Pipeline to the Posterior Segment New Devices Target Uveitis, Macular Edema, and AMD

EyeNetMAY 2019

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The Academy’s Global Directory of Training Opportunities (aao.org/ training-opportunities) is the best way to reach the broadest pool of candidates. It is free References and only takes 2 to 3 minutes 1. Alcon Data on File (Jul 2016). 2. AcrySof® IQ ReSTOR® +2.5 D Multifocal Toric IOL Directions to post your observership for Use. 3. Vega F, Alba-Bueno F, Millán MS, Varon C, Gil MA, Buil JA. Halo and through- focus performance of four diffractive multifocal intraocular lenses. Invest Ophthalmol Vis Sci. or fellowship available to 2015;56(6):3967-3975 (study conducted with corneal model eye with 0.28µ spherical aberration). ophthalmologists outside 4. Wirtitsch MG, Findl O, Menapace R, et al. Effect of haptic design on change in axial lens position after cataract surgery. J Cataract Refract Surg. 2004;30(1):45-51 5. Visser N, Bauer NJ, Nuijts RM. Toric your country: intraocular lenses: historical overview, patient selection, IOL calculation, surgical techniques, clinical outcomes, and complications. J Cataract Refract Surg. 2013;39(4):624-637. 6. Potvin R, Kramer BA, Hardten DR, Berdahl JP. Toric intraocular lens orientation and residual refractive astigmatism: an 1. Go to analysis. Clin Ophthalmol. 2016;10;1829-1836. aao.org/gdto-submission. AcrySof® IQ ReSTOR® Family of Multifocal IOLs Important Product Information CAUTION: Federal (USA) law restricts this device to the sale by or on the order of a physician. 2. Click “Submit a Training INDICATIONS: The AcrySof® IQ ReSTOR® Posterior Chamber Intraocular Multifocal IOLs include Opportunity.” AcrySof® IQ ReSTOR® and AcrySof® ReSTOR® Toric and are intended for primary implantation for the visual correction of aphakia secondary to removal of a cataractous lens in adult patients with 3. Log in. (This will save and without presbyopia, who desire near, intermediate and distance vision with increased spectacle independence. In addition, the you time.) AcrySof® IQ ReSTOR® Toric IOL is intended to correct pre-existing astigmatism. The lenses are 4. Enter opportunity intended to be placed in the capsular bag. WARNINGS/PRECAUTIONS: Careful preoperative evaluation and sound clinical judgment should be used by the surgeon to decide the risk/ information. benefit ratio before implanting a lens in a patient with any of the conditions described in the Directions for Use labeling for each IOL. Physicians should target emmetropia, and ensure that IOL centration is achieved. Care should be taken to remove viscoelastic from the eye at the close Questions? of surgery. The ReSTOR® Toric IOL should not be implanted if the posterior capsule is ruptured, if the zonules are damaged, or if a primary posterior capsulotomy is planned. Rotation can reduce Email [email protected] astigmatic correction; if necessary lens repositioning should occur as early as possible prior to lens encapsulation. Some patients may experience visual disturbances and/or discomfort due to multifocality, especially under dim light conditions. A reduction in contrast sensitivity may occur in low light conditions. Visual symptoms may be significant enough that the patient will request explant of the multifocal IOL. Spectacle independence rates vary; some patients may need glasses when reading small print or looking at small objects. Posterior capsule opacification (PCO), when present, may develop earlier into clinically significant PCO with multifocal IOLs. Prior to surgery, physicians should provide prospective patients with a copy of the Patient Information Brochure available from Alcon informing them of possible risks and benefits associated with the AcrySof® IQ ReSTOR® IOLs. Do not resterilize; do not store over 45° C; use only sterile irrigating solutions such as BSS® or BSS PLUS® Sterile Intraocular Irrigating Solutions. ATTENTION: Reference the Directions for Use labeling for each IOL for a complete listing of indications, warnings and precautions.

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105112 US-RES-17-E-3227 EN.indd 1 1/31/19 12:26 PM CONTENTS MAY 2019 VOLUME 23 • NUMBER 5

FEATURE 38-44 Drug Delivery for the Posterior Segment Born of necessity and scientific advance, new drug delivery devices for treatment of retinal disease and uveitis are now emerging.

CLINICAL INSIGHTS 13-15 News in Review Retina Impact of race and ethnicity on diabetic retinopathy risk. Public Health Update on safety of the Shingrix vaccine. Imaging OCT comes to the rescue in the eye ER. Cornea Lymphatic vessels may be involved 38 in graft failure.

17-21 Journal Highlights Key findings fromOphthalmology, Ophthal mology Retina, AJO, JAMA Ophthalmology, and more.

23-29 Clinical Update Zepto and miLoop A look at two innovative— and inexpensive—cataract tools that are giving 13 23 the femtosecond laser a run for its money. Descemet Stripping Only Experts discuss a new option for some Fuchs patients: surgical removal of the Descemet membrane without 27 31 subsequent endothelial transplantation.

31-33 Ophthalmic Pearls Serpiginous Choroiditis Learn to diagnose and manage this rare inflammatory disorder that causes geographic destruction of the retina and choroid in healthy middle-aged individuals.

EyeNet® Magazine (ISSN 1097-2986) is published monthly by the American Academy of Ophthalmology, 655 Beach St., San Francisco, CA 94109-1336, as a membership service. Subscription is included in U.S. members’ annual dues. International Member, IMIT, $135 per year. Nonmember in U.S., $150 per year. Nonmember outside U.S., $210 per year. Periodicals Postage Paid at San Francisco, CA, and at additional mailing offices. POSTMASTER: Send address changes toEyeNet , P.O. Box 7424, San Francisco, CA 94120-7424. American Academy of Ophthalmic Executives®, EyeSmart®, EyeWiki®, IRIS®, 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 CLINICAL INSIGHTS 35-37 Morning Rounds The Case of the Blind Bibliophile A 64-year- old had experienced a month of rapid decline in vision, followed by gradual deterioration. Five months later, reading was impossible. What’s your diagnosis?

IN PRACTICE 48 Savvy Coder Best Practices for Coding, Part 2 Reduce 35 denials and keep payments on track.

FROM THE AAO 49-50 Academy Notebook Academy creates volunteering web page. • Deadlines for MIPS and IRIS Registry. 51-52 Destination AAO 2019 Spotlight on Skills Transfer labs. • Hotels and registration. • Subspecialty Day lineup. 49 VIEWPOINTS 9-10 Letters A measure of comparative intraocular pressure: the glaucoma burden index. • A response. 11 Opinion Editorial jiu jitsu: covering innovation while sidestepping bias. 12 Current Perspective Private equity: an introduction.

MYSTERY IMAGE 54 Blink What do you see?

COVER ILLUSTRATION © Peter Bollinger xx54

® COPYRIGHT © 2019, American Academy of Ophthalmology, Inc.® All rights reserved. No part of this publication may be reproduced without written permission from the publisher. Letters to the editor and other unsolicited material are assumed intended for publication and EyeNet are subject to editorial review, acceptance, and editing. Disclaimer. The ideas and opinions expressed in EyeNet are those of the authors, and do not necessarily reflect any position of the editors, the publisher, or the American Academy of Ophthalmology. Because this publication provides information on the latest developments in ophthalmology, articles may include information on drug or device applications that are not considered community standard, or that reflect indications not included in approved FDA labeling. Such ideas are provided as information and education only so that practitioners may be aware of alternative methods of the practice of medicine. Information in this publication should not be considered endorsement, promotion, or in any other way encouragement for the use of any particular procedure, technique, device, or product. EyeNet, its editors, the publisher, or the Academy in no event will be liable for any injury and/or damages arising out of any decision made or action taken or not taken in reliance on information contained herein.

6 • MAY 2019 B:8.375” T:8.125” S:7” B:11.125” T:10.875” S:10”

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8 • MAY 2019 Letters

A Measure of Comparative Intraocular Pressure: effectiveness of one, two, and three glaucoma medications. The Glaucoma Burden Index When one medication was washed out, the IOP rose 5.4 mm Hg; two medications, 6.9 mm Hg; and three medications, 9.0 There is ever-intensifying interest in new glaucoma inter- mm Hg. ventions, from less invasive glaucoma surgeries to alterna- One study examined the effect of adding a fourth med- tive drug delivery systems. In assessing the efficacy of these ication and found that it resulted in a 3.5 mm Hg drop in interventions, invariably the primary outcome measure is IOP at 12 months.2 However, the period studied was January centered on intraocular pressure (IOP), as IOP is the only through December 2000, and the most frequently added modifiable risk factor for glaucoma. medication was a prostaglandin analog. This does not reflect Study confounders. The focus on IOP as an endpoint for current practice patterns for which a prostaglandin analog is studies is not without limitations. One major confounding considered first-line therapy and would rarely be the fourth factor is the concomitant use of medication at the time of agent added to a patient’s regimen. We chose 1.5 mm Hg as patient enrollment and for the duration of data collection. the postulated effect of the addition of a fourth glaucoma New medications might be introduced after a specific inter- medication. While this is somewhat arbitrary, it does reflect vention, and existing medications are sometimes tapered the authors’ clinical impression of the effectiveness of a and stopped during the study period. fourth glaucoma medication. These events can confound proper evaluation of the Thus, the algorithm we propose for the glaucoma burden treatment effect, and there are no agreed-upon methods to index (GBI) is as follows: account for this, other than burdensome washout events • If number of medications is zero, GBI = IOP at the start or end of a study or specifically prescribed • If number of medications is 1, GBI = IOP + 5.4 treatment events that may not be practical during the time • If number of medications is 2, GBI = IOP + 6.9 that the study is being conducted. Washout IOPs are also • If number of medications is 3, GBI = IOP + 9.0 time-consuming and costly in real-world studies and are • If number of medications is 4, GBI = IOP +10.5 often not supported by institutional review boards due to the The literature is clear that lowering IOP slows glaucoma possibility of a participant incurring an injury to the optic progression.3 We are not proposing replacing IOP as a mea- nerve during periods of nontreatment. sure of disease risk in an individual patient. Rather, the GBI These issues are magnified for retrospective studies in would allow assessment of comparative IOP across popu- which real-world data are interpreted with inability lations as well as objective to account for the medication effect as a whole. TABLE 1: Relationship between comparisons of interven- In addition, it may be of value to compare studies IOP, medication use, and glaucoma tions in different clinical retrospectively and tease out details on how one burden trials. treatment might compare to another treatment. IOP Meds GBI As a more objective Leveling the playing field regarding each study’s use 15 1 20.4 method of differentiating of medications would be valuable in these circum- between new medical and 15 2 21.9 stances. surgical interventions, the 15 3 24.0 Index of IOP. If we were to combine IOP and GBI can help researchers, medication use into a single measure, we might be 15 4 25.5 clinicians, and industry able to eliminate a major confounding factor and members alike. The hope provide a more objective comparison between study popu- would be that we would have a new tool to better guide lations in different studies. This idea that we are proposing our current understanding of available therapies as well as could be thought of as an index of comparative IOP. enhance our ability to categorize the therapeutic effects of In many respects, this index could represent glaucoma future interventions. burden. One could state that the higher the IOP, the greater Mohammed K. ElMallah, MD the “glaucoma burden” on any given optic nerve. Similarly, Ocala, Fla. one could postulate that the greater the number of medica- Khaled Bahjri, MD, PhD, MPH tions needed to achieve said IOP, the greater the glaucoma Loma Linda, Calif. burden. We are fortunate in that Jampel et al. have provided 1 Jampel HD et al. JAMA Ophthalmol. 2014;132(4):390-395. blueprints for such an index of comparative IOP.1 Using IOP 2 Neelakantan A et al. J Glaucoma. 2004;13(2):130-136. washout data from a prospective trial, they determined the 3 Heijl A et al. Arch Ophthalmol. 2002;120(10):1268-1279.

EYENET MAGAZINE • 9 A Response

“A Measure of Comparative Intraocular Pressure: The Glaucoma Burden Index” keenly sheds light on some of the challenges in comparing studies performed without rigorous medication washouts at baseline and last follow-up. The authors’ proposed solution, a glaucoma burden index (GBI), is an interesting concept and could prove valuable in assessing the burden of medications on patients’ quality of life and assessing costs related to glaucoma treatment. While the authors’ criticisms of randomized clinical trials (RCTs) do have some merit, they do not consider the fact that many seminal glaucoma RCTs in the last few decades have accounted for inclusion/exclusion criteria relatively well, and some have looked at optic nerve status or even visual fields rather than IOP alone as determinants. In the table that the authors have proposed, an increased number of medications is associated with increased GBI. Despite the letter’s attention to the confounding effects of medications on IOP, this design fails to account for the real impact on patients—in particular, further damage to the optic nerve and disease progression. The index also fails to account for issues such as patient forgetfulness, improper eyedrop administration, and financial barriers, all of which have the potential to affect patient responses to medications (and incremental washout) in variable ways that yet unfortunately cannot be accurately measured. Furthermore, medications vary in efficacy, dosing frequency, and side effects, which is why the FDA and the American Glaucoma Society recently concluded that medication washouts should be performed at baseline and last follow-up, which is the current standard for new devices.1 Ahmad A. Aref, MD, MBA Chicago Sarwat Salim, MD, FACS EyeNet Boston

Gives You 1 www.fda.gov/downloads/MedicalDevices/NewsEvents/.../UCM390327.pdf. the Full Picture Poll-topping, digestible coverage of all things ophthalmologic

EyeNetFEBRUARY 2018

MIGS Roundup New Options, Trends, and Caveats Visit Us Online SHARE YOUR INPUT. Sending a letter to EyeNet is just aao.org/eyenet one way to be heard. You also can contact your state, subspecialty, and specialized interest society’s repre- Facial Transplants Maximizing Periocular Results Write to Us DMEK Enters the Mainstream

OPINION Why Consensus Statements Matter [email protected] sentative(s) on the Academy Council, which presents concerns to the Board of Trustees. Academy members also can attend the Oct. 13 Fall Council Meeting in San Francisco. Find more information at aao.org/council.

10 • MAY 2019 2018.eyenet.QTR.indd 1 2/27/18 10:30 AM Opinion

RUTH D. WILLIAMS, MD Editorial Jiu Jitsu: Covering Innovation While Sidestepping Bias

nnovation in the ophthalmology space is accelerating. part of the study that many people read,” he said. Until just a few years ago, glaucoma was treated with the Not even scientific data at the heart of a study are free Isame medications, lasers, and surgeries that we’d used for of bias. In a recent editorial in Ophthalmology, Gerami decades. Now there are new topical medications and an array Seitzman and Thomas Lietman pointed out the pitfalls of of novel procedures to disrupt the well-worn algorithms of interpreting the data of randomized clinical trials glaucoma care. The pipeline is in full flow. for dry eye treatments.1 They discussed It’s no different in retina and uveitis, and—most amazing regression to the mean, placebo of all—gene therapy for Leber congenital amaurosis forecasts effect, and the natural course an era of treatments for genetic causes of blindness. What’s of dry eye disease—and, most more, our patients arrive with information about an emerg- interestingly, clinicians’ desire ing or expected new treatment and wonder if it’s right for to “believe our actions are them. How do we digest the deluge of innovation, assess new directly responsible for our ideas, and provide explanations to our patients? patients’ improvements.” By reading EyeNet, of course. Specifically, as authors Last month’s cover story was about alternatives for drug parse the data, internal moti- delivery in the anterior chamber; this month’s addresses vations and beliefs can affect new drug developments for the posterior chamber. Every the analysis. Another example product discussed in these two articles either is in devel- of unconscious bias is when physi- opment or was recently approved. And here’s the editorial cians want to be friendly to innova- conundrum: Many of the ophthalmologists with detailed tion and, as Henry said, “can become knowledge about such products have also participated in the echo chambers for the company.” A few Ruth D. phase 1-3 trials. naysayers are important, and a “smart Williams, MD How, then, do we discuss new and emerging products— company will find several physicians Chief Medical medications, devices, or technology—when industry funds who critically analyze the early-stage Editor, EyeNet the research and the ophthalmologists we interview are the proposals,” he said. researchers? How does EyeNet, or any other ophthalmic pub- Although the challenges are different at a newsmagazine, lication, approach innovation? EyeNet also works hard to be fair and unbiased. We often ask I turned to Henry Jampel, editor-in-chief of Ophthal- several experts to share their experience and perspectives on mology Glaucoma, because editors of peer-reviewed jour- a topic. However, when we present innovative treatments, nals have an important role as gatekeepers of the scientific as in these two cover stories on drug delivery, the ophthal- literature. “It’s our job to assess the quality of the research mologists who share their insights typically have financial and hold early series trials to a high standard,” he said. interests related to the products under discussion. It’s a ten- Henry emphasized “the constant striving for our core value sion inherent in our system of drug and device development, of providing unbiased evidence,” which is a surprisingly because industry drives this stage of research. challenging process. The editors and the peer reviewers The cutting edge is where, arguably, the most interesting analyze the studies for methodological bias—and the editors developments lie, and it’s also where only those closest to the must be on the lookout for conscious or unconscious bias products can provide real news and valuable insight. Our among the peer reviewers. Henry also noted that even when goal: to approach this tension with attention to the facts, the evidence is sound, it’s important that the abstract and the balanced questions, and full disclosure. conclusion are consistent with the evidence. “It’s particularly important to keep the abstract bias free since this is the only 1 Seitzman GD, Lietman TM. Ophthalmology. 2019;126(2)192-194.

