PIE Issue 20: The ebook version (The 'Gaming Issue', APVRS and VRSI 2021 Edition)

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THE WORLD’S FIRST FUNKY OPHTHALMOLOGY MAGAZINE

20 m maaggaazziinnee posterior posteriorsegment segment••innovation innovation••enlightenment enlightenment

At the Crossroads of Gaming and Ophthalmology P18

THE GAMING ISSUE Dec 2021/Jan 2022 piemagazine.org


OZURDEX® acts fast1,2 and lasts3–5 with less treatment visits compared with anti-VEGFs,5 making it the enduring partner you need. Effective DME treatment doesn’t have to be a burden.6

The most commonly reported adverse events reported following treatment with OZURDEX® are those frequently observed with ophthalmic steroid treatment or intravitreal injections (elevated IOP, cataract formation and conjunctival or vitreal haemorrhage respectively). Less frequently reported, but more serious, adverse reactions include endophthalmitis, necrotizing retinitis, retinal detachment and retinal tear. Licences may vary by country, please refer to your local country SmPC. DME, diabetic macular edema; IOP, intraocular pressure; VEGF, vascular endothelial growth factor. 1. Lo Giudice G et al. Eur J Ophthalmol 2018;28(1):74–79. 2. Veritti D et al. Ophthalmologica 2017;238(1–2):100–105. 3. Escobar-Barranco JJ et al. Ophthalmologica 2015;233(3–4):176–185. 4. Allergan. OZURDEX® Summary of Product Characteristics. 5. Kodjikian L et al. Biomed Res Int 2018:8289253. 6. Boyer DS et al. Ophthalmology 2014;121:(10):1904–1914.

INDICATIONS & USAGE: OZURDEX® contains a corticosteroid indicated for the treatment of macular edema following branch retinal vein occlusion (BRVO) or central retinal vein occlusion (CRVO), for the treatment of non-infectious uveitis affecting the posterior segment of the eye, and for the treatment of patients with visual impairment due to diabetic macular edema (DME) who are pseudophakic or who are considered insufficiently responsive to, or unsuitable for non-corticosteroid therapy. DOSAGE & ADMINISTRATION: For ophthalmic intravitreal injection only. The intravitreal injection procedure should be carried out under controlled aseptic conditions. Following the intravitreal injection, patients should be monitored for elevation in intraocular pressure and for endophthalmitis. DOSAGE FORMS & STRENGTHS: Intravitreal implant containing dexamethasone 0.7 mg in the NOVADUR™ solid polymer drug delivery system. CONTRAINDICATIONS: Ocular or periocular infections. Advanced glaucoma. Aphakic eyes with ruptured posterior lens capsule. Eyes with ACIOL, iris or transscleral fixated IOLs and rupture of the

posterior lens capsule. Hypersensitivity. WARNINGS AND PRECAUTIONS: Intravitreal injections have been associated with endophthalmitis, eye inflammation, increased intraocular pressure, retinal detachments, and implant migration into the anterior chamber. Patients should be monitored following the injection. Patients who has a tear in the posterior lens capsule (e.g., due to cataract surgery), or who had an iris opening to the vitreous cavity (e.g., due to iridectomy) are at risk of implant migration into the anterior chamber. Use of corticosteroids may produce posterior subcapsular cataracts, increased intraocular pressure, glaucoma, and may enhance establishment of secondary ocular infections due to bacteria, fungi, or virus. Corticosteroids should be used cautiously in patients with a history of ocular herpes simplex. ADVERSE REACTIONS: In controlled studies, the most common adverse reactions reported by 20–70% of patients were cataract, increased intraocular pressure and conjunctival haemorrhage.

Licenses may vary by country, please consult your local Summary of Product Characteristics. Adverse events should be reported to your Ministry of Health and local Allergan office. JOB CODE: INT-OZU-2050218 DATE OF PREPARATION: NOVEMBER 2020

OZURDEX® is not licensed for use in DME in China.


IN THIS ISSUE...

Posterior Segment magazine

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posterior segment • innovation • enlightenment

Matt Young

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Refining Definitions of “Nonadherence” and “Non-persistence” in Neovascular AMD Treatment Laser Remains an Effective Option for DME and CSCR Treatments

Shedding Light on Autoimmune Retinopathy

CEO & Publisher

Hannah Nguyen COO & CFO

Robert Anderson Media Director

Gloria D. Gamat Chief Editor

Brooke Herron Editor International Business Development

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Genes Don’t Lie, but the Cipher Remains Elusive (Not?!)

Cover Story

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Ruchi Mahajan Ranga Brandon Winkeler Writers

Andrew Sweeney April Ingram Hazlin Hassan Joanna Lee Nick Eustice Sam McCommon Tan Sher Lynn

At the Crossroads of Gaming and Ophthalmology

Innovation

Maricel Salvador

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Graphic Designer

Published by

Enlightenment

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#realtalk with Dr. Apoorva Ayachit: Making Her Voice Heard

iCare COMPASS Detects Retinal Defects Early

Conference Highlights Media MICE Pte. Ltd.

6001 Beach Road, #19-06 Golden Mile Tower, Singapore 199589 Tel: +65 8186 7677 / +1 302 261 5379 Email: enquiry@mediamice.com www.mediaMICE.com

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Some Notable Highlights from ASRS 2021 In Brief: 3 Fantastic Posters from EURETINA 2021

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OIS Webinar Highlights Remarkable Retina Developments

We are looking for eye docs who can contribute articles to PIE magazine. Interested? Let's talk! Send us an email at editor@mediamice.com. To place an advertisement, advertorial, symposium highlight, video, email blast, or other promotion in PIE magazine, contact sales@mediamice.com.


ADVISORY BOARD MEMBERS

SOCIETY FRIENDS

Arunodaya Charitable Trust (ACT)

Prof. Gemmy Cheung, MBBS, FRCOphth (UK), FAMS, MCI, is currently a professor at Duke-NUS Medical School, National University of Singapore, and head of the Medical Retina Department at Singapore National Eye Center (SNEC). Her research focuses on retinal diseases, including age-related macular degeneration (AMD), polypoidal choroidal vasculopathy (PCV) and myopic macular degeneration, as well as risk factors for these conditions that may be unique to Asian populations. Prof. Cheung has more than 200 peer-reviewed publications and serves on the editorial boards of several journals, including the American Journal of Ophthalmology, Retina and Eye. Prof. Gemmy Cheung

Asean Ophthalmology Society

Asia-Pacific Academy of Ophthalmology

gemmy.cheung.c.m@singhealth.com.sg

Asia-Pacific Vitreo-retina Society

Prof. Mark Gillies

Prof. Mark Gillies, MBBS, PhD, FRANZCO, presently holds a number of positions including: director of research and director of the Macula Research Group for the Save Sight Institute; foundation fellow for the Sydney Medical School; professor in the Department of Clinical Ophthalmology at the University of Sydney; head of the Medical Retina Unit at the Sydney Eye Hospital; deputy chair for the Ophthalmic Research Institute of Australia; and director of Eye Associates in Sydney. Prof. Gillies has served as a principal investigator or associate investigator in more than 70 clinical trials, and his research regarding macular degeneration and drug safety and efficacy has been published in 188 journals. He has also received a number of grants to study treatments for age-related macular degeneration, retinal disease and Muller cell dysfunction — among other treatments and studies. Prof. Gillies is a dedicated and multi-awarded researcher. mark.gillies@sydney.edu.au

Prof. Dr. Vishali Gupta

Prof. Dr. Vishali Gupta, MD, is an accomplished vitreo-retina and uvea expert of international repute. She currently works as a professor of ophthalmology at Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India. Throughout her career, she has completed original work in the fields of intraocular tuberculosis, optical coherence tomography, diabetic retinopathy and fungal endophthalmitis. In addition, she is actively studying vitreoretinal and uveitis diseases. Prof. Gupta also holds a U.S. patent for the development of multiplex PCR for uveitis. In addition, she is a sought-after speaker and has delivered more than 870 invited lectures and conducted sev eral instruction courses at various international and national meetings. She has more than 200 publications in peer-reviewed journals; has edited five books and contributed 72 book chapters in textbooks. She is the secretary of the International Uveitis Study Group, and member of the AAO, Club Jules Gonin and the Macula Society. She is currently the president of the Uveitis Society of India. Prof. Gupta has received several awards for her work, including the first JN Pahwa award from the Vitreo-Retinal Society of India (VRSI), the first NA Rao Award from the Uveitis Society of India, and the first NA Rao award from All India Ophthalmological Society (AIOS).

He Eye Specialist Hospital

Ophthalmology Innovation Summit

Orbis International

Retinawesome Retina & Vitreous International

Russian Ophthalmology Society (ROS)

Subthreshold Ophthalmic Laser Society

Vitreo-Retinal Society India

vishalisara@yahoo.co.in

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Young Ophthalmologists Society of India ( YOSI )


nAMD Barometer

Developing evidence-based initiatives for the optimal management of neovascular age-related macular degeneration (nAMD) The nAMD Barometer programme aims to investigate barriers and opportunities to improved patient-focused care for people living with nAMD, by developing evidence-based interventions that support adherence and persistence to treatment and improved outcomes.

Co-chairs of the nAMD Barometer Leadership Coalition (LC)

Dr Jane Barratt International Federation on Ageing

Professor Anat Loewenstein Tel Aviv Sourasky Medical Center, Tel Aviv University

Systematic literature review (SLR) of factors affecting non-adherence (NA) to and non-persistence (NP) with anti–vascular endothelial growth factor (VEGF) therapy for nAMD Do you know what the greatest correlates are to increased risk of NA to and NP with intravitreal anti-VEGF therapies in your patients? Read this SLR so you can understand the evidence, better identify your at-risk patients and target them for interventions to keep them on treatment.1 Click here to access the literature review

Standardisation of definitions of NA to and NP with anti-VEGF therapies in nAMD How would you define NA and NP? Would you consider a patient who has missed one appointment non-adherent? How about a patient who has been transferred to another clinic – are they still considered persistent? These are the questions tackled by the nAMD Barometer Leadership Coalition in their latest publication in JAMA Ophthalmology.2 Read the article to ensure you understand the difference and are using the correct definitions in your research. Click here to access the article

‘A Chat with Anat’ podcast series Are you interested in delivering care that is more patient-focused? Would you like to hear how other physicians have altered their practice approaches to improve care and outcomes for their patients? You can find our new podcast series ‘A Chat with Anat’ on Spotify and Apple Podcasts!

