows the following: CPT code 67113 Repair of complex can bill for all four codes. • a chief complaint and a minimum retinal detachment (e.g., proliferative Some procedure codes may be of four elements to the history of the vitreoretinopathy, stage C-1 or greater, “bundled” together. Bundled codes are present illness were noted; diabetic traction retinal detachment, pairs of codes that can’t both be billed • past, family, and social history were retinopathy of prematurity, retinal when performed by the same physician obtained, plus a review of 10 body tear of greater than 90 degrees), with on the same eye on the same day. These systems; vitrectomy and membrane peeling, pairs are sometimes referred to as CCI • all 12 exam elements were performed including, when performed, air, gas, or NCCI edits, which is a reference to (unless unable to obtain due to the or silicone oil tamponade, cryotherapy, the National Correct Coding Initiative. trauma) and exam was done through endolaser photocoagulation, drainage of If you submit two codes that are bun- dilated pupils (unless contraindicated); subretinal fluid, scleral buckling, and/or dled together, you might be paid only • a mental assessment was noted; and removal of lens. for the one with the lower payment. • the three components of risk have • Repair of zone 2 ruptured globe Assess the four codes. You can been met. with resection of uveal tissue, right find out which CPT codes are bundled together by looking at their listings in the AAOE’s Coding Coach (which BY SUE VICCHRILLI, COT, OCS, OCSR, ACADEMY DIRECTOR OF CODING you can buy at aao.org/coding) or by AND REIMBURSEMENT. scrolling through an NCCI spreadsheet

EYENET MAGAZINE • 49 (which you can download at www.cms. Don’t forget the modifiers.To in Injection, anterior chamber of eye (sep- gov/Medicare/Coding/NationalCorrect di cate that the procedures took place arate procedure); air or liquid. CodInitEd/NCCI-Coding-Edits). on the left eye, append modifier –LT • Canalicular lid laceration—CPT Coding Coach also lists the number to all three codes. And since all these code options: 67930 Suture of recent of relative value units (RVUs) that have procedures have a 90-day global period, wound, eyelid, involving lid margin, been assigned to each code. The more you should append modifier –57 to the tarsus and/or palpebral conjunctiva di- RVUs a code has, the higher its reim- exam code to indicate to the payer that rect closure; partial thickness or 67935, bursement rate. the exam took place to establish the which is for the full thickness version of Here is the key RVU and bundling need for surgery. the same procedure. information: Assess the four codes. As in Case 1, • 67113 has 38.26 RVUs and is not Case 2: Spring in Eye you can use Coding Coach to learn if bundled with 65285, 65260, or 66852 Open globe injury repair requiring any of the CPT codes are bundled and • 65285 has 31.42 RVUs and is not reattachment of extraocular muscles see how many RVUs each one has: bundled with 65260, 66852, or 67113 and canalicular lid laceration. A 64- • 65285 has 31.42 RVUs and is not • 65260 has 27.52 RVUs and is not year-old man arrived at the ED with bundled with 67311, 67930, 67935, or bundled with 65285, 66852, or 67113 a metal spring in his left eye. 66020. • 66852 has 24.18 RVUs and is bun- Pre-op diagnosis. The pre-op diag- • 67311 has 16.89 RVUs and is not dled with 67113, but not with 65285 or nosis included these elements: bundled with 65285, 67930, 67935, or 65260. (Note: In certain circumstances, • Presumed zone 2/3 ruptured globe 66020. 66852 and 67113 can be unbundled.) with uveal and vitreous prolapse • 67930 and 67935 have 6.78 and How should you code for surgery? • Canalicular laceration repair, left 12.52 RVUs, respectively, and are not Under the multiple procedure payment lower lid bundled with 65285, 67311, or 66020. rules, payment will be 100% of the Title of operation. The patient un- • 66020 has 3.70 RVUs. If the patient allowable for the first procedure that derwent the following procedures: has Medicare Part B, this code isn’t you submit and 50% of the allowable • Repair of zone 3 open globe injury bundled with 65285, 67311, 67930, or for subsequent procedures. Because repair, including removal and reattach 67935. But, because 66020’s descriptor 67113 has the highest RVUs, submit it ment of lateral rectus—CPT code 65285 includes the term separate procedure, first and submit 65260 and 65285 on Repair of laceration; cornea and/or most commercial payers will bundle it the next lines. Don’t submit 66582, as it sclera, perforating, with reposition or with all other surgeries, and even with is bundled with 67113. resection of uveal tissue and CPT code the exam if performed on the same day. Why bundling matters. If you had 67311 Strabismus surgery, recession How should you code for surgery? disregarded the CCI bundling edits and or resection procedure; 1 horizontal If you submit 65285–LT as the first submitted all four procedure codes, muscle. procedure on the claim, payment for your payment may have been reduced • Injection of intracameral vancomy- it will be 100% of the allowable. On by about $500. cin and ceftazidime—CPT code 66020 subsequent lines, submit 67311–LT and either 67930–LT or 67935–LT (payments will be 50% of the allowable). If Take Nine Steps the payer is Medicare Part B, you also should submit 66020–LT; however, There are nine steps to follow when coding multiple procedures in the same non-Medicare payers typically have a operative session: policy of bundling this injection with 1. Identify all CPT codes involved, and read their full CPT descriptors. all other surgeries. 2. Comply with the payer’s documentation guidelines, including preauthoriza- Note: Because 65285, 67311, and tion requirements. 67935 are all major surgical procedures, 3. Identify the global period for each CPT code. you should append modifier –57 to 4. List the surgeries in order of highest to lowest allowable for that payer. the appropriate level of exam code. Payment is 100% of the allowable for the first procedure and 50% for the sec- Furthermore, if you also submit 66020 ond, third, and fourth procedures regardless of whether it is done in the same or 67390—which are both defined as eye or both eyes. minor surgical procedures—you also 5. If applicable, look at the site of service differential. should append modifier –25 to the 6. Look at the CCI or commercial payer edits. Check every combination for exam code. edits. If codes are bundled, and it is not appropriate to unbundle them, elimi- Acknowledgments: EyeNet thanks Ravi R. Pandit, nate the lower paying of the two codes. MD, MPH, Grant A. Justin, MD, and Fasika A. 7. Append the appropriate modifier(s). Woreta, MD, MPH, for the two case reports. 8. Link the appropriate diagnosis codes. 9. Submit the claim and check the remittance advice (RA) to confirm that MORE ONLINE. See this article at aao. proper payment has been made. org/eyenet for a tip about follow up.