EYENET MAGAZINE • 11 Current Perspective

DAVID W. PARKE II, MD Private Equity: An Introduction

henever I’m speaking to a group of ophthalmol- ation, and amortization) and is typically adjusted for physi- ogists, I can count on someone asking, “What is cian compensation. It generally creates a substantive liquidity Wthe Academy position on private equity [PE]?” event. As the most strategically valuable practices leave the I always start my response by saying, “The Academy market, the multiples frequently decrease. doesn’t have a position on PE purchase of ophthalmology Will my practice run the same way with PE as a partner? practices, but…” The “but” is that the Academy cares very It’s not likely to do so. The PE company intends to grow the much that each ophthalmologist who is considering PE has net income. That occurs in only a limited number of ways— done complete due diligence and understands the econom- increasing revenue (better payer or procedure mix, adding ics, the nonfinancial terms, and the operational and profes- doctors, or simply adding patients), decreasing expenses sional implications. The Academy believes that the structure, (particularly staff), or paying you less. This may be good or operation, and sustainability of each member’s practice is bad, obviously. critical to her/his professional satisfaction and to the best What happens when the PE firm wants to sell the prac- patient care. tice? You likely won’t have any veto powers over a change Occasionally, I will encounter colleagues who have entered in control. And the new owner/manager may into negotiations without understanding the fundamentals do things differently than the previous of a business relationship with a PE firm. They seem to as- owner/manager. sume that it means getting a big check followed by “business What ophthalmologist profile as usual.” Others assume that it is exactly the same as all the benefits the most? Generally Physician Practice Management (PPM) companies in the (but not always) the senior 1990s. Neither is correct. Here are a few things to consider: ophthalmologist who is within PE isn’t new. PE firms have been purchasing equity in five years of retirement. The physician practices for over a decade, including dermatology, early- to mid-career ophthal- dentistry, gastroenterology, urology, primary care, emergen- mologist may, however, garner cy medicine, and cardiology. We can learn a lot from their more of the upfront cash as experience. more of their future income What do PE firms seek? A healthy return on their in- has been sold. Future potential vestment—ideally north of 20%. And then a sale to anoth- partners may be most economi- er investor/company in three to seven years. Particularly cally vulnerable and less enthusiastic attractive practices are those that are poorly run, fixable, and about joining the practice. On the other leaving money on the table; those successful high-profile hand, if the PE firm can “grow the pie,” David W. practices that can be leveraged as “platform practices”; those everyone may win. Parke II, MD with revenue streams that don’t depend on insurance (think It’s clearly a very complicated issue. Academy CEO cosmetic oculoplastics and refractive); and those positioned Fortunately, there are many resources to take advantage of a growing market. What we have seen in available to help you learn about the PE other specialties suggests that PE interest tops out at about issue in much more detail—including at the upcoming AAO 20% of the practice market. 2019 in San Francisco, where there will be many courses and What does the upfront cash distribution represent? lectures. The Academy urges every physician who is consid- This is a key question. It reflects anticipated future earnings. ering a PE practice equity acquisition to perform careful due So upfront cash will be offset downstream by PE taking a diligence and seek good counsel. And, as when acquiring percentage of future earnings. Upfront cash is calculated as a another practice, remember that cultural fit can be at least as multiple of EBITDA (earnings before interest, taxes, depreci- important as the economics.

12 • MAY 2019 News in Review COMMENTARY AND PERSPECTIVE

RETINA author Kevin J. Moore, MD, MPH, now at the Univer- Time to Rethink sity of Central Florida in Glycemic Targets Orlando. Advising patients. Dr. for Diabetes? Moore said the researchers hope their results will THE GLYCEMIC THRESHOLD ABOVE help physicians offer more which diabetic retinopathy (DR) can be individualized advice to their predicted to develop is lower for whites patients who have diabetes. than it is for blacks and Hispanics, “This shows that you can GLYCEMIC CONTROL. Tight glycemic control in researchers have found. have individuals that are patients with diabetes is recommended as a way In a retrospective study, a team of considered well-controlled to prevent complications, such as the prolifera- researchers at the University of Miami for diabetes but who, based tive DR seen here. But should the thresholds be used data from 5,338 participants on their race or ethnicity, revisited? in the 2005-2008 National Health are still at risk for diabetic and Nutrition Examination Survey retinopathy,” Dr. Moore said. “We edged, the lower complication rates (NHANES). All had diabetes and had would hope that our paper would achieved in studies have been accom- undergone digital retinal imaging to inspire ophthalmologists and primary panied by increases in the incidence of determine their retinopathy status. care providers to emphasize to patients serious hypoglycemia. The analysis showed that the hemoglo- that it’s still important to follow up, Because of this risk, it would be

. bin A (HbA ) predictive threshold 1c 1c regardless of how well their diabetes is “reasonable” for physicians to recom- for the incidence of DR among white controlled.” mend a lower glycemic target of 6.5% participants was 6.0%.1 In contrast, the A look at the guidelines. Racial dif- for certain patients, if it can be met predictive thresholds for DR in His- aao.org/eyenet ferences in mean HbA levels have been without hypoglycemia or other adverse panics and blacks were 6.4% and 6.5%, 1c discussed in the diabetes literature, but effects, the ADA report said. This respectively. the reasons for these differences are includes patients with a short duration Adequate—but inadequate? “Im- poorly understood, and their potential of diabetes, long life expectancy, type portantly, all three race/ethnicity– clinical significance is unknown.2 The 2 disease being treated with lifestyle specific glycemic thresholds are less American Diabetes Association (ADA) or metformin only, or no significant than the recommended 7.0% [for opti- makes no recommendations that glyce- cardiovascular disease. mal HbA control] for people with dia- 1c mic targets be modified based on race By comparison, the Japan Diabetes betes,” the authors wrote. “This finding or ethnicity.3 Society adopted practice guidelines4 suggests that adequate glycemic control Large, prospective treatment trials in 2013 that endorse setting the HbA does not guarantee protection from 1c have demonstrated that retinopathy target at 6.0% or less when the physi- diabetic complications, such as DR.” and other microvascular complications cian judges that glycemic control can Indeed, the researchers calculated decrease at HbA levels below 7.0%, be achieved through diet, exercise, or that above these thresholds the risk of a 1c and this is the appropriate target for medication. The guidelines set 7.0% as diabetic patient developing retinopathy most patients, according to the ADA’s the ceiling for most other patients, with was approximately 4 to 6 times as high 2019 recommended standards of care.3 the goal of preventing complications. as it would be below them, said lead

The American Society of Retina Specialists. For full credit, see this article at see this article at full credit, For Specialists. American Society of Retina The However, the ADA report acknowl- —Linda Roach

EYENET MAGAZINE • 13 1 Moore KJ et al. JAMA Ophthalmol. Published ophthalmicus (HZO). online Feb. 21, 2019. The second-generation 2 Selvin E. Diabetes Care. 2016;39(8):1462-1467. vaccine for the prevention of 3 American Diabetes Association. Diabetes Care. shingles was licensed by the 2019;42(Suppl 1):S61-S70. FDA for adults age 50 and 4 Araki E et al. Diabetol Int. 2016;7(4):327-330. older in October 2017. Since Relevant financial disclosures—Dr. Moore: None. then, however, the vaccine supply has been plagued PUBLIC HEALTH with shortages, and some patients have reported side Update on Shingles effects that prevented them Vaccine Safety from following through with the two-dose protocol. SHINGLES RISK. This 40-year-old woman pre- PUBLIC HEALTH OFFICIALS AND Although the shortages sented with acute retinal necrosis due to HZO. cornea specialists heralded the release are expected to persist of recombinant zoster vaccine (Shin- throughout this year,1 there is good from prelicensure clinical trials.2 grix, GlaxoSmithKline), given its ability news: According to the CDC, safety “Systemic and local reactions were to prevent herpes zoster (shingles) data for the eight months following most commonly reported, but [they] and ward off one of the disease’s most FDA approval of Shingrix are tended to be nonserious and self- serious complications, herpes zoster consistent with comparable data limited,” said lead author Elisabeth

IMAGING had increased reflectivity of the inner retinal layers and Emergencies After Hours: a loss of definition on OCT, confirming a suspected diagnosis of reperfused CRAO. She was transferred to OCT in the Eye-Only ER Mount Sinai’s main ER for a cardiovascular workup. Impact on providers. Eighteen residents and seven OPTICAL COHERENCE TOMOGRAPHY (OCT) HAS COME fellows completed a survey about after-hours access to out of the workday setting and into the night. Doctors the imaging modality. Of the 25 participants, 21 felt that at New York Eye & Ear Infirmary (NYEE) of Mount Sinai use of the automated OCT system improved patient Hospital in New York report that access to OCT in the satisfaction and reduced delayed or missed diagnoses, hospital’s after-hours emergency eye clinic has led to and 19 reported feeling less stress while using the sys- timely diagnoses and vision-saving treatment. Other tem, as it reduced their uncertainty over subtle pathol- benefits included improved patient satisfaction and ogies. “Both patients and physicians benefited by the reduced physician stress.1 reassurance that the correct diagnosis and appropriate The OCT system used in this study (iScan, Optovue) triage plan could be confidently implemented in such a is described by the manufacturer as automated; it uses setting,” Dr. Rosen said. computerized voice directives in multiple languages to Critical caveat. This system was not effective in . direct patient positioning and fixation. The technical patients with a visual acuity of 20/400 or worse, as the training of the NYEE ophthalmology residents took less device’s minimum vision requirement stipulates that

than 30 minutes, the authors said. “Automated OCT patients should be able to find fixation cues without aao.org/eyenet minimizes user training, allowing the technology to slip operator redirection. into this acute setting seamlessly,” said coauthor Rich- Bottom line. Further study may reveal the utility of ard B. Rosen, MD, at NYEE. automated OCT in sight-threatening conditions such as Review of records. Over a period of 15 months, an unusual presentation of acute retinal arterial occlu- 202 patients (359 eyes) underwent automated OCT sion requiring interventional radiology, Dr. Rosen said. scanning in the hospital’s resident-run urgent eye care Automated OCT “in an urgent care setting can be a clinic. The most common complaint that prompted powerful tool for triaging a variety of sight-threatening imaging was decreased vision (120, 59%), followed by conditions that require immediate attention,” he said. flashes/floaters (32, 16%), then metamorphopsia, sco- The use of such a system “reduces the need to relegate toma, and pain. this important diagnostic technology to workday set- Impact on patient care. The imaging system proved tings where skilled operators are available.” its worth in furthering rapid triage in appropriate cases, —Miriam Karmel Dr. Rosen said. For example, OCT can be helpful in diagnosing subtle cases of CRAO without characteris- 1 Kaplan RI et al. BMJ Open Ophthalmol. 2019;4:e000187. tic fundus findings and decreased vision. One patient Relevant financial disclosures—Dr. Rosen: Optovue: C. The American Society of Retinal Specialists. For full credit, see this article in full credit, For Specialists. American Society of Retinal The

14 • MAY 2019 M. Hesse, MD, at the CDC in Atlanta. 1 CDC. Current vaccine shortages & delays. www. In addition, for two of these cases, they Safety data. The postlicensure safety cdc.gov/vaccines/hcp/clinical-resources/shortages. used fluorescence in situ hybridization profile is based on reports to the Vac- html. Updated November 2018. Accessed March (FISH) to detect lymphatic mRNAs, cine Adverse Event Reporting System 20, 2019. including podoplanin. All IF and FISH (VAERS), a national passive surveil- 2 Hesse EM et al. MMWR Morb Mortal Wkly Rep. samples were compared with positive lance system. VAERS received 4,381 2019;68(4):91-94. and negative controls and visualized by reports of adverse events, including Relevant financial disclosures—Drs. Colby and confocal microscopy. reports from health care providers and Hesse: None. Results. Podoplanin-immunoreac- the public, between October and June tive lymphatics were detected in all nine 2018. During that time, some 3.2 mil- CORNEA failed grafts by IHC; of these, seven also lion doses of Shingrix were distributed. were positive by IF. Moreover, two of Adverse reactions. Signs and symp- Lymphatic Vessels the cases were positive for at least two toms included the following: Detected in Failed lymphatic markers simultaneously. • Chills, headache, fatigue, and my- H&E stained sections of failed grafts algia were commonly reported, along Corneal Transplants showed mononuclear inflammatory with injection site reactions. CANADIAN RESEARCHERS HAVE cells at both low and high power, and • Most common signs and symptoms shown that lymphatic vessels are impli- neovascularization was confirmed in included fever (23.6%), injection site cated in corneal transplant graft failure every case of corneal graft failure by pain (22.5%), and injection site erythe- with neovascularization.1 “Our study detection of CD31-positive profiles. ma (20.1%). proves for the first time the presence Varying lymphatic sizes and morphol- • All told, 130 (3%) of events were of lymphatics in failed vascular corneal ogies were seen both among separate classified as serious. grafts and [shows] that they are distinct cases and within a single case, and • People between the ages of 50 and from blood vessels,” said Neeru Gupta, myriad unique lymphatic morpholo- 69 reported a high percentage of sys- MD, PhD, MBA, at the University of gies were seen. temic signs and symptoms (e.g., chills Toronto. “This work highlights the role Next steps. The researchers em- and headache). In contrast, those age of lymphatics in corneal transplant phasized that their findings stress the 70 and older reported a high frequency failure and points to a need to develop importance of developing new tools, of local symptoms (e.g., injection site novel treatments that target lymphatic therapies, and imaging modalities to pain). vessels to help manage the failing graft,” bring about improvements in graft Reassurance. Overall, Dr. Hesse she added. survival. —Arthur Stone said, the CDC team was “reassured” by Tissue collection. For this study, the findings. She added that providers failed corneal transplant cases were 1 Diamond MA et al. Br J Ophthalmol. 2019; should expect that some patients will selected from the Toronto Ophthal- 103(3):421-427. experience reactions to the vaccine— mic Pathology database. Of 273 cases, Relevant financial disclosures—Dr. Gupta: None. but that most reactions will be self-lim- 39 contained documented ited and should resolve in a few days. neovascularization. Of these, The CDC and FDA will continue to nine cases (six men, three A B monitor the vaccine’s safety profile, as women) also contained the vaccine is still in the early uptake suspected lymphatics. The period. researchers then obtained Cornea risk reminder. Kathryn A. conjunctival tissue from six Colby, MD, PhD, at the University of patients (three men, three Chicago, urged ophthalmologists to women) with healthy corneas. C D continue to educate patients that the These control cases were vaccine is safe, effective, and can pre- acquired from the Human vent HZO. “Herpes zoster ophthalmic- Eye Biobank for Research,

. us can cause serious cornea complica- also located in Toronto. tions that can lead to permanent vision Methods. The researchers loss and chronic pain that impacts selected the nine failed grafts FAILED GRAFTS. These images show neovascu-

aao.org/eyenet quality of life,” she said. “It’s good for based on results of immu- larization and suspected lymphatics within failed ophthalmologists to educate patients nohistochemistry (IHC), corneal grafts. Blood vessels shown at 20× magni- on the benefit—because we’re the ones immunofluorescence (IF), fication (rectangular area, A) and at 40× magni- who will end up managing the compli- H&E staining, and immu- fication (arrows, B). Immunoperoxidase images cations. We need to get the word out.” noperoxidase staining for show podoplanin-antibody staining lymphatics —Miriam Karmel CD31, a blood vessel marker. (arrows, C and D).

For full credit, see this article at see this article at full credit, For See the financial disclosure key,page 8. For full disclosures, including category descriptions, view this News in Review at aao.org/eyenet.

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Ophthalmology according to retreatment status. Can Patient-Reported Outcomes Selected by Stephen D. McLeod, MD Among patients in the open-label Serve as Endpoints in Trials? extension, 121 (24%) did not require May 2019 Durability of DR Improvement further ranibizumab treatment. DR was With As-Needed Ranibizumab evaluable for 367 patients at months On behalf of the United Kingdom May 2019 36 and 48. When comparing all three Glaucoma Treatment Study (UKGTS) study groups (sham/crossover, ranibiz investigators, Jones et al. gathered and In this open-label extension of the RIDE umab 0.3 mg, and ranibizumab 0.5 compared self-reported outcomes for and RISE studies, Sun et al. looked mg), of the 279 patients who required UKGTS participants. In the flagship at the durability of improvement of continuation of ranibizumab, 84% to trial, patients with open-angle glauco- diabetic retinopathy (DR) after patients 94% experienced stability of DR (0- to ma (OAG) had been assigned to receive were switched from monthly ranibiz 1-step change), and 2% had improve- latanoprost or placebo drops, and vi- umab to pro re nata (PRN) dosing. ment of 2 steps or more. However, 3% sual field progression was the outcome They found that the DR improvements to 14% had worsening of at least 2 steps of interest. Eligible for the subsequent attained with monthly ranibizumab between months 36 and 48. In general, study were patients from UKGTS with were maintained in more visual improve- newly diagnosed OAG and self-report- Volume 126 | Number 5 pp. XXX–XXX Volume 126 | Number 5 | May 2019 than 70% of patients after Elsevier | ISSN 0161-6420 ment was main- ed outcome measures at both baseline the switch to PRN dosing. tained throughout and study completion. Because the The extension study was the extension average changes in patient-reported a pooled analysis of data study, regardless outcome measures (PROMs) for health- for patients with DR and of changes in DR and vision-related quality of life were diabetic macular edema severity. found to be similar for the placebo and

(DME) who participated OPHTHALMOLOGY The authors active-treatment groups, the research- in RIDE or RISEINSERT ADVERT for 36 recommend that ers surmised that PROMs may not be months. In those studies, careful moni- sensitive enough to function as primary patients were assigned toring be part of endpoints in clinical trials of early- randomly (1:1:1) to receive the long-term stage glaucoma. ranibizumab 0.3 mg/month, May2019 management of The PROM study included 182

ranibizumabOPHTHA_v126_i5_COVER.indd 1 0.5 mg/month, 25-01-2019 10:21:16 DR, particularly patients who received latanoprost and or a monthly sham injec- because the con- 168 placebo recipients. At baseline and tion. After 24 months, the sham group dition often worsens. They added that trial exit, participants completed gen- received ranibizumab 0.5 mg/month. their findings suggest the possibility eral health PROMs (European Quality After 36 months in the core studies, of a paradigm shift in DR treatment— of Life in 5 Dimensions [EQ-5D] and patients in the open-label extension that is, focusing on early treatment 36-item Short Form [SF-36]) as well (n = 500) could receive ranibizumab to reduce DR severity and prevent vi- as glaucoma-specific PROMs (15-item 0.5 mg PRN. DR severity was assessed sion-threatening complications, rather Glaucoma Quality of Life [GQL-15] photographically, using the scale from than using a wait-and-watch approach and 9-item Glaucoma Activity Limita- the Early Treatment Diabetic Retinop- in which treatment is reserved only for tion [GAL-9]). The percentage change athy Study. The primary outcome of advanced eye disease. (Also see related between PROM values was calculated the extension study was the change commentary by Robert N. Frank, MD, in for each patient and compared between in DR severity from months 36 to 48, the same issue.) treatment arms. Also compared were