“While good management and treatment can achieve good visual outcomes for those with nAMD, patients have a responsibility to adhere to the agreed treatment regime to realise the best vision they can to live their lives.” Jane Barratt, Secretary General, International Federation on Ageing, Canada Co-chair of the nAMD Barometer Leadership Coalition

References:

To learn more, visit amdbarometer.org

1. Okada M, et al. Ophthalmology. 2021;128:234–247. 2. Okada M, et al. JAMA Ophthalmol. 2021;139:769–776.

VISION ACADEMY p e o p le | re s e a rc h | e d u c a t io n

The nAMD Barometer Programme is managed by clinical leaders in ophthalmology as well as representatives from the International Federation on Ageing (IFA), International Agency for Prevention of Blindness (IAPB) and Bayer. The activities of the nAMD Barometer Programme are funded and facilitated by Bayer where the scientists and representatives from IFA, IDF and IAPB retain decision authority to the research scope, methods, analysis of findings and dissemination of the outputs of the programme.

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MA-PFM-OPHT-ALL-0695-1 | November 2021 MA-PFM-OPHT-SG-0014-1 | November 2021


LETTER TO READERS

The age of digital media has finally arrived in eye care

Dear Reader,

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t's clear from everyone we talk to globally, print media — which for years had been on the decline in popular media — has become more and more insignificant.

So that we can tell you with certainty the metrics behind each view of our content. Our competitors haven't a clue, because they're still printing hardcopies that cannot be tracked in the same way.

The invasion of mobile devices, from the iPhone to tablets, is complete in eye care.

As a global publication — truly the one and only in eye care that reaches East to West — it never, ever made sense to mail the publication to hundreds of countries globally. It only made sense to print the publication and distribute at conferences, along with our trademark antics and style to assist that.

My own reading habits include having a few books on my nightstand for nighttime reading, but the last time I picked up a hardcopy magazine was on an international flight nearly two years ago. When I cross compare those habits with others, I'm told periodical reading isn't happening on European subways anymore — not like I used to see on the Underground in the United Kingdom. The globe, instead, has adapted habits similar to what I've seen on the MRT subway in Singapore. Everyone with their mobile phones out, communicating silently in cyberspace. That's not to say doctors and industry are riding subways. But if you're reading this, that means you're reading digitally on your phone, tablet or possibly a laptop. That's the only way you're reading because we aren't printing PIE with the release date of this issue. Why?

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Post-pandemic, the conference business is drastically affected. From one month to the next, we don't yet know what will be virtual, hybrid, or physical. When we do know, attendance figures are severely affected, and it is still nowhere near business-as-usual. As a result, with our PIE, as well as CAKE (for anterior segment surgeons), and COOKIE (for optometry and opticians) media, we are actively finding new ways to make greater, qualitative and metrics-backed impact like never before. We don't yet know everything about modern distribution, but we are learning fast what works. Here's an example of how we are adapting to the times. In the past, we would distribute a maximum of 3,000 hardcopies of a magazine at a particular conference. But we didn't know anything about what happened after that. We didn't find many magazines in the trash at conferences. But we didn't know what was read, and we didn't have much feedback. This was typical, because in the early 2000s, I was a reporter at another eye care magazine (sometimes


an investigative one at that), and never more than a dozen times did I get considerable feedback from readers commenting on stories after 1,000 articles! That's print media for you — a black hole on the feedback loop. Meanwhile, here are the Top 10 ways we distribute in a much more cutting-edge way. 1. We produce a roughly 40 page digital magazine, the content of which is e-blasted to our database of about 70,000 ophthalmologists worldwide. Open rates are decent, and doctors can click to view or download the full ebook and/or PDF. 2. We then embed the full magazine on social media, such as LinkedIn. I have more than 5,000 followers that are highly engaged on LinkedIn, with an SSI score (the measure of influence on LinkedIn) of the top 1% of our industry and the top 1% of my network. Is there engagement there? Absolutely! 3. Individual article pages are then chopped up, and posted individually throughout our social media accounts -- CAKE, PIE, COOKIE respectively, so that you only need to swipe once or twice to see the full article. 4. Now here's some new special distribution sauce. As we are the makers of the world's first funky ophthalmology magazines, you better believe our social media is funky! We create animated infographics, summary swipe books, and dynamic videos to summarize and spread the word about key articles. Interested readers can then click to the full article if they would like to learn more. Even if they don't read the full article, they get the gist with a dynamic infographic or swipe book, and can delve deeper if they wish. 5. Our 50 KOL Influencers — who we screened for prominence on social media — are true allies, helping to share content we create together in their social feeds. Our combined influencers followers are 128,900 followers on LinkedIn, and 58,135 on Facebook (not including our optometry influencers, one of which has about 30,000 followers on LinkedIn herself). Every time they like, share or comment, critical eye education is getting out to their followers, who also are prominent doctors in their own right! 6. Every issue of our magazines are translated into Mandarin, and sent out to more than 20,000 eye doctors via WeChat, China's preferred social media network.

7. Our social media team sends our publications into eye care interest groups on Facebook, accumulating thousands more reads per publication. 8. We embrace distribution via WhatsApp in far reaching places like India and Brazil. 9. Our society friends, such as the APAO, eblast our magazines to their own databases. Last time we checked, they had more than 50,000 subscribers themselves. 10. We have a new relationship with a distributor in Latin America, which also eblasts our magazines to their database of more than 10,000 eye doctors throughout the region. Now, after reviewing this Top 10 list, do you really want to go back to the days of print? We don't. In fact, for all the trouble we took to print in the past — the thousands upon thousands of hardcopies we printed and distributed at global conferences since 2017 — we have never received more feedback about our publications. We have never had stronger society and KOL alliances. We have never been contacted more via LinkedIn about our services. We have never had a better revenueproducing year (yes, 2021 was the best ever). Ultimately, we are here to serve our media consumers, providing eye care education globally. You know us. It is with full passion that we do this. If we thought print could do it better, we would do that. Print magazines can't do it better. It can do it much, much worse. And kill some trees in the process. Meh. All the best,

M at t Young

CEO & Publisher Media MICE, PIE, CAKE and COOKIE magazines

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POSTERIOR SEGMENT

RETINOPATHY

Shedding Light on Autoimmune Retinopathy

by Tan Sher Lynn

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utoimmune retinopathy (AIR) remains a poorly understood immune-mediated disease. We talked to cataract surgeon and uvea specialist Dr. Parthopratim Dutta Majumder who has been investigating the condition.* AIR refers to a group of rare autoimmune retinal degenerative diseases that cause inflammation due to circulating antibodies that target and attack certain retinal antigens, which are usually retinal proteins with immunogenic properties. To date, population-based epidemiological studies in regard to AIR seem to be lacking. Nevertheless, the disease has been estimated to constitute less than 1% of all cases seen at a tertiary eye clinic, noted Dr. Dutta Majumder. The pathogenesis of AIR remains largely presumptive and there are a significant number of anti-retinal antibodies that have been detected in association with AIR. It is not clear what triggers these

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antibodies to recognize retinal proteins as antigens. Almost all retinal cell lines can be affected, although photoreceptors, ganglion cells and bipolar cells are primarily affected. Vision loss in recoverin-associated retinopathy has been observed to be more severe when compared with enolase-associated retinopathy, usually with an acute onset with relatively faster progression. (Recoverin and enolase are two retinal proteins that have been studied extensively.)

Diagnosis The spectrum of AIR is broad and contains various clinical entities with an overlapping clinical and immunological phenotype. Common clinical features observed in various conditions in this spectrum include rapidly progressive, bilateral, painless deterioration of vision. Nevertheless, despite the common

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features, AIR remains one of the most challenging diagnoses because of the lack of definitive tests and standardized criteria. The diagnosis of AIR is largely based on the demonstration of anti-retinal antibodies in the serum along with suggestive clinical features and ancillary investigations. According to Dr. Dutta Majumder, a clinician needs to rely on clinical signs, electroretinogram (ERG) evidence of retinal damage and detection of antibodies against specific retinal antigens for confirming the diagnosis of AIR. “In addition to these, various ancillary imaging and laboratory investigations may help to rule out other uveitic and non-uveitis entities, such as white dot syndrome spectrum disorders (particularly acute zonal occult outer retinopathy [AZOOR]), retinal degenerative disorders (such as retinitis pigmentosa [RP] and cone-rod dystrophy), and non-infectious and


infectious uveitis syndromes,” he said. He stressed that the diagnosis of AIR needs a high index of suspicion, as this may play a critical role to lower the risk of irreversible immunological damage to retinal cells. “Any patients with subacute vision loss, scotomas, photopsia, nyctalopia in the absence of intraocular inflammatory cells and heredomacular degeneration, should raise suspicion of AIR. An extensive search for neoplasm should be carried out in elderly patients. Thus, good multidisciplinary communication between the ophthalmologist and clinician is essential,” he explained.

Treatment and management approaches A multi-disciplinary approach is often needed for complete evaluation and management of AIR. “There is no standard treatment protocol currently, but various therapeutic options have been advocated. These include systemic and/or local (intravitreal/ sub-tenon/depot) corticosteroids, immunosuppressive agents, and biologicals. Many authors have reported the use of intravenous immunoglobulin and plasmapheresis. Use of antioxidant vitamins like lutein, vitamin C, vitamin E and beta carotene (in non-smokers) also have been reported,” he noted. According to Dr. Dutta Majumder, the management course should also be guided by follow-up testing with ERG, visual field testing, visual acuity,

optical coherence tomography (OCT) — especially for cystoid macular edema (CME) — and color vision testing, generally every 3-6 months, which can be individualized. The role of follow-up testing with repeat serum antibodies, however, has questionable clinical significance, as the response to treatment is variable and depends on many factors, and generally worse responses have been reported in patients with family history of autoimmune diseases. “Normal individuals may have antiretinal antibodies which may originate due to degradation of cells, following exposure of self-antigens to the immune system. A study showed that antiretinal antibodies were detected in 42% normal healthy controls. Also, antiretinal antibodies have been detected in various systemic autoimmune diseases with or without ocular inflammation,” he said. The patient should also be counselled for the prognosis and treatment expectations aiming at stabilization or prevention of further deterioration of vision.

Looking ahead “The diagnosis of AIR remains very challenging. The signs and symptoms are highly nonspecific, overlapping with many other retinal conditions and there are no definitive tests or standardized criteria for the diagnosis of these

entities. AIR can progress rapidly and cause irreversible immunological damage to the retinal cells leading to diffuse retinal degeneration. Thus, ophthalmologists should be aware of this spectrum of entities. “Although anti-retinal antibody testing is available commercially, the scope for such testing is very limited in developing countries. Also, the high cost of antiretinal antibody testing and the lack of standardization between various laboratories are important concerns. A universal standardized diagnostic guideline with validated criteria with respect to antiretinal antibody testing (such as number of bands, intensity, molecular weight and isotype) are the need of the hour. Similarly, there is urgent need for prospective, placebo controlled, and/or randomized studies to understand the exact role of various immunomodulation in AIR,” said Dr. Dutta Majumder.