50 • JULY 2021 DO YOU HAVE ENOUGH LIFE INSURANCE?

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WHAT’S HAPPENING

Dr. Parke to Step Down as Academy CEO, Search for Next Leader Underway On April 23, Academy CEO David W. Parke II, MD, announced to the Board of Trustees that he wishes the Academy to choose his successor. The Board of Trustees has created a committee to begin the search process with the goal of putting the new CEO in place by the end of the year. Dr. Parke has commit- STEPPING DOWN. During his 12 years as Academy CEO, Dr. Parke has overseen the ted to staying on until his replacement founding of the IRIS Registry, the creation of the Truhlsen-Marmor Museum of the is found. Eye, and the Academy’s response to COVID-19. Dr. Parke’s tenure. During his 12 years as Academy CEO, Dr. Parke has initiatives. I couldn’t be prouder of the thorization in the Medicare Advantage overseen the founding of the IRIS Reg- work they do and its impact. I pledge program, help ensure veterans’ access istry, the launch of the Minority Oph- to remain active in whatever way best to high-quality eye care, and increase thalmology Mentoring program, and serves the organization and my beloved vision research funding. the creation of the Truhlsen-Marmor profession.” The event drew ophthalmologists Museum of the Eye. He also expand- CEO applications due July 6. Can- from 39 states, plus Puerto Rico. They ed the Ophthalmology journal family, didates for the CEO role must be an connected via teleconferences and raised an unprecedented amount of Active or Life Fellow of the Academy; Zoom for 132 scheduled meetings with funding to support the profession, have an active, unrestricted license to senators, representatives, and their staff and led the Academy’s response to practice medicine; have experience in members. As part of the event, some COVID-19. leadership and organizational manage Academy members had the opportuni- “Helping to lead the American ment; and be willing to live in commut- ty to meet with congressional leaders, Academy of Ophthalmology and serve ing proximity to the Academy head- key committee members, and new my colleagues and their patients has quarters in San Francisco. members of the 117th Congress. been, and always will be, the highlight The event marked the second time of my professional career,” Dr. Parke Highlights of the Second the Academy held its Congressional said. “It is an honor to work with the Virtual Congressional Advocacy Day virtually. Academy staff dedicated professionals who staff the Advocacy Day scheduled all meetings, provided train- Academy and who volunteer in its On May 5, more than 180 ophthalmol- ing, and issued materials to prepare ogists, including Members in Training, participants for a successful call. from across the country participated “This was my first congressional ad- in a virtual Congressional Advocacy vocacy experience, and even though it Day. These ophthalmology advocates was via Zoom, it was still an invaluable urged lawmakers to improve Medicare experience for me,” said Samantha A. payments for surgery, reform prior au- Sauerzopf, MD, an Academy Member

EYENET MAGAZINE • 53 in Training serving as a sponsored Ad- neurs, clinicians, and investors. This summer, you have the oppor- vocacy Ambassador from Pennsylvania. The schedule includes the following: tunity to honor your mentor or other “The meetings were brief but poignant • Mini Keynote, by Chris Cooley, special people with a tribute gift to the opportunities to get our issues across.” CFA. A Stephens Inc. managing direc- Foundation. You can share what this Dr. Sauerzopf met with staff in the tor offers a peek behind the investment person means to you, and your story offices of Rep. Daniel Meuser (R-Pa.), banking curtain for a critical assess- will be published on the Foundation’s Sen. Robert Casey Jr. (D-Pa.), and Sen. ment of the challenges and opportuni- website. Your gift will also be featured Pat Toomey (R-Pa.). ties in the ophthalmology and health in the Foundation’s 2022 annual report. Missed the meeting? Head to aao. care markets. Get started at aao.org/foundation/ org/volunteering and click “Advocate” • Industry Spotlight, Part I, moder- honor-a-mentor. to learn how you can get involved. ated by Richard L. Lindstrom, MD. In this session, a panel of global strategic Volunteer: Write an EyeNet The Academy Launches executives will examine the impact of Ophthalmic Pearls Article Diversity, Equity, and COVID-19 on ophthalmic companies Want to be featured in EyeNet? Each Inclusion Web Page and consider where they will focus re- 1,500-word Pearls article reviews a The Academy has committed to nur- sources in the coming years. medical or surgical entity or procedure. turing an inclusive ophthalmologist • Ophthalmic Consolidation, moder- Many of the articles offer step-by-step community that optimally meets the ated by Kerry Solomon, MD. This ses- overviews of etiology, diagnosis, treat- complex eye care needs of a diverse pa- sion considers industry consolidation ment, and follow-up. See this month’s tient population. In keeping with that from a variety of viewpoints, including article, titled Diagnosis and Manage- commitment, the Academy launched a hospitals, private practice, and equity ment of Macular Holes on page 32. Diversity, Equity, and Inclusion section investments. Learn how to submit your topic idea on its website in April. • Presbyopia: Everybody Gets It but at aao.org/volunteering, then choose This section has a wide range of . . . Can It Be Fixed?, moderated by “Write.” (This is just one of many Acade- resources for ophthalmologists, includ- John P. Berdahl, MD. The competition my volunteer opportunities.) ing information about two Academy to create pharmacologic treatments for task forces—one on the Academy’s presbyopia is heating up. This session Volunteer: Submit Your organizational diversity and inclusion, offers a look at the companies inno- Clinical Images to the the other focusing on disparities in eye vating in one of the world’s largest Academy care. It also contains information about ophthalmic markets. Images convey more than words, espe- the Minority Ophthalmology Mento- • Dry Eye: Satisfying the Itch for cially in ophthalmology. Your classic ring program, resources for residents, Innovation, moderated by Edward J. and rare clinical images will help to relevant Academy articles, and links Holland, MD. Dry eye represents one of build the Academy’s image library to diversity and inclusion education the biggest unmet needs in eye care. In and may be used by other members materials from the Academy and other this session, hear from the innnovative and subscribers as well as in various valued medical resources. companies developing new treatments publications, such as Basic and Clinical Learn more at aao.org/diversity- with a variety of MOAs. Science Course and EyeNet. equity-and-inclusion. • Industry Spotlight, Part II, mod- Get started at aao.org/volunteering, erated by Cathleen McCabe, MD. then choose “Develop Interactive Con- Attend Eyecelerator on Industry executives of major ophthal tent.” (This is just one of many Academy July 22 mic companies will discuss how their volunteer opportunities.) Eyecelerator, a partnership between businesses are preparing for the coming the Academy and the American Society years. Visit the Academy at of Cataract and Refractive Surgery • Glaucoma Innovation: The Future ASCRS, July 24–26 (ASCRS) that’s designed to accelerate Is Bright, moderated by Thomas Sam- Heading to Las Vegas for ASCRS/ASOA innovation in ophthalmology, will uelson, MD. In this session, take a look 2021? Stop by the Academy booth, hold its first in-person conference on at the companies that are pioneering #2212, to see the latest clinical educa- July 22 in Las Vegas. The program runs new treatments and bringing innovation, practice management, and patient 11:30 a.m.-5:30 p.m. PST and will take tion into the specialty of glaucoma. education materials—or chat with place at the Oceanside BCD Ballroom Learn more at eyecelerator.com. Academy staff. You can also get demos at the Mandalay Bay Resort, a day of the Ophthalmic News & Education before the ASCRS annual meeting TAKE NOTICE (ONE) Network and IRIS Registry, begins. Attendees will be among the have your Merit-Based Incentive first to see new technology and clinical Honor a Mentor Payment System (MIPS) and coding advancements while enjoying unique Who has made a positive impact on questions answered, pay your dues, networking opportunities with oph- your life? A mentor? A family member and learn more about AAO 2021 in thalmology’s most innovative entrepre- or friend? A colleague? New Orleans.

