PIE Issue 23: The ebook version (The 'East Goes West' Issue)

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THE WORLD’S FIRST FUNKY OPHTHALMOLOGY MAGAZINE

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m maaggaazziinnee

THE 'EAST GOES WEST' ISSUE Sept/Oct 2022

posterior posteriorsegment segment••innovation innovation••enlightenment enlightenment

The dawn of digital ophthalmology in Asia is finally here! p14

piemagazine.org


Choose OZURDEX® (dexamethasone intravitreal implant) 0.7mg for suitable naïve DME patients or those with insufficient response to anti-VEGF.1 With an MOA shown to inhibit multiple inflammatory processes, OZURDEX® can help DME patients get real world visual acuity gains with a light injection schedule.1-3

IS IT TIME TO TREAD A DIFFERENT PATH?

OZURDEX® is indicated for the treatment of adult 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.1 Real world evidence is collected outside of controlled clinical trials and has inherent limitations including a lesser ability to control for confounding factors. 1. OZURDEX® SPC, June 2021. 2. Boyer D et al. Ophthalmology 2014; 121(10):1904-14. 3. Kodjikian A et al. 2018. https://doi.org/10.1155/2018/8289253 Abbreviated product information OZURDEX® (dexamethasone intravitreal implant) Active Ingredient & Strength: Intravitreal implant containing dexamethasone 0.7 mg in the NOVADUR™ solid polymer drug delivery system. Indications: 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 noninfectious 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 and 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. 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

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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 had 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 the establishment of secondary ocular infections due to bacteria, fungi, or viruses. Visual disturbance may be reported with systemic and topical corticosteroid use. • 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. Full prescribing information

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is available upon request. Please read the full prescribing information before prescribing, available from AbbVie Pte Ltd. Adverse events should be reported to your Ministry of Health and local Allergan office. Please refer to your local Summary of Characteristics and Prescribing Information. Allergan Singapore Pte Ltd, 20 Pasir Panjang Road, Mapletree Business City, #09-25, Singapore 117439 For Healthcare Professionals only. Date of preparation: November 2021. ALL-OZU-210321


IN THIS ISSUE...

Posterior Segment magazine posterior segment • innovation • enlightenment

Matt Young CEO & Publisher

Hannah Nguyen COO & CFO

Robert Anderson Media Director

Gloria D. Gamat Chief Editor

Brooke Herron Editor International Business Development

Ruchi Mahajan Ranga Brandon Winkeler

07 08 10

A Case of Submacular Hemmorhage When Blood Suddenly Appears… Lowering Treatment Burden and Maintaining Vision Gains with Aflibercept Heat Things Up Exploring the potential therapeutic effects of SRT and STR on AMD

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The Sinister Side Dealing with the dangers of laser toxicity in vitrectomy

Cover Story

14 Keeping Up with the West The dawn of digital ophthalmology is here!

Writers

April Ingram Hazlin Hassan Joanna Lee Matt Herman Tan Sher Lynn Contributors

Dr. Sibylle Scholtz Lee MacMorris Maricel Salvador Graphic Designer

Published by

Innovation

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Super Cells to the Rescue Looking to stem cells to nip age-related macular degeneration in the bud

Enlightenment

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War in Ukraine Ophthalmology in a state of emergency Women Who Mean Business As Asian countries roll out innovations amid the ongoing war against COVID-19, women ophthalmologists remain on the frontline

Conference Highlights

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Of Bubbles, Tumors and… Sushi? Uncovering some medical mysteries in vitreoretina

Media MICE Pte. Ltd.

6001 Beach Road, #09-09 Golden Mile Tower, Singapore 199589 Tel: +65 8186 7677 Email: enquiry@mediamice.com www.mediaMICE.com

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. | Sept/Oct 2022 3


LETTER TO READERS

From East to West, It’s All About Outcomes Dear Readers,

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ne of the best things about ophthalmology — and perhaps medicine in general — is the information shared across borders. Those practicing medicine need to be the best that they can be, and that takes knowledge and insight from everyone, from East to West. Indeed, physicians, researchers and academics from all walks of life often come together to contribute — and all ultimately work alongside one another to advance the science and practice of ophthalmology. This “coming together” is evident during some of the bigger industry conferences — attend an AAO, APAO or ESCRS meeting, and you’re bound to encounter colleagues from around the globe. And it’s at these conferences where the latest data, techniques and discoveries are shared. And although it seems like the technology and conversation seem to move from West to East, it’s remiss not to acknowledge the many innovations the East has contributed to ophthalmic, and medical practice, in general. In this issue, we look at those advances that were developed in the East and have since been adopted or studied in the West. Not only in this issue, but in our company Media MICE, we strive to share knowledge that goes both ways — most recently at our CAKE & PIE Expo 2.0, which was held as a hybrid event in Da Nang, Vietnam. There, we not only crossed international boundaries, but also segments and specialities — bringing ophthalmologists and optometrists together to share knowledge. We believe that we are stronger — and smarter — together, and that by sharing our resources we can all contribute to elevating patient care and improving outcomes.

Cheers,

Brooke Herron Editor, PIE, CAKE & COOKIE magazines

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nAMD A Chat withBarometer Anat

Developing evidence-based initiatives for the optimal management of neovascular age-relatedThe macular degeneration Podcast series that (nAMD) puts patients at the centre

Host: Professor Anat Loewenstein

Are you an ophthalmologist or eye health enthusiast who is keen to improve the delivery of care and outcomes for patients living with neovascular age-related macular degeneration (nAMD)? Listen to the nAMD Barometer podcast series ‘A Chat with Anat’ hosted by Professor Anat Loewenstein, Chair of the Department of Ophthalmology at Tel Aviv Sourasky Medical Center in Israel, Professor of Ophthalmology, Vice-Dean at Tel Aviv University and Co-Chair of the Barometer Programme. Follow now to listen to the latest episodes: How to motivate my patient to be adherent with Professor Richard Gale, Consultant Medical Ophthalmologist, and the Clinical Director at the York Teaching Hospital NHS Foundation Trust, UK.

How to improve your clinic organisation to ensure a better patient experience, and optimise adherence to treatment with Mr James Talks, Consultant Ophthalmologist at the Newcastle Eye Centre, UK.

Ways to engage with patients to enable realistic expectation-setting with Dr Jane Barratt, Secretary General of the International Federation on Ageing, Canada, and Co-chair of the Barometer Programme.

Evolution of nAMD: Patients’ expectations through the 21st century with Professor Paul Mitchell, Emeritus Professor of Ophthalmology, University of Sydney and Director of Centre for Vision Research, Westmead Institute of Medical Research.

Look out for future episodes with Professor Tariq Aslam (consultant ophthalmologist at Manchester Royal Eye Hospital, and Professor at the University of Manchester, UK) and Professor Richard Gale.