* Dutta Majumder P, Marchese A, Pichi F, et al. An update on autoimmune retinopathy. Indian J Ophthalmol. 2020; 68(9): 1829–1837.

Contributing Doctor Dr. Parthopratim Dutta Majumder is a cataract surgeon and uvea specialist in India. He was awarded with the Dr. TLK Row Endowment Award for the best associate consultant 2010-11. He has received the Dr. Nataraj Pillai award and Dr K. R. Dutta award for best paper. His areas of interest include medical management of uveitis and scleritis, as well as phacoemulsification in uveitic cataracts. He is now working as consultant in the uvea and intraocular inflammation department, Sankara Nethralaya, Chennai. He has published many articles in various peer and non-peer-reviewed journals. He serves as the editor of “INSIGHT,” the scientific journal of medical and vision research foundation, and section editor of the Indian Journal of Ophthalmology. He is also the founder cum chief editor of popular ophthalmology portal www. eophtha.com. drparthopratim@gmail.com]

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POSTERIOR SEGMENT

INHERITED RETINAL DISEASES

Genes Don’t Lie, but the Cipher Remains Elusive (Not?!) by April Ingram

normal genes from both parents, meaning they will have no IRD and will not be a carrier. Genetic testing has become the benchmark for the diagnosis and management of patients and their families with IRDs, as it complements the observed clinical features and facilitates a more precise clinical diagnosis. Whole genome sequencing (WGS) is a relatively new technology, falling under the umbrella term, “nextgen sequencing,” that rapidly sequences large amounts of DNA. WGS determines the order of DNA nucleotides that make up our genetic code, as well as variations that show up in any part of the genome. As WGS has become more accessible in some regions, logistically and financially, it is being increasingly used in healthcare and research to accurately identify genetic variations.

T

here are those days that we feel more like detectives than clinicians, spending so much time chasing the imaging and diagnostic clues. Despite all the technology and advancements at our fingertips, we can be left with more questions than answers. Diagnosing and managing inherited retinal diseases, or IRDs, when relying on the observable characteristics of the presenting phenotypic features alone, can be incredibly challenging and often misleading. Although considered rare, IRDs are among the most common genetic diseases in humans, showing up at any age with variable rates of progression. That said, the outcome is usually the

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same, degeneration of the retina and eventually, severe vision loss. There are more than 80 IRDs that have been clinically and genetically described, and to date, more than 270 genes have been implicated. Meaning 270 genes are not fulfilling their intended role, in one way or another. As well, most IRDs are recessively inherited, which means that the parents do not exhibit the trait, they are carriers, with one variant copy of the gene and one normal copy. If a child has both parents who are carriers, they have a 25% chance of inheriting a variant from both parents and developing the IRD, a 50% chance of being a carrier themselves, and a 25% chance of inheriting the

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These exciting steps forward in interpreting the genomic architecture do come with some startlingly disappointing context. A study published by Popejoy and Fullerton examined more than 2500 studies, including 35 million samples from the GWAS Catalog (a database of human genome-wide association studies) and found that >80% were from people of European decent, and only 5% were linked to non-Asian minority populations.1 These findings caution the reliability of clinical genomic interpretation for less-represented minorities, creating an unfortunate disparity of information. That is, until now. This past October, PLoS Genetics published a breakthrough study, featuring the efforts of researchers from around the world, Deciphering the genetic architecture and ethnographic


distribution of IRD in three ethnic populations by whole genome sequence analysis.2 The study characterized the genetic architecture of IRD by performing whole-genome analysis and ophthalmic evaluation on 409 individuals from 108 unrelated pedigrees with IRDs. A pedigree is like a family tree that shows the relationships between family members and indicates which individuals express, or silently carry, the IRD. What makes this study so unique is that the IRD patients included those recruited from previously understudied populations in Mexico and Pakistan, in addition to a well-studied population of European Americans. Senior, and corresponding author, Radha Ayyagari, PhD, professor of ophthalmology and pathology at the University of San Diego and director of the Shiley Eye Institute Biobank, shares why this work was so desperately needed: “Findings on understudied populations help in designing effective treatments for patients with IRD worldwide.” Following a blood sample collection for genome analysis and ophthalmic evaluation to establish the retinal phenotype, the analysis detected causative variants in 62 out of the 108 pedigrees and a total of 94 gene variants were found in the 62 families. Interestingly, of the 94 gene variants, 52 had been previously reported as causative variants, not a big surprise, but the remaining 42 had not ever, before now, been reported within IRD pedigrees. Even more striking, was that 52% of the novel variants uncovered were not even listed in gnomAD. This is a huge deal, because gnomAD, the Genome Aggregation Database, is a consortium of geneticists and researchers from around the world that have created the largest publicly available catalog of human genomic data … and they did not have more than half of the novel variants found in this study. If that wasn’t astounding enough, researchers additionally observed complex causative genotypes in 21% of pedigrees. Overall, these causative variants were detected in 63% Mexican, 60% Pakistani and 48% European American pedigrees.

Accurate diagnosis is the gateway to appropriate treatment, connection to supportive services, education of family members about their risk for the disease, and where possible, provides information about clinical trials and potential therapies. Prior to study entry, all patients had their initial IRD clinical diagnosis, pedigrees included 18 with retinitis pigmentosa (RP); 2 for each Leber congenital amaurosis (LCA) and Usher syndrome; 1 each for cone dystrophy and macular dystrophy; while the majority (37) were unclassified retinal degeneration. Following the analysis, there were no more unclassified pedigrees; RP increased to 45; cone dystrophy to 7; LCA in 3; congenital stationary night blindness, macular dystrophy, nephronophthisis, Ceroid lipofuscinosis, choroideremia and Usher syndrome all with 1 each. This means that many more families could be directed to the most appropriate care, support and counseling. It is also important to point out what a collaborative effort this study was, including researchers from across the United States, India, Pakistan, Brazil and Canada. As study author Kelly Frazer, PhD, director of UC San Diego Institute for Genomic Medicine and founding chief of the Division of Genome Information Sciences in the Department of Pediatrics, shared, “This work is a testament to what can be accomplished when researchers with complementary expertise work together to apply advanced genomic methods to understand the genetics of IRD in diverse patient populations.” The study authors explained the importance of this work: “This study has really revealed the important distribution of IRD causative variants in pedigrees with diverse ethnic and geographic backgrounds.” These results provide insight into the population-specific genetic architecture of IRD and has allowed for comparisons to be made with other populations, globally. These findings will be instrumental in the design of population-specific tools for molecular diagnosis, genetic counseling, and therapeutic decision-making, moving forward.”

References: Popejoy AB, Fullerton SM. Genomics is failing on diversity. Nature. 2016;538(7624):161-164.

1.

Biswas P, Villanueva AL, Soto-Hermida A, et al. Deciphering the genetic architecture and ethnographic distribution of IRD in three ethnic populations by whole genome sequence analysis. PLoS Genet. 2021;17(10):e1009848.

2.

Contributing Doctors Radha Ayyagari, PhD, is a professor of ophthalmology and pathology, Viterbi Family Endowed Chair and director of the Shiley Eye Institute Biobank, at the Shiley Eye Institute and University of California, San Diego, California. Dr. Ayyagari obtained her PhD in biochemistry from the National Institute of Nutrition, Hyderabad, India. Subsequently, she completed a fellowship in ophthalmic genetics at the National Eye Institute, NIH, Bethesda, Maryland. After completing her training, she joined the faculty of the Department of Ophthalmology at the University of Michigan, Ann Arbor. In 2007, she joined the Shiley Eye Institute at UCSD as an associate professor and currently, Dr. Ayyagari is a professor of ophthalmology, pathology and biomedical sciences graduate program and Viterbi Family Endowed Chair of ophthalmology. Dr. Ayyagari serves on several national and international scientific advisory boards/ committees, has published more than 130 peer-reviewed articles, mentors students of all levels including high school, graduate and medical school and postdoctoral scholars. Dr. Ayyagari enjoys painting and hiking during her free time. rayyagari@health.ucsd.edu Kelly A. Frazer, PhD, is the director of the Institute for Genomic Medicine and a Professor and founding chief of the Division of Genome Information Sciences in the Department of Pediatrics at the University of California, San Diego. Dr. Frazer is an internationally renowned leader in the field of genome biology. kafrazer@ucsd.edu

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POSTERIOR SEGMENT

AMD TREATMENT

Refining Definitions of “Nonadherence” and “Non-persistence” in Neovascular AMD Treatment by Joanna Lee

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etinal experts have refined the definitions of what the terms “non-adherence” and “non-persistence” mean, particularly for neovascular age-related macular degeneration (nAMD) patients undergoing antiVEGF treatment.1

established a foundation for the definitions. First, they drafted the proposed definitions for adherence and persistence. These were then refined and the most suitable definitions were selected for further rounds of consensus validation. Each member of the full leadership coalition assigned a score from 1 to 10 according to the degree of consent or agreement with the definitions. If the mean score was less than 7.5, they would amend the definition and resubmit it for the next round of assessment.

This clarification provides a more clear and consistent reference system for physicians to assess the reasons why real-world nAMD patients discontinue treatment. And lack of adherence has consequences, as noted by the Comparison of AgeRelated Macular Degeneration Treatment Trial (CATT),2 which reported worse visual acuity in patients who missed or delayed treatment visits. This began with literature review that looked into factors affecting compliance and non-compliance to anti-VEGF in nAMD patients. During their search, the group of retina specialists, known as the nAMD Barometer Leadership Coalition, encountered substantial variations in how adherence and persistence were described. They realized that a set of more uniformed definitions was needed.

Let the definition games begin Led by vitreoretinal surgeon Dr. Mali Okada from the Royal Victorian Eye and Ear Hospital in Melbourne, Australia, the coalition set out to develop improved terminologies.

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Once the consensus was reached, the coalition sent the definition to the Vision Academy, a collaboration of 80 international experts for further evaluation and their endorsement through an online survey. After the review of literature yielded various synonymous terms such as “compliance, nonattendance, discontinuation, dropout, cessation and loss to follow-up,” the coalition selected “non-adherence” and “non-persistence” based on several articles which included one on a systematic review3 published by the coalition itself. The word compliance carries a negative and passive connotation of blame on patients. Thus, the term adherence was singled out for validation as it was deemed to reflect “a more proactive health care interaction.” For the same reasons, the term persistence was preferred over discontinuation. Using the modified Delphi approach, the researchers systematically

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The result? A more uniform set of terms to define non-adherence and nonpersistence was established.