54 • JULY 2021 D.C. REPORT Academy and Others Working to Increase Global Payments for Postoperative Ophthalmology Services

The CMS Physician Fee Schedule the global surgical payment, and E/M portion of these codes. The increased the payment values for it uses this belief to justify its current failure to adjust the global evaluation and management (E/M) decision to not give surgical post- code payment is equivalent to service, but it only applied those operative visits the E/M boost. paying some physicians less. increased values to the post-op However, there is a process Organized medicine is ad- visits in some select global codes in place to reevaluate codes vocating for equitable pay. The like the maternity and ER codes. that CMS feels are misvalued. AMA and its RUC are recom- Ophthalmology is on the losing For example, based on the mending that CMS incorporate end—to the tune of over $100+ Academy’s robust survey data on the revised office and outpatient million a year. Reversing this the global surgical service, CMS E/M values in the global codes. inequity is a top priority for the agreed with the AMA Specialty The Academy and the Surgical Academy, the American College Society Relative Value Update Care Coalition are leading strong of Surgeons, and the American Committee’s (RUC) 2019 recom- advocacy efforts to maintain the Medical Association (AMA). mendation that cataract surgery relativity in the Medicare Physician Under the new schedule. Oph- reimbursement include payment Fee Schedule and gain fair pay- thalmology global surgical codes for three post-op visits within the ments for all surgeons. have a number of E/M office visits 90-day global period. Since CMS The Academy has encouraged included in the payment package. accepted the RUC’s recommenda- its champions in Congress to Because the adjustments in the tions, ophthalmologists should press CMS to apply the increased 2021 Physician Fee Schedule do receive the same payments as E/M payment values to the post- not apply to postoperative E/M other physicians when they are operative visits included in 10-day visits included in the 10- and 90- providing the same level of ser- and 90-day global surgical codes. day global surgical codes, ophthal- vice per patient. The Academy is urging CMS to mologists and surgeons in other In the past. When payments reconsider its current policy and specialties are not being paid fairly for new and established office to ensure that ophthalmologists for this follow-up care. visits were increased, CMS would are paid equitably for equivalent CMS is not convinced that usually adjust the global surgery services. It will update members surgeons are providing all of the bundled payments to account when the proposed rule comes postoperative visits included in for the increased values for the out.

OMIC Tip: Terminating Care sign for the certified letter. Registry is the least onerous way to for Financial Reasons OMIC’s risk management recom- report quality data for the Merit-Based In 2020, some patients delayed care for mendations for terminating the physi- Incentive Payment System (MIPS). If fear of contracting COVID-19. The pan cian-patient relationship (omic.com/ you met the June 1 deadline to register demic also caused financial stress that terminating-the-physician-patient- for integration, you should now be impacted both medical practices and relationship) provide step-by-step working with the IRIS Registry vendor, their patients. Because of this, some pa- instructions for you and your staff and FIGmd, on mapping your data to the tients may delay paying their medical sample letters to assist in the process. registry. bills. OMIC offers professional liabili- Aug. 1 is a key date. To make sure In these situations, OMIC recom- ty insurance exclusively to Academy that you can report 2021 MIPS quality mends the following three steps: members, their employees, and their data via IRIS Registry–EHR integration, 1. Ensure that acute conditions are practices. you should complete the integration stabilized, or that another ophthalmol- process by Aug. 1. Meeting this deadline ogist has agreed to take over care. ACADEMY RESOURCES requires that you are actively involved 2. Send the patient the 30-day notice in the process and respond promptly to warning of termination if payment is New to IRIS Registry–EHR emails from FIGmd. not received. Integration? Don’t Miss the The IRIS Registry is your one-stop 3. Send the letter certified and by Aug. 1 Deadline shop for MIPS reporting. You also can regular mail, as well, in case the Integrating your electronic health use the IRIS Registry to manually attest patient is not home or refuses to record (EHR) system with the IRIS to promoting interoperability (PI)