EYENET MAGAZINE • 17 differences between patients whose the modified Oxford scale). a useful noninvasive imaging option, glaucoma remained stable and those During the four-month study, particularly if ICG angiography is not who experienced progression (deter- patients were assigned randomly to available. mined by visual field changes). receive high-dose treatment (CsA For this cross-sectional study, the The average percentage change in CE 0.1% eyedrops, four times daily), researchers assessed 50 consecutive PROMs was similar for the placebo low-dose treatment (CsA CE 0.1% treatment-naive patients (50 eyes) with and latanoprost groups, with no signifi- twice daily plus vehicle twice daily), or PCV. Patients were evaluated with mul- cant between-group difference for vehicle four times daily. The primary tiple imaging technologies, including any measure (EQ-5D overall, p = .98; endpoint was a mean composite score multicolor imaging, fluorescein and EQ-5D visual analog scale, p = .88; reflecting corneal fluorescein staining, ICG angiography, and color fundus SF-36, p = .94; GQL-15, p = .66; GAL-9, use of rescue medication (dexameth- photography. Each patient underwent p = .87). As expected, there were signif- asone 0.1% four times daily), and all imaging modalities on the same day. icant differences in glaucoma-related corneal ulceration. QoL was assessed by One eye was selected for analysis. The PROMs between patients with and a visual analog scale and questionnaire. color fundus and ICG angiography without progressing glaucoma (GQL- For the primary endpoint, differenc- images were independently graded by 15, p = .02; GAL-9, p = .02), and the es in least-squares means versus vehicle retina specialists to identify the pres- differences in general health PROMs were significant for the high dose of ence of polyps and distinguish lesion were similar for these subgroups (EQ- CsA CE (0.76; p = .007) as well as the components. 5D, p = .62; EQ-5D visual analog scale, low dose (0.67; p = .010); treatment Overall, the researchers found that p = 0.23; SF-36, p = .65). effect was driven mainly by corneal the location and shape of lesions detect- The low sensitivity of PROMs may fluorescein staining score. Compared ed with multicolor imaging correlated render these tools inadequate as primary with low-dose CsA CE, the higher dose well with those seen on color fundus endpoints in trials of early-stage glau- resulted in larger improvements in photography and ICG angiography. coma. Although sensitivity to clinical photophobia and mucous discharge Multicolor imaging was able to detect meaningfulness is a common criterion and much greater improvement in both polyps in 49 of the 50 eyes (98%). for outcomes selection, quality of life QoL domains. The need for rescue Other clinical features detected via is important as well. Even if PROMs medication differed significantly multicolor imaging included branching cannot capture the disease-modifying between the vehicle group and each vascular network (BVN, seen in 60% of effects of treatment, these tools may active-treatment arm. VKC symptoms eyes), drusen (seen in 66% of eyes), and help to assess other consequences of and QoL improved in all three groups, subretinal hemorrhages (seen in 40% of therapy, such as side effects and dosing and improvement was significant for eyes). On the multicolor composite im- convenience. (Also see related commen- high-dose treatment versus vehicle. ages, the polyps appeared as dark green tary by Scott Wallace, MD, and Jane —Summaries by Lynda Seminara oval lesions. When infrared reflectance Edmond, MD, in the same issue.) imaging was used, the polyps appeared Ophthalmology Retina as dark grey oval lesions with distinct Cyclosporine A Cationic Selected by Andrew P. Schachat, MD margins. Subretinal hemorrhages ap- Emulsion for Pediatric Vernal peared red on the multicolor composite Keratoconjunctivitis Using Multicolor Imaging to images, while BVNs typically appeared May 2019 Detect Polypoidal Choroidal as an area of mottling. Vasculopathy The authors noted that optical Leonardi et al. evaluated the efficacy May 2019 coherence tomography (OCT) and and safety of an investigational therapy for severe vernal keratoconjunctivitis Multicolor imaging is a novel tech- (VKC) in children: cyclosporine A (CsA) nology that can be used to visualize Ophthalmology Retina cationic emulsion (CE). Compared pathology in the posterior pole. Images Now in PubMed with conventional CsA formulation, the are produced separately from three The Academy is pleased to new product (an oil-in-water emulsion) color wavelengths and can be combined announce that Ophthalmology demonstrated better bioavailability. to produce a composite image. Tan et Retina has been accepted by the This research indicates that high-dose al. evaluated the ability of multicolor National Library of Medicine for CsA CE is safe and improves keratitis, imaging to discern features of polypoi- inclusion in Medline/PubMed, its symptoms, and quality of life (QoL) dal choroidal vasculopathy (PCV) and making the publication the first for children with severe VKC. compared those results with those seen monthly, print U.S. ophthalmol- This phase 3 trial involved 169 on standard color fundus photography ogy journal to be accepted in pediatric patients with active severe and indocyanine green (ICG) angiog- more than 12 years. Indexing is VKC (grade 3 or 4 on the Bonini sever- raphy, the gold standard. They found expected to begin this month ity scale) and severe keratitis (corneal that multicolor imaging could detect (May). fluorescein staining score of 4 or 5 on features suggestive of PCV, making it

18 • MAY 2019 from 2003 to 2014. They also concerns about functional vision and 1 3 identified the following pre- eye-related quality of life (ER-QOL). In dictive factors: female sex, a new study, these authors applied the hypertension, carotid artery patient-derived concerns to a different stenosis, aortic valve disease, cohort of patients, with the goal of smoking, and alcohol depen- developing FDA-compliant question- dence/abuse. naires and testing their validity. This During the 12-year study approach proved effective for devising period, the estimated number questionnaires that separately assess the 2 4 of CRAO inpatient admis- domains of functional vision and ER- sions was 17,117. The mean QOL in children of any age, with any age was 68.4 years, and 53% eye condition. (In subsequent research, were female. The overall in- the authors will test the reliability, cidence of in-hospital stroke construct validity, and responsiveness and acute MI was 12.9% of these tools.) and 3.7%, respectively. The The researchers’ goal was to create incidence of stroke increased short forms that represent individual, PCV WITH HEMORRHAGE. In this image set, the significantly over time, from analysis-driven, unidimensional do- color fundus photograph (1) shows areas of sub- 7.7% in 2003 to 15.3% in mains within the separate constructs retinal hemorrhage with retinal edema and hard 2014. Among this CRAO of functional vision and ER-QOL, for exudates. The ICG angiogram (2) illustrates polyps population, the combined use in any clinical setting. The research- with a small BVN. On the multicolor composite risk of stroke, transient isch- ers enrolled 444 children (0 to <18 image (3), the polyps are dark green and oval, the emic attack, and acute MI years of age) from two centers, with BVN appears as a mottled green area, and the (or mortality) was 19%. the children representing 10 diagnostic hemorrhages are red. On the infrared reflectance This research shows that categories. image (4), the polyps appear as dark grey round the burden of vascular risk Parents filled out a master question- lesions. in this patient population naire and proxy questionnaires for their is sizable and growing. children. Younger children had ques- OCT angiography were not used in At present, there are no options to tions read to them; older children were this study, which opens the door to significantly improve visual outcomes given forms to fill out. Factor analysis follow-up research on whether the in patients with CRAO; therefore, was applied to identify unidimensional combination of OCT and multimodal clinical management involves prevent- domains, and Rasch analyses (differ- imaging would increase diagnostic ing vascular ischemic events. Because ential item functioning, targeting, fit) accuracy. —Summary by Jean Shaw stroke risk is highest at the time of were performed to reduce the number occlusion, prompt clinical evaluation is of items. Rasch lookup tables were used American Journal of warranted, along with timely execution for scoring, and the data were analyzed Ophthalmology of stroke prevention measures. separately by age group and for each Selected by Richard K. Parrish II, MD To the authors’ knowledge, their factor. study is the largest of its kind to date. The number of items per question- CRAO-Associated Vascular The findings confirm that CRAO is an naire/proxy ranges from 29 to 42. Ischemic Events on the Rise important marker for subsequent vas- The form for the youngest children April 2019 cular ischemic events. As the incidence (0-4 years) consists of three domains: of CRAO-associated stroke continues functional vision, bothered by eyes/ Central retinal artery occlusion (CRAO) to rise, it would be prudent to have vision, and social. For ages 5-11 and confers a high risk of acute vascular an adjunctive risk-prediction model ages 12-17, the forms include four ischemic events, including myocardial to assist in triaging and referral, the unidimensional domains: functional infarction (MI) and stroke. Under- authors said. This would optimize early vision, bothered by eyes/vision, social, standing the burden and risk-factor evaluation of patients with the highest and frustration/worry. profile of ischemic events can help risk for ischemic events. For parents, the master question- ophthalmologists in managing and naire includes four domains: impact referring patients. Mir et al. performed New Questionnaires to Assess on parent/family, worry about child’s a nationwide cross-sectional study to Functional Vision and QOL in eye condition, worry about child’s determine the incidence and predictors Children With Eye Disease self-perception and interactions, and of in-hospital ischemic events among April 2019 worry about child’s visual function. inpatients with a diagnosis of CRAO The number of domains on parental in the United States. They found that In previous research based on inter- proxy forms vary according to the age

Ophthalmology Retina the incidence of stroke nearly doubled views, Hatt et al. identified children’s of the child.

EYENET MAGAZINE • 19 Next steps include testing the reli- people were more likely than nonim- more boys than girls (10.4% vs. 4.5%, ability and validity of the new question- paired individuals to use eye care (OR, respectively), and parental disapproval naires in another cohort of patients. 1.54; p < .001), but they had greater directed more at girls than boys (11.4% —Summaries by Lynda Seminara difficulty affording eyeglasses (OR, vs. 4.2%, respectively). 3.86; p < .001). Overall, women were Students with poorer presenting VA JAMA Ophthalmology more likely than men to use eye care and greater correction of VA were more Selected and reviewed by Neil M. (OR, 1.42; p < .001) and to have diffi- likely to be wearing their eyeglasses: Bressler, MD, and Deputy Editors culty affording eyeglasses (OR, 1.68; p Those whose uncorrected VA was less < .001). Compared with non-Hispanic than 6/18 (20/60) in the better eye Trends in Eye Care Use and whites, those who are Hispanic, Asian, were nearly three times more likely to Spectacle Affordability or black were less likely to use eye care, be wearing their spectacles than were April 2019 and Asians and blacks were more able those whose VA ranged from less than to afford eyeglasses. 6/9 to 6/12 (20/30 to 20/40; adjusted In an analysis of data from the U.S. Na- odds ratio [OR], 2.84). Compared with tional Health Interview Survey (2008- Why Children Do—and Don’t— correction resulting in improvement of 2016), Varadaraj et al. looked at trends Wear Their Eyeglasses 3 lines or less, correction of 3 to 6 lines in eye care use and the affordability of April 2019 was associated with an adjusted OR of eyeglasses. They found that those least 2.31, and correction of at least 6 lines likely to use eye care or to be able to Nearly 13 million children worldwide had an adjusted OR of 2.57. afford eyeglasses were women, racial/ have visual impairment resulting from The fact that most students were ethnic minorities, and visually im- uncorrected refractive errors. Although wearing their eyeglasses at follow-up paired people, regardless of study year. eyeglasses are a simple and cost-effec- supports the use of prescribing guide- Since 2014, spectacles were deemed tive solution, low adherence to specta- lines in this study. (Spectacles are pro- more affordable than in previous years, cle wear can occur in any income set- vided for students who require correc- which may relate to economic recovery ting. Morjaria et al. looked at predictors tion of at least 2 lines in the better eye.) and/or health care reform. of spectacle adherence among students The authors emphasized the impor- Survey participants were adults 18 aged 11 to 15 years. They found that tance of interventions to reduce teasing years and older. They were grouped the greatest predictors of spectacle wear and bullying. However, they also ac- into nine annual cross-sectional pop- were “poorer presenting visual acuity knowledged that it would be difficult to ulation-based samples, ranging from [VA]” and “greater improvement in address the issues underlying parental 21,781 to 36,697 people. Visual im- VA with correction.” The main reason disapproval. (Also see related commen- pairment was defined as self-reported for nonwear was bullying or teasing tary by Vivian Manh, OD, MS, in the difficulty with seeing despite wearing by peers. The predictors of adherence same issue.) eyeglasses. Outcome measures included support using prescribing guidelines —Summaries by Lynda Seminara visits to eye care professionals and the such as those in this study. inability to afford eyeglasses if deemed The study was a planned analysis OTHER JOURNALS needed in the preceding year. Survey of secondary objectives from a non- Selected by Deepak P. Edward, MD logistic regression, with adjustment for inferiority study among students who demographics and other factors, was fulfilled eligibility criteria, including Early Detection of HCQ used to detect associations between correction improvement of at least 2 Retinopathy With OCT survey years and eye care outcomes. lines in the better eye. Participants were British Journal of Ophthalmology Compared with the first year of the recruited from government schools in Published online Feb. 28, 2019 survey, the final year was associated Bangalore, India. Masked observers with higher proportions of Asians, documented the rate of compliance to Early detection of hydroxychloroquine Hispanics, and older adults in the U.S. spectacle wear during unannounced (HCQ) retinopathy is crucial because population. Throughout the study pe- visits to the schools several months the drug may cause severe irreversible riod, substantial trends were observed after the spectacles had been distributed. vision loss, even after discontinuation. for both outcomes. The fully adjusted Of the 460 participants, follow-up Garrity et al. evaluated optical coher- models showed that people were less information was available on 362 ence tomography (OCT) findings of likely to use eye care in 2016 than in (78.7%). At that time, 92 (25.4%) were patients who had taken HCQ for many 2008 (odds ratio [OR], 0.90; p < .001). not wearing their eyeglasses. The main years and had also undergone Hum- Compared with 2008, spectacle afford- reason for nonwear was teasing or phrey visual field (VF) testing. They ability was easier from 2014 onward bullying by peers (48.9%), followed by found that OCT was able to detect (2014 OR, 0.82; p < .001; 2015 OR, lost, forgotten, or stolen spectacles HCQ-related abnormalities before they 0.81; p < .001; 2016 OR, 0.70; p < .001). (26.1%). Headaches and parental were picked up by VF testing. After adjustment for all covariates, disapproval also had an impact, with For this retrospective, observation- including survey year, visually impaired headaches and discomfort reported by al study, the researchers identified 10

20 • MAY 2019 patients (17 eyes) with HCQ-related to the photographs to predict time- abnormalities detected on spectral- domain optical coherence tomography domain OCT (SD-OCT) and normal (TD-OCT)–equivalent MT measures, VF results. The researchers conducted including central subfield thickness several ancillary tests—including color (CST) and central foveal thickness fundus photography, fundus autofluo- (CFT). Two conventional TD-OCT rescence, and microperimetry—as part cutoff points—250 μm and 400 μm— of a comprehensive examination. were used to identify abnormal MT. The mean duration of treatment A deep learning regression model was with HCQ was 11 years (range, 3-26 created to quantify actual CST and CFT years), and the mean dose of HCQ was measurements from the fundus photo- 1,611 g (range, 730-3,796 g). (Of note, graphs. Four models of deep convolu- the recommended dosage is 5 mg/kg tional neural networks were analyzed of actual—not ideal—body weight.) (two each for CST and CFT). At baseline, all 10 patients had visual The best deep learning model was acuity between 20/20 and 20/30 in the able to predict CST ≥250 μm and CFT eye(s) with HCQ retinopathy. Three of ≥250 μm, with area under the curve the patients reported no visual symp- (AUC) of 0.97 and 0.91, respectively. toms; the remainder reported blurry For CST and CFT predictions of ≥400 vision, floaters, or photopsia. μm, AUC of the best model was 0.94 All 10 patients presented with nor- and 0.96, respectively. The best neural mal 10-2 perimetry testing. However, network regression model to quantify features of early HCQ macular toxicity CST and CFT had an R2 of 0.74 and were evident on SD-OCT, including 0.54, respectively. The models were less attenuation of the parafoveal ellipsoid accurate when images were of poor zone (relative to the central ellipsoid quality or if laser scars were present. band) and loss of a clearly identifiable The researchers cautioned that their continuous parafoveal interdigitation findings may not be generalizable to zone. These observations were bilat- the overall population of patients with eral in seven patients and unilateral in diabetes. In addition, it’s possible that three. Six eyes eventually developed the deep learning model is not truly Ophthalmology Job Center advanced HCQ retinopathy with char- detecting macular thickening but rather acteristic paracentral VF defects and/or retinal phenotypes. Although abnormal Ophthalmology Job Center advanced outer retinal disruption. thickening does correlate with such phenotypes, the authors affirmed that Find the Using Deep Learning to Evaluate the deep learning model can detect Find the Macular Thickening abnormal MT regardless of diabetic Right Fit Investigative Ophthalmology & retinopathy severity or the presence of Visual Science hard exudates. More research is needed Right Fit 2019;60(4):852-857 to validate such models with real-world Fast data. —Summaries by Lynda Seminara Choose the #1 job site Arcadu et al. set out to determine forFast ophthalmology. whether deep learning could be used Choose the #1 job site to predict optical coherence tomogra- Apply Now for a Big phy–equivalent quantitative measures Data Research Grant Startfor ophthalmology. your search today: of diabetic macular thickening (MT), A research fund established last aao.org/jobcenter using color fundus photographs. They year gives Academy members Start your search today: found that it could, and they suggested in private practice an opportu- aao.org/jobcenter that, when used in this manner, deep nity to harness the power of big learning models could significantly data—but you must submit your benefit teleophthalmology initiatives. application by May 31, 2019. For this study, the authors obtained To learn more about the eligibility data from the phase 3 RIDE and RISE requirements and the application studies of diabetic macular edema process, go to aao.org/iris-regis (DME); nearly 18,000 color fundus im- try/data-analysis/hoskins-center- ages were included. Deep learning with research-fund. a transfer-learning cascade was applied

EYENET MAGAZINE • 21

Discoveries and Analysis from Experts You Can Rely On

The Academy’s growing family of journals keeps you in tune with the most impactful research and breakthroughs in ophthalmology.