Non-adherence Non-adherence is now based on the total of missed visits, instead of the total of missed injections, within a 12-month period. Adherence is also now sub-categorized as full-adherence; this is when 100 percent of scheduled appointments are attended. However, in this all-or-nothing approach, the patient is classified as non-adherent after one appointment is missed. Therefore, a second category — adherence — was created to allow for those who have only missed one appointment within a 12-month period.


This reflects the general medical practice of having an 80 percent cut-off when classifying good treatment adherence.

Non-persistence Non-persistence occurs when patients do not attend any treatment or appointments for six months. This can be due to the variations in treatment regimens (i.e., treat-andextend (T&E), pro re nata).

577nm FIBER TECHNOLOGY LASER

Two additional new terms, “planned discontinuation” and “transfer of care,” were also added. These cover patients who intentionally cease their treatment and not due to nonpersistence. If a patient continues their follow-up care with another doctor and treatment details are unknown, the patient is classified under “transfer of care.” The study fills a gap in the definitions and general consensus of the terms “adherence” and “persistence” in anti-VEGF treatment in nAMD. The coalition said their proposed definitions are designed to afford flexibility in covering the paradigm of injection regimens for nAMD patients.

Based on the new subcategories, the nAMD Barometer Group has further launched their next two projects. One is a qualitative study using patient and caregiver interviews to determine barriers to care and the association with visual health outcomes. The second project is a quantitative-based study to find out how cultural and other socioeconomic differences could affect patient adherence. The pandemic has also seen considerable treatment interruptions. Therefore, having a set of more clearly defined, universal terminology, as well as a more in-depth understanding of barriers to adherence and persistence, could help guide future strategies toward improving outcomes for nAMD patients who receive anti-VEGF.

Reference: 1.

Okada M, Tien Wong TY, Mitchell P, et al. Defining Nonadherence and Nonpersistence to Anti-Vascular Endothelial Growth Factor Therapies in Neovascular Age-Related Macular Degeneration. JAMA Ophthalmol. 2021;139(7):769-776.

2.

Maguire MG,Martin DF, Ying GS, et al; Comparison of Age-related Macular Degeneration Treatments Trials (CATT) Research Group. Five-Year Outcomes with Anti-Vascular Endothelial Growth Factor Treatment of Neovascular Age-Related Macular Degeneration: The Comparison of Age-Related Macular Degeneration Treatments Trials. Ophthalmology. 2016;123(8):1751-1761.

3.

Okada M, Mitchell P, Finger RP, et al. Nonadherence or nonpersistence to intravitreal injection therapy for neovascular agerelated macular degeneration: a mixed-methods systematic review. Ophthalmology. 2021; 128(2):234-247.

XL_EASYRET_MOSAR_PUB_AN_211103

Furthermore, the coalition has introduced subcategories more specific to nAMD patients on anti-VEGF treatment. This is in addition to the World Health Organization’s classified categories of reasons for non-adherence and non-persistence (these are patient-associated, conditionassociated, therapy-associated, health system-associated and social-economic reasons).

Peripheral and Macular Photocoagulation NEW High definition imaging system:

Now available with the Easyret® Laser Pure yellow 577 nm wavelength for central and peripheral treatments: - SubLiminal® mode for DME & CSCR treatments, - MultiSpot mode for PRP treatments.

www.quantel-medical.com www.subliminal-laser-therapy.com | Dec 2021/Jan 2022 13


POSTERIOR SEGMENT

LASER THERAPY

Laser Remains an Effective Option for DME and CSCR Treatments by Hazlin Hassan

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iabetic macular edema (DME) is the leading cause of irreversible visual loss in the diabetic population. Laser plays a very important role in the treatment of DME despite the use of anti-VEGF agents, said Dr. Victor Chong, consultant ophthalmic surgeon at London Medical, United Kingdom, during a symposium at the recently held APAO 2021 Virtual. Indeed, studies have shown that even after anti-VEGF injections, some patients still require laser therapy.

SubLiminal laser therapy in DME Dr. Chong, who is an experienced pioneer of SubLiminal laser therapy and has published widely in this area for the last 15-20 years, cited a study on the comparative effectiveness of aflibercept, bevacizumab or ranibizumab for DME. “The first point I want to raise is that, when you go to conferences in the United States in the past few years, you would have thought that our American colleagues are no longer using laser. However, they should look at one of the studies that was only finished a few

years ago, the Protocol T,” he said.

in the majority of patients.”

In the DRCR.net Protocol T, the three different types of anti-VEGF agents for treating DME are compared. He noted that some 37-56% of patients required more laser treatment within the first year of the trial.

In the randomized, double-masked, multicenter, laser-controlled phase III RESTORE study involving 345 patients, results showed that ranibizumab 0.5mg combined with laser therapy was significantly more effective in treatment naive cases.

“When you start with around 40% of patients who had laser before joining the trial, and then another 40-50% requiring treatment in the first year despite injections, you will realize that laser is still very commonly used in the United States for diabetic macular edema,” he continued. “The basic concept is that even in a recent study, laser is still used

While conventional lasers, such as those used in the DRCR.net study, can sometimes cause collateral damage, Dr. Chong explained that with the SubLiminal laser therapy, laser energy is delivered in pulses with less collateral retinal damage, and there is no visible scarring. To summarize the role of lasers in DME, Dr. Chong said: “Lasers are still used in real life. Lasers are similar to anti-VEGF in early DME with mildly-increased central retinal thickness. Combined laser and anti-VEGF in treatment naive patients showed slightly better outcomes." “So don’t be afraid to use laser if the patient has never had treatment before. In DME with very good vision, lasers can delay the needs of anti-VEGF. SubLiminal laser might improve outcomes further,” he added.

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Safety first with the SubLiminal laser The 577nm SubLiminal laser is a safe option for the treatment of DME and central serous chorioretinopathy (CSCR), said Dr. Kenneth Fong, consultant ophthalmologist and vitreoretinal surgeon at OasisEye Specialists, Kuala Lumpur, Malaysia. “The benefits of SubLiminal laser is that you can preserve the retinal tissues, while having an effect on reducing macular edema at the macula area,” he said. SubLiminal laser therapy is known to have a durable effect, and can be combined with intravitreal therapies including injections and implants. SubLiminal laser refers to a laser beam that is broken into small pockets of pulses, and these small shots are controlled with a mechanism known as duty cycle. Duty cycle is the percentage of time that the laser is on, compared to the percentage of time that the laser is off. The laser’s off time helps to cool the retinal pigment epithelium and prevent the formation of scars on the retina. “By adjusting the on and off setting for the SubLiminal laser, we manage to reduce heat diffusion around the surrounding tissue, and this prevents the formation of laser scars,” said Dr. Fong. “The benefits are such that you can preserve retinal tissues while having the effect of reducing macular edema at the macula area,” he explained. “I use the SubLiminal laser with the 577 nanometer wavelength, which I believe is the ideal wavelength to create a good laser reaction at the retinal

pigment epithelium, without damaging the xanthophyll pigment, which is found predominantly at the macular region. Additionally, there is good penetration through opacities, like in cataracts, and it can allow you to titrate the power quite efficiently,” added Dr. Fong. It is important to titrate the power because every patient has different pigmentation in the retinal pigment epithelium. For best effects, Dr. Fong recommends a dense treatment, a large laser spot size of 160 micrometers and a duty cycle of 5%. His treatment strategy involves first testing with a 5% duty cycle, then reducing the power by 50% if he sees a mild reaction, and then lasering over the macula in the thickened area — although he cautions surgeons not to exceed 1.2W of power while titrating. If no visible threshold happens at 1.2W, keep this power as a reference level and use half of it for treatment (i.e., 600mW). During the SubLiminal treatment, no visible reaction must be observed, and there is no need to change power with different degrees of edema. Laser impacts must be confluent, Dr. Fong said.

In addition, transfoveal is not necessary and not recommended especially for new SubLiminal users. In cases of DME, the SubLiminal may be used with optical coherence tomography (OCT) to treat identified edematous areas. In non-center involved DME, SubLiminal treatment can be used alone; meanwhile for foveal involved DME, the best treatment option still remains an open question. “In general, the thicker the retina, antiVEGF therapy is more likely to be the first line treatment. Once the edema is settled, SubLiminal laser can be used to reduce the number of injections,” noted Dr. Fong. In patients without visual loss, SubLiminal laser can be used as the first-line treatment. If the edema deteriorates, then anti-VEGF therapy can be added. The SubLiminal treatment can be used in chronic CSCR and is an excellent alternative to mid-fluence PDT in first line treatment, said Dr. Fong.

Editor’s Note: APAO 2021 Virtual was held from September 5 to 11, 2021. Reporting for this story took place during the event.

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INDUSTRY UPDATE

New Website on Retinal Lasers available today and their clinical applications, Quantel Medical, a leader in ophthalmological laser, recently launched a new website dedicated to laser therapies for retinal disorders: www.subliminal-lasertherapy.com.

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herapeutic lasers have played a critical role in treating retinal pathologies and preventing blindness for decades, and its technologies have grown by leaps and bounds. In order to promote a better understanding of new lasers technologies

The development and introduction of new and innovative laser technologies has confirmed that, alongside intravitreal injections, retinal laser therapy still plays a valuable role in the surgeons’ treatment armamentarium. Today, thanks to 577 nm fiber laser technology featuring MultiSpot and SubLiminal® treatment modes, ophthalmologists can offer their patients enhanced laser treatment options, with greater safety and efficacy than ever before.

It provides a comprehensive database and an easy access to the latest clinical content about laser therapies for retinal disorders”, explains Julien Tixier, Laser Range Manager of Quantel Medical. With over 25 years of knowledge and experience in the field of ophthalmic lasers, Quantel Medical provides ophthalmologists with therapeutic laser solutions to treat the four main causes of blindness: glaucoma, cataracts, diabetic retinopathy and macular degeneration. Its products are available for direct purchase and via 100 independent distributors in over 110 countries. This website is already available in English and will be translated to Spanish by the end of the year.

"Our new website aims to promote a better understanding of the retina lasers of today.