Follow the ‘A Chat with Anat’ podcast series: Visit nAMD Barometer to learn more about the programme:

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

The nAMD Barometer Program is managed by clinical leaders in ophthalmology as well as representatives from the IFA, IAPB and Bayer. The activities of the nAMD Barometer Program are funded and facilitated by Bayer where the scientists and representatives from IFA and IAPB retain decision authority to the research scope, methods, analysis of findings and dissemination of the outputs of the nAMD Barometer Program. MA-PFM-OPHT-ALL-0957-1 For healthcare professionals only. Podcasts are not intended for UK healthcare professionals. | S e p t / O c t, MA-M_AFL-SG-0354-1 2022 5

August 2022


ADVISORY BOARD MEMBERS

Dr. Alay S. Banker

Prof. Gemmy Cheung

Dr. Hudson Nakamura

Banker’s Retina Clinic and Laser Centre Ahmedabad, India

Singapore National Eye Centre (SNEC) Singapore

Bank of Goias Eye Foundation Goiânia, Brazil

alay.banker@gmail.com

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

hudson.nakamura@gmail.com

Dr. Kenneth Fong

Prof. Mark Gillies

Dr. Saad Waheeb

OasisEye Specialists Kuala Lumpur, Malaysia

University of Sydney Sydney, Australia

King Faisal Specialist Hospital & Research Centre Riyadh, Saudi Arabia

kcsfong@gmail.com

mark.gillies@sydney.edu.au

saadwaheeb@hotmail.com

SOCIETY FRIENDS

Arunodaya Charitable Trust (ACT)

Asia-Pacific Vitreo-retina Society

Orbis Singapore

Subthreshold Ophthalmic Laser Society

ASEAN Ophthalmology Society

He Eye Specialist Hospital

Retinawesome Retina &

Vitreo-Retinal Society - India

Asia-Pacific Academy of Ophthalmology

Ophthalmology Innovation Summit

Vitreous International

Russian Ophthalmology Society (ROS)

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Young Ophthalmologists Society of India ( YOSI )

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World Ophthalmology Congress


CASE REPORT

A Case of Submacular Hemmorhage When Blood Suddenly Appears…

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itreoretinal surgeon Dr. Kenneth Fong from Kuala Lumpur, Malaysia, shared a case of submacular hemorrhage after an attempted subretinal proliferative vitreoretinopathy (PVR) band removal during the LV Prasad Eye Institute (LVPEI) Vitreoretinal Surgery Masterclass 2022 webinar. Subretinal PVR band removal can be a tricky business, especially when the band is located near blood vessels, thereby increasing the risk of submacular bleeding. Dr. Fong told of a 28-year-old patient who presented at his clinic with chronic retinal detachment for about six months. The delayed presentation occurred due to the pandemic. By the time the patient came to the clinic, his macula was already detached, his vision was counting fingers, and he had a large inferior tear. The patient had cataract surgery 10 years prior. Initially during the surgery, things went smoothly as Dr. Fong performed diathermy on some edges of the tear and was able to remove part of the subretinal band. However, as he attempted to remove another band, which is located more posteriorly, by moving it away from the macula, it did not come out through the retinotomy hole as expected, even though he spent much time trying to grab it with the forceps. Changing to a soft tip cannula, he tried to find the edge of the band again in order to aspirate it but the attempt was not successful. Hence, Dr. Fong decided to change the position of the retinotomy. He made another retinotomy inferior to the macula, a move that was a bit risky. Using the forceps, he tried to find the plane of the band through

by Tan Sher Lynn

that retinotomy. He was able to grasp the band and as he tried to pull it out through the retinotomy, blood suddenly started oozing out in the submacular area at the site of his attempted band removal. “This is quite bad news, as such a large bleed would clot fast and that would be a big problem,” he said. He tried to remove the blood quickly. Using the soft tip backflush, he tried to aspirate the blood through different retinotomy holes but unfortunately, the blood has solidified and would not come out easily. As the patient, who was under local anesthesia, was becoming restless, Dr. Fong decided to wrap up the operation. He filled the eye with air, lasered the three retinotomy holes and inserted silicone oil into the eye. He also postured the patient on his side in an attempt to push the submacular blood away temporally. On the first day post-op, the optical coherence tomography (OCT) scan showed that the submacular clot was directly over the fovea. Patient’s vision remained poor at counting fingers. So, three weeks later, Dr. Fong attempted to redo the surgery with the advice of his colleague Dr. Manoharan Shunmugam. They injected heavy liquid into the eye and used the 41-gauge subretinal needle for the surgery. They also injected balanced salt solution (BSS) into the clot in order to mobilize it. “The plan was to lay the patient onto the side and try to push the clot away from the fovea. My aim was just to get the clot away from the fovea so that the patient can have some vision,” he said. After injecting the BSS, some of the clotted blood came out from the retinotomy holes, and Dr. Fong was able

POSTERIOR SEGMENT

to move some of the blood away from the fovea. They proceeded to do the fluid air exchange while at the same time positioning the patient temporally. Unfortunately, the attempted subretinal BSS injection to disperse the clot temporally was not sufficient to remove the clot. The patient subsequently developed severe re-detachment with clot lysis and giant retinal tear which was inoperable. Summing up, Dr. Fong noted that one of the things he learned from this case is to avoid doing retinotomy near major blood vessels. “And perhaps, I could have done a 180-degree inferior retinotomy at the first surgery, fold over the macular to remove the whole blood clot, put in heavy liquid and do the laser at one sitting. But again, the first surgery took more than an hour and the patient was getting restless under local anesthesia,” he said. During discussion, some of the points suggested by the doctors in the panel in regards to this case included: raising the pressure in the eye to stop the bleeding; putting in heavy liquid immediately to the posterior pole to keep the blood away from the fovea; and doing a peripheral retinotomy away from the macula; and putting the forceps underneath the macula to get to the band. One doctor from the panel also commented that he would never use diathermy during punch-through retinotomy, and that he thought that in this case, the bleed was from the forceps tip reaching the choroid instead of a major blood vessel.

Editor’s Note: The LV Prasad Eye Institute’s Vitreoretinal Surgery Master Class, aptly titled “Tough case or a surgical surprise, let’s learn the enterprise” was held from February 26 to 27, 2022. A version of this article was first published on piemagazine.org.

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POSTERIOR SEGMENT

ANTI-VEGF

Lowering Treatment Burden and Maintaining Vision Gains with Af libercept by Brooke Herron

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he introduction of anti-vascular endothelial growth factor (antiVEGF) therapy revolutionized the management and treatment of exudative retinal diseases — and over the past decade the evolution has continued. In 2011, aflibercept was FDA approved to treat neovascular age-related macular degeneration (nAMD). Since then, its commercial use has increased along with its efficacy in achieving meaningful vision gains across indications, including diabetic macular edema (DME) and retinal vein occlusion (RVO), among others. To share the latest updates and best practices in managing and treating exudative retinal disease, experts will convene during a Bayer-sponsored symposia at the 22nd European Society of Retina Specialists Congress (EURETINA 2022) in Hamburg, Germany. Below are preview of some of the highlights…

Ten years of delivering outcomes that matter To see how far we’ve come, sometimes

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we need to look back — so, Prof. Focke Ziemssen of Leipzig University, Germany, will present with a background on aflibercept during his presentation entitled A Decade Long Legacy: From Clinical Trials to the Real World. According to Prof. Ziemssen, aflibercept has transformed the management of exudative retinal disease — both in the approach to clinic management and patient outcomes — and real world outcomes have been similar to those in clinical trials. He says that a key component of the treatment’s efficacy can also be attributed to the proactive treat-and-extend (T&E) dosing regimen, which has shown to maintain vision gains while reducing the treatment burden through interval extensions up to 16 weeks. Not only that, Prof. Ziemssen will share that aflibercept has a wellestablished safety profile with more than eight million patient-years of exposure.

Looking behind the molecule To understand how aflibercept works, it’s crucial to understand the science behind it. During his presentation, entitled Aflibercept: Behind the Molecule, Prof.

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Richard Gale of York Teaching Hospital NHS Foundation Trust, United Kingdom, will dissect the different mechanisms at play and how those contribute to the drug’s efficacy. He explains that VEGFR-1 and VEGFR-2 play a critical role in angiogenesis; excessive activation of VEGFR-1 and VEGFR-2 by ligands VEGF-A and PlGF activates three pathways involved in pathogenesis: inflammation, neovascularization, and retinal vascular leakage and edema. Aflibercept is a multi-targeted fusion protein, incorporating domains from two VEGFRs for tight binding of VEGF-A and PlGF, blocking all VEGFR-1 ligands including PlGF, and the key VEGFR-2 ligand VEGF-A. This means aflibercept has the highest binding affinity for VEGF and the longest half-life when compared with other anti-VEGFs. Continuing the momentum gained from positive patient outcomes and research, Prof. Nicole Eter, University of Münster, Germany, will share her insight during her talk entitled A Vision for the Future: What do the Next 10 Years Hold? According to her, there are three top spots to watch — those are novel antiVEGF formulations, home monitoring, and cell and gene therapies. Prof. Eter says that previous targeting of novel pathways has failed to deliver additional functional benefits over currently available anti-VEGF agents in multiple trials, including those that target the Ang-2 pathway. In this example, she referred to the FDA approval package for faricimab: Patients treated with faricimab q12 experienced large central subfield thickness (CST) fluctuations and lost vision over time in TENAYA and LUCERNE, as did patients treated with faricimab q8 in TENAYA. Further, whether a higher dose of the anti-VEGF may increase duration of VEGF suppression, and therefore allow for a reduced treatment burden, is currently evaluated in phase III studies of aflibercept 8 mg (increased from 2 mg) in nAMD and DME.