Ophthalmology® is the most read original- research journal in our field and has an impressive 7.5 Impact Factor.* First published January 2017, Ophthalmology® Retina is already among the most-read ophthalmic journals and is read cover to cover with high frequency.* Ophthalmology® Glaucoma, published in partnership with the American Glaucoma Society, is the newest and most promising journal for this dynamic subspecialty.

*Source: Kantar Media

Delve deeper at aao.org/journals CATARACT CLINICAL UPDATE

Out of Femto’s Shadow: Two New Devices Seek to Change Cataract Surgery

nterior capsulotomy and nucleus fragmentation are two Aof the most important steps in cataract surgery. And since its FDA approval in 2010, the femtosecond laser has introduced a way to automate these key maneuvers. However, the technology has been met with mixed reviews and uneven acceptance. To begin with, the femtosecond laser is unavailable to many surgeons around the world. Moreover, its use requires a large outlay of capital and addition- CLOSER LOOK. A Zepto capsulotomy in a mature cataract with no red reflex (left). al space within the surgery center or The capsular button is stained with trypan blue and shows contracted edges. The OR, adds procedural time, and results miLoop (right) is shown encircling the nucleus with the capsular bag. in significant extra costs. In addition, clinical studies have shown higher inci- the silicone cup over the visual axis and a perfectly round, reproducibly sized dences of postoperative corneal edema applies the necessary suction to gently capsulotomy centered on the visual and capsular tears with its use com- draw the capsular membrane toward axis, such as when implanting premium pared with manual cataract surgery.1,2 the ring. A 4-ms pulse of energy is de- IOLs, said Dr. Hooshmand. “For this Enter two femto-free alternatives for livered to the ring via a small console, purpose, the Zepto might be a more facilitating capsulotomy and nucleus instantaneously creating a complete efficient and less expensive alternative fragmentation: Zepto and miLoop. “precision pulse capsulotomy”3 roughly to the femtosecond laser,” commented 5.2 mm in diameter, along with a David F. Chang, MD, in private practice Zepto free-floating capsular button. in Los Altos, California. How it works. The Zepto (Mynosys) Because the surgeon can simply Pearls for success. Although the consists of a single-use, disposable replace normal capsule forceps with device does require a surgical assistant handpiece with an elastic nitinol cut- the Zepto during the surgical sequence, to apply the energy and release the ting ring at its tip. (Nitinol is a nickel- there is no disruption to the normal suctioning, “it’s quite easy to incorpo- titanium alloy with superelastic and surgical workflow, said Joobin Hoosh- rate into routine cataract surgery,” Dr. shape memory characteristics.) This mand, MBBS, at the Sydney Eye Hospi- Hooshmand said. “The learning curve tip is encased in a soft silicone suction tal in Australia. is short—it takes roughly 15 to 20 cases cup. Once the cutting ring is inserted Cost. With an initial price of to get comfortable.” through a 2.2 mm or larger corneal $12,500 for the portable console, each Proper suction. In order for the incision, a pushrod is retracted, and the single-use handpiece runs $135. Zepto to create the circular capsular ring unfolds into a circular shape. The device may be particularly at- opening, it’s important that the sur- The ophthalmologist then centers tractive for ophthalmologists who want geon achieve consistent suction on the capsule. “To do so, the central pushrod must be fully retracted all the way back BY MIKE MOTT, CONTRIBUTING WRITER, INTERVIEWING DAVID F. CHANG, to its starting position” before suction

David F. Chang, MD F. David MD, JOOBIN HOOSHMAND, MBBS, AND RENGARAJ VENKATESH, MBBS. is applied, Dr. Chang said. “Otherwise,

EYENET MAGAZINE • 23 the insufficient suction could result in button, which might be the result of Notes on technique. The miLoop is an uneven cut and possibly a late radial dissipated thermal energy from the particularly adept at cutting through anterior capsular tear.” cutting ring.4-6 extremely dense nuclei, said Dr. Ven- Dr. Hooshmand added, “If the However, Dr. Chang explained, katesh. Even so, the surgeon must be suction cup isn’t fully opened to 360 “Because of the way in which Zepto careful not to traumatize the zonules by degrees, the nitinol ring won’t be in the utilizes suction to create a capsulotomy, displacing particularly large nuclei with correct proximity to the capsule. But in the button edge geometry is completely the loop, Dr. Chang said. “It is import- this case, you can always disengage the different than that of the anterior ant to master the technique with softer suction, reapproximate the device, and capsulotomy rim edge, which is what and medium density nuclei before then move forward.” is important. Human cadaver studies attempting brunescent cataracts.” Patient selection. The Zepto has have suggested that the rim edge is Dr. Chang added, “The cut will tend particular benefits for complicated structurally smooth and strong.”3,7,8 to prolapse the distal pole of a denser cases involving a poor red reflex, in- It remains to be seen whether or nucleus. So I use a second instrument adequate corneal visibility, or anterior not Zepto is widely accepted, said Dr. to prevent a firm nucleus from tipping capsular fibrotic bands, Dr. Chang said. Hooshmand. “The promise of perfect, and having its nasal pole prolapse “In my experience, there is no better repeatable capsulotomies is enticing,” through the capsulorrhexis. Many sur- technology for intumescent lens in but any lingering safety concerns geons then rotate the nucleus to make which the liquefied cortex raises the should be investigated, he said. a second cut 90 degrees from the first, intralenticular pressure,” he said. “This which produces nuclear quadrants.” is because the device cuts the entire miLoop Patient selection. Given the miLoop’s circumference of the capsulotomy How it works. The miLoop (Carl Zeiss) ability to cut through dense nuclei, simultaneously, at once, preventing any is a single-use, disposable instrument “its use definitely benefits the surgeon radial splitting.” designed to mechanically fragment any working with harder and mature cat- And because the Zepto bypasses the grade of nucleus without the need for aracts—especially the brunescent and cornea altogether, Dr. Hooshmand said ultrasound energy. The device uses a black cataracts that are more common that he finds the device particularly retractable nitinol loop and is designed in the developing world,” said Dr. Ven- useful for patients with corneal mor- to encircle and manually bisect the lens katesh. “The amount of phaco energy phology or scarring that prevents good into full-thickness segments. required to emulsify these cases is very visualization of the anterior capsule. “I hold the slender handpiece like a high, so the miLoop provides a more Pupil size. In Dr. Hooshmand’s pencil,” said Dr. Chang. After the capsu- efficient and beneficial alternative.” experience, a dilated pupil larger than lotomy is performed, he added, “the Is it safe? In a recent study of 6 mm is also necessary to achieve the microfilament loop is retracted into the 101 patients with advanced (grades best results with the Zepto. “In margin- instrument tip and inserted into the 3-4) cataracts, researchers compared al pupils, the device tip can slip under anterior chamber via a clear-corneal outcomes in those who underwent the pupil, but bear in mind that you incision. Advancing the sliding actua- phacoemulsification alone (n = 48) only get to insert the device once,” he tion button on the handle opens this and those who underwent phaco in said. “So if you’re in doubt regarding a loop in the horizontal plane, so that it combination with the miLoop (n = 53). patient’s pupil size, take the necessary expands within the capsular bag, but on They found that the device improved steps to enlarge the pupil beforehand.” top of the nucleus.” overall phaco efficiency and was 100% Is it safe? “In our initial study [of Once expanded, the loop is rotated effective in delivering ultrasound-free, Zepto], we found high incidences of in- around and behind the nucleus. The act full-thickness nucleus disassembly.9 complete capsulotomy in addition to a of sliding the button backward con- Four cases of posterior capsular tears significant number of radial tears,” said tracts the loop and initiates the cut. occurred in the miLoop/phaco group, Dr. Hooshmand. “We communicated Cost. The device carries a single-use while five cases occurred in controls. these findings to the manufacturer, and cost of $150 with no capital investment. A note on humanitarian applica- after several design improvements, a Pearls for success. The miLoop is tions. Dr. Chang is part of a group subsequent review of the device resulted particularly appealing to those ophthal- convened by ianTech, the company in a drastic improvement in the number mologists who are uncomfortable with that originally designed the miLoop, to of complete, free-floating capsuloto- chopping, said Rengaraj Venkatesh, develop a small-incision, manual extra mies. But tear rates remained high, MBBS, at the Aravind Eye Hospital in capsular cataract extraction method considerably higher than what you get Pondicherry, India. “It eliminates the using a version of the miLoop that is with manual capsulorrhexis.”4,5 need to sculpt the nucleus and there- less expensive than the original. Electron microscopy studies per- fore the need to use ultrasonic phaco The hope, Dr. Chang said, “is that a formed by Dr. Hooshmand and his power. And because the lens is cut from low-cost miLoop might provide a safer team also revealed areas of irregular periphery to center without aggressive and more cost-effective alternative to capsule margins and frayed collagen manipulation, there is much less trau- phaco in settings where phaco training fibers at the edge of the capsulotomy ma to the capsule and the zonules.” and proficiency is limited.”

24 • MAY 2019 Game Changers? Looking ahead, can a small box of pen- like tools such as the Zepto and miLoop truly revolutionize cataract surgery? It all comes down to affordability, Dr. Venkatesh said. “Will there be new iterations of these devices that allow for multiple uses in multiple patients? And just how cheaply can the manufacturers deliver these products around the world? If these issues are further refined, the future is very bright for these new technologies,” Dr. Venkatesh said. Find Training

1 Manning S et al. J Cataract Refract Surg. 2016; Opportunities 42(12):1779-1790. 2 Abell R et al. Ophthalmology. 2014;121(1):17-24. 3 Keller C et al. Ophthalmology. 2018;125(10): e72-e73. 4 Hooshmand J et al. J Cataract Refract Surg. 2018;44(3):355-361. 5 Hooshmand J et al. J Cataract Refract Surg. 2018;44(11):1333-1335. 6 Hooshmand J et al. Ophthalmology. 2018;125(3): 340-344. The Academy’s Global Directory of 7 Chang D et al. Ophthalmology 2016;123(2):255- Training Opportunities is the most 264. comprehensive list of observership 8 Thompson V et al. Ophthalmology 2016;123(2): and fellowship opportunities. It is 265-274. 9 Ianchulev T et al. Br J Ophthalmol. 2019;103(2): easy to find an opportunity for you: 176-180. 1. Go to Dr. Chang is clinical professor of ophthalmology aao.org/training-opportunities. at the University of California, San Francisco, and 2. Narrow your results by in private practice in Los Altos, Calif. Relevant financial disclosures: Carl Zeiss: C; ianTech: C,O; subspecialty and/or region. Mynosys: C,O. 3. Browse the listings. Dr. Hooshmand is an ophthalmology resident 4. Contact the programs that at the Sydney Eye Hospital in Sydney, Australia. interest you. Relevant financial disclosures: None. Dr. Venkatesh is chief medical officer of the Ara- vind Eye Hospital in Pondicherry, India. Relevant Questions? Email [email protected] financial disclosures: None. See disclosure key, page 8. For full disclosures, see this article at aao.org/eyenet.

MORE ONLINE. View videos of the procedures at aao.org/ clinical-video/zepto-capsulotomy- miloop-nuclear-fragmentation-com and aao.org/annual-meeting-video/ precision-pulse-capsulotomy-complex- cases, or view them with these QR codes.

EYENET MAGAZINE • 25 STATE ADVOCACY

Photo: Roger Barone/Wills Eye Hospital

Our Profession Is Under Attack Fight Alongside the Surgical Scope Fund

“ Hippocrates told us, ‘Life is short. Opportunity fleeting, experience perilous, and judgment difficult.’ The hours we have are to be spent wisely.

“To become a retinal surgeon, I devoted long hours to prepare for split- second judgment calls that are of critical benefit to my patients. Long hours help us earn their trust. It’s part of our commitment to protect sight. And it’s why I contribute to the Surgical Scope Fund.”

JULIA A. HALLER, MD Ophthalmologist-in-Chief, Wills Eye Hospital, Philadelphia

Be a Champion for Patient Safety by Supporting the Surgical Scope Fund When high surgical standards are threatened nationwide, the Academy’s Surgical Scope Fund can deliver resources, expertise and winning strategies for protecting patient safety and preserving surgery by surgeons.

Read more of Dr. Haller’s thoughts and make your confidential Surgical Scope Fund contribution at aao.org/ssf. CORNEA CLINICAL UPDATE

Beyond Corneal Transplants for Fuchs: Descemet Stripping Only

lthough endothelial corneal Fuchs dystrophy—but not in pseu- 1 transplants generally work well, dophakic bullous keratopathy (PBK).3 Athey’re certainly not perfect, “I knew immediately this was said Christopher J. Rapuano, MD. As it important because it told me there is technically challenging, “endothelial was some regenerative capacity in the corneal transplantation may require re- remaining endothelium in patients bubbling after a detachment or may fail with Fuchs dystrophy but not in those altogether,” he said. Accessibility of cor- with PBK,” said Dr. Colby, at the Uni- neal tissue can be an issue; complica- versity of Chicago. tions may include fungal infections and She waited for the right patient and steroid-related glaucoma or cataracts in performed her first DSO. “At his one- phakic patients; and transplants don’t month visit, the patient reported, ‘I’m last forever, he added. Dr. Rapuano is at clear,’” she said. “Lo and behold, his Wills Eye in Philadelphia. cornea had cleared. After five years, the “It would be great if a procedure patient is still doing really well,” said TECHNIQUE. Slit lamp shows edge of could get the job done without using Dr. Colby, who has treated about 35 stripped area in a DSO patient. transplanted tissue,” said Dr. Rapuano. patients to date. Surgical removal of the Descemet DSO success rates. Dr. Colby of Pittsburgh Eye Center, recently membrane without subsequent endo- recently reviewed all DSO case series conducted a retrospective case series thelial transplantation—or Descemet published as of 2018. She found an comparing 12 patients who had DSO stripping only (DSO)—may be an overall 82% corneal clearing rate in a with 15 who had a DMEK.4 alternative, at least for some patients total of 77 cases. Among other factors, “We compared the two groups to see with Fuchs dystrophy. patient selection, surgical protocol, if there were any differences in compli or extent of disease likely influenced cations, final visual acuity, and time Spontaneous Clearance outcomes, she said. to functional visual acuity,” she said. Around 2012, Kathryn A. Colby, MD, In reviewing all of the published “The average time to reach a ‘func- PhD, learned of case reports from series, Dr. Colby noted a correlation tional’ vision of 20/40 was 2.2 weeks Steven B. Koenig, MD, and J. Bradley between corneal clearance and size of in the DMEK group and 7.1 weeks in Randleman, MD, showing spontaneous the stripping. There’s a point at which the DSO group (this was statistically corneal clearance after graft detach- there’s not enough peripheral endothe- significant). However, the average final ment and after iatrogenic Descemet lium to repopulate the central cornea, best pinhole visual acuity was 20/25 in membrane stripping during cataract she said. One author also attributed DMEK eyes and 20/30 in DSO eyes and extraction.1,2 Also catching her eye were lack of clearance to an abundant use of was not statistically significant.” other case series of spontaneous clear- steroids after surgery, she said. ance after failed Descemet membrane DSO versus DMEK. Deepinder Best Candidates for DSO endothelial keratoplasty (DMEK) in K. Dhaliwal, MD, at the University DSO will not work for pseudophakic bullous keratopathy, said Dr. Colby. Focal guttae. “A patient has to have BY ANNIE STUART, CONTRIBUTING WRITER, INTERVIEWING KATHRYN A. Fuchs dystrophy with focal guttae COLBY, MD, PHD, DEEPINDER K. DHALIWAL, MD, LAC, AND CHRISTOPHER affecting 4 mm to 6 mm of the central

Kathryn A. Colby, MD, PhD MD, A. Colby, Kathryn J. RAPUANO, MD. cornea, but not involving the peripheral