INDUSTRY UPDATE

Therapeutic Indication of Aflibercept in Retinopathy of Prematurity Filed in EU and Japan

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etinopathy of Prematurity (ROP) requiring treatment is one of the most serious eye diseases that can lead to significant vision impairment and blindness. It is estimated that worldwide each year approximately 50,000 babies born prematurely who survive the neonatal period develop vision-threatening ROP. As a step forward in addressing the issue, Bayer had filed applications for a new therapeutic indication for aflibercept (solution for injection) in premature babies with treatment-requiring ROP in the EU and Japan. Bayer’s regulatory submissions are based on final results from the 6-month Phase 3 FIREFLEYE study of aflibercept

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0.4 mg versus laser surgery, which were presented at the 21st Congress of the European Society of Retina Specialists (EURETINA) in September 2021, as well as on interim data from the ongoing longterm follow-up Phase 3b FIREFLEYE NEXT study. “Results of the FIREFLEYE study show that treatment success was numerically higher with aflibercept than with laser,” said Professor Dr. Andreas Stahl, head of the University Department of Ophthalmology, University Medical Center, Greifswald, Germany, “and achieved with mostly single injections per eligible eye, less frequent need for rescue treatment and reduced requirement for general anesthesia compared to laser.”

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Aflibercept showed a positive benefit-risk profile in patients with ROP treated in 27 countries worldwide in the FIREFLEYE study, the first randomized prospective clinical trial comparing aflibercept to laser in premature babies with ROP requiring treatment. Although the FIREFLEYE Phase 3 study missed statistical significance for the primary endpoint of demonstrating non-inferiority of aflibercept 0.4 mg to laser (90% CI for treatment difference: −8.0% to +16.2%), the treatment success with aflibercept 0.4 mg (85.5%) is considered clinically relevant. In the control group (laser surgery), a response rate of 82.1% was observed. In this study, aflibercept has demonstrated to be efficacious, safe and well-tolerated.


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COVER STORY

At the Crossroads of Gaming and Ophthalmology by Brooke Herron

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ave you ever played a virtual reality game? If you have, then you know it’s a truly immersive experience. Not only are you “inside” the game visually, it’s interactive: The non-player (or computercontrolled) characters react to your behavior, as do the storylines (in some games, anyway). Indeed, in gaming, artificial intelligence (AI) creates a responsive, adaptive and interactive video game experience for the player. But in ophthalmology, we’re hearing a lot about AI as well. According to Prof. Jeff Henderer, chairman of ophthalmology at Temple University, (Philadelphia, Pennsylvania, USA), image-based specialties are more likely to have the opportunity to have AI-assisted image interpretation:

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“Radiology is probably the leader, but ophthalmology — for certain retinal image applications — is coming along,” he said. To learn more about the considerations, challenges and benefits of using AI in ophthalmic practice, we spoke with Prof. Majda Hadziahmetovic, MD, assistant professor, Department of Ophthalmology at Duke University, (Durham, North Carolina, USA). She shared that diabetic retinopathy (DR) is one condition that could benefit from AI-enabled screening and monitoring.

Using AI to create access According to the International Diabetes Federation, in 2019, 463 million adults had diabetes — this is expected to increase to 700 million by 2045. This large population with diabetes, combined with fewer physicians to treat them, could create a perfect storm of debilitating health conditions, including blindness.

“In addition to the devastating consequences on those with the disease, the care of DR creates a significant economic burden to the U.S. healthcare system. Fortunately, early detection and treatment have been shown to significantly improve clinical [outcomes] and cost-effectiveness.” — Prof. Majda Hadziahmetovic, MD In the United States, Prof. Hadziahmetovic said, diabetic retinopathy is a leading cause of blindness that affects millions of people: “In addition to the devastating consequences on those with the disease, the care of DR creates a significant economic burden to the U.S. healthcare system. Fortunately, early detection and treatment have been shown to significantly improve clinical [outcomes]

and cost-effectiveness.” Part of the reason for the burden is the need for annual screening — and it’s estimated that only 40-50% of patients are adherent to the recommended screening intervals, said Prof. Hadziahmetovic. “As a result, much emphasis has been placed on developing effective and accessible ways of screening,” she continued. “Screening for DR has clear guidelines and is becoming increasingly mandated in the U.S. Regardless, DR screening via traditional methods (e.g., dilated fundus exam by eye care specialists) is heavily dependent on resource availability in each community, and thus frequently, is not very successful.” She explained that although teleophthalmology can be very effective and has attempted to address this unmet need, barriers still exist for widespread implementation (i.e., cost and lack of universal standards). A potential solution, she suggests, would be to perform retinal imaging for DR screening at the patients’ primary care provider (PCP) or endocrinologist follow-up clinics. “Retina screening in this setting has multiple advantages, including accessibility, patient capture and cost-effectiveness,” said Prof. Hadziahmetovic. To achieve the best possible care and improve visual outcomes, she said standardized methods for retinal imaging and interpretation must be developed. This includes assessing the cost, visual outcomes, patients' satisfaction, and testing novel imaging modalities in these settings. “Last but not least, we should strengthen multidisciplinary collaboration focused on the development of deep-learning methods for high-accuracy, fast and inexpensive image interpretation,” said Prof. Hadziahmetovic. Patients who will benefit most are diabetic patients, but also this approach can be used for glaucoma screening, and in general, for the screening of any other retinal pathology (e.g., age-related macular degeneration; AMD).

Remote imaging and teleophthalmology Prof. Majda Hadziahmetovic was the co-author of a prospective, nonrandomized study that explored feasibility of remote ophthalmic imaging to identify referable retinal abnormalities and assess the effectiveness of color fundus photography (CFP) versus optical coherence tomography (OCT) cameras (MaestroCare, Topcon). The study included 633 patients with diabetes at Duke Primary Care.* “Besides the previously reported better image interpretability of OCT relative to fundus photography on the un-dilated pupil, using both imaging modalities independently could potentially lead to higher false-positive rates. Combining OCT and fundus photography was associated with improvements in operational outcomes,” she said. “On the other hand, we have demonstrated that color fundus photography was significantly more supportive in identifying DR relative to OCT (p<0.001). In contrast, OCT was substantially more supportive for retina-referable incidental findings (e.g., AMD, ERM. P<0.001).” Results showed that remote images from OCT were significantly more interpretable than CFP (98% vs 83%, respectively; P < .001). Among patients with DR, OCT and CFP were helpful in 58% and 87% of cases, respectively (P < .001). “Albeit requiring deeper insight, these findings are important to guide the choice of imaging modality depending on the targeted retinal pathology,” said Prof. Hadziahmetovic.

* Lee T, Amason J, Del Risco A, Kim J-B, Cousins SW, Hadziahmetovic M. Incidence of Referable Retinal Disease in Diabetic Patients at a Primary Care Practice. J Vitreoretin Dis. 2021: 24741264211044223

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COVER STORY

Further, EyeArt agreed with the human grade of no retinopathy (specificity) in 68% (67% to 69%), with a specificity of 54.0% (53.4% to 54.5%) when combined with non-referable retinopathy.1 These results led investigators to conclude that “AI machine learning and deep learning algorithms such as this can provide clinically equivalent, rapid detection of retinopathy, particularly in settings where a trained workforce is unavailable or where large-scale and rapid results are needed.”

Real world benefits For the last two years, Prof. Alan Wagner, retina surgeon at Wagner Macula and Retina Center, (Virginia Beach, Virginia, USA) has been working closely with Eyenuk (Los Angeles, California, USA) on its EyeArt platform, the first FDA-cleared AI technology that autonomously detects both mild and vision-threatening DR. “Their product [EyeArt] on diabetic eye disease is extremely good … there's no question that it’s better than humans, or as good,” he continued. “We found it to be exceptional. And the idea that they can do the reading for us on the fly … it’s fast, it’s real time. That’s very helpful when you're out in the public, and with different kinds of people coming through.” A study published in the British Journal of Ophthalmology showed that EyeArt’s “algorithm demonstrated safe levels of sensitivity for high-risk retinopathy in a real-world screening service, with specificity that could halve the workload for human graders.” In the study, 30,405 retinal images were both manually graded and assessed by EyeArt (v2.1). The authors found that sensitivity (95% CIs) of EyeArt was 95.7% (94.8% to 96.5%) for referable retinopathy (human graded ungradable, referable maculopathy, moderate-tosevere non-proliferative or proliferative).

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Prof. Alicja Rudnicka, one of the study’s authors, said that with this technology, “people with diabetes may get their results quicker from screening visits, with potential savings to the NHS as fewer images would need to be graded by humans.” Using AI to grade these images will not only improve DR screening in countries like England, it will also assist in less developed countries or areas with fewer resources. “It’s probably quite important for less developed countries with limited healthcare facilities,” said Prof. Rudnicka. “The possibility of a digital interface to analyze retinal images may be the only option.”

AI in practice Prof. Jeff Henderer has been using EyeArt in practice for the past year, and in a research study prior to that. “I'd say it [AI] has replaced our screening practices. We used to take photos and have our optometrists read the photos and the turnaround time was a couple days at best. Now the AI interprets the photos at the point of care, so the patient leaves the camera with an answer,” said Prof. Henderer. He hopes that these improvements will lead to better follow-up rates: “First, the patient knows if they need a follow-up exam. Second, the primary care doctor

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(PCP) knows if they need a follow-up exam, which makes for happier primary care doctors; it also allows for the primary care doctor to participate in scheduling the patient for the eye exam if needed, rather than asking the patient to do it.” Prof. Henderer explained that one thing has remained the same — and that’s having optometrists review the images (at least) every three years. This helps ensure that other eye diseases like AMD and glaucoma aren’t missed. Screening for eye disease is a threelegged stool, added Prof. Henderer. “One leg is making sure you can actually do the screening (e.g., the location, camera, software, photographer training, the ability to bill and get paid for the image).” Then, he said, the second leg is getting the patient to the camera. “If the location is in a primary care doctor's office, this requires buy-in from the PCP to ensure a workflow is established to enable photos. Whether that is while patients are having a regular doctor visit or a separate appointment type, without the PCP's help, the program will fail.”

“Getting patients to the camera and closing the loop between screening and follow-up care doesn’t attract a lot of attention, but it's critical to ensuring the screening program works. In fact, without all three legs symmetrically in place, the screening program will fail.” — Prof. Jeff Henderer, MD The third leg is what happens after the patient is screened: “You have to make sure the PCP has a place to send the patient and that the receiving ophthalmologist accepts the insurance and understands why the patient was referred,” said Prof. Henderer. He also says it’s important to track down


Contributing Doctors patients who missed their follow-up to ensure they’re able to get care. “Getting patients to the camera and closing the loop between screening and follow-up care doesn’t attract a lot of attention, but it's critical to ensuring the screening program works. In fact, without all three legs symmetrically in place, the screening program will fail.” Prof. Henderer added: “Now the issue is the cost of the cameras and how you will handle those patients who fail the screening. It's not helpful, and probably not ethical, to screen for disease if you have no plan to care for the patients after the screening.”