Patient outcomes across indications Experts will highlight patient cases across four indications, including nAMD, DME, RVO and polypoidal choroidal vasculopathy (PCV). Prof. Justus G. Garweg, Berner Augenklinik, University of Bern, Switzerland, will share his experience during his presentation, entitled Exploring Patient Cases in DME. He says that a proactive, individualized approach to treatment with aflibercept is well suited to patients with DME. Further, aflibercept T&E regimen can achieve meaningful vision gains with extended intervals of ≥12 weeks in patients with DME — and this is especially important for patients who may have difficulty making frequent visits to the clinic. During his presentation entitled Exploring Patient Cases in nAMD, Prof. Varun Chaudhary of McMaster University, Canada, will share details from a case of an 81-year-old patient with nAMD and 20/200 visual acuity (VA) in her right eye. The patient received monthly anti-VEGF for six months and asked to stop treatment; she could not sustain the monthly visits and said her vision wasn’t improving. Prof. Chaudhary says this is when he switched her to aflibercept — and under T&E, not only did her vision improve, her treatment intervals were proactively extended up to 16 weeks in her first year of treatment. Next, Professor Gemmy Cheung of Singapore National Eye Centre, Singapore, will share her experience during her talk entitled Exploring Patient Cases in PCV. A key takeaway? She says that unlike other anti-VEGF agents in PCV — which may require concurrent treatment with photodynamic therapy to maximize VA gains — aflibercept q16 monotherapy reduces treatment burden with favorable long-term vision gains. Finally, Exploring Patient Cases in RVO will be presented by Prof. Sobha Sivaprasad of Moorfields Eye Hospital, United Kingdom. She will share pearls from patient cases backed by studies, including the potential for a reduced treatment burden when compared with other anti-VEGF agents for patients with CRVO (LEAVO study). Meanwhile, Prof. Sivaprasad says that in CENTERA,

patients treated with aflibercept T&E for macular edema secondary to CRVO gained an average of four lines of vision over 76 weeks.

The future and next level in patient care It’s clear that in the past 20 years, there has been major progress in surgery, imaging and therapies for managing retinal disease. However, there is still much work to be done — including access to diagnosis and treatment, along with increasing the understanding of disease mechanisms and advanced cell death. Discussing some of these innovations will be Prof. Paolo Lanzetta (University of Udine, Italy) and Prof. Francine Behar-Cohen (Paris Descartes University, France) during their respective presentations on Innovating Treatments: Novel Approaches with Aflibercept and Treating the Currently Incurable: What is Coming Next? Among the highlights: There are a number of potential therapeutic targets under investigation to meet unmet needs in retinal disease. For example, targeting of the nitric oxide (NO) pathway using a novel oral formulation is currently under investigation in NEON-NPDR for the treatment of non-proliferative diabetic retinopathy. Researchers are also looking toward the future with aflibercept: The phase II CANDELA study has assessed the safety profile of aflibercept 8 mg and experts are optimistic about the data. Additionally, with the aim of restoring vision after cell death, cell therapies aim to replace degenerative cells and/or supplement trophic factors to restore vision using stem/progenitor cells for their abilities of self-renewal and multidirectional differentiation. They noted that preclinical studies have shown promising results and early

phase trials for the treatment of retinal degeneration are ongoing. Bayer is also involved in a collaboration investigating next-generation cell therapies for AMD and inherited retinal diseases. But it’s not just our understanding of disease or continued innovations in treatments that will contribute to improving patient outcomes — technology can help, too. In particular, home monitoring has the potential to improve timing of intervention and therefore preserve vision – thereby reducing treatment burden, as Prof. Chaudhary will discuss during the presentation on Optimizing Treatment Outcomes Through Technological Innovation. Some of these tools are already available, and others may be available soon, including smartphone applications, at-home medical devices, handheld non-mydriatic fundus cameras, preferential hyperacuity perimetry devices, and home OCT devices. The final speaker, Prof. Anat Loewenstein of Tel Aviv Medical Center, Israel, will remind delegates of the importance of education and collaboration during her talk, Improving Patient Care Through Holistic Disease Understanding. She says that ongoing initiatives supported by Bayer are striving to advance clinical knowledge and create a network of worldwide expertise; some of these initiatives include The Global Retinal Network Program and Vision Academy, among others. All in all, it’s refreshing to have such a comprehensive overview — backed by clinical and real-world studies — that illustrate the progress made in managing exudative retinal diseases. With aflibercept T&E, it’s clear that patient outcomes are improving while their treatment burden is being reduced. And in the future, more advances promise even greater returns.

Disclaimer This publication, produced on behalf of Bayer Consumer Care AG, summarizes presentations and discussions from satellite symposia organized and funded by Bayer and held during the EURETINA 2022 Congress, September 1-4, 2022. The views of faculty speakers do not necessarily reflect the opinion of Bayer. Medical writing assistance was provided by Media MICE and was funded by Bayer. Prescribing Information for aflibercept solution for injection (Eylea®, Bayer AG) can be found on www. Ophthalmology.Bayer.com PP-EYL-ALL-1117-1 AUGUST 2022

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POSTERIOR SEGMENT

AMD

Heat Things Up Exploring the potential therapeutic effects of SRT and TSR on AMD by April Ingram

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ou may have heard that 60 is the new 40 — but what does that even mean? As current generations get older, we have access to more knowledge and resources to maintain health and live longer. People aren’t just surviving longer and hitting middle age later, they are really LIVING long and active lives! However, despite all the good things we do to stay active and reduce risk factors for age-related diseases, vision loss remains a top concern for active and vital seniors. Advanced age-related macular degeneration (AMD), in its wet, neovascular form has very efficacious treatments, with more durable options hitting the market at a rapid pace. What about intermediate AMD, dry AMD, or geographic atrophy? Although multiple therapies are in development for non-neovascular AMD, patients and

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physicians are desperate for effective options for treatment or, ideally, intervention before vision loss occurs.

All about regenerating RPE cells The answer may be to shake things up, heat things up, and disrupt our current way of thinking. Recently, researchers from the Department of Ophthalmology at Christian-Albrechts-University of Kiel and the Department of Ophthalmology at the Hannover Medical School, both in Germany, did exactly that. In a study* published in BMC Ophthalmology in November 2021, lead author Elisabeth Richert and colleagues explored the differences between selective retina therapy (SRT) and thermal stimulation of the retina (TSR), and the therapeutic potential of each for AMD.

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SRT uses photodisruptive micropulsed laser that can selectively destroy retinal pigment epithelium (RPE), which then regenerate — all while leaving neurosensory retinal tissues unharmed. As we know, the RPE is where macular degeneration begins, acting as a critical layer between the photoreceptors and blood vessels in the choroid. The role of the RPE is to nourish the retina, helping it to maintain optimum health by modulating immune factors, secreting hormones, transporting molecules, and clearing out cellular debris. If an inflammatory cascade is triggered, the functions of the RPE can become impaired, eventually leading to cell death. Regeneration of RPE cells with SRT could be the big therapeutic win for intermediate AMD we’ve been waiting for.


SRT has already demonstrated benefit in the treatment of central serous chorioretinopathy and diabetic macular edema, but getting the energy level just right for human AMD has proven to be a challenge. TSR heats things up to a sublethal temperature within RPE cells using stimulative photothermal continuous wave laser, which has already demonstrated therapeutic effects in mouse models of AMD.