EYENET MAGAZINE • 27 cornea,” she said. “Someone with guttae Regulatory approval for the trial is in from limbus to limbus will not be a 2A progress. good candidate. You have to be able to remove most of the guttae but still What to Expect After Surgery have an adequate reserve of peripheral Dr. Colby recommends postoperative endothelium.” care similar to that which follows a Dr. Rapuano agreed that patients cataract surgery. This includes topical with mild or moderate, but very antibiotics for about a week after the central, Fuchs dystrophy are the ideal procedure and topical steroids until candidates, especially if they have corneal clearance. cataracts. “The surgeon is doing the Post-op patience required. “Patients cataract anyway and can also do the 2B have to understand that their cornea DSO and see how the patient does,” will be swollen afterward and their said Dr. Rapuano. He noted that he has vision will be worse, not better, until it not yet had what he considered an ideal clears,” said Dr. Colby. This could take candidate, although he’s offered the OUTCOMES. Five years after DSO (2A) anywhere from three weeks to three procedure to several patients. external photograph and (2B) optical months, she said. “The length of recov- One good eye. Dr. Dhaliwal also coherence tomography. ery is not predictable. If you remove considers it important for patients to a larger area, however, the cornea will have one good eye to be considered has worked pretty well, but it does make take longer to clear.” for DSO. “If someone is marginally sense that a smoother edge provides These patients have to be tolerant functional and you make their vision less resistance to endothelial migration.” because the recovery will be a slow worse, that can be problematic,” she No matter how you remove the one, agreed Dr. Dhaliwal. “I always tell said. “Even rapid responders have poor membrane, she said, you need to use patients that their vision will get a lot vision right after surgery.” When she a gentle hand, avoid leaving tags of worse before it gets better. If a patient has a patient with bilateral decreased Descemet membrane, and make the is not prepared for that or not able to vision from Fuchs dystrophy, she does a cornea as smooth as possible. “In some deal with worsened vision in one eye, DMEK because she wants the patient’s unsuccessful cases, you can see scarring DMEK is probably a better option.” vision to recover quickly. in the photos, which means the surgeon Access to care. Although a cornea dug the Sinskey hook into the stroma surgeon does the DSO procedure, said An Evolving Procedure during the stripping.” Dr. Colby, the patient doesn’t need to The DSO technique is in evolution, said Consider ROCK inhibitors. “What’s be followed by the surgeon after the Dr. Rapuano. “No one knows exactly new since about 2016 is the adjuvant cornea has cleared. This may be benefi- how big a circle to take out,” he said. use of a topical rho kinase (ROCK) cial for improving access to care. “Some take more with success, but the inhibitor to facilitate endothelial migra- more you take out, the greater the risk tion,” said Dr. Colby. “Ripasudil is not When DSO Fails of failure.” FDA approved, so we can’t prescribe it. Just because the cornea clears after Even as cornea surgeons are on a But patients can order it online, and we DSO doesn’t mean it will necessarily learning curve, they are taking steps to can observe them using it.” stay clear, said Dr. Dhaliwal. “In our enhance the procedure. Although netarsudil (Rhopressa) study, all the patients did quite well. Create smoother surfaces. Mark is approved in the United States for However, since we published our case Gorovoy, MD, has created special glaucoma, said Dr. Rapuano, ripa- series in 2018, we have already per- forceps and refined the technique to sudil (Glanatec) is theoretically more formed DMEK on one patient in that help maximize DSO results, said Dr. effective. “At the time of the Acade- cohort, and another is showing some Dhaliwal. “We used to score 360 degrees my’s 2018 annual meeting, there were recurrent edema.” and then strip the membrane. Now, about 75 cases that had been published DMEK after DSO. The good news is there’s a belief we should strip in one or presented at various meetings of there doesn’t appear to be any signifi- area and tear it around using forceps. supplementation with topical ripasudil cant risk in doing a DMEK after a failed Then, endothelial cells can migrate after DSO,” said Dr. Colby. “It appears DSO, said Dr. Rapuano. DMEK after over a smoother edge with no stromal to speed the resolution of the corneal DSO is a straightforward procedure disruption.” edema and to potentially increase the with good results, added Dr. Colby.6 Dr. Colby also cited a study by Davies final endothelial cell count.” Don’t delay. That said, it’s important et al., in which 10 of 10 patients cleared Dr. Colby said plans are underway to not wait too long to do a DMEK when the authors used a peeling, rather for a multinational clinical trial in the after DSO. If edema is severe and long- than stripping, technique.5 “Does that United States, Europe, and the United lasting in the front of the cornea— mean peeling is better?” asked Dr. Colby. Kingdom that will assess ripasudil’s whether from Fuchs dystrophy or after

“I don’t know. My stripping technique effectiveness when used after DSO. DSO—it can decrease the success rate PhD MD, A. Colby, Kathryn

28 • MAY 2019 of the DMEK because there is scarring remove all the guttae with 4-mm strip- 1 Koenig SB. Cornea. 2013;32(6):886-888. that is not removed, said Dr. Rapuano. ping, put a ROCK inhibitor on for two 2 Shah RD et al. Ophthalmology. 2012;119(2):256- “When a patient’s cornea stays swol- months, and end up with a cell count of 260. len for a long time, we’re doing them a 1,000 or 1,500, I think we will be able to 3 Dirisamer M et al. Am J Ophthalmol. 2012; great disservice because the cornea may offer it to people earlier in the disease 154(2):290-296. not become totally clear again,” agreed than would typically be done with a 4 Huang MJ et al. Cornea. 2018;37(12):1479-1483. Dr. Dhaliwal. “To optimize outcomes, corneal transplant.” 5 Davies E et al. Cornea. 2018;37(2):137-140. we need to know when to intervene How long lasting? Of course, the 6 Rao R et al. Cornea. 2017;36(7):763-766. surgically with DMEK.” And the oph- $64,000 question is, how long will thalmologist and patient need to be on DSOs last? “We assume the cornea will Dr. Colby is chair of ophthalmology and visual the same page about this, she said. get swollen at some point in the pa- science at the University of Chicago Medicine & tient’s life,” said Dr. Rapuano. “If DSO Biological Sciences, in Chicago. Relevant financial Potential Implications of DSO only delays this by a year, it’s not a big disclosures: None. Dr. Rapuano said he thinks that most help. However, if it delays it by five or Dr. Dhaliwal is director of refractive surgery Fuchs dystrophy patients aren’t can- 10 years, that’s a different story.” and the cornea services, UPMC Eye Center, and didates for DSO given their extensive If the endothelial stem cell niche a professor of ophthalmology at the University disease. However, he noted that some has truly awakened and created new of Pittsburgh School of Medicine, in Pittsburgh. patients getting transplants now may endothelial cells that migrate and cover Relevant financial disclosures: None. have done very well if DSO had been that area, said Dr. Dhaliwal, then DSO Dr. Rapuano is director of the cornea service and performed earlier in the disease course. should last a long time, and it thus codirector of the refractive surgery department at Dr. Colby said she thinks as many as might even be an option for many Wills Eye Hospital and professor of ophthalmolo- half of all Fuchs dystrophy patients may more patients. “But if this is just a gy at Jefferson Medical College, both in Philadel- be candidates for DSO. “We know that migration of existing endothelial cells, phia. Relevant financial disclosures: None. up to 4% of people in the United States I think the jury is still out on how long have an early form of Fuchs, which is it will last. We simply don’t yet fully See the disclosure key, page 8. For full disclosures, a lot of people,” she said. “If we can understand what is happening.” view this article at aao.org/eyenet.

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EYENET MAGAZINE • 29 MEMBERSHIP

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3270.MKT_MBR.AMAd.FP.indd 1 3/28/19 10:04 AM RETINA OPHTHALMIC PEARLS

Diagnosis and Management of Serpiginous Choroiditis

erpiginous choroiditis (SC) is a 1A 1B rare, bilateral, idiopathic inflam- Smatory disorder that results in geographic destruction of the retinal pigment epithelium (RPE), retina, and choriocapillaris. It is a chronic, recurrent, and progressive disease that typically affects patients 30 to 60 years of age. There is a slight male predom- inance, but no racial predilection or 2A 2B consistent genetic factors have been associated with the disease. Histopathologic studies have shown extensive loss of the RPE and destruction of the overlying retina. Diffuse and focal accumulation of lymphocytes has been observed in the choroid. More- over, there is an increased frequency of HLA-B7 in patients with SC; these FUNDUS PHOTOS. Characteristic yellow-gray geographic lesions are visible in the features are indicative of an inflamma- right eye (1A) and left eye (1B). FAF. Hypoautofluorescent (inactive) and hyper- tory process. autofluorescent (active) lesions are present in the right eye (2A) and left eye (2B). The clinical course is characterized by multiple recurrences at intervals of choroiditis: classic and macular. Diagnosis months to years. Areas of reactivation Classic SC. This type comprises 80% The diagnosis of SC is based primar- are often seen adjacent to old scars. Un- of cases and demonstrates the charac- ily on clinical examination, imaging fortunately, patients are often asymp teristic bilateral asymmetric serpiginous findings, and a thorough laboratory tomatic until the fovea is involved, and (snakelike) or geographic yellow-gray evaluation. Imaging modalities that they typically present with painless chorioretinal lesions that typically start are helpful in confirming the diagnosis blurry vision and central or paracentral at the peripapillary region and can include fundus autofluorescence (FAF), scotomas. Other ocular complications extend into the macula (Fig. 1). fluorescein angiography (FA), indo- associated with SC include choroidal Macular SC. This variant involves cyanine green angiography (ICGA), neovascularization (CNV), which the macula and spares the peripapillary optical coherence tomography (OCT), occurs in up to 20% of cases, cystoid region. It may initially be confused and OCT angiography (OCTA). macular edema (CME), retinal vein with geographic atrophy, as seen in FAF (Fig. 2). FAF is a very sensitive, occlusion, retinal vasculitis, and macu- macular degeneration, or with mac- noninvasive modality that is used lar hole.1,2 ular ischemia associated with various to differentiate active from inactive There are two types of serpiginous vasculopathies. lesions, as new lesions often occur at the border of old lesions. Acute active lesions appear hyperautofluorescent, BY AMELIA M. TODD, MD, NILOOFAR PIRI, MD, AND DENIS JUSUFBEGOVIC, whereas old lesions are hypoautofluo-

Denis Jusufbegovic, MD Denis Jusufbegovic, MD. EDITED BY INGRID U. SCOTT, MD, MPH, AND SHARON FEKRAT, MD. rescent. Red/green wavelength ultra-

EYENET MAGAZINE • 31 widefield FAF imaging is considered the best modality 3A 3B 3C 3D to monitor disease activity. FA (Fig. 3). Acute lesions appear hypofluorescent, with irregular and poorly defined borders in early phases of the study. This appearance is likely due to hypoperfu- FA PHASES. Fluorescein angiography, right eye. (3A) Early arterial, (3B) arterial, (3C) arterio- sion of the choriocapillaris venous, and (3D) late phases. (See text for description of findings.) and blocked fluorescence from edematous RPE and outer retina. dal vascular anatomy that can be useful pattern, whereas SLC often demon- In the later phases, hyperfluorescent in assessing SC progression. Chorio- strates a more stippled appearance. borders are seen, representing leakage capillaris flow disruption is an early Both diseases are treated with oral of fluorescein from the surrounding sign of the disease, preceding structural steroids, but antitubercular medications intact choriocapillaris. Inactive lesions involvement of the outer retinal layers. are extremely important in treating are hypofluorescent with sharp borders Prompt treatment at this early stage SLC. Testing for TB with labs and a in early phases of the study and become may allow for resolution without cho- chest x-ray prior to initiating steroids is progressively hyperfluorescent with rioretinal scarring.3 critical, as steroids may worsen SLC if variable levels of staining. used without concomitant antitubercu- ICGA (Fig. 4). Lesions appear Masquerading Conditions lar therapy.2 hypofluorescent on ICGA throughout Before treatment for SC is initiated, an APMPPE and relentless placoid all phases of the study, representing extensive workup is needed to rule out chorioretinitis (RPS). These two clin- disruption in choroidal perfusion. other inflammatory or infectious etiol- ical entities can present a diagnostic Early subclinical lesions may be better ogies that may mimic the disease. The challenge and may mimic SC or one appreciated on ICGA than on fundu- differential diagnosis for SC includes another early in the course of disease. scopic examination or FA, and they other inflammatory processes such APMPPE. Acute APMPPE lesions may appear as hypofluorescent spots as acute posterior multifocal placoid clinically appear similar to active SC or resulting from isolated choriocapillaris pigment epitheliopathy (APMPPE), RPS lesions as deep yellow-gray patches involvement. ICGA may also be useful ampiginous choroiditis, multifocal at the level of the outer retina and inner in differentiating active new lesions, chorioretinitis, and persistent placoid choroid. They are typically multiple, which are hypofluorescent, from CNV, maculopathy; infectious etiologies such discrete, and plaquelike in appearance which appears hyperfluorescent during as tuberculosis (TB), herpesvirus, toxo- and predominantly involve the posteri- the middle to late phases of the study. plasmosis, and syphilis; autoimmune or pole. OCT (Fig. 5). Acute lesions primarily diseases such as sarcoidosis; vascular APMPPE lesions usually resolve on affect the outer retinal layers and cho- diseases that cause retinal ischemia; their own in a few weeks without treat- riocapillaris and appear as increased and degenerative changes, such as ment, with residual mild to moderate reflectivity localized to the outer retina age-related macular degeneration. RPE changes. New lesions can develop and disruption of the photoreceptor Laboratory testing for sarcoidosis, over several subsequent weeks. Recur- bands. OCT of older lesions demon- syphilis, herpes, toxoplasmosis, and TB rent disease is uncommon and usually strates outer retinal atrophy and RPE should be part of the routine workup. appears as new multifocal patches disruption. If testing is negative and all diagnostic not associated with previously healed OCTA. OCTA is a newer, noninvasive tests confirm idiopathic SC, treatment lesions. CNV is very rare in APMPPE. method of imaging retinal and choroi- should be started promptly.1,2 RPS (also known as ampiginous Mycobacterium tuberculosis. This choroiditis). The clinical appearance bacterium can cause serpiginous-like of acute RPS lesions is similar to 4 choroiditis (SLC). It is important to APMPPE. However, RPS results in differentiate SLC from SC, as their recurrent and progressive destruction treatments differ. Patients with SLC of the choroid and retina. Lesions are often present with multifocal lesions usually widespread and may involve involving the periphery rather than both the posterior pole and periphery. peripapillary region. Anterior chamber The clinical course and multifocal cellular reaction and vitritis are also appearance of the RPS lesions distin- more common in SLC compared to guish it from SC, whereas the relentless ICGA. Late-phase ICGA of the right eye SC. FAF may be helpful in distinguish- progression of the disease differentiates shows persistent hypofluorescence of ing the two disease entities, as SC has it from APMPPE.2 Treatment of RPS is

the lesions. a homogeneous hypoautofluorescent similar to that of SC. MD Denis Jusufbegovic,

32 • MAY 2019 Prognosis. Overall 5A prognosis for this disease is Coming in the next poor despite treatment. Final visual acuity is <20/200 in ® about 25% of treated cases.7

Key Points Serpiginous choroiditis is Feature 5B a rare bilateral, idiopathic Dry Eye Treatment inflammatory disorder that Experts weigh in on causes geographic destruc- management of five tion of the retina and cho- cases, from exposure roid in healthy middle-aged keratopathy to neuro- individuals. This chronic, pathic pain, and post- recurrent, progressive dis- LASIK dry eye. See what OCT. Imaging of the right eye (5A) and left eye ease has a poor visual prog- they recommend. (5B) shows complete RPE and outer retinal atro- nosis if the fovea is involved. phy with subfoveal involvement in the left eye. Symptoms include blurred vision and central and para- Clinical Update Management central scotomas. A thorough workup is Cataract Aqueous mis Initial therapy for SC includes systemic necessary prior to initiating treatment direction syndrome—what corticosteroids to treat active lesions as to exclude other inflammatory or in- it is and how to manage it. well as concurrent immunosuppressive fectious etiologies that may mimic SC. Glaucoma Introducing a therapy to prevent recurrences. Oral Treatment includes corticosteroids and novel surgical technique for corticosteroids are the mainstay of immunosuppressive therapy. Patients angle-closure glaucoma. treatment for acute disease, but some should be monitored closely for disease studies have also shown that immediate progression and complications, includ- Pearls intravitreal steroids may be beneficial ing CNV and CME. Pneumatic Retinopexy in patients with foveal lesions.2 Knowing when to use this Triple therapy, including predni- 1 Mirza RM, Lee MJ. White spot syndromes and procedure is key. A guide sone, cyclosporine, and azathioprine, related diseases. In: Schachat AP et al., eds. Ryan’s to indications, contraindica- has been found effective in controlling Retina. Vol 1. 6th ed. Philadelphia: Elsevier; tion, and more. SC.4 Monotherapy with mycophenolate 2017:1516-1561. mofetil, azathioprine, or cyclophos- 2 Khanamiri N, Rao NA. Surv Ophthalmol. 2013; phamide has shown some success, as 58(3):203-232. Practice Perfect described in several case reports.2 3 Pakzad-Vaezi K et al. Ophthalmol Retina. 2018; Why Yoga? Biologic therapy with a tumor 2(7):712-719. Eye M.D.s are at risk for necrosis factor α (TNF-α) inhibitor 4 Hooper PL, Kaplan HJ. Ophthalmology. 1991; specific injuries, but such as adalimumab has been found 98(6):944-951. these yoga moves can help. effective in patients who progressed 5 Chinchurreta Capote A et al. Ocul Immunol despite therapy with other immuno- Inflamm. 2014;22(5):405-408. Blink suppressants.5 Now, adalimumab is 6 Ebrahimiadib N et al. Ocul Immunol Inflamm. Take a guess at the next also frequently used as a first-line agent 2018;26(2):228-238. issue’s mystery image. for SC. It is imperative to rule out TB 7 Christmas NJ et al. Retina. 2002;22(5):550-556. before starting a TNF-α agent. A recent study found that treatment Dr. Todd is a second-year ophthalmology resident, For Your Convenience with chlorambucil over six to nine and Dr. Jusufbegovic is an assistant professor of These stories also will be months was effective in preventing clinical ophthalmology; both are at the Eugene available online at recurrence and maintaining vision and Marilyn Glick Eye Institute, Indiana University aao.org/eyenet. in 17 patients with SC. Of these, 12 School of Medicine, Indianapolis. Dr. Piri is a third- patients had an average of 45 months of year ophthalmology resident at the Department FOR ADVERTISING INFORMATION drug-free remission, and 14 maintained of Ophthalmology and Visual Sciences, University Mark Mrvica or Kelly Miller visual acuity within two Snellen lines.6 of Louisville, Kentucky. Financial disclosures: None. M. J. Mrvica Associates Inc. Complications of SC should also be 856-768-9360 addressed promptly (e.g., with anti- MORE ONLINE. For a case [email protected] VEGF agents for CNV or intravitreal report and additional images,

Denis Jusufbegovic, MD Denis Jusufbegovic, corticosteroids for CME). see this article at aao.org/eyenet.