Impacts beyond screening AI has other potential uses outside of screening, said Prof. Alan Wagner. It can be used to predict patient behavior as well. Before the patient walks in the door, it can help identify if they will show up — for example, will the weather impact their presence? He said this helps them maximize the experience for the patient and enhance compliance. “If you know what it takes to make sure they show up, that’s the first step,” he said. “Second, if we can understand how to get all their information together (i.e., pathology, medications, comorbidities, etc.) that helps too.” AI can also help with simple things, like determining the best pathway through the practice. All of this ensures a far more streamlined and orchestrated event for the patient, said Prof. Wagner. “The patient is getting more efficient care as opposed to getting unnecessary tests. With the use of AI, it’s possible to deliver the highest quality and lowest cost care, continued Prof. Wagner. “You're going to be able to predict what you need, where you need to be … to predict when is the right time to give someone an injection — 3 weeks, 5 weeks or 8 weeks? “There's also at-home monitoring of subretinal fluid, and whether fluid should or shouldn't be there, treating to dry, all that data all is crunchable,” he said. “This will reduce the demands on the population, doctors and resources. It should be able to significantly reduce the

spend that we have on drugs, too.”

In the end, patients win At the end of the day, Prof. Wagner said the patients will benefit most from AI: “If we're really, truly patient-focused, if we’re really community-focused … the concept of rebuilding the world anew every day, then it's the exact right thing we need. I can tell you, ‘embrace it, don't fight it.’ Let's make the world better, let's help people, let’s do the right thing,” he said. Prof. Jeff Henderer agreed and shared that patients will benefit most from using AI to screen for DR. “They will be able to get a rapid test result in a setting other than an eye doctor's office. “No one wants to see AI replace a human, but we don't have enough humans to manage all the patients. Using automated image analysis to help us ensure that we are only seeing those patients who need to be seen will be a great help. There is no bigger waste of time and money than the annual diabetic eye exam when the patient is normal,” he continued. “Figuring out how to better target those who need to be screened and using AIimage interpretation to make sure the normal patients aren't coming in for eye exams are two keys to helping a limited number of providers manage a growing population of diabetics.” Secondary to patients, the use of AI will be beneficial to primary care doctors: “They will be able to trigger quality incentive payments which can be worth a great deal of money,” said Prof. Henderer. “The third beneficiary will be ophthalmologists. We will no longer be seeing diabetics without disease and will be able to target our resources more efficiently toward those who need care.”

Reference: Heydon P, Egan C, Bolter L. Prospective evaluation of an artificial intelligence-enabled algorithm for automated diabetic retinopathy screening of 30,000 patients. Br J Ophthalmol. 2021;105(5):723-728.

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Prof. Jeffrey D. Henderer, MD, is a professor of ophthalmology and has been the Edward Hagop Bedrossian Chair of Ophthalmology at the Lewis Katz School of Medicine since 2008. He served for six years as the secretary for curriculum development for the American Academy of Ophthalmology, has published over 50 peer-reviewed papers, has won several honor and secretariat awards from the AAO and has been the Temple Ophthalmology teacher of the year six times. He recently added a new role as the chief medical officer of Ambulatory Practices for the Temple Faculty Practice Plan, Inc. jeffrey.henderer@tuhs.temple.edu Prof. Majda Hadziahmetovic, MD, is an assistant professor in the department of ophthalmology at Duke University in Durham, North Carolina. The author reports no related disclosures. majda.hadziahmetovic@duke.edu Prof. Alicja Rudnicka is a professor in statistical epidemiology in the Population Health Research Institute and has expertise in large-scale population based artificial intelligence (AI) retinal imaging projects. She has been involved in evaluating AI technology to analyze retinal images from diabetic patients to detect sight-threatening diabetic eye disease, and recently secured funding from NHSX and the Health Foundation. arudnick@sgul.ac.uk Prof. Alan Wagner, MD, FACS, FICS, is a vitreoretinal surgeon and ocular oncologist serving as an associate professor of ophthalmology at Eastern Virginia Medical School and the Via College of Osteopathic Medicine. He established one of the very first telemedicine networks to address diabetic eye disease screening in 1992. He has been a pioneer in the application of Lean Six Sigma principles to clinical practice, published dozens of peer-reviewed papers, and has won several honor and secretariat awards from the AAO and state medical societies. Recent federal grant funding has recognized and supported the ongoing efforts of his team actively addressing health disparities using telemedicine, advanced data analytics, and community partnerships. Prof. Wagner discloses that he is now an investor with EyeNuk. awagner@wagnerretina.com

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INNOVATION

RETINA TRACKER

iCare COMPASS Detects Retinal Defects Early

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by Andrew Sweeney

laucoma is the second leading cause of blindness worldwide, and the earlier you can reliably detect it the better for the patient, the doctor, and the society. The iCare COMPASS perimeter is focused on identifying retinal diseases like glaucoma accurately making early and correct diagnosis possible. Additionally, the clinic enjoys benefits from workflow improvements iCare COMPASS brings along.

Value for the clinic and the patient The COMPASS perimeter represents a significant step forward in ophthalmic technology. It combines what clinicians need — which includes visual field tests, active retinal tracking for fixation loss correction and confocal TrueColor fundus imaging. Overall, the iCare COMPASS is a simpleto-use device that offers considerable benefits for patients and the clinic. It can perform standard visual field threshold tests, suprathreshold tests, fundus imaging and fundus stereo imaging. Plus, the device is patient- and user-friendly

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as the tests are straightforward thanks to non-mydriatic and trial lens free operation, touch screen, auto-alignment, auto-focus, and the feature that a test can be discontinued any time and continued again without data loss.

be unstable and organizing of separate fundus imaging in a separate space with a separate machine.

In addition, the iCare COMPASS’ retinal tracking is perhaps its most important feature. iCare reports that it’s able to ensure strong correlation between retinal threshold values and retinal locations without the process being disrupted by artefacts created by eye movements or blinking. This will make the progression analysis reliable and the entire procedure smooth and comfortable for the patient.

Another key feature that’s likely to be of note to eye care professionals are the COMPASS’s suprathreshold tests, particularly the new Quick Suprathreshold test which can be used to screen for visual field loss and takes only 30-90 seconds per eye having high agreement with clinical judgement. The test then returns a measured response rating of “seen at lower intensity”, “seen at higher intensity” or “not seen at higher intensity”, while also analyzing fixation stability, false positives and optionally full foveal sensitivity threshold using Zest strategy. The test report also includes TrueColor images of the optic nerve head and fundus.

There are also tangible workflow benefits for an everyday practice. The time and effort that is usually consumed by technicians to find out the refraction values and the corresponding trial lens is saved as COMPASS automatically focuses correctly without trial lenses. Neither is there any surface like a bowl that would require special cleaning between patients. Non-existing with COMPASS are also frustrating re-tests just because the patient’s fixation might

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New: Quick Suprathreshold

To learn more about the iCare COMPASS, visit the iCare COMPASS website: www.icare-world.com/icarecompass-trade-in-campaign.


Unique , Smart and A.I. solutions for Eye Care Specialists!

FAST Get all the measurements in 3”

FRIENDLY Easy-to-use and patients friendly

ACCURATE Suitable for adults and kids

PORTABLE Take it everywhere

MULTIFUNCTIONAL Widest range of Application

SAFE Safety Working distance > 1 m

www.adaptica.com contact@adaptica.com Adaptica srl: Via San Marco 9/H, 35129 Padova (PD), Italy

MADE IN ITALY

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25


ENLIGHTENMENT

WOMEN IN OPHTHALMOLOGY

#realtalk with

Dr. Apoorva Ayachit

Making Her Voice Heard by Tan Sher Lynn

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r. Apoorva Ayachit came from a household of ophthalmologists from the city of Hubballi in South India. “My father is a vitreoretinal surgeon and has been practicing for 35 years. His maternal uncle started the M.M. Joshi Eye Institute in 1967 and it has grown by leaps and bounds ever since. I am a third-generation ophthalmologist. There are eight other ophthalmologists in my family,” she shared.

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The M.M. Joshi Eye Institute, a 54-year-old super-specialty eye care hospital, caters to several districts across four states of India. “I have seen my family serving the needy selflessly. Hundreds of thousands of vision-restoring surgeries have been performed free-of-cost. Our small city attracts thousands of villagers — poor farmers, laborers, government-school teachers, sanitation and construction workers — who come here for health care every single day. Our institute has

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a huge influx of medical and surgical cases encompassing all subspecialties and it is immensely gratifying to see our patients getting advanced eye treatment, without having to travel to a “big city.” My patients are my driving force and the reason I love my job,” she stated.

A young leader One of the highlights in Dr. Apoorva’s


career was being chosen as the academic-in-charge of the Young Ophthalmologists Society of India (YOSI). “We had a great time organizing conferences, webinars, case competitions and quizzes. Many young ophthalmologists have benefitted from YOSI in terms of overcoming challenges in residency, fellowship and the early practice years. Our society meetings are focused and have high-yield topics. Young ophthalmology leaders speak about how to apply for grants, making the best of international conferences, and how to make award-winning videos and presentations. We have had group meetings about how to go about publishing, from the very basics like writing a case report, writing a good thesis, learning statistics, to writing a high-quality manuscript. Our colleagues with flourishing private practices shared their secrets like choosing equipment, maintaining ophthalmic assets, etc., in society meetings to benefit the younger ophthalmologists,” she shared. Apart from being a clinician and having a leadership role on a national forum, Dr. Apoorva mentors research projects and is a thesis guide for residents and fellows at her institute.

Breaking the glass ceiling Dr. Apoorva is not only blessed with a surgical oncologist husband and a 2-year-old toddler, but parents and parents-in-law that are supportive of her career. “My parents and parents-inlaw are instrumental in helping me care for my daughter while my husband was pursuing his onco-surgery residency in a different city. Truly, behind every woman who seems to have-it-all, there is a loving family and great friends,” she remarked. Nevertheless, she noted that gender bias, both overt and subtle, still exists in the field. “The biases we encounter are usually the result of an ingrained patriarchy, and hence women ophthalmologists still face

condescension from some of our colleagues. In India, a subset of patients still want to see a “real doctor” after I’ve seen and examined them. Some colleagues find it harder to believe that I operate on extremely challenging cases. And there is a strange stereotype reserved for women in retina, that if a woman publishes a lot, it’s probably because she is not a good surgeon! One of my mentors told me very simply that it is not my job to fight real or perceived biases. We must let our work speak for itself,” noted Dr. Apoorva. She added that apart from the above, other setbacks include the lack of autonomy women ophthalmologists face even after being fully trained as specialists. “Getting married and moving elsewhere to facilitate the spouse’s career or training, and having to take a long break for child-rearing are still issues that are expected from a woman by no real logic except by default. As such, we must ensure that talented women do not pass up on career opportunities because of responsibilities that are supposed to be shared and not borne alone. Some simple measures could be setting up a creche [nursery] in fellowship institutes, providing a nursing/ pumping room and flexible work time for young mothers. Super specialist moms should have time for their careers and the dads need to avail paternity breaks,” she commented. To women ophthalmologists, Dr. Apoorva has this simple but allimportant advice: “Prioritize yourself over everything else. You are the only person who can look out for yourself. Do not depend on others for your Ikigai*.”