Therapeutic potentials of SRT and TSR for AMD Richert and colleagues have been working in this space for several years, already establishing the effects of TSR and SRT on inflammatory mediators. They have shown that TSR has initial anti-inflammatory action, followed by chemotaxis (removing cell debris). Alternatively, SRT causes an initial inflammatory response, followed by mild inflammatory mediator suppression a week later. What does this all mean? The authors explained their hypothesis: “In SRT, RPE regeneration is the consequence of selective RPE necrosis. In TSR, RPE regeneration might be the consequence of delayed RPE cell death.” The short answer, regeneration of RPE is good news. Researchers treated six eyes of murine AMD model mice with either neuroretina-sparing TSR or SRT, and untreated litter mates were used as controls. Did you know that it is not advised to use the fellow, untreated eye as a control? Some groups have shown that laser treatment of one eye may also lead to altered gene expression and changes in Bruch’s membrane thickness of fellow eyes. The eyes were enucleated either one or seven days after receiving treatment and evaluated. Richert and co-investigators found

that TSR did not induce the expression of cell mediators connected to cell death, and the actions of TSR were slower to take effect. In a morphological examination, there was no cell damage one hour after TSR, but one and three days later, they observed dense chromatin and cell destruction.

previous work, 45 degrees Celsius is the magic number to induce apoptotic cell death. The sweet spot therapeutic window resides somewhere between stimulation and apoptosis induction. Below 44 degrees, no cell death was seen; and heating things up to 50 degrees Celsius leads to necrosis.

Interestingly, five days post-TSR, signs of migration and proliferation were detected, which were not accompanied by necrosis-related inflammation. Quicker to action, SRT delivered a defined necrotic area within the laser spot within one hour, inducing inflammation, followed by migration and proliferation of adjacent cells that closed over the necrotic lesion within days.

Determining the magic temperature for therapeutic effect is made more challenging because an optoacoustic or reflectometric feedback device is required to provide a real-time temperature of every single laser spot within RPE. These devices do not exist for use in mice eyes, so the authors have also added this to their to-do list and are currently in the process of designing an optoacoustic feedback system for mice to enable doseresponse examinations in the future.

The quest to find effective therapies for AMD is complex due to the multifactorial aspects of its pathogenesis, and current therapies only aim at specific parts of the disease development. Often, the more we learn, the more questions and hypotheses arise. Richert and co-authors concluded that both TSR and SRT delivered positive findings and have the potential to be a therapeutic option for the treatment of AMD. But it remains unclear if either one is better for treating certain types or stages of AMD over another.

A work in progress The authors acknowledge that this work was conducted on a small number of eyes, but even so, the differences in the regenerative properties of each modality became very clear. “SRT leads to necrosis followed by regeneration,” the authors shared. “TSR does not induce instant cell death. The sublethal temperature increase is initially not lethal but stimulating. It might lead to delayed RPE cell death in absence of inflammation, followed by regeneration.” Future studies will target determining the optimal temperature for TSR. The authors estimate that based on their

Although more work needs to be done to resolve the uncertainties of laser for early and intermediate AMD, and before these modalities will be available in a clinic near you, the potential for SRT or TSR has been established. As Richert and colleagues described: “Hypothetically, TSR, due to its anti-inflammatory and small-scale regenerative properties, might be a preventive or therapeutic option for early AMD with small drusen. SRT, due to its large scale RPE regenerative/ rejuvenating properties might be a better option for intermediate AMD.” We look forward to seeing more exciting work from Elisabeth Richert and its translation toward a thorough evaluation in humans — offering hope for currently untreated types and stages of AMD.

Reference *

Richert E, Papenkort J, von der Burchard C, et al. Selective retina therapy and thermal stimulation of the retina: different regenerative properties - implications for AMD therapy. BMC Ophthalmol. 2021;21(1):412.

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POSTERIOR SEGMENT

LASER TOXICITY

The Sinister Side

Dealing with the dangers of laser toxicity in vitrectomy

by Hazlin Hassan

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hile vitrectomy can save a patient’s vision, there may be a sinister side to it. Ultraviolet (UV) light may cause damage to the eyes, particularly to the cornea and the lens. And the cumulative effects of UV exposure can cause cataracts.

A case of the blues Blue light reaches even deeper into the eye, and its cumulative effects can cause damage to the retina. Harmful UV and infrared radiation (IR) rays are usually filtered by the cornea and lens of the eye, but this natural protective barrier is bypassed during endoillumination for vitrectomies. Furthermore, blue light damage can destroy cells in the retinal pigment epithelium (RPE), also known as phototoxicity. The irradiation causes oxidative stress on the photoreceptors in the RPE1, in which oxygen radicals (ROS) can form due to the photochemical processes. This ultimately results in increased cell death and encourages the development of other pathologies, such as age-related macular degeneration (AMD), a leading cause of blindness that affects more than 30% of people over 75 years of age.

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The pathogenesis of AMD usually advances with retinal photic injury caused by excessive light exposure and consequent oxidative stress. Numerous studies confirm that cumulative lifetime exposure to blue light causes photo-oxidation of retinal cells that leads to AMD. Studies show that high-energy, visible wavelengths of 415 nm to 455 nm have the highest potential for oxidative stress on the RPE. Moreover, other factors affecting the degree of phototoxicity include intensity and exposure duration of the irradiation, as well as the size and type of the endoilluminator. In addition, the distance to the retina can also be a factor.

A tough balancing act According to a study on endoillumination during vitrectomy and phototoxicity thresholds by Pieter R. van den Biesen and co-authors, commercially-available light sources for endoillumination during vitrectomy are not safe when it comes to photochemical retinal damage. “Even with maximal precautions,

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macular phototoxic damage remains a factual danger during vitrectomy,” the study said. The study was carried out to assess the retinal phototoxicity hazards and to provide safety margins for endoillumination during vitrectomy. The absolute power and spectral distribution from various light sources and filter combinations that are commercially available for vitreous surgery were measured. The maximal exposure times based on the International Commission on NonIonizing Radiation Protection (ICNIRP) safety guidelines for photochemical and thermal injury of the aphakic eye were calculated. The results showed measurements of the spectrum and energy indicated that the ICNIRP safety guidelines for photochemical retinal damage are exceeded within one minute for nine out of 10 combinations tested.


With an additional 475 nm long pass filter, light levels below 10 mW, and a distance from the light probe to the retina of at least 10 mm, the allowable exposure time can be increased up to 13 minutes – which is not sufficient for even the average O.R. time of one to several hours of performing a pars plana vitrectomy (PPV). Thermal damage can occur in longer wavelengths (Infrared) or high power outputs with bad design for heat distribution that come too close to the retina. In vitreoretinal surgery, surgeons must ensure there is sufficient illumination for visualization without causing phototoxic exposure. To say the least, this is a tough balancing act.

Solutions and safety precautions In vitreoretinal surgery, phototoxicity due to nonionizing radiation to the retina can occur. The higher the energy used for illumination, the higher the energy of the photon beam, resulting in increased damage to the retina. Several solutions have been proposed to prevent this. The American National Standards Institute has advised that photoexposure should not exceed 10 joules/ cm² with a maximum illumination time of 30 minutes. Many retinal surgeries (ISO 15752:2010 and 15004-2), however, may exceed the allocated time frame, and the light emitting from most endoilluminators goes beyond these guidelines. Some precautions can be taken to minimize the risk of inducing phototoxicity in retinal surgery. For example, employing a shorter surgery time and maintaining a distance from the retina to the light source help lower the potential risk of exposure. Another option would be to use different wavelengths of light to reduce exposure to blue light wavelengths. Different kinds of light sources can be employed during vitreoretinal surgery, including halogen, xenon, and metal halide. These come with their own set of pros and cons.