EYENET MAGAZINE • 55 measures and improvement activities. Submit your plan to the ABO no sive symptoms, mental health distress, Those practices that aren’t able to later than Aug. 31. Using the IRIS and even suicide. The Academy offers report quality via IRIS Registry–EHR Registry dashboard, select one or two wellness information and practical integration may manually enter data quality measures in which to improve tools that everyone can use to improve for quality measures. your performance. Then, set goals for their mental health and increase their Free for members. Why pay fees to those measures and submit your plan resiliency regardless of their personal your EHR vendor for MIPS reporting? for achieving those goals to the Ameri- situation. The IRIS Registry is a free benefit for can Board of Ophthalmology (ABO). Learn more about the Academy’s U.S. Academy members. If the ABO approves your plan, wellness resources at aao.org/wellness. Learn more at aao.org/iris-registry. implement it for 90-120 days. Use the IRIS Registry dashboard to track your Attend a Free VKC Disease Got New Clinicians? Notify progress and fine-tune your processes Education Webinar the IRIS Registry ASAP as needed. Once the project is complete, Join EyeNet as it hosts a free webinar How have you been reporting quality review its effectiveness and send a sum- sponsored by Santen on July 20 at 5:00 data for the Merit-Based Incentive mary to the ABO. p.m. PST. Payment System (MIPS)? Learn more at aao.org/iris-registry/ Speakers will present topics to If you have been uploading data maintenance-of-certification and include the pathophysiologoy, epide- for MIPS quality measures from your https://abop.org/IRIS. miology, and clinical presentation of electronic health record (EHR) system vernal keratoconjunctivitis (VKC); into the IRIS Registry, make sure that Now Available: Download the challenges in diagnosis, complica- you are not leaving any clinicians out. the Free 2021 IRIS Registry tions, and risk factors; and treatment New MIPS eligible clinicians in your Preparation Kit approaches and impacts on patients’ practice? Has a new clinician joined The 2021 IRIS Registry Preparation quality of life. This webinar is intended your practice or has an existing clini- Kit is a detailed user guide that sup- for all ophthalmologists. cian become newly eligible for MIPS? ports you throughout the year as you Learn more at aao.org/eyenet/corpo If you are reporting MIPS via IRIS use the IRIS Registry to optimize rate-webinars. Registry–EHR integration, notify patient outcomes, report your per- FIGmd, which is an IRIS Registry formance on quality measures, and MEMBERS AT LARGE vendor, as soon as you can—and no efficiently report Merit-Based Incentive later than Sept. 1. Make sure that Payment System (MIPS) measures. The KAEPS Honors Award Recip- you include the clinician’s National kit includes: ients at 2021 Spring Meeting Provider Identifier and, if the person is • updated roadmaps for small and On May 7-8, the Kentucky Academy of an ophthalmologist, his or her large practices; Eye Physicians and Surgeons (KAEPS) Academy member ID. • tips to avoid held its annual spring meeting in Louis How do you contact FIGmd? common pitfalls; ville and honored the following award For instructions on submitting • frequently recipients: a help desk ticket, you can visit asked questions; • Advocate of the Year: Woodford aao.org/iris-registry/user-guide/ and Van Meter, MD. This award is given submit-help-desk-ticket. • quality measure to an ophthalmologist who has best benchmarking promoted and defended the art and Use the IRIS Registry tables and specifi- science of ophthalmology in the state of to Create an ABO- cations. Kentucky. Approved Improvement This valuable • Humanitarian of the Year: Marianne Project resource is avail- Cowley, MD. This award is reserved for Is your electronic health record able as a free down- the recognition of an ophthalmologist (EHR) system integrated with loadable PDF or for who has made significant contributions the IRIS Registry? If so, you can use purchase as a spiral notebook. Partic- to the welfare of others throughout her data from your IRIS Registry dash- ipation in the IRIS Registry is a free lifetime and who supports the practice board to design an improvement Academy member benefit. of ophthalmology. project that can earn you credit for For information about the IRIS Reg- • Ophthalmologist of the Year: Joern both American Board of Ophthalmol- istry and to download this resource, Soltau, MD. This award is granted to ogy (ABO) Continuing Certification visit aao.org/iris-registry. an ophthalmologist who has made and the Merit-Based Incentive Payment outstanding contributions to KAEPS System (MIPS). For the 2021 MIPS per- Don’t Forget to Prioritize and enhanced the profession of oph- formance year, this project would count Your Mental Health thalmology. as a medium-weighted improvement Even in the best of times, physicians Learn more about KAEPS at www. activity. can be at high risk for burnout, depres- kyeyemds.org.

56 • JULY 2021 Keep your staff healthy and your office open.

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Come travel this anatomical landscape, where: • Loss of tear film homeostasis is the unifying characteristic of all dry eye1 • The parasympathetic nervous system plays a major role in tear film homeostasis2 • The lacrimal functional unit (LFU) is far more than just the lacrimal gland3

Allow us to be your guide to dry eye—visit DryEyeland.com to see the sights. Because a whole world awaits beyond the ocular surface.

References: 1. Craig JP, Nelson JD, Azar DT, et al. Ocul Surf. 2017;15(4):802-812. 2. Efron N, Jones L, Bron AJ, et al. Invest Ophthalmol Vis Sci. 2013;54(11):TFOS98-TFOS122. 3. Ocul Surf. 2007;5(2):75-92.