EYENET MAGAZINE • 33 CODING & REIMBURSEMENT

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f.3279.MKT_OCS.AdUpdate.FP.indd 1 2/28/19 10:23 AM WHAT’S YOUR DIAGNOSIS? MORNING ROUNDS

The Case of the Blind Bibliophile

ee Berry* was a distraught 64- We Get a Look 1A 1B year-old bibliophile who could Ms. Berry told us that her Lno longer read. Six months prior central vision seemed worse to seeing us, she had experienced a rapid than her peripheral vision, decline in vision, lasting one month, in and she reported no associ- both eyes. Over the next five months, a ated pain or photopsias. Her continuing, more gradual deterioration medical history was notable made her daily activities, such as read- for hypertension, coronary ing and grocery shopping, increasingly artery disease, dyslipidemia, difficult and, ultimately, impossible. depression, and anxiety. FUNDUS. Color fundus photos demonstrating mild Initial testing. Perplexed by Ms. Surgical history included temporal optic nerve pallor bilaterally in the right Berry’s normal eye exam, several eye a cholecystectomy and a eye (1A) and left eye (1B). care providers coordinated a thorough remote hysterectomy for diagnostic workup. Her medical record benign fibroids. Her medications in- and intraocular pressures were normal indicated normal or unremarkable re- cluded buproprion, fluoxetine, clopido- bilaterally. sults for the following imaging studies: grel, spironolactone, atorvastatin, and Her slit-lamp exam was notable magnetic resonance imaging (MRI) of metoprolol. She admitted to drinking for a posterior chamber IOL in good the brain and orbits with and without two vodka cocktails and smoking half location in the right eye, and a 1 to 2+ contrast, optical coherence tomography of a pack of cigarettes daily for the past nuclear sclerotic cataract in the left eye. (OCT) of the macula and peripapillary 40 years. She also reported an affinity The funduscopic exam was normal retinal nerve fiber layer (RNFL), and for junk food but denied any restrictive in both eyes, apart from mild bilateral fluorescein angiography. dietary practices or eating disorders. temporal optic nerve pallor (Fig. 1). Concern for possible occult cancer Her family history was significant for Automated static perimetry (size V, and cancer-associated retinopathy a deceased maternal uncle who had 30-2) demonstrated similar findings (CAR) prompted computed tomogra- ill-defined vision problems. in both eyes: global depression on the phy (CT) scans of the chest, abdomen, Testing. On examination, her total deviation plot and cecocentral and pelvis. The latter showed only a few best-corrected visual acuity was count- scotomas on the pattern deviation plots borderline enlarged mediastinal lymph ing fingers at 3 feet in both eyes. Her (Fig. 2). nodes. pupils were isocoric, with sluggish reac- Spectral-domain OCT (SD-OCT) During the search for an answer, Ms. tivity to light and no afferent pupillary of the peripapillary RNFL revealed Berry underwent bilateral blepharoplas- defect. The remainder of the cranial normal thickness in both eyes (Fig. 3). ty for potentially vision-obstructing nerve exam was unremarkable. She Macular sections were grossly normal dermatochalasis and cataract surgery failed to recognize any of the Ishihara in the right eye, and a subtle epiretinal in the right eye. Neither procedure color plates in either eye, including membrane was seen in the left eye. improved her vision. She was referred the control plate. Her ocular motility, Fundus autofluorescence was unre- to us for a neuro-ophthalmologist’s peripheral visual fields to confrontation markable. opinion. (finger counting in each quadrant), A full-field electroretinogram was essentially normal in both eyes. There was a normal cone response in both BY COLTEN WENDEL, MD, MICHAEL S. LEE, MD, AND COLLIN M. MCCLELLAND, eyes, which was not consistent with

Collin M. McClelland, MD M. McClelland, MD Collin MD. EDITED BY STEVEN J. GEDDE, MD. CAR.

EYENET MAGAZINE • 35 Differential Diagnosis In the context of Ms. Berry’s bilateral 2 3 cecocentral visual field defects and normal macular exam, our differential diagnosis included both optic neuropathies and occult retinopathies. Retinal etiologies to consider included CAR, autoimmune retinopathy, or one of the enlarged blind spot syndromes (e.g., acute zonal occult outer TESTS. (2) Low vision protocol 30-2 automated static perimetry demonstrating retinopathy, multiple evanescent white global depression in the right eye (top left) and left eye (bottom left) on total dot syndrome, idiopathic big blind spot deviation plot and a cecocentral scotoma in the right eye (top right) and left eye syndrome, etc.). (bottom right) on pattern deviation plot. (3) SD-OCT of the optic nerve showing Narrowing the possibilities. While normal RNFL bilaterally as compared to age-matched controls. Ms. Berry had risk factors for occult malignancy such as her age, smoking, and drinking, she denied photopsias are marked by bilateral, often sym- tation, males are up to nine times more typical of CAR and had a negative body metric, cecocentral visual field loss, likely to manifest with vision loss, while CT. Autoimmune retinopathy and dyschromatopsia, and acuity loss. De- females tend to remain asymptomatic occult CAR were essentially excluded pending on the cause of mitochondrial carriers.2 with a normal ERG. She lacked typical failure, the rate of vision loss varies Mutations. Three primary mtDNA clinical features of the big blind spot from rapid (Leber hereditary optic point mutations constitute approxi syndromes, including outer retinal dis- neuropathy [LHON]) to subacute mately 90% of LHON cases: 11778G> ruption on SD-OCT, extensive enlarged (ethambutol toxicity, thiamine defi- A, 14484T>C, and 3460G>A. The blind spots on automated perimetry, ciency) to chronic (most nutritional 11778G>A point mutation is the most photopsias, and acute-onset nonpro- optic neuropathies). common in North America and the gressive vision loss. least likely to show late spontaneous Organic vision loss. The presence Diagnosis visual recovery compared with the of mild temporal optic nerve pallor, Although the SD-OCT showed normal other LHON mutations. cecocentral scotomas, and sluggish pu- peripapillary RNFL, which could point Pathophysiology. Retinal ganglion pils made it clear that there was organic away from a diagnosis of optic neurop- cells (RGCs) within the papillomacular vision loss and indicated the possibility athy, we looked at the segmentation bundle are selectively affected early in of bilateral optic neuropathies. Bilat- of retinal layers, which allowed quanti- LHON, accounting for the disease’s eral optic neuropathy from chiasmal fication of macular ganglion cell layer characteristic visual acuity loss, dys compression (e.g., meningiomas, (GCL) thickness. Compared with the chromatopsia, and dense central or pituitary adenomas, craniopharyngio- normative data published in the litera- cecocentral scotoma. While the under mas) is relatively common but typically ture among similarly aged Caucasians lying pathophysiology remains incom demonstrates a bitemporal pattern of (Fig. 4A), Ms. Berry’s GCL was diffusely pletely defined, it is thought that the visual field loss and is visible on a good and severely thinned bilaterally1 (Fig. small caliber of papillomacular bundle quality MRI. Similarly, optic neuritis 4B), which pointed us back to an occult RGC axons makes them more vulner- can be bilateral and cause any pattern optic neuropathy diagnosis. The prom- able to reactive oxygen species and of visual field loss, but it is usually inent discordance between GCL thin- oxidative phosphorylation energy painful, occurs in patients younger than ning and normal RNFL in the presence impairment related to mitochondrial 50, is rarely progressive for six months, of rapid-onset central vision loss is a dysfunction.3 and should be visible on MRI with characteristic feature of LHON. Given In addition, individual patient fac- dedicated orbital sequences. this information, we ordered mito- tors, including poor nutrition, smok- Further options. Nonarteritic anteri- chondrial point mutation testing for ing, and excessive alcohol consump- or ischemic optic neuropathy (NAION) Ms. Berry, which revealed a pathogenic tion, may contribute to mitochondrial is characterized by acute painless vision 11778G>A homoplasmic mutation. damage and visual loss. loss with associated optic disc edema at Signs and symptoms. At the time the time of vision loss, nerve fiber layer Discussion of acute loss of vision, the optic nerves type visual field defects, and marked LHON is a prototypical inherited mito- usually appear normal but may demon- atrophy within several months of vision chondrial optic neuropathy, character- strate mild peripapillary telangiecta- loss. Vision loss progression beyond istically presenting with sequential or sias and pseudoedema, which slowly the first month is highly atypical in simultaneous bilateral painless central changes to pallor. Similarly, over a NAION. vision loss in young men. Among those variable period of months, OCT shows

Mitochondrial optic neuropathies who harbor a pathogenic LHON mu- a transition from either normal or M. McClelland, MD Collin

36 • MAY 2019 4A 4B include bilateral (sequential or simultaneous), progressive, and painless central visual loss with subtle or no optic nerve findings early. Although LHON is most commonly seen in males aged 10 to 30 years, it can also occur in women and can present at later stages of life. In individuals with unexplained bilateral vision loss of less than three to six SEGMENTATION DATA. (4A) Diagram displaying the first percentile normative val- months in duration, an OCT demon- ues of GCL thickness per macular region in Caucasians aged 51 to 68 years based strating normal peripapillary RNFL upon published data.1 (4B) The patient’s right eye segmentation data from SD-OCT may not be sufficient to exclude optic of the macula displaying the volume and average thickness of the GCL correspond- neuropathy from LHON. A macular ing to each macular region. segmentation analysis demonstrating thinning of the GCL out of proportion mildly thickened RNFL to thin RNFL. Ms. Berry enrolled in a multicenter to RNFL thinning can facilitate early A longitudinal study using high reso- randomized controlled trial of ideben- diagnosis. Patients can then be educat- lution OCT imaging of patients with one treatment for LHON. ed to optimize their nutritional status LHON revealed that thinning of the In LHON patients, it is important and to minimize behaviors that are tox- temporal peripapillary nerve fiber layer to identify and treat any concomitant ic to mitochondria; beyond that, they typically occurs within three months medical conditions or habits that could may consider enrolling in randomized of the onset of visual loss.4 Pathologi- contribute synergistically to impairment controlled trials of promising exper- cal thinning within the macular RGC of mitochondrial function. Among imental therapies being conducted at layer occurs within weeks of onset of these are poor nutrition and vitamin large academic centers. vision loss and can even be seen as an deficiencies (vitamin B12, thiamine, *Patient name is fictitious. early sign of impending vision loss folate, copper), smoking, and alcohol during the presymptomatic phase in abuse. These factors may be associated 1 Nieves-Moreno M et al. PLoS One. 2017;12(7): patients with LHON mutations. Ms. with expression of vision loss among e0180450. Berry’s normal-thickness RNFL after six carriers of Leber mutations and/or lead 2 Meyerson C et al. Clin Ophthalmol. 2015;9: months of visual loss was uncharacter- to further progression of vision loss 1165-1176. istic for LHON and made the diagnosis after onset of LHON if not addressed. 3 Sadun AA et al. Clin Exp Ophthalmol. 2013; particularly challenging. Ms. Berry’s vitamin testing was normal. 41(7):702-712. To recap, Ms. Berry’s bilateral, severe She was advised to stop smoking and 4 Hedges TR et al. Neuroophthalmology. 2016; central vision loss with sparing of the limit alcohol consumption. 40(3):107-112. peripheral fields, mild temporal optic nerve head pallor disproportionate Genetic Counseling Dr. Wendel is a fourth-year resident at the De- to her degree of vision loss, lack of a Ms. Berry was referred to a genetic partment of Ophthalmology and Visual Sciences structural cause for optic neuropathy counselor for a detailed family pedi- at the University of British Columbia in Vancou- on MRI, and prominent GCL thinning gree and discussion of risks of vision ver. Dr. Lee is professor and Dr. McClelland is as- on OCT segmentation of the macula in loss in family members. She had two sociate professor of neuro-ophthalmology; both the setting of normal RNFL thickness daughters who were obligate carriers are with the Department of Ophthalmology and cumulatively implicated LHON. Thus, of her homoplasmic LHON mutation, Visual Neurosciences at the University of Min- LHON should be considered in the ap- and several of her male grandchildren nesota in Minneapolis. Financial disclosures—Dr. propriate clinical context, even among were carriers. Because they would be Lee: EvolveMD: L; NEI: S; Quark: S; Springer: P; patients who do not fit the typical at greatest risk for expression of vision UpToDate: P; Vindico: L. Dr. McClelland and Dr. LHON demographic. loss, all carriers were advised to avoid Wendel: None. malnutrition, smoking, and heavy al- See the disclosure key, page 8. Treatment cohol use for life. The ill-defined vision There is currently no evidence-based, loss Ms. Berry described in her mater- effective treatment for LHON. Idebe- nal uncle might have been attributable Write a Morning Rounds none (a ubiquinone [coenzyme Q10] to LHON. Most patients with LHON Article analog) holds promise for patients with (approximately 60%) are aware of a Have you solved a medical early LHON but is not approved by the family history of vision loss compatible mystery? If so, share your intrigu- FDA. However, several clinical trials with the disease. ing case report with your col- are underway to evaluate the efficacy leagues! Find more information of idebenone, as well as gene therapies, Conclusion at aao.org/eyenet/write-for-us.

Collin M. McClelland, MD M. McClelland, MD Collin for LHON (see www.clinicaltrials.gov). Clinical features suggestive of LHON

EYENET MAGAZINE • 37 38 • MAY 2019 Drug Delivery for the Posterior Segment

Born of necessity and scientific advance, new drug delivery devices for treatment of retinal disease and uveitis are now emerging.

By Lori Baker-Schena, MBA, EdD, Contributing Writer

DVANCES IN POSTERIOR SEGMENT DRUG DELIVERY SYSTEMS ARE occurring at breakneck speed—and are a “welcome and timely addition to our Aarmamentarium,” said Dilraj S. Grewal, MD, a vitreoretinal and uveitis specialist. “The number of patients we are treating has increased exponentially, and often we are seeing them frequently for regular intravitreal injections,” said Dr. Grewal, at Duke Univer- sity in Durham, North Carolina. “We need to find ways to reduce the treatment burden on the patients, of course, as well as on the providers because it takes an entire army to get these injections to the patients every month.” Dr. Grewal sees great promise in the latest developments in drug delivery approaches that are designed to help retina and uveitis patients improve and maintain vision over longer time frames than are provided by currently available treatments. Interestingly, the spate of next-generation devices using sustained-release technology and minimally invasive techniques has its roots in a decades-old history of innovation (see “Legacy of Innovation,” page 41). As the field advances,EyeNet asked its editorial board members to indicate which devices —either brand-new to the market or still in trials—they consider the most intriguing or important in terms of potential to change patient care. Then Emmett T. Cunningham, MD, PhD, MPH, founder of the Ophthalmic Innovation Summit, helped refine the list. For each device, an ophthalmologist close to the product (see financial disclosures, page 44) provided information and opinions. Invariably those who consult or serve as an investi- gator for emerging products are also the most qualified to knowledgeably discuss them. For more about the ins and outs of reporting on early-stage drugs, devices, and techniques, see

EYENET MAGAZINE • 39 Yutiq Manufacturer: EyePoint Pharmaceuticals Status: FDA approved on Oct. 12, 2018; commercially launched on Feb. 4, 2019 Interviewing Quan Dong Nguyen, MD, MSc

How does this technology work? Approved for the treatment of chronic noninfectious posterior segment uveitis, Yutiq is a nonbioerodible intravitreal microinsert containing 0.18 mg fluocinolone acetonide. It uses the company’s proprietary Durasert technology to release the How has the device affected patient drug consistently over 36 months. quality of life? Yutiq is supplied in a sterile single-dose In selected patients—whether the disease man- preloaded applicator that can be administered ifests solely in the eye or in association with through a 25-gauge needle in the physician’s systemic diseases—it is not advised to employ sys- office. temic treatment, with its potentially debilitating side effects, when local therapy may be possible to What are the benefits of this device? control the inflammation and preserve the vision. Yutiq offers convenience because it can be injected Yutiq has shown that it can help patients achieve with a small-gauge needle as an office procedure. and maintain inflammation control, thus poten- Also, Yutiq is injected into the vitreous, not an- tially decreasing disease recurrences and prevent- chored in a particular location, so it may reduce ing cumulative ocular damage that can lead to the incidence of cataract compared with static suboptimal visual function. placement. According to the company, you can use J-code J7313 to bill for 18 units. Xipere Manufacturer: Clearside Biomedical What are the research findings? Status: Phase 3 trials complete; NDA submitted In a phase 3, double-masked, randomized trial, to FDA on Dec. 19, 2018 87 eyes of patients with chronic noninfectious Interviewing Rahul N. Khurana, MD posterior segment uveitis were treated with Yutiq and 42 eyes received sham injections.1 At 24 How does this technology work? months of the three-year trial, the recurrence Xipere (formerly suprachoroidal CLS-TA) is a rate in Yutiq eyes was 59.8% versus 97.6% with proprietary suspension of triamcinolone aceton- the control eyes. Macular edema was resolved in ide for treatment of macular edema associated 84.1% of Yutiq-treated eyes and 57.1% of control with uveitis. It is formulated for injection in eyes that had edema recorded at baseline. Drops the suprachoroidal space using a microneedle to lower intraocular pressure (IOP) were used in measuring 1,000 µm in length. Once injected, the 41.4% of Yutiq treated eyes and 33.3% of control corticosteroid rapidly disperses to the choroid eyes. Cataracts were extracted from 64.3% of Yutiq and retina, where it is designed to remain for an patients with phakic eyes and 14.3% of control extended amount of time. The injection can be patients with phakic eyes. performed in the clinic.

What are the drawbacks to this device? What are the benefits of this device? Before inserting this device into the vitreous of Not surprisingly, ophthalmologists traditionally potential patients, physicians must thoroughly have tended to associate “suprachoroidal space” evaluate the uveitis to rule out any infectious with “hemorrhage,” assuming that delivering ther- causes. Yutiq is indicated for noninfectious uveitis, apeutics to that area would result in complications and if a case is of infectious etiology, the steroid with bleeding, and that the high choroidal blood insert could activate the pathogen. Additionally, flow would wash away the drug. Yet I was excited physicians need to discuss with the patients the about the possibility that we could deliver drugs to potential risk of cataract worsening and IOP the choroid and retina while minimizing exposure elevation. to the anterior segment—this could be a great

40 • MAY 2019 benefit to patients in minimizing complications 157 µm at week 24 compared with a 19-µm mean from steroids. And the research has demonstrated reduction in the control patients. PEACHTREE that the incidence of elevated IOP is low com- showed resolution of uveitic inflammation, with pared with other local injections of steroids. 68% of study patients having resolution of vitreous haze versus 23% in the control arm. What are the research findings? No serious adverse events were reported. The phase 3 PEACHTREE trial randomized 96 Elevated IOP included high pressure, ocular patients to receive two 4.0 doses of suprachoroi- hypertension, and glaucoma. All told, 9.4% had dal CLS-TA 12 weeks apart, and 64 patients as elevated IOP of greater than 10 mm Hg; 10% were controls to receive a sham procedure at the same prescribed IOP-lowering drops. 12-week interval.2 Results showed that 47% of the CLS-TA treated patients gained at least 15 letters What are the drawbacks to this device? in best-corrected With any new technology, there will be a learning visual acuity from curve for mastering the technique; it will take time baseline at week for retina specialists to get comfortable accessing 24, compared the suprachoroidal space. But we are accustomed with 16% of to doing injections in the vitreous already, and it’s control patients. a relatively small step to learn to inject into the Additionally, the suprachoroidal space. treated patients In addition, 12% of study patients complained experienced a of eye pain during the procedure compared with mean reduction 4.7% of controls, and the pain resolved after the from baseline of procedure.