A safe, novel approach? One of the latest innovations in light sources involves the use of light-emitting diodes, or LED light. In order to balance the need for optimal illumination while decreasing the potential to induce phototoxicity, one of the advantages of LED endoilluminators is that their wavelengths can be split. This allows the operator to customize the spectral composition of the light. One of the latest innovations to overcome this problem is by Geuder AG (Heidelberg, Germany). Its SOLEA LED light source for endo-illumination can display up to 16.7 million colors of the visible spectrum. This enables freedom in color composition and visualization of the finest tissue structures at color temperatures of 3,500 - 6,000 K. The operating field is illuminated with a maximum luminous flux of 45 lumens. With the Geuder SOLEA, the phototoxic amount is low because of its integrated retinal protection mode that can deactivate the blue LED, protecting the safety of the patient and allowing for longer illumination times with comparable light intensity. Additional UV or IR filters are also not required, because of the narrow-band spectrum of the LEDs. The Geuder SOLEA also has the unique function of reducing the phototoxic amount of blue light through additive color mixing of all three primary colors – red, green and blue – to obtain adjacent colors, such as turquoise or purple. Modern narrow-band RGB LEDs prevent harmful radiation in the UV or IR range without requiring extra filters. With the retinal protection mode, Geuder SOLEA can reduce phototoxic effects by fully

deactivating the blue LED which has the highest risk for phototoxicity. Its red and green LED can provide enough light as each output provides up to 45 lumens of luminous flux.

Treading slowly but surely In a nutshell, many diagnostic and therapeutic devices in ophthalmology are equipped with a bright light source to illuminate the fundus of the eye, but the light emitted can pose a potential danger to the retina. Short wavelengths in the UV and visible spectrum of the color blue, in certain conditions, can be hazardous, too. In most instances, the light is applied through the eye. As the lens is a good absorber of blue and UV light, the irradiance threshold for retinal damage is relatively high. During a trans pars plana vitrectomy, however, the fiber optic endoillumination bypasses natural barriers, and the threshold for damage by visible radiation to the retina is substantially reduced. Modern light sources like the Geuder SOLEA ensure highest patient safety and user comfort to support the surgeon at any time in controlling this balancing act. The ICNIRP provides safety guidelines for the illumination of the fundus in both phakic and aphakic subjects. But macular phototoxic damage remains a risk during vitrectomy, even with maximum precautions. The good news, however, is that innovations and technology may be able to combat this phenomenon. Now finally, somebody (Geuder AG) cares about these thresholds that were neglected in the past.

References • Yanagi Y, Inoue Y, Jang W-D, Kadonosono K. A2e mediated phototoxic effects of endoilluminators. Br J Ophthalmo. 2006;90(2):229-232. • Koelbl PS, Lingenfelder C, Spraul CW, et al. An intraocular micro light-emitting diode device for endoillumination during pars plana vitrectomy. Eur J Ophthalmol. 2019;29(1):75-81. • Kuse Y, Ogawa K, Tsuruma K, et al. Damage of photoreceptor-derived cells in culture induced by light emitting diode-derived blue light. Sci Rep. 2014;4:5223. • Tosini G, Ferguson I, Tsubota K. Effects of blue light on the circadian system and eye physiology. Mol Vis. 2016;22:61-72. • van den Biesen PR, Berenschot T, Verdaasdonk RM, et al. Endoillumination during vitrectomy and phototoxicity thresholds. Br J Ophthalmol. 2000;84(12):1372-1375. • Lougheed T. Hidden blue hazard? LED lighting and retinal damage in rats. Environ Health Perspect. 2014;122(3):A81. • Linton E, Walkden A, Steeples LR. Retinal burns from laser pointers: a risk in children with behavioural problems. Eye (Lond). 2019;33(3):492-504.

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COVER STORY

by Joanna Lee

W

e can all agree that never has there been a worldwide event that has accelerated innovations for vitreoretina in AsiaPacific like the COVID-19 pandemic. Indeed, the coronavirus has inadvertently pushed works that have long been in progress prior to 2020 to the forefront. The need to mitigate the risk of infections via lockdowns halted faceto-face meetings and resulted in disruptions of operations. However, these, in turn, accelerated the growth of telehealth and other digitalbased innovations in the industry — particularly in a region where diabeticrelated eye diseases are more common than in other parts of the world.

Growth of AI for ophthalmology in Asia Although ophthalmic innovations in the West have seen much progress in the development of therapeutics, diagnostic imaging, molecular medicine, and even gene and stem cell therapies, ophthalmology in Asia has been cranking up its own progression — more so in particular in the area of digital imaging and artificial intelligence (AI). If the increasing number of publications coming from this part of the world is any indication, then the world could be

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observing growth in the area of AI in ophthalmology in Asia in this decade onwards. Home to around two-thirds of the world’s population, Asia’s diversity in terms of ethnicities, size of populations, and differing access to technology makes it a unique landscape to observe the adoption and proliferation of digital technologies, especially in ophthalmology.1 The large number in terms of population size is a boon when it comes to data collection, and subsequently a background against which data could be analyzed and validated. For one, the use of AI has long been most applied particularly in the analysis of color fundus photography (CFP) for diabetic retinopathy (DR) screening in Asia. Given the prevalence of diabetic retinopathy in Asia,2,3 along with glaucoma and myopia, it is not surprising that data from this region would also provide a beneficial base of informative insights into the management

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of the diseases via digital means and AI. Studies on machine learning (ML) for DR screening had been conducted in Thailand ever since the availability of digital CFP in the late 1990s. Through time, it was found that automated retinal disease assessment (ARDA) could


achieve high sensitivity and specificity. Sensitivity refers to how accurately a model could predict a positive result, while specificity refers to how accurately a model could predict true negative results.

Backed by breakthrough studies This was also due to a breakthrough in 2016, where a Google Health team along with a group of researchers from India, led by Dr. Varun Gulshan, et al., pioneered a study that showed how deep learning (DL) algorithms based on 100,000 retinal scans attained an above-99% accuracy. The technology is currently being used in India, Thailand, and several countries in the European Union to help detect DR while being also studied in the

United States. In 2018, another team of researchers in India found that it was possible to use a smartphone-based fundus camera to screen and detect DR with high sensitivity and specificity. More recently, a review of studies showed that smartphone ophthalmoscopy works well in the process of detecting DR, and particularly well for proliferative DR.4 Singapore also records several breakthrough studies carried out by researchers at the Singapore Eye Research Institute (SERI) — namely in developing a customized convolutional neural network, VGG-19, upon which a DL system was based where it could detect DR, glaucoma, and age-related macular degeneration (AMD). They further tested the resulting algorithm for validation and generalizability against 10 testing data sets.

Building upon this study, a multi-center investigation was also then conducted using data involving 19,000 patients from Singapore, the United States, Australia, and China. The study focused on Chinese, Malay, Indians, African Americans, and white Americans and demonstrated the link between more severe forms of diabetic diseases and uncontrolled systemic risks, such as poorer blood sugar control, higher blood pressure, a longer diabetes duration, and younger age. What was remarkable was that the AI system tested also performed better against 17 human accessors within a significantly shorter duration of one month compared to two years. The AI laboratory in SERI has also teamed up with Moorfields Eye Hospital to test the use of DL in Zambia with favorable results, to boot — where human and AI models also singled out higher blood sugar levels, higher systolic blood pressure, and longer duration of diabetes as risk factors related to DR that are referable. In China, researchers tested deep learning systems using original images derived from real world data and discovered excellent results within the local validation data set.5 From this data set, researchers are hoping to see the establishment of a regional telemedicine screening platform for detecting DR. More recently, a team of researchers from around the world, also funded by Google, has created a deep learning system capable of predicting the risk of developing diabetic retinopathy using CFP.6

Beyond screening for diabetic retinopathy In Malaysia, a group of researchers is also exploring the possibilities of leveraging AI in the advancement of eye care.