Revised with Dry Eyeland™, code OP-COM-000101 MECHANICAL

FILE NAME: OYSCOR_721489_HCP_DED_DSA_Print_8_125x10_875_wTM_OP-COM-000101_M APPROVALS

NOTES / INSTRUCTIONS: Eyenet // Journal Of Cataract & Refractive Surgery Studio MP ED TODAY’S DATE / TIME: April 21, 2021 9:59 AM LIVE: 7.5”w x 10.375”h

SCALE %: 100 TRIM: 8.125”w x 10.875”h Print AT

COLOR: 4c BLEED: 8.25”w x 11”h Art Med. PUBLICATION: n/a FLAT: n/a M DUE DATE: FOLDED: n/a Copy PM Destination AAO 2021 GET READY FOR NEW ORLEANS • PART 2 OF 6

SPOTLIGHT New Orleans and/or viewing ON CATARACT AAO 2021 Virtual content online. Celebrating 20 Years Events not included. At AAO 2021, join your Tickets must still be pur- colleagues in celebrating chased for Skills Transfer the 20th anniversary of the labs and AAOE Master Spot light on Cataract. Classes, and you must Cochairs David F. Chang, register separately for Sub- MD, and Nicole R. Fram, specialty Day meetings. MD, will present rapid-fire SPOTLIGHT ON CATARACT. Dr. Chang (left) and Dr. Fram Find more registration mini-lectures and sponta- (right) will cochair the 20th Spotlight on Cataract during information at aao.org/ neous panel discussions built AAO 2021 (Friday, Nov. 12 to Monday, Nov. 15). registration. around eight video cases of intra- and postoperative complications. REGISTRATION Can’t Join in Person? Throughout the session, audience Register for the Virtual members will be asked to weigh in with Register for AAO 2021 Meeting their case management choices via Members can register now for AAO For the same cost ($200) as the in-per- audience polling. 2021, Subspecialty Day meetings, and son meeting, you can register for AAO This popular session will conclude the American Academy of Ophthalmic 2021 Virtual and get these benefits: with the Charles D. Kelman Lecture Executives (AAOE) Coding Sessions. • annual meeting sessions, including given by Michael E. Snyder, MD, who Registration for nonmembers opens highlights streamed live and available combines clinical activities with teach- July 7. later to view on demand; ing and research at the Cincinnati Eye The early registration fee for Acad- • annual meeting on-demand–only Institute and the University of Cincin- emy and AAOE members, including content; nati School of Medicine. retired and life members, is $200. Fees • videos and posters; The Spotlight on Cataract takes increase starting Aug. 19. • access to the Virtual Expo; and place the morning of Cataract Monday, Registration benefits.Your AAO • the opportunity to earn a maximum and is followed in the afternoon by 2021 registration includes: of 50 AMA PRA Category 1 Credits. The American Society of Cataract and • new this year: all AAO and AAOE You can also register separately for Refractive Surgery symposia “Essen- instruction courses; the Subspecialty Day virtual meeting by tials for the Cataract Surgeon in 2021.” • clinical sessions and original papers; day: Friday, Saturday, or both. Registra- When: Monday, Nov. 15, from 8:00 • Skills Transfer lectures; tion includes: a.m. to 12:15 p.m. • videos and posters; • content from all Subspecialty Day Learn more at aao.org/program. • Expo; sessions on that day, streamed live and • Industry Showcases; available later on demand; • AAO 2021 Virtual annual meeting • detailed course syllabi online; content (see next article); and • access to the Virtual Expo; and • the opportunity to earn a maximum • the opportunity to earn 12 AMA of 50 AMA PRA Category 1 Credits PRA Category 1 Credits per day. for attending the in-person meeting in Learn more at aao.org/registration.

EYENET MAGAZINE • 59 Reserve Your Hotel Room and How to Keep Momen- Members may reserve a hotel room tum Going.” The meeting now. The online hotel booking sys- will also cover pearls and tem opens to nonmembers on July 7. the latest techniques that all Remember that this year’s Opening refractive surgeons should Session is on Friday, Nov. 12 and the know regarding different ap- meeting runs through Monday, Nov. proaches to the surgical cor- 15. rection of refractive errors: The Academy works with the official cornea-based, lens-based, hotel reservation provider, Expovision, and combined refractive-cat- to help you get the lowest price avail- aract procedures. able, as well as your hotel loyalty points. In addition to a video- Fraud alert! Several companies based section on compli- pretending to be associated with the cation management, this Academy and AAO 2021 may appear ORBITAL GALA. The Host Committee is working Subspecialty Day meeting in web searches or may contact you hard on exciting auction offerings. Bid high, bid of- will showcase the future of via email. These companies claim that ten, and support the Academy programs you love. refractive surgery, including they can book hotel rooms for the lectures on future trends and Academy’s annual meeting, but they are Nov. 14, at the House of Blues in New innovation. It will be an exciting pro- unaffiliated with the Academy. Book Orleans. Swap stories at the cocktail gram that will have a positive impact only through AAO 2021’s official hotel party and bid on one-of-a-kind auction on your current and future practice. reservation provider, Expovision. treasures to support the Academy’s vital The Refractive Surgery Subspecialty Find more hotel reservation infor- educational programs. You will also Day is also the annual meeting of ISRS. mation at aao.org/hotels. have the opportunity to celebrate David J. Noonan, former Academy OCULOFACIAL PLASTIC SURGERY HEALTH & SAFETY deputy executive vice president, for 2021: Face Forward. his numerous contributions to ophthal- Program Directors: Catherine J. Hwang, Your Safety Is Top Priority mology. Can’t attend in person? Join MD, and Thomas E. Johnson, MD. For AAO 2021 in New Orleans, the virtually. When: Saturday, Nov. 13 (8:00 a.m.- Academy is implementing enhanced Learn more at aao.org/gala. 4:48 p.m.) health and safety measures in com- This meeting will cover a variety of pliance with CDC guidelines, as well SUBSPECIALTY DAY trending topics in oculofacial plastic as state and local regulations, to help surgery, including advanced facial filler you remain safe. Layout and cleaning Subspecialty Day Previews: techniques, the addition of corneal procedures for all session rooms, labs, What’s Hot neurotization to your practice, and and public areas are currently under This month, program directors from updates in thyroid eye disease, as well review. Meeting planning will evolve as two Subspecialty Day meetings preview as tips on improving your practice’s regulations and guidelines change. some of this year’s highlights. social media presence and cosmetic Find the latest information at aao. View the schedules at aao.org/ offerings. There will also be a new org/health-safety. programsearch. section of surgical videos and pearls that will feature Kyung In Woo, MD, PROGRAM & ACTIVITIES REFRACTIVE SURGERY 2021: How on Asian blepharoplasty; Julian Perry, Can We Do Better? MD, on managing festoons; and Evan Search the Program Program Directors: Burkhard Dick, Black, MD, on the nuances in brow lift- Available now, Program Search (aao. MD, and Deepinder K. Dhaliwal, MD. ing. The meeting will close with a risk org/programsearch) is an online tool to When: Friday, Nov. 12 (8:00 a.m.- management talk by Rob Fante, MD, find course information and abstracts. 5:27 p.m.) and Linda D. Harrison, PhD, of the It allows you to look up information One result of the pandemic is a Ophthalmic Mutual Insurance Com- by day, topic, format, or presenter. You growing interest in refractive surgery in pany (OMIC members who attend this may log in on the search page to add many countries. This year, the theme of event will receive a discount on their items to your calendar. the International Society of Refractive annual premium). This year’s Oculofa- Surgery (ISRS) meeting is “How Can cial Plastic Surgery Subspecialty Day is Celebrate at the 2021 We Do Better?” In other words, how not to be missed! Orbital Gala Masquerade can refractive specialists deliver the best The Oculofacial Plastic Surgery meet- Join the pageantry and reconnect with results to patients? Highlighting this ing is organized in conjunction with the your colleagues at the 18th annual theme will be a lecture titled “Building American Society of Ophthalmic Plastic Orbital Gala fundraiser on Sunday, on New Interest in Refractive Surgery and Reconstructive Surgery.