A Legacy of Innovation

Today’s innovations are part chronic noninfectious uveitis treatment of noninfectious of a pioneering legacy in affecting the posterior seg- uveitis affecting the posterior research for vitreoretinal ment. Its microdrug reservoir segment of the eye in 2010 diseases. Dr. Grewal points to contains 0.59 mg fluocino- and diabetic macular edema Vitrasert (Chiron, later Bausch lone acetonide and delivers in 2014.* + Lomb), the first sustained- sustained levels of the drug • Iluvien (Alimera). The FDA release posterior segment for approximately 30 months. approved this nonbioerodible, drug delivery system that “This is a great product in sustained-release intravitreal laid some of the foundation terms of controlling inflamma- implant on Sept. 26, 2014, for today’s breakthroughs. tion but requires surgery for for the treatment of diabetic Approved by the FDA in March placement, and its side effects macular edema. It delivers 36 1996, Vitrasert consists of a are increased incidence of cat- months of continuous low- 4.5 mg pellet of ganciclovir aract and IOP elevation, which dose corticosteroid dosing coated with a biocompatible may also require concurrent or with a single injection. polymer and is designed to additional surgery for control,” “We continue to see good deliver the drug over five to Dr. Grewal said. safety data on the long-term eight months. It was indicat- • Ozurdex (Allergan). This tolerance of these sustained- ed for the local treatment of biodegradable sustained- release drug delivery systems cytomegalovirus retinitis in pa- release intravitreal corticoste- as well as their effectiveness,” tients with acquired immuno- roid implant containing 0.7 mg said Dr. Grewal. deficiency syndrome (AIDS). dexamethasone, designed to Other breakthroughs that last approximately six months, *On Dec. 28, 2018, Allergan volun- followed included: was FDA approved for the tarily recalled 22 lots of Ozurdex, • Retisert (Bausch + Lomb). treatment of macular edema noting that a silicone particle of The FDA approved this intra following retinal vein occlu- approximately 300 µm in diameter vitreal implant on April 8, sion on June 17, 2009, said Dr. may detach from the needle sleeve 2005, for the treatment of Grewal. It was approved for during administration.

EYENET MAGAZINE • 41 How has the device affected patient quality of life? Xipere represents an approach that is viable and extremely efficacious. Data from the phase 3 trial show that 1 in 2 patients had significant vision gain with resolution of macular edema, and 2 of 3 patients had resolution of their intraocular inflammation.

Port Delivery System tion, vision outcomes were comparable to those Manufacturer: Roche/Genentech achieved with monthly ranibizumab injections. Status: Phase 3 trial began in September 2018 Interviewing Carl C. Awh, MD What are the drawbacks to this device? A surgical procedure in the OR is necessary to How does this technology work? implant the PDS and this must be considered The Port Delivery System with ranibizumab when comparing the PDS to standard intravitreal (PDS) consists of a permanent intraocular injections. In the LADDER trial, the optimized implant filled with a specialized formulation of surgical and refill procedures were generally well ranibizumab. The device, which is slightly longer tolerated. In the PDS arms, the rate of postop- than a grain of rice, is surgically implanted at the erative vitreous hemorrhage with the optimized pars plana and covered by conjunctiva and Tenon surgery procedure was 4.3%. The rate of endoph- capsule. It can be refilled in the office using a thalmitis in the primary analysis population was customized needle. The PDS provides continuous 1.6%. We will learn more in the phase 3 trial. As delivery of ranibizumab into the vitreous. with all surgical procedures, there will be continu- al refinement as surgeons gain experience. What are the benefits of this device? The PDS may reduce the treatment burden on How has the device affected patient patients, caregivers, and physicians. Real-world quality of life? analyses consistently demonstrate that [because of In the LADDER trial, patients with the PDS were treatment burden] many patients with neovascular evaluated monthly, so there was no reduction in AMD (nAMD) receive fewer than the optimal office visits. However, if the phase 3 trial shows number of intravitreal injections over time, with similar outcomes and leads to commercial avail- outcomes inferior to those demonstrated in pivotal ability, there could be significant improvements trials.3 in outcomes for patients who might otherwise Continuous delivery of ranibizumab into the struggle to get the optimal number of intravitreal vitreous with the PDS offers an expected interval injections. between in-office refills that is significantly longer than the current monthly or bimonthly intravitreal anti-VEGF injections, and it has the potential GB-102 for Wet AMD for equivalent outcomes. Manufacturer: Graybug Vision Status: Phase 1/2a study initial data analysis What are the research findings? reported January 2019; phase 2b study enroll- The phase 2 LADDER (Long Acting DElivery ment expected to begin in 2019 of Ranibizumab) trial compared the PDS to Interviewing Pravin U. Dugel, MD monthly ranibizumab injections in patients with nAMD and a history of favorable response to How does this technology work? prior anti-VEGF treatment.4 The trial enrolled GB-102, for the treatment of wet AMD, encapsu- 243 patients and evaluated three different doses of lates sunitinib malate within bioabsorbable micro- ranibizumab in the PDS. Outcomes were favor- particles. After intravitreal injection (IVT), these able in all groups, but of particular note were the particles aggregate to form a depot in the inferior outcomes in the highest dose group using 100 mg/ vitreous. This depot elutes the drug such that mL. Most patients in this group (80%) went at IVT may be necessary only twice a year. Sunitinib least six months without requiring a refill, with a blocks cell receptors associated with angiogenesis, median time to first refill of 15 months. In addi- proliferation, vascular permeability, and fibrosis.

42 • MAY 2019 What are the benefits of this device? of injections necessary to positively impact the GB-102 will allow us to provide a more sustain- patient’s quality of life. able treatment strategy. In contrast to monthly injections, GB-102 delivers the drug on a constant rather than pulsatile basis. Also, because it is a Dexamethasone Intravitreal tyrosine kinase inhibitor delivery device, it has Implant (AR-1105) With possibilities for wider applications, such as treat- PRINT Technology ment of diabetic macular edema and retinal vein Manufacturer: Aerie Pharmaceuticals occlusion. Status: AR-1105 phase 2 trial began in spring 2019; AR-13503 (Rho kinase/protein kinase C What are the research findings? inhibitor) phase 2 trial to be initiated Q2 2019 In the phase 1/2 ADAGIO study, GB-102 demon- Interviewing Theresa G.H. Heah, MD, MBA strated safety and efficacy, with the duration of effect reaching six to eight months from a single How does this technology work? IVT injection.5 The study involved 32 patients AR-1105 is a bioerodible implant for treatment of with wet AMD who were evenly divided into four patients with macular edema due to retinal vein dosing groups: 0.25 mg, 0.5 mg, 1 mg, and 2 mg. occlusion or diabetic macular edema. Delivered GB-102 was well-tolerated with no dose-limiting through an intravitreal injection using a 25-gauge toxicities, drug-related serious adverse events, or needle, the im- inflammation, and 88% and 68% of patients were plant is intended maintained on a single dose of GB-102 at three to release dexa- and six months, respectively. methasone over a six-month What are the drawbacks to this device? period. It uses In the clinical trial, at the highest dose, some PRINT (particle microparticle dispersion caused a slight decrease replication in in visual acuity. A new manufacturing process nonwetting tem- was developed that eliminated the microparticle plates) technology dispersion, and this newer version of the drug in which a mold will be used for phase 2b clinical studies. is created that contains precisely shaped and sized drug particles How has the device affected patient from the nanometer to millimeter range. This quality of life? technology allows for drug delivery directly to the Current treatment alternatives for wet AMD back of the eye and control of the elution rate. illustrate the great divide between clinical studies and real life. Whereas clinical studies are done What are the benefits of this device? in a pristine fashion, the reality is that patients The potential benefits include six-month duration have a difficult time handling the monthly IVT of sustained efficacy, improved administration injection requirements. Taking off work, finding due to a smaller needle size, and possibly a better a ride, depending on a caregiver—this is a huge safety profile due to lower peak drug levels. treatment burden on the patient and is not re- The versatility of the PRINT technology also flected in clinical trials. I see this new technology allows us to explore novel drug pathways in retinal closing the gap and reducing the number disease. For example, in the first quarter of 2019 the company filed an investigational new drug (IND) application with the FDA for its second retinal product—a bioerodible implant containing the Rho kinase/protein kinase C inhibitor AR-13503 to treat wet AMD and diabetic macular edema via a 27-gauge needle with an intended release over a four- to six-month period.

What are the research findings? A study was conducted focusing on the reproducibility and uniformity of PRINT manufacturing using dexamethasone intravitreal implants.6 © Peter Bollinger © Peter

EYENET MAGAZINE • 43 Results showed that PRINT could be used to 1 Nguyen QD. 24-month evaluation of fluocinolone acetonide manufacture fully biodegradable dexamethasone intravitreal insert treatment for noninfectious posterior uveitis. intraocular implants with uniform size, shape, and Presented at Retina Subspecialty Day 2018, Oct. 26, 2018; dosages—with high reproducibility. Chicago. 2 Khurana RN. Suprachoroidal delivery of CLS-TA for uveitic What are the drawbacks to this device? macular edema: Results of the phase 3 PEACHTREE trial. Pre- One challenge: ensuring the drug molecules can sented at Uveitis Subspecialty Day 2018, Oct. 27, 2018; Chicago. be kept in an efficacious concentration in the 3 Ciulla TA et al. Ophthalmol Retin. 2018;2(12):1179-1187. implant. 4 Awh C. LADDER trial of the port delivery system for ranibizumab: Preliminary study results. Presented at the Annual How has the device affected patient Meeting of the American Society of Retina Specialists, July 25, quality of life? 2018; Vancouver, British Columbia, Canada. We believe that AR-1105 and AR-13503 will poten- 5 Boyer DS. New developments in drug therapy for retinal tially provide a longer duration of efficacy with disorders. Presented at the Hawaiian Eye & Retina Annual reduced number of injections, positively impact- Meeting, Jan. 21, 2019; Kona, Hawaii. ing patients’ quality of life. 6 Sandahl M et al. Invest Ophthalmol Vis Sci. 2018;59(9):5671.

Meet the Experts Carl C. Awh, Graybug Vision: C; Irenix: C,O; N.J. Financial disclosures: MD Vitreo Kodiak Sciences: C; Lutronic: Aerie: E,O. retinal surgeon C; Lux BioScience: C; Macu Rahul N. and president of sight: C; NeoVista: C; Neuro- Khurana, MD Tennessee Retina tech: C; Novartis: C; Oculis SA: Vitreoretinal sur- in Nashville, Tenn. Financial C; Omeros: C; Ophthotech: geon and part- disclosures: Allergan: C; Apellis C,O; Opthea: C; Optovue: C; ner at Northern Pharmaceuticals: S; ArcticDx: ORA: C; Orbis: C; PanOptica: California Retina Vitreous C,O,P; Bausch + Lomb: S,C; C,O; Pentavision: C; pSivida: C; Associates in Mountain View, Genentech: S,C; Hoffman- QLT C; Regeneron: C; Roche Calif., and a clinical associate LaRoche: S; Katalyst Surgical: Diagnostics: C; Santen: C; professor of ophthalmology C,O,P; Merck: S; Ophthotech: S; SciFluor Life Sciences: C; Shire at the University of California, PanOptica: S; Volk: C. Human Genetics: C; Spark: C; San Francisco Medical Center. Pravin U. Dugel, Stealth Biotherapeutics: C; Financial disclosures: Alkahest: MD Vitreo ThromboGenics: C; Topcon: C; C; Allergan: C,S; Clearside retinal surgeon TrueVision: C; Zeiss: C. Biomedical: C,S; Genentech: and managing Dilraj S. Grewal, C; Regeneron: C; Roche: S; partner of Retinal MD Vitreoretinal Santen: S. Consultants of Arizona in and uveitis spe- Quan Dong Phoenix. He is a clinical profes- cialist, and asso Nguyen, MD, sor of the Roski Eye Institute ciate professor M.Sc. Uveitis at the Keck School of Medicine of ophthalmology at the specialist and at the University of Southern Duke University School of vitreoretinal California. Financial disclo- Medicine in Durham, N.C. surgeon and professor of sures: Acucela: C; Aerie: C; Financial disclosures: Alimera: ophthalmology at the Byers Aerpio: C,O; Alcon: C; Alimera: C; Allergan: C; Clearside: C. Eye Institute at the Stanford C,O; Allergan: C; Amgen: C; Theresa G.H. University School of Medicine AMO: C; Annidis: C,O; Arctic- Heah, MD, MBA in Palo Alto, Calif. Financial Dx: C,O; Avalanche: C; Baus- Ophthalmologist disclosures: AbbVie: C; Bayer ch + Lomb: C; Beyeonics: C; and vice presi- Healthcare: C; EyePoint: C; Boehringer Ingelheim: C; CDR- dent of Clinical Genentech: C; Gilead: C; Life: C; Chengdu Kanghong: C; Research, Medical and Profes- Regeneron: C; Santen: C. Clearside: C,O; Digisight: C,O; sional Affairs, Aerie Pharma- Dose Medical: C; Genentech: C; ceuticals in Bedminster, See disclosure key, page 8.

44 • MAY 2019 SMART is Better AIDRIVEN EHR & PM FOR OPTIMAL EFFICIENCY

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Find Your Explore What’s New Inspiration in at AAO 2019 Enhanced Scientific ePoster Theatre and Lounge – the City Examine e-posters on large touch-screens and interact with presenting authors. by the Bay American Society of Ophthalmic Registered Nurses The two-day ASORN AAO 2019 October 12 – 15 nursing track is now officially Subspecialty Day October 11 – 12 part AAO 2019.

AAOE Program October 11 – 15 Stimulate Your Senses ASORN Nursing Program October 11 – 12 in San Francisco The Bay Area boasts 57 Michelin-starred restaurants. Registration and Hotel Reservations Open Soon Don’t miss the chance to dine June 12 Academy and AAOE members at Atelier Crenn, headed by chef Dominique Crenn, the June 26 Nonmembers first female chef in the United Register by Aug. 7 and save! States to earn three stars.

Watch this Discover Invaluable Pearls in the short video at Jackson Memorial Lecture aao.org/2019 Emily Y. Chew, MD, will deliver the most prestigious and discover what inspires you. lecture in ophthalmology — the 76th Edward Jackson Memorial Lecture, titled “Age-related Macular Degeneration: Nutrition, Genes and Deep Learning.” Dr. Chew’s talk will offer pearls on diabetic- and age- related eye diseases.

Where All of Ophthalmology Meets®

aao.org/2019

Where All of Ophthalmology Meets® aao.org/2019 CODING & REIMBURSEMENT SAVVY CODER

Best Practices for Coding, Part 2: Reduce Denials and Keep Payments on Track

o help you stay current on pay- any point during the calendar year. ers’ ever-changing coding rules, 10. Get preauthorization for surger- Help Us to Help You TEyeNet published “Best Practices ies and some tests. Preauthorization— for Coding: Six Do’s and Don’ts” in the also known as prior authorization, Boost Academy advocacy: Tell us January 2019 Savvy Coder (available at precertification, or prenotification— about your preauthorization problems. aao.org/eyenet/archive). This follow-up involves contacting the payer and The Academy’s D.C. office is working to article provides six more tried-and-true obtaining a certification number for reduce—and perhaps eliminate—the strategies. you to include when you submit your administrative burden of preauthori- claim for a service. Medicare Advantage zation. If you’ve had cases in which Best Practices 7 Through 12 plans, Medicaid plans, and commercial preauthorization delayed medical care 7. Have a consistent process for alert- plans change their preauthorization and/or instances where payment was ing staff and physicians about coding requirements often. (Medicare Part B denied even with preauthorization, updates. The requirements for coding doesn’t require preauthorizations.) please email [email protected]. and documentation are constantly in Note: Preauthorization for a surgery flux, and your compliance plan should doesn’t necessarily take into consider- include procedures for communicating ation coverage of every test; nor does appears on his or her insurance card; such changes throughout the practice, it consider Correct Coding Initiative • site of service issues; whether by email, via interoffice memo, (CCI) bundling edits, which is why you • wrong or missing modifier; or in a staff meeting. should always check with the payer to • CCI edits not followed; 8. Catalog your communications on see whether multiple CPT codes can be • mislinked diagnosis; and coding updates. By keeping a record paid when the services that they rep- • frequency edits on Eye visit codes or of changes to your coding policies, resent are performed during the same testing services. you create a historical resource that session. (Many payers have a look-up Tip: Keep a list of denials and share could be critical in an audit. Remember feature on their website.) To help you it with all in your practice so that the that documentation must support the with preauthorization, the Academy same denials are not perpetuated. policy that was in place at the time of has published a detailed checklist (see 12. Know which commercial payers the encounter. Furthermore, if an audit a link for it at aao.org/practice-manage still recognize consultation codes. A outcome isn’t positive, the payer will ment/coding/updates-resources). few commercial payers still recognize take into consideration any evidence 11. Correct and resubmit denied the 99241-99245 code family, but CMS that demonstrates your desire to be claims within 24 hours. When submit- and Medicare discontinued payment compliant. ted electronically, a clean claim—mean- for these consultation codes a long time 9. Verify insurance every time. For ing one without errors—typically takes ago (Jan. 1, 2010). Consequently, if each office visit, confirm the details of 14 days to process. If a claim is denied, you include Medicare as the secondary the patient’s insurance—ideally before promptly submit a corrected form to payer for a consultation code (whether the patient presents at the practice. Do keep payments on track. it is for an office or an inpatient exam), this even for established patients, since Common reasons for denial include: you will end up writing off the 20% they may change or lose insurance at • patient’s name is not listed as it balance.