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Dr. Nor Fariza Ngah, a senior consultant ophthalmologist at Shah Alam Hospital in Selangor, has been working on an AI grading system for DR along with her colleagues from different local institutions. Telemedicine has only come to the forefront recently, even though it has been around for more than 10 years, “proving itself during the pandemic,” she said. She added that there have been a lot of work on telemedicine, data analytics, and artificial intelligence in the region. “There has been also a lot of work on artificial intelligence, particularly in posterior segment diseases, especially diabetic retinopathy,” she continued. “As diabetes mellitus is emerging as one of the most prevalent non-communicable diseases in the Asia-Pacific region, screening tools for DR have been improvised to ensure they are more costeffective and more efficient.” Another ophthalmologist, Dr. Nor Anita Che Omar, consultant ophthalmologist (Public Health Ophthalmology) at Hospital Sultanah Nur Zahirah in Kuala Terengganu, Malaysia, said: “Besides DR, data analytics on myopia has been published for the past few years. Since myopia is more prevalent among Asians, undeniably a lot of studies have been done in Asia to understand the factors contributing to its progression as well as towards its control.” “Now, AI has not only been developed for the posterior segment but has also been utilized to study the anterior segment of the eye,” Dr. Fariza said. “It is not only used for diagnostic purposes but it has also been made useful for monitoring eye conditions as well as for decision-making in disease management.” For instance, in recent years, scientists in China and India have also been exploring the possibilities of using AI to help predict the efficacy of anti-vascular endothelial growth factor (anti-VEGF) treatment in individual patients with diabetic macular edema (DME) through examining optical coherence tomography (OCT)-derived images.7 AI is not only used for DR screening but also in screening for glaucomatous optic neuropathy (GON), even if highly trained accessors and glaucoma specialists are

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required for the purpose of interpreting the spectral-domain optical coherence tomography’s (SD-OCT’s) results.8

place for retinal imaging to be beneficial in the study of other diseases such as Alzheimer’s.10,11

Fast-forward to 2021, researchers at RMIT, Australia, have succeeded in creating an AI-powered infrared sensor rapid glaucoma screening test that could indicate accurate results within 10 seconds of use.9

Dr. Zalifa Zakiah Asnir, a consultant ophthalmologist and head of department at Hospital Ampang in Selangor under the Ministry of Health in Malaysia, is also involved in a team researching the development of AI for diabetic patients’ screening. Although some countries in Asia still have some catching up to do, she is optimistic about her team’s efforts in studying the use of AI.

“Though our project is still in progress, we hope to come up with our own algorithm for detection of diabetic retinopathy changes and creating a timely referral pathway for the affected patients, to ensure they can be treated early and diabetic blindness be prevented.” — Dr. Zalifa Zakiah Asnir, Selangor, Malaysia Lead researcher Professor Dinesh Kumar from RMIT said their research would “allow a non-contact, easy-to-use, and low-cost test that can be performed routinely at general clinics.” Currently, glaucoma screening tests require patients to sit still for about 10 minutes while the entire test administered by an ophthalmologist takes up to 30 minutes. “It could also promote a communitywide screening program, reaching people who might not otherwise seek treatment until it’s too late,” Prof. Kumar said in a statement published on the university’s website. The Australian team is looking into expanding the technology for smartphone usage. At the same time, it is also being considered for application in the screening of other neurological conditions. As neural networks being built for the study of eye diseases mimic the pathways of the human brain, and especially since the retina shares similarities with the brain, there’s a

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“We might be lagging behind, but we are moving forward to utilize AI for DR screening in Malaysia,” she enthused. “Though our project is still in progress, we hope to come up with our own algorithm for detection of diabetic retinopathy changes and creating a timely referral pathway for the affected patients, to ensure they can be treated early and diabetic blindness be prevented.”

Telemedicine at the forefront According to the Centers for Medicare and Medicaid Services, telemedicine is a subgroup of telehealth that “delivers remote patient care through two-way live interactive communication between the patient and the provider using telecommunication technology.”12 It is divided into two categories: “Synchronous” when interactions between patients and care providers are live, and “asynchronous” or “store and forward” if data collected from the patient is kept for later reviews During the height of the pandemic, telehealth platforms report that virtual patient visits have increased between 257% and 700%.13 Dr. Igor Kozak, vitreoretinal surgeon and director of the Center for Innovation at Moorfields Hospital Eye Centre in the Middle East, a branch of Moorfields in London, shared how the hospital has incorporated telemedicine into their routine since 2020. “We have adopted a practice of teleconsultation (both phone and video) at the height of the COVID-19 pandemic


and have been doing home vision monitoring since the beginning of 2021,” Dr. Kozak said. “The latter has been limited to retinal diseases such as age-related macular degeneration and diabetic macular edema, and data have been collected for more detailed analysis of visual behavior in these conditions in the Middle Eastern population,” he added. Dr. Kozak also observed a few benefits of telemedicine in current practice thus far. “These technologies have a huge potential to collect an abundance of data otherwise not possible with regular clinic visits,” he continued. “Analytical methods can then be applied to find details not detectable by human observers. This can increase diagnostic precision.” Needless to say, the incorporation of telemedicine into the usual process of consulting patients, administering treatment, and monitoring their progress with follow-ups has impacted the field in various ways. While it could provide more efficient care, such as reducing the waiting periods for patients, reaching remote places, and limiting in-patient visits, the adoption of telemedicine would need to take into account each institution’s workflow processes. Not to mention, the need to train staff with the necessary responses (creating new customer service scripts, for instance) for situations peculiar to teleconsulting and having contingencies in case of hardware or electricity supply failure.

Stepping into the metaverse and beyond

the idea of home screening or self-home monitoring,” explained Dr. Anita.

Delving into AI along with telemedicine and digital health would not be complete without a look at how the metaverse could play into bringing solutions for ophthalmologists. Researchers in Singapore pondered upon the potentials of the metaverse, including possible applications for eye care.

Access to technology, the costs of running such systems, having the appropriate infrastructure, and the issue of ethics and medico-legal challenges need to be addressed, along with the problem of not having enough educated and trained experts to handle the screening system.

The creation of avatars for teleconsultations, for instance, could be one of the benefits of the metaverse besides the creation of more personalized care via interconnectivity. Screening, diagnosis, and management could be done via teleophthalmology, while some research also delved into how telemedicine branches into “telementoring” and even “telesurgery.”

Dr. Fariza said limited research grants still pose a challenge for some researchers. However, at times, creativity would be needed to overcome these challenges.

Challenges in the adoption of AI in ophthalmology Granted, there are still challenges to be overcome in many Asian countries when it comes to incorporating more advanced technology into the ecosystem of ophthalmology. Patient receptivity to AI in screening14 can be a barrier as much as the limits posed by patients adhering to self-monitoring practices. “For example, a majority of our patients are not ready to receive and adapt to

“There are many intelligent ideas and support that can come at a lower cost,” she said. “The innovations in disease screening tools and imaging techniques would be very advantageous and will undeniably help prevent blindness by doing regular and early screening. The same goes for other imaging techniques that can help us in making diagnoses and monitoring disease progression.” Dr. Fariza concluded: “I am hoping to see more young researchers with inquisitive and creative minds in the field of ophthalmology come forward and share their thoughts and ideas for future innovation and research. Analytical minds will generate greater ideas that can enhance powerful thinking, creativity, and better productivity.”

Dr. Kozak is taking things in his stride. “In the vitreoretinal field, we are always ready to cope with challenges that time brings us,” he said. “The pandemic was one such challenge that has brought some modifications to our routines.” Looking forward, he deemed there’s value in looking back on the past while adapting to the “new normal.” “Now, we are excited to move on and use patterns and practices from before the pandemic with high caution still applicable. We are keen to continue to investigate novel therapies and surgical techniques — activities that were slowed down during the pandemic,” he concluded. | Sept/Oct 2022

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References 1.

2.

3.

4.

5.