Prioritizing eye health Looking into the future, she hoped that more emphasis will be put on eye health and care. “The ophthalmology industry is the most tech-savvy

specialty with huge advances in the last decade alone. Tech increases cost. If the healthcare system understands that quality eye- care costs a lot more than, say, medication for diabetes, then preventive ophthalmology can be prioritized and worked on. For this, in developing countries like India, governments should be conversant with eye health and its needs. Pediatric eye health, cataract surgeries, diabetic eye health and corneal transplant drives should be the priority. The only way we can do this is by education and knowledge sharing. We as ophthalmologists have a huge responsibility of using our resources to empower the public and public health authorities about eye-related issues. Using social media soundly and creating awareness in the digital space is the way forward. Advocacy by each one of us for a better pro-patient eye care system is the need of the day,” she stressed. * Ikigai (pronounced “eye-ka-guy”) is, above all else, a lifestyle that strives to balance the spiritual with the practical.

Contributing Doctor Dr. Apoorva Ayachit is a vitreoretinal (VR) consultant involved in teaching, research and surgical training at M.M. Joshi Eye institute, Hubballi. Her competencies include complex VR surgery, macular imaging and uveitis. She has 26 indexed publications and six book chapters to her credit so far. She holds the position of assistant editor in the Indian Journal of Ophthalmology (IJO) and is an active reviewer in international ophthalmology, clinical ophthalmology, ocular immunology and inflammation. She leads the Young Ophthalmologists’ Society of India (YOSI) as academic in-charge and has conducted several academic programs for young ophthalmologists-in-training, education and practice in association with the All-India Ophthalmic Society (AIOS). In her free time, she loves to read and work out. apoorva.ag@gmail.com

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CONFERENCE HIGHLIGHTS

ASRS 2021 COVERAGE

Some Notable Highlights from ASRS 2021 In Case You Missed It! Ye e -

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by Nick Eustice several recorded and remote video presentations interspersed among those present.

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The bringing together of people, whether in-person, through online engagement, or as samples in testing data, was a recurring theme throughout the many lectures at this year’s meeting. Across quite various topics in retinal medicine, speakers encouraged their audience to seek the inclusion of a more diverse spectrum of individuals in the field.

A wider sampling in diabetic retinopathy Following an opening reception on the previous evening, the conference kicked off on the morning of October 9th with two successive symposiums on the subject of diabetic retinopathy. While much of the big news in this area concerned exciting new treatment options such as gene therapy and antiVEGFs, the first speakers presented on topics more demographic than technological.

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n a much-anticipated return to normalcy, the American Society of Retina Specialists (ASRS), the largest retina society in the world, hosted its annual conference live and in-person this past October. Due to restrictions and concerns surrounding the COVID-19 pandemic, the society was forced to put together a limited and online-only event last year. At this year’s event in San Antonio, Texas, the ASRS was once again

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able to welcome its members and guests for presentations on the field’s cuttingedge developments in retina research. While the effects of the pandemic were still clearly being felt during the conference, the atmosphere among presenters and attendees alike showed a lot of relief at being able to meet inperson once again. All the while, many more still chose to attend virtually, with

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In the first such lecture, Professor Rahul Khurana of the UCSF Medical Center (USA) addressed the dangers of lack of follow-up among diabetic retinopathy patients. He presented a series of alarming statistics from a study aimed at finding out how and why patients abandon their treatment regimens, and offered a number of suggestions on what might be done to keep patients receiving the care they so badly need. Though improvements in treatment are of course vital to improving peoples’ lives, it is of primary urgency to make sure that patients are receiving that care in the first place. Continuing in a similar vein, Dr. Abdul-


Hadi Kaakour and Dr. M. Ali Khan each presented separately on the inaccurate representation of different racial groups in clinical research studies. Dr. Kaakour’s lecture highlighted discrepancies between the sample sizes of racial groups in test studies as opposed to their representation in census data. These studies typically represented a less-than-accurate proportion of the population on the basis of race, with a disproportionately low number of minority participants being reflected in the broader pool of results.

retinal conferences, that number only increased from 19.6 to 25.4% from 2015 to 2019. What is in many ways a bigger concern, is the finding that the greater bulk of this participation has been in collaboration on abstracts, but not as presenters themselves. Thus, while women are making strides in their involvement, there is still a long way to go.

Dr. Khan also used statistical data to show that only Black patients (themselves underrepresented) and White patients had large enough sample sizes to yield relevant results to compare their results and risk factors. No other minority groups were tested in such numbers as to make for relevant comparisons. Both Drs. Khan and Kaakour advocated for a more realistic sampling of patients in order to produce more complete data, which could hopefully lead to more effective treatment methods.

Another major topic in retinal science was the subject of numerous lectures on Day 3 of the conference: age-related macular degeneration (AMD). Striking a similar note to the first lectures during the conference, Dr. Franco Recchia presented a study concerned with the way we process data in clinical studies. Much like the diabetic retinopathy lectures that questioned why patients do not pursue follow-up care and the underrepresentation of different racial groups in studies, Dr. Recchia’s focus was not on what information we can get from studies, but rather what factors — and what patients — are missing from studies.

Gender diversity in the professional community Turning from the subject of patients to that of their doctors, Dr. Jayanth Sridhar presented some very encouraging figures on the growing number of women involved in ophthalmology, and especially those taking a leadership role in the field as well. Speaking during the Socioeconomic/Practice Management Symposium, Dr. Sridhar shared statistics on the number of women doctors who had presented in conferences such as the ASRS meeting over a period of five years. Women now represent a majority of medical school graduates. While not yet a majority in the specialization of ophthalmology, their numbers have grown impressively in recent years to 41% of residents. This positive trend shows a growing place for women doctors in a field where a substantial gender imbalance remains.

Being objective with AMD studies

Dr. Recchia’s study concerned a simple, but extremely important, omission in medical testing data: those patients who, for whatever reason, are not eligible for studies. In a study conducted in his own clinic, Dr. Recchia noted that the majority of his patients with a new diagnosis of active choroidal neovascularization (CNV) in neovascular AMD were ineligible for research studies in this area. This was due mainly either

to patients’ vision characteristics and prior treatment. In sharing these findings, Dr. Recchia reminded the audience that studies do not always show us an accurate picture of what might be happening out in the real world. While it is of course necessary to maintain a degree of control in a research study’s pool of patients, we must keep those limitations in mind when applying a study’s results in the real world.

The take home message While the topic of greater inclusivity seemed to be a running theme through many of the ASRS meeting’s lectures, there were a great many more topics that were addressed at substantial length. Clearly, an overview article like this one can only scratch the surface of the many fascinating topics covered during this year’s ASRS meeting. For a much more in-depth look at this year’s lectures, make sure to check out our combined coverage of this year’s ASRS & ESRCS conferences, or you can also check out the recorded lectures on-demand from the ASRS website. All in all, it was great to see people coming together again for a conference much more in line with the past. In many ways, the challenges of having to meet online have led to a greater degree of inclusion in the meeting than ever before. Perhaps, then, it’s no accident that many of the speakers found themselves talking about bringing more and more people to the table.

Editor’s Note: ASRS 2021 took place online and in-person in San Antonio, Texas, USA, from Oct. 8-12. Reporting for this story took place during the event.

While Dr. Sridhar’s study shows considerable growth in the number of women who have participated in peer-oriented

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CONFERENCE HIGHLIGHTS

EURETINA 2021 COVERAGE

IN BRIEF

3 Fantastic Posters from EURETINA 2021 by Sam McCommon

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very great ophthalmic conference is chock full of posters — and EURETINA 2021 was no exception. They’re more like the rule, really, as 465 posters were presented on all your favorite posterior segment news. We’re just as excited about that as you are, so we’re doing a retrospective on some of our favorite posters from the session — for our own edification and, more importantly, for that of our dear readers. Do you know just how much we love you? Before we start waxing sentimental, let’s get into the posters. There’s a lot of ground to cover here.

Anti-VEGF and IOP: Any link? A study out of the United Kingdom helped shed some light on the connection between intraocular

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pressure (IOP) and anti-VEGF injections. Clearly, glaucoma needs to be taken into consideration when making any ophthalmic decision. Dr. Daisy Bassey-Duke, from Birmingham, U.K., led the presentation. The study took place in an anti-VEGF clinic in a tertiary care unit, with around 200 largely elderly patients being measured for IOP using rebound tonometry. Patients who were known to have glaucoma, ocular hypertension (OHT) or were on IOP-lowering medications were excluded. So, what’s the word? As Dr. BasseyDuke noted, “no significant link was found between the number of anti-VEGF injections and a rise in IOP.” So, that’s good news. However, as most patients were elderly (averaging 74-80-yearsold), their advanced age remains a risk factor for glaucoma. Some cases

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developed a rise in IOP in untreated eyes. Dr. Bassey-Duke suggests routine assessment of IOP as part of a regular diagnostic process in anti-VEGF patients can help identify patients at risk of developing glaucoma.

The LIGHTSITE II Study: Photobiomodulation and dry AMD A team of doctors from across Europe presented the results of LIGHTSITE II, which studied the effects of the Valeda® photobiomodulation (PBM) light delivery system (LumiThera, Poulsbo, Washington, USA). The results are quite uplifting, but let’s cover a bit of background here first. As the poster noted, Valeda uses multi-


wavelength LED light for treatment consisting of 590, 650, and 850nm wavelengths. The device is applied to a patient’s eyes for about 4-5 minutes per eye. The study covered all the gold standard bases: double-masked, randomized, sham-controlled, parallel group and multi-center. So, the testrunners really did their homework to make sure this was set up and run correctly. The test ran up to 9 months, with checkup at 10 months. Among the successes was a potential reduction from dry to wet AMD conversion. In the study, 3.1% of PBM patients converted from dry to wet AMD, compared to 5.6% in sham-treated patients and 4.8% in overall eyes. PBM was also shown to improve bestcorrected visual acuity (BCVA), with consistent improvement over the course of the treatment and a significant change over 9 months. How significant, you ask? The improvement was to the tune of a 4-letter improvement in BCVA, with 35% of patients improving 5 letters or better. This was roughly double the improvement in the sham-controlled group. PBM additionally showed positive effects on drusen and geographic atrophy (GA). PBM patients did not show any drusen growth, as opposed to sham-treated patients — who did experience drusen growth. Similarly, sham patients showed increased GA, whereas PBM patients showed a 44% reduction in GA at 9 months. Those are some significant numbers for some fairly simple treatment. Perhaps best of all, there were no adverse events reported — so this

appears to be one of those golden treatments that poses little to no risk to patients while promising significant benefits. We’re always happy to hear stories like this.