60 • JULY 2021 Photo courtesy of Nir Shoham-Hazon, MD

MicroPulse® Transscleral Laser Therapy A non-incisional and versatile procedure that can be performed before,1-4 in combination with,1 or after other glaucoma treatments.2-5

 Achieves a success rate of 60% to 80%6-22 and IOP reduction of 30% to 45%6, 8, 11, 14-20, 22, 23  Patient downtime is significantly low and leaves future treatment options open  More than 150,000 patients have been treated in 80 countries since 2015  The procedure can be performed in the office or operating room  Requires limited amount of immediate follow-up  The equipment is portable and easy to setup

Studies, webinars, and case examples available at iridex.com/micropulsep3 1 Yelenskiy A, et al. J Glaucoma. 2018. 2 Kaba Q, et al. Ophthalmol Glaucoma. 2020. 3 Subramaniam K, et al. Cornea. 2019. 4 Sanchez FG, et al. Arch Soc Esp Oftalmol. 2018. 5 De Crom R, et al. J Glaucoma. 2020. 6 Zaarour K, et al. J Glaucoma 2019. 7 Subramaniam K, et al. Cornea 2019. 8 Nguyen AT, et al. Eur J Ophthalmol 2019. 9 Barac R, et a. Romanian J Ophthalmol 2018. 10 Sanchez FG, et al. Arch Soc Esp Oftalmol 2018. 11 Lee JH, et al. J Glaucoma 2017. 12 Sarrafpour S, et al. Ophthalmology Glaucoma 2019. 13 Awoyesuku EA, et al. JAMMR 2019. 14 Abdelrahman AM, et al. J Glaucoma 2018. 15 Aquino MC, et al. Clin Exp Ophthalmol 2015. 16 Jammal AA, et al. Arq Bras Oftalmol 2019. 17 Tan A, et al. Clin Experiment Ophthalmol 2010. 18 Williams AL, et al. J Glaucoma 2018. 19 Varikuti VNV, et al. J Glaucoma 2019. 20 Souissi S, et al. Eur J Ophthalmol 2019. 21 Magacho L, et al. Lasers Med Sci 2019. 22 Magacho L, et al. J Glaucoma 2019. 23 Yelenskiy A, et al. J Glaucoma 2018. © 2021 Iridex. All rights reserved. Iridex, the Iridex logo, MicroPulse, MicroPulse P3, and Cyclo G6 are trademarks or registered trademarks of Iridex. AD0214 06.2021 MYSTERY IMAGE BLINK Nahyoung G. Lee, MD, MD, G. Lee, Nahyoung Massachusetts Eye and Ear, Boston. Boston. and Ear, Eye Massachusetts

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

LAST MONTH’S BLINK Corneal Herpetic Dendrite Identified by UWF Photography

71-year-old man presented to the clinic with complaints of a red left eye. He was Asent for imaging before seeing the physician, and this fundus autofluorescence image of his left eye was taken using ultra-widefield (UWF) fundus photography (Optos). UWF imaging is used to document and evaluate the posterior segment of the eye. However, UWF fundus imaging may also reveal anterior segment findings, which artifactually appear to be on the surface of the retina and inverted. Slit-lamp examination of the patient’s left eye confirmed the presence of a corneal herpetic dendrite. This case demonstrates that UWF fundus photography could be a useful tool for documenting potentially sight-threatening anterior segment pathology when a slit lamp is not available.

WRITTEN BY JULIA CANESTRARO, OD, DAVID H. ABRAMSON, MD, FACS, AND JASMINE H. FRANCIS MD, FACS. PHOTO BY DAVID K. MOCK, COA. ALL ARE AT MEMORIAL SLOAN KETTERING CANCER CENTER, NEW YORK. DRS. ABRAMSON AND FRANCIS ARE ALSO AT WEILL CORNELL MEDICAL CENTER, NEW YORK.