Ruamviboonsuk P, Cheung CY, Zhang X, et al. Artificial Intelligence in Ophthalmology: Evolutions in Asia. Asia Pac J Ophthalmol (Phila). 2020;9(2):78-84. Yang QH, Zhang Y, Zhang XM, Li XR. Prevalence of diabetic retinopathy, proliferative diabetic retinopathy and non-proliferative diabetic retinopathy in Asian T2DM patients: a systematic review and Meta-analysis. Int J Ophthalmol. 2019;12(2):302-311. Yaow CY, Lin SY, Xiao J, et al. A meta-analysis of prevalence of diabetic retinopathy in Asia. Minerva Endocrinol (Torino). 2022;10.23736/ S2724-6507.21.03585-5. Tan CH, Kyaw BM, Smith H, Tan CS, Tudor Car L. Use of Smartphones to Detect Diabetic Retinopathy: Scoping Review and Meta-Analysis of Diagnostic Test Accuracy Studies. J Med Internet Res. 2020;22(5):e16658. Lu L, Ren P, Lu Q, et al. Analyzing fundus images to detect diabetic retinopathy (DR) using deep

Contributing Doctors

6.

Bora A, Balasubramanian S, Babenko B, et al. Predicting the risk of developing diabetic retinopathy using deep learning. Lancet Digit Health. 2021;3(1):e10-e19.

7.

Chakroborty S, Gupta M, Devishamani CS, et al. Narrative review of artificial intelligence in diabetic macular edema: Diagnosis and predicting treatment response using optical coherence tomography. Indian J Ophthalmol. 2021;69(11):2999-3008.

Alzheimer’s Disease. Duke University School of Medicine. Available at: https://medschool.duke. edu/news/ai-model-uses-retinal-scans-predictalzheimers-disease. Accessed on August 12, 2022. 11.

Zafar S, McCormick J, Giancardo L, Saidha S, et al. Retinal Imaging for Neurological Diseases: "A Window into the Brain". Int Ophthalmol Clin. 2019;59(1):137-154.

12.

Ko MW, Busis NA. Tele-Neuro-Ophthalmology: Vision for 20/20 and Beyond. J Neuroophthalmol. 2020;40(3):378-384.

8.

Ruamviboonsuk P, Cheung CY, Zhang X, et al. Artificial Intelligence in Ophthalmology: Evolutions in Asia. Asia Pac J Ophthalmol (Phila). 2020;9(2):78-84.

13.

9.

Saleem SM, Pasquale LR, Sidoti PA, Tsai JC. Virtual Ophthalmology: Telemedicine in a COVID-19 Era. Am J Ophthalmol. 2020;216:237242.

Ngo QC, Bhowmik S, Sarossy M, Kumar DK. Pupillary Complexity for the Screening of Glaucoma. IEEE Access. 2021;9:144871144879.

14.

10.

Yap A, Wilkinson B, Chen E, et al. Patients Perceptions of Artificial Intelligence in Diabetic Eye Screening. Asia Pac J Ophthalmol (Phila). 2022;11(3):287-293.

AI Model Uses Retinal Scans to Predict

study on the usage of stem cell for retinitis pigmentosa).

Datuk Dr. Nor Fariza Ngah is a senior consultant ophthalmologist and head of the Ophthalmology Department at Shah Alam Hospital, Selangor, Malaysia, where she specializes in medical retina and is a uveitis subspecialist. Currently, she is the national head of Ophthalmology Services apart from being deputy director of the Institute of Clinical Research at the National Institute of Health. Dr. Fariza played a key role in setting up a tertiary center for the very first medical retina service in the Ministry of Health Malaysia — she established a formal training structure in medical retina diseases and transformed the unit into the largest medical retina center in Malaysia. Dr. Fariza completed her fellowship in medical retina and uveitis disease at the Moorfields Eye Hospital, University College of London, United Kingdom. She is actively involved with research and publications in relation to retina disease and has presented at many local, national, and international ophthalmic conferences. Her current research includes PI for ophthalmology research (PI/sub PI), either industrysponsored research (ISR) or investigator-initiated research (IIR); while her fields of interest include the development of eModule training for diabetic retinopathy screening (DRS), being in a technical working group in DRS and AI grading algorithm for Diabetic Retinopathy (ongoing research), AMD, uveitis and retinal hereditary disease (ongoing case

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learning system in the Yangtze River delta region of China. Ann Transl Med. 2021;9(3):226.

drfarizangah@gmail.com Dr. Nor Anita Che Omar is a consultant ophthalmologist (Public Health Ophthalmology) at Hospital Sultanah Nur Zahirah Kuala Terengganu at the Ministry of Health, Malaysia (MOH). She is a member of the MOH’s Prevention of Blindness Committee with a special interest in diabetic retinopathy where she is involved in developing an e-training module for diabetic retinopathy screening, being in the Technical Working Group for Diabetic Retinopathy Screening and Development of AI for Diabetic Retinopathy. She is also a member of the MOH’s Primary Eye Care Committee, its Ophthalmology PostGraduate Training Committee, as well as a member of the Ophthalmology Parallel Pathway Program Committee. drnoranitaomar@gmail.com Dr. Zalifa Zakiah Binti Asnir is a consultant ophthalmologist and head of department at Hospital Ampang, Selangor, Ministry of Health Malaysia (MOH). She is a member of the College of Ophthalmologist, Academy of Medicine Malaysia while also being a member of the MOH’s Prevention Of Blindness Committee, its Ophthalmology Postgraduate Training Committee, and the Ophthalmology Parallel Pathway Program Committee. Her special interest is in the area of diabetic retinopathy where she was a

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past member of the MOH’s Technical Working Group For Diabetic Retinopathy Screening, being a coordinator for the Selangor Retina Disease Awareness Programme, facilitator for the Selangor DR Grading and Fundus Camera Credentialing and Privileging, and development of Diabetic Retinopathy Screening e-module and AI for Diabetic Retinopathy Screening. zalifazakiah@gmail.com Dr. Igor Kozak is a renowned specialist in the whole range of vitreoretinal surgical procedures, including pediatric ophthalmic surgery. He undertakes advanced surgical procedures and has pioneered some retinal laser techniques. Dr. Kozak received his medical and ophthalmology training in Slovakia, before a Vitreoretinal Clinical Rotation at Moorfields Eye Hospital in London, and Fellowships in corneal immunology, and vitreoretinal and uveitis, in the USA. He has also practiced and researched at leading institutions in the Kingdom of Saudi Arabia. He has extensively researched, undertaken clinical trials, published, and lectured around his specialist areas of interest. He is board certified in ophthalmology and holds a number of supplementary specialty certificates. He is the recipient of several academic awards and honors, and a member of leading professional bodies in the U.S., Europe, and Slovakia. In addition to his medical roles, Dr. Kozak has been actively involved in public service programs and education. igor.kozak@moorfields.ae


Elements of a supportive ecosystem behind implementing AI solutions in Asian eye care

What’s Needed Medical ethics Medicolegal and product regulation Cyber-security Telecommunication capabilities (4G/5G) Supercomputing powers Health economic analysis Education of current and next generation healthcare professionals about basic concepts and dos & don’ts in applications within medical settings

Vital Clinical Stakeholders Clinicians Nurses Allied health professionals Graders Research scientists

Tools for Translation into Asian Health Care Super smart scientists Good clinical datasets Datasets contributed by multiple stakeholders Clinical deployment of AI products with a great business & product management team Platforms and solutions built around AI product deployment Sustainable stream of funding for implementation and continued R&D Support within a robust ecosystem of medical ethics, regulation, technology, and education

Reference Ruamviboonsuk P, Cheung CY, Zhang X, Raman R, Park SJ, Ting DSW. Artificial Intelligence in Ophthalmology: Evolutions in Asia. Asia Pac J Ophthalmol (Phila). 2020;9(2):78-84

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INNOVATION

VISION RESEARCH

Super Cells to the Rescue

Looking to stem cells to nip age-related macular degeneration in the bud by Matt Herman