MORE ONLINE. For nine key BY SUE VICCHRILLI, COT, OCS, OCSR, ACADEMY DIRECTOR OF CODING (and free) resources, see this AND REIMBURSEMENT. article at aao.org/eyenet.

48 • MAY 2019 Academy Notebook NEWS • TIPS • RESOURCES

WHAT’S HAPPENING

Academy Creates Volunteering Web Page Many Academy members volunteer their time and talent on Academy committees. Many more members would like to volunteer, but committee opportunities are limited. In March, the Academy launched a concise volunteering web page in the Member Services area of aao.org. This guide is designed to increase awareness among members of the many volunteer ADVOCATE. Academy members volunteered to advocate to senators on ophthal- opportunities available outside the mic issues during Congressional Advocacy Day 2018. scope of committee work. It describes opportunities to speak, write, review, emy will build a permanent home on burdensome way to report MIPS quality advocate, connect, and develop inter the ground floor of its headquarters measures is to integrate your electronic active content to further the work with five galleries and state-of-the-art health record (EHR) system with the of various Academy programs. Each interactive displays. The museum will IRIS Registry. opportunity provides instructions and open to Academy members during AAO June 1 deadline for getting started outlines expectations. 2019, with a grand opening to the pub with IRIS Registry/EHR integration. If This effort is intended to help lic in 2020. The Academy anticipates you haven’t yet integrated your EHR members find volunteer opportunities, welcoming more than 30,000 visitors in system with the IRIS Registry, you must enhance member engagement, and the first year alone. sign up or—if you signed up last year strengthen Academy programs. Explore the collection at aao.org/ but didn’t integrate—notify the IRIS To get involved, visit aao.org/ museum and contribute toward the Registry by June 1 and complete the member-services/volunteer. Academy’s $12 million goal to build the integration process by Aug. 1. Museum of Vision at aao.org/museum The IRIS Registry is a one-stop shop Support the Museum’s campaign. for MIPS reporting. You also can use Permanent Location the IRIS Registry to manually attest Until now, the Academy’s 38,000-piece TAKE NOTICE to promoting interoperability (PI) Museum of Vision collection has been measures and improvement activi accessible only by appointment or 2019 MIPS: June 1 Deadline ties, and—if you aren’t able to report online. With your support, the Acad for EHR-Based Reporting quality via IRIS Registry/EHR integra The IRIS Registry can streamline your tion—manually enter data for quality reporting for the Merit-Based Incentive measures. If you are new to the IRIS Payment System (MIPS) as long as you Registry, you will need to sign up for meet the appropriate deadlines. manual reporting by Oct. 31. Report quality measures using For more information, go to aao.org/ automated data extraction. The least iris-registry/medicare-reporting.

EYENET MAGAZINE • 49 In Private Practice? Apply for Research Grant by May 31 D.C. REPORT A research fund established last year gives Academy members in private Loss of ‘15 Letters of Visual Acuity’: practice an opportunity to harness One Medicare Advantage Plan’s the power of big data—but those in terested must submit their applications Definitions of Step Therapy Failure by May 31. The H. Dunbar Hoskins Jr., The Centers for Medicare & Medicaid Services now permits Medicare MD, Center for Quality Eye Care IRIS Advantage plans to use fail-first policies for Part B drugs. A Medicare Registry Research Fund will support Advantage plan that currently serves Idaho, Montana, and Oregon at least four IRIS Registry analytics defines an anti-VEGF drug’s failure as resulting in patients’ worsening projects in 2019. vision after a minimum three-month trial, “such as losing greater than Learn more about the eligibility re 15 letters of visual acuity.” quirements and the application process At least eight other Medicare Advantage plans are implementing at aao.org/iris-registry/data-analysis/ step therapy in 2019 to curtail physicians’ choice in treating patients. hoskins-center-research-fund. Many requirements for intravitreal anti-VEGF therapy are similarly egregious. Some require three months of failed treatment before the Follow @AAOjournal for the physician can administer a different drug. Latest Research The Academy, along with Prevent Blindness and American Society Stay up-to-date on research from Oph of Retina Specialists, is focused on convincing the executive branch thalmology, Ophthalmology Retina, and that step therapy interferes with the patient-physician relationship. Ophthalmology Glaucoma on Twitter. If you have had negative experiences with step therapy, you can Content is posted every day including support the Academy’s efforts by relaying the following towww. articles in press, “Pictures & Perspec preventblindness.org/patient-step-therapy-stories: tives,” editorials, and new issue alerts. • the condition you treated; Follow @AAOjournal at twitter.com/ • the medication that was first recommended and then denied; AAOjournal. • the reason for the denial; and • the case’s outcome. Submit Your Research to Ophthalmology Glaucoma Last summer, the Academy and the American Glaucoma Society collab advance order start 9 Get Updated orated in launching Ophthalmology ing in mid-May and Fundamental Glaucoma. will ship by mid- Surgical Texts Uveitis and Ocular This journal provides an oppor June (eBooks are Inflammation Residents and trainees, tunity to disseminate your glaucoma available starting in build a solid foundation research directly to those who find it mid-June). of ophthalmic surgical most relevant. Joining the ranks of the The 2019-2020 2019–2020 knowledge with new Academy’s esteemed Ophthalmology edition includes BCSC editions of Basic Principles Basic and Clinical and Ophthalmology Retina, Ophthal major revisions Science Course™ of Ophthalmic Surgery, mology Glaucoma provides readers with to the following: fourth edition, and Basic innovative, peer-reviewed works on a • Section 1: Techniques of Ophthalmic Editorial Committee H. Nida Sen, MD, MHSC, Chair Thomas A. Albini, MD bimonthly basis. Update on General Bryn M. Burkholder, MD Surgery, third edition. Sam S. Dahr, MD, MS Emilio M. Dodds, MD Thellea K. Leveque, MD, MPH Submit your original research at Medicine; Wendy M. Smith, MD Together, these books Daniel V. Vasconcelos-Santos, MD, PhD www.evise.com/profile/#/OGLA/login. • Section 2: Fun provide step-by-step waiting for spine spec Subscribe at www.ophthalmology damentals and Principles of Ophthal instructions for more than 80 common glaucoma.org. mology; procedures. Images and videos are used • Section 7: Oculofacial Plastic and extensively to increase understanding. ACADEMY RESOURCES Orbital Surgery; and These essential texts are available • Section 9: Uveitis and Ocular for advance order starting in mid-May Order the Updated Inflammation. and will ship by mid-June (eBooks are 2019-2020 BCSC Choose from the print or eBook available starting in mid-June). Both The 2019-2020 edition of the Basic format. Purchase an individual section texts are available in print or eBook and Clinical Science Course (BCSC), the or save when buying a complete set of format and are included in 2019-2020 definitive source of clinical information all 13 sections of the BCSC. BCSC Residency Sets. for ophthalmologists and residents Find pricing and information at aao. Find pricing and information at aao. throughout the world, is available for org/bcsc. org/bcsc.

50 • MAY 2019 Destination AAO 2019 GET READY FOR SAN FRANCISCO • PART 1 OF 6

WELCOME The group meets twice a year, once shortly after the annual meeting and Get Inspired in San Francisco once in January. At both committee It’s time to start preparing for the meetings, we review the labs and deter- world’s largest, most comprehensive mine which were successful and unsuc- ophthalmic meeting. At AAO 2019, cessful, and which could be improved. you’ll have the opportunity to learn At the January meeting in particular, from leaders in the field, discuss hot we look at what’s hot in ophthalmology topics in medicine, connect with col- and consider new courses. For instance, leagues, and explore the city. what’s hot right now is placement of When to be there. AAO 2019 runs IOLs without sufficient support, or Oct. 12-15 and is preceded by Subspe- Jack A. Cohen, MD, FACS. gluing and suturing of lenses. cialty Day programs, held Oct. 11-12. Q: How are the labs executed? You can also attend AAOE’s program provided by the Academy at the annual A: It’s like an orchestra with differ- Oct. 11-15. meeting for physicians to learn or re- ent parts that all come together on the How to prepare. Over the next five learn skills that they want to perform. day of the course. These labs require months, this “Destination AAO 2019” Ophthalmology and other medical models, animal and human eyes, micro- section will guide you through dead- specialties are changing so quickly: scopes, and special machines. Central lines, preview the scientific program, New studies are constantly coming to the labs’ execution is Susan Oslar, and highlight key events. out, as are new techniques, drugs, and the Academy’s Technical Programs equipment. Manager. We also rely on the help of SPOTLIGHT ON SKILLS Q: What is the structure of the labs? instructors, all of whom are volunteers TRANSFER LABS A: During the labs, we provide pig and often very busy. eyes, human eyes—all sorts of models, Q: What’s new for AAO 2019? Dr. Cohen’s Insider as well as equipment that allows partic- A: We are focused on making things Perspective ipants to simulate performing eye sur- clearer for the participants—we always Jack A. Cohen, MD, FACS, is currently gery on a real person. We try to make want them to know what they are sign- serving his fifth year as Chair of the the ratio of attendees to instructors as ing up for. For example, we have revised Skills Transfer Program, his eighth close to one-to-one as possible. some course descriptions to make them on this committee. Below, Dr. Cohen Thirty-five of the 57 courses have more accurate. Several courses offer previews the Skills Transfer learning related didactics, meaning that a multiple techniques, and often partic- opportunities at AAO 2019. separate lecture takes place a couple ipants will walk in and say, “I want to of hours before the lab, a day before, do all these techniques,” which doesn’t Q: What are the Skills Transfer labs? etc. This allows participants to gain always work with our time frame. This A: The Skills Transfer labs are some knowledge before they sit down year, these labs will have a poster that and start doing a technique that they lists the techniques, explains how they haven’t otherwise studied. differ, and tells participants how many Q: How are the labs planned? techniques they may choose to learn. A: It starts with the Skills Transfer We hope this eliminates any confusion Program Committee, which comprises about expectations. members from various subspecialties. Q: What is one of the best memories

EYENET MAGAZINE • 51 or experiences you’ve had with this Find more information at aao.org/ • Oculofacial Plastic Surgery 2010- program? registration and aao.org/hotels. 2019: A Decade to Remember A: Last year, I took a course on IOL • Pediatric Ophthalmology: San Fran- placement because I wanted to expe- Course Pass and Tickets: cisco Sound Meets Science rience a Skills Transfer lab firsthand. Buy Them Early Register. Online registration for As a retina specialist, I was excited to Registration for AAO 2019 gives you Subspecialty Day meetings opens June take the lab because I do a lot of suture access to all Spotlight sessions, sympo- 12 for Academy and AAOE members. fixation and thought the course might sia, papers sessions, e-posters, videos, Nonmembers may register starting expand my repertoire. What I experi- Academy Café sessions, and more. June 26. Visit aao.org/subspecialty-day enced was phenomenal. I had one-on- Academy Plus. Purchase an Acad- for more information. one instruction, and my instructor was emy Plus course pass for unlimited fantastic: He was patient, courteous, access to all Academy and AAOE Improve Your Practice With and kind; he showed me videos; and he instruction courses, including Skills the AAOE Program took extra time to explain things to me. Transfer lectures. Discover innovative ways to increase It was nice to see what the courses are Ticketed Events. The following practice efficiency: Attend the AAOE like from a participant’s perspective. courses are special offerings not covered Program, Oct. 11-15. Choose from Q: Who should take a Skills Transfer by general registration or the Academy more than 80 special sessions, which lab? Plus course pass and must be purchased are free with registration, as well as A: We offer courses for all physi- separately: instruction courses on topics rang- cians; it’s just a matter of need. Our 57 • AAOE Practice Management Master ing from coding to electronic health courses cover cataract, cornea, plastics, Classes; records. Admission to courses is via the retina, glaucoma, and skills with testing/ • Friday AAOE Coding Master Class Academy Plus course pass, which must imaging interpretation. and Saturday Coding Sessions; be purchased separately. The skills we offer also vary from • Skills Transfer labs; For deeper immersion, attend three- simple to complex. Many of the simpler • Subspecialty Day meetings; and hour Master Classes and intensive ones are excellent for residents who • Specific special meetings and events. coding sessions (ticketed separately) on want to enhance what they’re learning Seats for these sessions are limited. Friday and Saturday. in their residency programs. Remember to purchase tickets early. Review the program at aao.org/aaoe. Course pass and ticket prices rise Aug. 8. BEAT THE CLOCK Visit aao.org/registration for more Full AAO 2019 Program In- information. formation Available in June Registration and Hotels Program Search will launch as part of Open Next Month PROGRAM online meeting registration on June 12. Get ready to attend AAO 2019 in San Look up annual meeting sessions by Francisco, Oct. 12-15. On June 12, Attend Subspecialty Day day, topic, type of event/course, special Academy and AAOE members can Subspecialty Day meetings feature interest, or presenter. You don’t have to register and reserve hotel rooms. Non- world-renowned ophthalmologists log in or be a member to view program members can do so starting June 26. presenting the latest developments and information, though you will need to Online registration will remain open pearls in the field of ophthalmology. log in to build a personal calendar and through the meeting. When you register for a meeting, you to register. Fraud alert! Several fraudulent com- can float among all the Subspecialty Learn more about AAO 2019 at aao. panies, pretending to be associated with Day meetings taking place that day. org/annual-meeting. the Academy and AAO 2019, may ap- Meeting dates are as follows: pear in web searches or may have con- One-day meeting on Friday, Oct. 11. EVENTS tacted you via email. These companies • Refractive Surgery: As Far as the Eye claim that they can book hotel rooms Can See Attend the Red-Carpet Gala and/or register you for the Academy’s Two-day meeting on Friday, Oct. 11, Join the Foundation for lights, cameras, annual meeting, but they are unaffili- and Saturday, Oct. 12. and action at the 2019 Orbital Gala on ated with the Academy. Make sure that • Retina: I2—Inspire Innovation Sunday, Oct. 13. At this Hollywood, you book only through the Academy’s One-day meetings on Saturday, red-carpet–themed fundraiser, you’ll website and AAO 2019’s official hotel Oct. 12. have the rare opportunity to dine, bid reservation provider, Expovision. • Cornea: Keeping Disease at Bay on silent auction items, and dance the If you are ever in doubt, email • Glaucoma: Crossing the Golden night away at the historic Palace Hotel. [email protected] or call 415-561-8500. Gate to Exceptional Glaucoma Care All proceeds support the Academy’s You can also contact Expovision directly • Neuro-Ophthalmology: Diagnos- programs. at [email protected], or call tic Errors and Challenges—Avoid the Purchase tickets beginning May 16 toll-free at 866-774-0487. Traps! at aao.org/foundation.

52 • MAY 2019 Foundation Join William F. Mieler, MD, and Jennifer Kang-Mieler, PhD, in Supporting Academy Programs Become a Leadership Council Donor

Make a bigger impact than you ever thought possible by giving to the American Academy of Ophthalmology Foundation at the Leadership Council level ($2,500 and up). Your support of Academy programs will help us educate more ophthalmologists and do even more good for patients worldwide.

Learn how your support can make a difference at aao.org/foundation/our-impact

“When it comes to giving, the decision really comes down to supporting an organization that is most prominent in what we do on a day-to-day basis — and that’s the American Academy of Ophthalmology. It’s investing in the future of ophthalmology; this is the way we can pay it forward.”

WILLIAM F. MIELER, MD, & JENNIFER KANG-MIELER, PHD LEADERSHIP COUNCIL WINNETKA, ILL. MYSTERY IMAGE BLINK

Arun Kapil, Advanced Eye Centre, Post Graduate Institute of Medical Education and Research, and Research, of Medical Education Institute Graduate Post Centre, Eye Advanced Arun Kapil, Chandigarh, India. WHAT IS THIS MONTH’S MYSTERY CONDITION? Visit aao.org/eyenet to make your diagnosis in the comments.

LAST MONTH’S BLINK Conjunctival Lymphoma

68-year-old man presented with a 1 2 Atwo-month history of mild visual blurring and watery discharge from his right eye. On slit-lamp exam, a large, homogeneous, salmon- colored conjunctival mass (Fig. 1) was noted with enlarged feeder vessels (Fig. 2); these findings vealed no involvement beyond the orbit and optic raised suspicion of conjunctival lymphoma. He nerve sheath. The suggested treatment was a total displayed right globe ptosis (5 mm) and propto- dose of 24 Gy external beam radiotherapy, divided sis (6 mm)—an external appearance typical of a in 12 consecutive doses, for stage IAE marginal slowly enlarging mass—without pain or diplopia. zone non-Hodgkin lymphoma of the right eye.1,2 Visual acuity was 20/30 in the right eye, and pupillary reactions and color vision were normal. 1 Dhakal B et al. Clin Lymphoma Myeloma Leuk. 2017;17(5): Computed tomography showed a conforming, 305-311. homogeneous, soft tissue mass extending from 2 Kirkegaard MM et al. JAMA Ophthalmol. 2016;134(4):406-414. the superior rectus laterally to the lacrimal region and posteriorly behind the orbit to the optic nerve WRITTEN BY JAIME BADILLA, MD, AND SYLVIA H. sheath without bony erosion. CHEN, MDCM, MBA, FRCSC, UNIVERSITY OF AL- Biopsy confirmed the presence of B-cell BERTA, EDMONTON, ALBERTA, CANADA. PHOTOS lymphoma. The patient was referred to a cancer COURTESY OF ROYAL ALEXANDRA HOSPITAL EYE institute for treatment, where a full assessment re- CLINIC, EDMONTON, ALBERTA, CANADA.

54 • MAY 2019 CLINICAL EDUCATION

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