Geographic atrophy and quality of life Delving a bit deeper into GA and dry AMD led us to a poster presented by a team out of the United States, led by Dr. Daniel L. Jones. The study examined the clinical and humanistic burden of GA, and, well, it’s not pretty. As you likely know, GA is essentially the end-stage, advanced form of dry AMD. There is no treatment for it yet, though you can be certain pharmaceutical companies are hard at work trying to find one. Oddly enough, as the poster noted, the epidemiology and pathophysiology of GA are not well documented. We do know however, that GA will continue to grow as a problem as populations age worldwide, especially in countries with advanced economies. For example, Denmark had roughly 23,000 GA cases in 2020, but is projected to have 41,000 in 2040 and 50,000 in 2060. This problem isn’t going away. So what does that mean for the quality of life of patients who suffer from GA? These sorts of questions become important to the functioning and wellbeing of society in general when so many people are affected. Well, here it is: Patients with GA have a poor quality of life (QoL). That may not be a shocker to most, but the causes

and effects of life being rough tell some more tales. Specifically, the study covered three main QoL factors: reading, transportation/driving and everyday activities. Or, as most of us refer to it, “life.” Because GA patients have more difficulty reading, they’re less engaged in current events and religious services. Because they’re limited in their ability to drive, they become isolated and lonely, as well as reliant on others. Because they have vision problems, they have to carry visual aids everywhere and take extra time to prepare for unfamiliar settings. On top of that, patients reported reduced exercise, less engagement with friends, more spoiled food, difficulties keeping their abode clean, and a loss of self-esteem. Reduced visual function is also linked to depression, as the presenters noted. Everyone in the medical community (and world, for that matter) cannot forget the human. Society is broadly tending toward a more mechanized view of life and human interaction, but humans themselves have not changed. Isolation, a loss of freedom and a loss of self-respect are serious problems in an individual’s life — and when it becomes more common, societies will suffer. Minimizing GA or doing anything at all to reduce its effects will be one of the holy grails of ophthalmic science in the near future. It shouldn’t just be a medical priority, but a national one. Yes, we’re an ophthalmic publication and we’re not entirely neutral, but come on. Let’s get cracking on this one.

Editor’s Note: The EURETINA 2021 Virtual Congress was held from September 9 to 12, 2021. Reporting for this story took place during the event. The sun may have set on EURETINA 2021, but we’ll always have its posters...

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CONFERENCE HIGHLIGHTS

OIS @ASRS COVERAGE

OIS Webinar Highlights Remarkable Retina Developments by Andrew Sweeney

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hen it comes to the most rip-roaringly riveting subjects in the field of ophthalmology, it’s hard not to become enraptured by the retina — it’s an exciting field full of innovation, and at Media MICE, we’re just a little bit obsessed by it (as we should be). Whether it be diabetic retinopathy, macular hole, retinitis pigmentosa or the humble retinal tear, our enthusiasm runs high. So, when we get to cover a symposium about all the latest developments in this specialty, we get pretty excited.

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The Ophthalmology Innovation Summit (OIS) became familiar to many of us during the COVID-19 lockdowns — and the institution’s high-quality online events kept us from going crazy with boredom. They’ve covered everything from glaucoma, to dry eye and presbyopia, and offer showcases that highlight the companies worldwide that are working on new developments. Some of the webinars we highly recommend you watch include those focused on Israel and Europe.

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The OIS Retina Innovation Showcase streamed live on October 7, 2021 and was another well-produced webinar; it also had a physical presence at the Grand Hyatt Hotel (San Antonio, Texas) in time for the ASRS 2021 Annual Meeting — a welcome sign that ophthalmology events are beginning to return to normal. What was immediately apparent to the online viewer however, was how enlarged this particular event was, offering more videos than one would normally expect. Some of the company


showcases were fascinating and are well worth watching on-demand — we included some of our favorites here.

I’ve got a need, a need for improved delivery systems One of the standout company presentations during OIS was by Dr. Clark E. Telford PhD, the co-founder, president and CEO of LumiThera (Poulsbo, Washington). This company has created the Valeda Light Delivery System, which is described as a new treatment delivery system that takes less than five minutes to treat an eye without the requirement of pupil dilation. It’s specifically designed for the treatment of dry age-related macular degeneration (AMD) and is currently undergoing trials in the U.S. Dr. Telford reported on several of the studies involving the Valeda Light Delivery System, pointing in particular to LIGHTSITE I, which was published in Retina. In this study, 46 eyes were studied, of which 50% of patients experienced a greater than five letter improvement, along with notably improved quality of vision. In the follow-up EU study, LIGHTSITE II, 35% of eyes experienced the same level of improvement.

and protects against hyperglycemia, with a potential for monthly or semimonthly dosing. RZ402 is marketed as an alternative to anti-VEGF and targets the Kallikrein–Kinin System (KKS) to address inflammation and vascular leakage. What’s particularly interesting is that it’s delivered orally, and reportedly suppresses vascular leakage (up to 80%) in relevant animal studies.

Wake me up before you re-grow We are, unfortunately, unable to re-grow human tissue in a lab to any great degree, though to be sure, who knows what the future holds — incredible new developments may occur after all. In the meantime, we can look to the work of companies like Regenerative Patch Technologies (RPT; Santa Barbara, California), a company developing cell-based implant technology for the treatment of retinal diseases. In a presentation on behalf of the company by Dr. Suber Huang, CEO of the Retina Center of Ohio and Voluntary Assistant Clinical Professor of Ophthalmology at Bascom Palmer Eye Institute at the

University of Miami, we heard about the development of a bioengineered implant for improved vision in dry AMD patients. Dr. Huang described how RPT’s flagship product — California Project to Cure Blindness-Retinal Pigment Epithelium 1 (CPCB-RPE1) — is poised to revolutionize dry AMD treatment via a polarized monolayer of human embryonic stem cellderived RPE (hESC-RPE), specifically designed to mimic Bruch's membrane. He said that the device is implanted via already established retinal procedures, making it accessible and achievable in an outpatient setting. A phase 1/2a study assessing the safety and efficacy of CPCB-RPE1 in patients with dry AMD is currently underway — we look forward to hearing the results. There are dozens of other videos from the OIS Retina webinar that we highly recommend you watch, and not just company showcases. There are several panel discussions for you to view, as well as an award ceremony or two … so, check out their website. We’ll be covering the next OIS event as well, so make sure you drop by when we do!

Another presentation (especially notable for its fantastic use of the letter ‘z’) was about metabolic drug development company Rezolute (Redwood City, California). Given by the company’s Vice President of Clinical Development and Ophthalmology Lead Dr. Rajat N. Agrawal, the seminar’s audience heard about how Rezolute is focused on two products. These are RZ358, for congenital hyperinsulinism, and RZ402 for diabetic macular edema (DME). Dr. Agrawal reported that RZ358 is a fully-humanized monoclonal antibody that binds to the insulin receptor at a non-competitive site

What does he know about re-growth technologies?

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INDUSTRY UPDATE

RetinAI–Heidelberg Engineering Collaboration Gives Customers Access to RetinAI’s Analysis Models

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etinAI Medical AG and Heidelberg Engineering recently announced a collaboration which will enable Heidelberg Engineering’s customers to utilize RetinAI’s portfolio of artificial intelligence (AI) analysis tools in combination with high-quality OCT images. Thanks to cloud exchange and application marketplace technologies, SPECTRALIS® users will have the option of sending OCT volume scans for analysis using RetinAI’s tools in a convenient and secure manner. The exponential growth of retinal disease globally, along with the increase in innovative therapeutics requiring frequent patient monitoring, have created pressure on healthcare systems to scan and process images for enhanced clinical information. AI models such as those developed by RetinAI can improve the speed, efficiency, and consistency with which image data is processed. RetinAI’s tools support diagnostic analyses and clinical workflows for monitoring of patient and

treatment outcomes across several eye conditions such as Age-Related Macular Degeneration (including Geographic Atrophy), Diabetic Retinopathy, Diabetic Macular Edema, Glaucoma, and Retinal Vein Occlusion.

efficiency in research and clinical studies and we expect they can also improve medication and treatment regimens for patients by providing enhanced data insights”, said Dr. Carlos Ciller, CEO of RetinAI.

RetinAI will initially provide access to its CE-marked AI analysis models, to support the efficient processing of image data. Additional features will also become available to Heidelberg Engineering customers as the portfolio of regulatory approved AI solutions expands. “We clearly see the value that RetinAI can bring to existing customers and the potential to improve the patient standard of care. Our AI tools are enablers to increase

INDUSTRY UPDATE

Eyenuk Applauds CMS Final Rule that Establishes National Payment for CPT Code 92229

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lobal artificial intelligence (AI) medical technology and services company Eyenuk, Inc., applauded the Center for Medicare & Medicaid Service (CMS) determination to set a national payment rate for autonomous AI diagnostic technology for the detection of diabetic retinopathy including Eyenuk’s EyeArt® AI technology.

“Eyenuk appreciates CMS’ efforts to establish a national price for CPT code 92229 which will allow autonomous AI to close care gaps related to diabetes eye exam”, said Kaushal Solanki, PhD, founder and CEO of Eyenuk.

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On November 2, CMS issued the CY 2022 Medicare Physician Fee Schedule (PFS) final rule and the CY 2022 Outpatient Prospective Payment System (OPPS) final rule that updated payment rates. The Final Rule (found in Federal Register Document pages 106-114) establishes a national payment amount for CPT code 92229 (Imaging of retina for detection or monitoring of disease; point-of-care automated analysis and report, unilateral or bilateral). The PFS Final Rule also confirmed that autonomous AI can be used to close care gaps (Quality #117) for the Merit-

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based Incentive Payment System (MIPS). Specifically, CMS revised its policy to read “The [diabetes] eye exam must be performed by an ophthalmologist or optometrist, or there must be evidence that fundus photography results were read by a system that provides an artificial intelligence (AI) interpretation.” In the OPPS final rule (Federal Register Document), CMS assigned CPT code 92229 to APC 5733 (Level 3 Minor Procedures) with a payment rate of $57.12.


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