62 • JULY 2021 B:8.375" T:8.125" S:7"

The following additional adverse drug reactions occurred in less than 1% of patients: hyphema, iridocyclitis, uveitis, corneal opacity, product administered at inappropriate site, corneal decompensation, cystoid macular edema, and drug hypersensitivity. The most common nonocular adverse reaction was headache, which was observed in 5% of patients. Brief Summary—Please see the DURYSTA™ package insert for USE IN SPECIFIC POPULATIONS full Prescribing Information Pregnancy: There are no adequate and well-controlled studies of DURYSTA™ administration in pregnant women to inform a drug associated risk. Oral INDICATIONS AND USAGE administration of bimatoprost to pregnant rats and mice throughout DURYSTA™ is a prostaglandin analog indicated for the reduction of intraocular organogenesis did not produce adverse maternal or fetal effects at clinically pressure (IOP) in patients with open angle glaucoma (OAG) or ocular relevant exposures. Oral administration of bimatoprost to rats from the start hypertension (OHT). of organogenesis to the end of lactation did not produce adverse maternal, CONTRAINDICATIONS fetal or neonatal effects at clinically relevant exposures. ™ DURYSTA is contraindicated in patients with active or suspected ocular In embryo/fetal developmental studies in pregnant mice and rats, abortion was or periocular infections; corneal endothelial cell dystrophy; prior corneal observed at oral doses of bimatoprost which achieved at least 1770 times the transplantation, or endothelial cell transplants; absent or ruptured posterior maximum human bimatoprost exposure following a single administration of lens capsule, due to the risk of implant migration into the posterior segment; ™ DURYSTA (based on plasma Cmax levels; blood-to-plasma partition ratio of 0.858). or hypersensitivity to bimatoprost or any other components of the product. In a pre/postnatal development study, oral administration of bimatoprost WARNINGS AND PRECAUTIONS ™ to pregnant rats from gestation day 7 through lactation resulted in reduced Corneal Adverse Reactions: The presence of DURYSTA implants has been gestation length, increased late resorptions, fetal deaths, and postnatal pup associated with corneal adverse reactions and increased risk of corneal ™ mortality, and reduced pup body weight at 0.3 mg/kg/day (estimated 470-times endothelial cell loss. Administration of DURYSTA should be limited to a single the human systemic exposure to bimatoprost from DURYSTA™, based plasma implant per eye without retreatment. Caution should be used when prescribing ™ Cmax and a blood-to plasma partition ratio of 0.858). No adverse effects were DURYSTA in patients with limited corneal endothelial cell reserve. observed in rat offspring at 0.1 mg/kg/day (estimated 350-times the human ™ ™ Iridocorneal Angle: Following administration with DURYSTA, the intracameral systemic exposure to bimatoprost from DURYSTA, based on plasma Cmax). ™ implant is intended to settle within the inferior angle. DURYSTA should be Lactation: There is no information regarding the presence of bimatoprost used with caution in patients with narrow iridocorneal angles (Shaffer grade in human milk, the effects on the breastfed infants, or the effects on milk < 3) or anatomical obstruction (e.g., scarring) that may prohibit settling in the production. In animal studies, topical bimatoprost has been shown to inferior angle. be excreted in breast milk. Because many drugs are excreted in human Macular Edema: Macular edema, including cystoid macular edema, has been milk, caution should be exercised when DURYSTA™ is administered to a reported during treatment with ophthalmic bimatoprost, including DURYSTA™ nursing woman. B:11.125" ™ T:10.875"

intracameral implant. DURYSTA should be used with caution in aphakic patients, The developmental and health benefits of breastfeeding should be considered, S:10" in pseudophakic patients with a torn posterior lens capsule, or in patients with along with the mother's clinical need for DURYSTA™ and any potential adverse known risk factors for macular edema. effects on the breastfed child from DURYSTA™. ™ Intraocular Inflammation: Prostaglandin analogs, including DURYSTA, have ™ ™ Pediatric Use: Safety and effectiveness of DURYSTA in pediatric patients been reported to cause intraocular inflammation. DURYSTA should be used have not been established. with caution in patients with active intraocular inflammation (e.g., uveitis) because the inflammation may be exacerbated. Geriatric Use: No overall differences in safety or effectiveness have been observed between elderly and other adult patients. Pigmentation: Ophthalmic bimatoprost, including DURYSTA™ intracameral implant, has been reported to cause changes to pigmented tissues, such NONCLINICAL TOXICOLOGY as increased pigmentation of the iris. Pigmentation of the iris is likely to be Carcinogenesis, Mutagenesis, Impairment of Fertility permanent. Patients who receive treatment should be informed of the possibility Bimatoprost was not carcinogenic in either mice or rats when administered of increased pigmentation. The pigmentation change is due to increased by oral gavage at doses up to 2 mg/kg/day and 1 mg/kg/day respectively for melanin content in the melanocytes rather than to an increase in the number 104 weeks (approximately 3100 and 1700 times, respectively, the maximum ™ of melanocytes. While treatment with DURYSTA can be continued in patients human exposure [based on plasma Cmax levels; blood-to-plasma partition ratio who develop noticeably increased iris pigmentation, these patients should be of 0.858]). examined regularly. Bimatoprost was not mutagenic or clastogenic in the Ames test, in the mouse Endophthalmitis: Intraocular surgical procedures and injections have been lymphoma test, or in the in vivo mouse micronucleus tests. associated with endophthalmitis. Proper aseptic technique must always be ™ Bimatoprost did not impair fertility in male or female rats up to doses of used with administering DURYSTA, and patients should be monitored following 0.6 mg/kg/day (1770-times the maximum human exposure, based on plasma the administration. Cmax levels; blood-to-plasma partition ratio of 0.858). ADVERSE REACTIONS PATIENT COUNSELING INFORMATION Because clinical trials are conducted under widely varying conditions, adverse Treatment-related Effects: Advise patients about the potential risk for reaction rates observed in the clinical trials of a drug cannot be directly compared complications including, but not limited to, the development of corneal adverse to rates in the clinical trials of another drug and may not reflect the rates events, intraocular inflammation or endophthalmitis. observed in practice. Potential for Pigmentation: Advise patients about the potential for increased The most common ocular adverse reaction observed in two randomized, brown pigmentation of the iris, which may be permanent. active-controlled clinical trials with DURYSTA™ in patients with OAG or OHT was conjunctival hyperemia, which was reported in 27% of patients. Other When to Seek Physician Advice: Advise patients that if the eye becomes red, common ocular adverse reactions reported in 5-10% of patients were foreign sensitive to light, painful, or develops a change in vision, they should seek body sensation, eye pain, photophobia, conjunctival hemorrhage, dry eye, eye immediate care from an ophthalmologist. irritation, intraocular pressure increased, corneal endothelial cell loss, vision blurred, and iritis. Ocular adverse reactions occurring in 1-5% of patients were Rx only anterior chamber cell, lacrimation increased, corneal edema, aqueous humor leakage, iris adhesions, ocular discomfort, corneal touch, iris hyperpigmentation, anterior chamber flare, anterior chamber inflammation, and macular edema. DUR133688-v2 02/21 based on v1.0USPI9652

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PREPARED BY 11580917 DUR Eyenet A Size M1FR Job info Images Fonts Special Instructions Date: 5-7-2021 6:38 PM DUR_Brief PI_8.5x11_DUR133688v2_0221_ None None Client: ALLERGAN Print-Ready.pdf (87%; 1.2MB) Product: DURYSTA Client Code: DUR146489 Additional Information WF Issue # 8925310 None Releasing as: None Final Size: None Finishing: None Gutter: None Inks Additional Comments for Sizing Colors: 4 color process Cyan, Magenta, Yellow, Black None Team Producer: None AD: Steven Solares AE: Katie Clark Scale: 1" = 1" QC: None Bleed 8.375" w x 11.125" h 8.375" w x 11.125" h Production: Leslie Weber Trim/Flat 8.125" w x 10.875" h 8.125" w x 10.875" h Digital Artist: Harker, Gregory (NYC-FCB) Live/Safety 7" w x 10" h 7" w x 10" h FR Spellcheck: None

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INDICATIONS AND USAGE DURYSTA™ (bimatoprost intracameral implant) is indicated for the reduction of intraocular pressure (IOP) in patients with open angle glaucoma (OAG) or ocular hypertension (OHT). IMPORTANT SAFETY INFORMATION B:11.125" T:10.875"

Contraindications S:10" DURYSTA™ is contraindicated in patients with: active or suspected ocular or periocular infections; corneal endothelial cell dystrophy (e.g., Fuchs’ Dystrophy); prior corneal transplantation or endothelial cell transplants (e.g., Descemet’s Stripping Automated Endothelial Keratoplasty [DSAEK]); absent or ruptured posterior lens capsule, due to the risk of implant migration into the posterior segment; hypersensitivity to bimatoprost or to any other components of the product. Warnings and Precautions The presence of DURYSTA™ implants has been associated with corneal adverse reactions and increased risk of corneal endothelial cell loss. Administration of DURYSTA™ should be limited to a single implant per eye without retreatment. Caution should be used when prescribing DURYSTA™ in patients with limited corneal endothelial cell reserve. DURYSTA™ should be used with caution in patients with narrow iridocorneal angles (Shaffer grade < 3) or anatomical obstruction (e.g., scarring) that may prohibit settling in the inferior angle. Macular edema, including cystoid macular edema, has been reported during treatment with ophthalmic bimatoprost, including DURYSTA™ intracameral implant. DURYSTA™ should be used with caution in aphakic patients, in pseudophakic patients with a torn posterior lens capsule, or in patients with known risk factors for macular edema. Prostaglandin analogs, including DURYSTA™, have been reported to cause intraocular in ammation. DURYSTA™ should be used with caution in patients with active intraocular in ammation (e.g., uveitis) because the in ammation may be exacerbated. Ophthalmic bimatoprost, including DURYSTA™ intracameral implant, has been reported to cause changes to pigmented tissues, such as increased pigmentation of the iris. Pigmentation of the iris is likely to be permanent. Patients who receive treatment should be informed of the possibility of increased pigmentation. While treatment with DURYSTA™ can be continued in patients who develop noticeably increased iris pigmentation, these patients should be examined regularly. Intraocular surgical procedures and injections have been associated with endophthalmitis. Proper aseptic technique must always be used with administering DURYSTA™, and patients should be monitored following the administration. Adverse Reactions In controlled studies, the most common ocular adverse reaction reported by 27% of patients was conjunctival hyperemia. Other common adverse reactions reported in 5%-10% of patients were foreign body sensation, eye pain, photophobia, conjunctival hemorrhage, dry eye, eye irritation, intraocular pressure increased, corneal endothelial cell loss, vision blurred, iritis, and headache. Please see Brief Summary of full Prescribing Information on the following page. References: 1. DURYSTA™ [Prescribing Information]. Irvine, CA: Allergan, Inc.; 2020. 2. Data on le, Allergan, 2020. 3. Standring S. Orbit and accessory visual apparatus. In: Gray’s Anatomy: The Anatomical Basis of Clinical Practice. 41st ed. Philadelphia, PA: Elsevier Limited; 2016: 666-708.

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PREPARED BY 11580917 DUR Eyenet A Size M1FR Job info Images Fonts Special Instructions Date: 5-7-2021 6:38 PM Allergan_logo_Primary_CMYK.eps (12.5%; Helvetica Neue LT Std (75 Bold, 55 Roman, None Client: ALLERGAN 1.5MB), NY_ALLE_A057645_4C.tif (CMYK; 576 57 Condensed, 77 Bold Condensed, 67 Medium Product: DURYSTA ppi; 52%; 61.4MB), NY_ALLE_A057644_4C. Condensed), ITC Avant Garde Gothic Std Client Code: DUR146489 psd (CMYK; 572 ppi; 52.4%; 39.7MB), NY_ALLE_ (Demi, Book) Additional Information WF Issue # 8925310 A057691_4C.psd (CMYK; 4286 ppi; 7%; 2.3MB), None Releasing as: None Durysta_2021_TM_Logo_4C.ai (22.58%; 1.1MB) Final Size: None Finishing: None Gutter: None Inks Additional Comments for Sizing Colors: 4 color process Cyan, Magenta, Yellow, Black None Team Producer: None AD: Steven Solares AE: Katie Clark Scale: 1" = 1" QC: None Bleed 8.375" w x 11.125" h 8.375" w x 11.125" h Production: Leslie Weber Trim/Flat 8.125" w x 10.875" h 8.125" w x 10.875" h Digital Artist: Harker, Gregory (NYC-FCB) Live/Safety 7" w x 10" h 7" w x 10" h FR Spellcheck: None

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