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new study1 out of Sweden aimed to document the transformation of stem cells into retinal pigment epithelium cells — and the results could change AMD treatment forever. The adage “the journey is the reward” may be an eye-rolling cliché for some, but for a group of researchers led by Dr. Gioele La Manno and Prof. Frederick Lanner at the Karolinska Institute in Sweden, it could just be an eye-saving credo. By studying the transformation of stem cells into retinal pigment epithelium (RPE) cells, they believe that they may have unlocked a powerful new way to combat age-related macular degeneration (AMD) — a sight-robbing disease that affected around 196 million people worldwide in 2020 alone.2

RPE is the way to be Stem cells, everyone’s favorite pluripotent purported panacea, have long been the star of the show when it comes to battling insidious conditions like AMD. But in order to be of use, they must be coaxed and convinced to turn into something useful. In the case of current research vectors in AMD, that something is a retinal pigment epithelium cell, or RPE for short. RPEs are something of a renaissance man in the retina; they clean up, absorb light, and repair other cells. But most critically, they nourish and maintain the eye’s photoreceptor cells, and this is what has made them such a darling of AMD researchers. The issue with RPE cells lies in the process of differentiation, which is the way that a baby stem cell decides what it's going to grow up and be in life (at the cellular scale, of course). Differentiation is often messy and large quantities of stem cells, such as might be used for

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medical purposes, contain heaps of errors or unwanted cells mixed in with the desired ones. This is what got the wheels turning for Dr. La Manno. “Overall, the field has been so focused on the product of differentiation, that the path undertaken has been sometimes overlooked,” he said. “The path to maturity could be as important as the end state, for example, the safety of a treatment or for improving cell purity and reducing production time.”3 In other words, an understanding of the journey the stem cell takes could potentially have an outsized impact on everything — from cost to time to treatment efficacy. And this journey is exactly what Dr. La Manno and his team decided to hone in on.

A closer look at the RPE journey The study,1 entitled Molecular Profiling of Stem cell-derived Retinal Pigment Epithelial Cell Differentiation Established for Clinical Translation, documented the intermediate states of stem cells as they turned into RPE cells. Using single-cell RNA sequencing (scRNA-seq), which gives researchers a peek at all the active genes in a cell at a particular time, the team studied the stem cells throughout the six-month differentiation protocol, recording the intermediate states all the while. Studying the process and taking painstaking measurements produced several key results. The first was that researchers learned how to suppress the growth of non-RPE cells, meaning a purer end product. “The aim is to prevent mixed cell populations at the time of transplantation, and to make sure the cells at the endpoint are similar to original RPE cells from a patient's

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eye,”3 explained Alex Lederer, a doctoral student who was one of the study’s lead authors. The other important finding was that RPE cell formation took on a very familiar pattern — that of early embryonic development. The investigators recognized a pattern known as “rostral embryo patterning,” a process typically seen as the precursor to the brain and sensory system of the organism.

Encouraging results from animal testing With all these exciting and potentially groundbreaking revelations in hand, it was time for the study to shift into its final phase: testing the results. After all, the information gleaned from the intermediate study is all well and good. But what about results for the hundreds of millions facing AMD every year? The scRNA-seq-monitored differentiated RPE cell sample, higher in purity, was then transplanted into the eyes of two rabbits. Not only was the transplantation successful, but it also showed that the transplanted RPE cells are able to continue on their journey towards maturation after transplantation — a big win across the board.

References 1.

Petrus-Reurer S, Lederer AR, Baqué-Vidal L, et al. Molecular profiling of stem cell-derived retinal pigment epithelial cell differentiation established for clinical translation. Stem Cell Reports. 2022;17(6):1458-1475.

2.

Wong WL, Su X, Li X, et al. Global prevalence of age-related macular degeneration and disease burden projection for 2020 and 2040: a systematic review and meta-analysis. Lancet Glob Health. 2014;2(2):e106-16.

3.

Ecole Polytechnique Fédérale de Lausanne. Streamlining stem cells to treat macular degeneration. ScienceDaily. Available at: https://www.sciencedaily.com/ releases/2022/06/220614122635.htm Accessed on June 28, 2022.

Editor’s Note: A version of this article was first published on piemagazine.org.


OPHTHALMOLOGY IN CRISIS

ENLIGHTENMENT

War in Ukraine Ophthalmology in a state of emergency by Dr. Sibylle Scholtz and Lee MacMorris

H

ere's something no one believed would happen today: A war of aggression in the middle of Europe.

only about 1,700 km between Frankfurt (Germany) and Kyiv (Ukraine); and from Berlin (Germany), it is not even 1,300 km.

On February 24, 2022, we all learned better. Since then, Russia has been waging a brutal war against Ukraine and its people. Instead of submitting, Ukraine is fighting with all its might — not only militarily, but also medically and scientifically. What does this mean for the current situation of ophthalmology in Ukraine?

With its approximately 3,080 ophthalmologists, Ukraine, as of 2012, offers good coverage of 69 ophthalmologists per million inhabitants — compared to Germany (81), Austria (92), and Switzerland (91). The medical standard and equipment are also comparable with the European standard, as is the scientific quality of the training courses and congresses.

With a different script in its own language and the culture of the prevailing Orthodox Church, Ukraine seems to be very far away from us. However, please keep in mind that it is

It is noteworthy that Ukraine is far ahead of many European countries in terms of technology, internet supply/ use, and online training — well before COVID-19.

The war in Ukraine — and ophthalmology Russia's war against Ukraine began in 2014 with the annexation of the Crimean peninsula. It is impossible to forget the morning of February 24, 2022, when the whole country was rocked simultaneously by sirens, massive explosions, the roar of airplanes, and the whistles of rockets. Since then, Ukraine has been attacked by a hostile army, bringing death, annihilation, and destruction to the principles of humanity and civilization. Within three months, Ukraine was pounded by 2,275 rockets, more than 3,000 airstrikes aimed mainly at destroying civilian infrastructure. As

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ENLIGHTENMENT

OPHTHALMOLOGY IN CRISIS

of June 1, 2022, 4,169 civilian deaths were reported in Ukraine, including 268 children. In addition, 4,982 people are said to have been injured. The names of the cities of Bucha, Irpin, and Mariupol are now known to the whole world. Over 6.9 million refugees fled their homes in Ukraine and moved to other countries.

Long before the COVID-19 pandemic, she founded two series of congresses (Ophthalmic Hub and Ophthalmic Light) associated with the Ukrainian Alliance of Ophthalmologists. In her latest project, the Ophthalmic iSchool, she currently offers up-to-date and short-term training for young ophthalmologists.

The war had a major impact on healthcare and ophthalmology; the first days of the invasion were highly chaotic. Many doctors had to flee to other regions, some clinics and pharmacies were closed, and their warehouses were destroyed.

Prof. Vitovska had already invested heavily in virtual training, which paid off during the COVID-19 pandemic. This commitment and her technological setup enabled her to maintain reliable and up-to-date scientific training, even in the current wartime with its highly unsettled conditions.

More than 600 hospitals and ambulances were damaged, and 100 of them were completely destroyed. Many of these institutions also operated ophthalmology departments. Many Ukrainians lost the opportunity to obtain medical care. Patients with glaucoma, age-related macular degeneration (AMD), and diabetic retinopathy remained without treatment. In addition, Ukrainian ophthalmology currently has to face war-wounded patients.

Ophthalmological training: Amid the war and the pandemic A beacon of Ukrainian ophthalmology is Prof. Oksana Vitovska, who, with her great commitment and enormous energy, has advanced scientific training at the highest level for many years.

A passion for ophthalmological education As early as 2016, Prof. Vitovska founded the Ukrainian Alliance of Ophthalmologists, a non-profit association of ophthalmologists devoted to medical and ophthalmological training and education. The association regularly organizes congresses and training events with the aim of integrating all professional groups in ophthalmology. The Alliance sees its central task as founding an association for everyone interested in ophthalmology, including ophthalmologists as well as nursing staff, technicians, optometrists, and opticians. More than 4,238 people currently follow the activities of the Alliance on

Facebook, and the society's YouTube channel currently has more than 4,000 subscribers.

Ophthalmic Hub In 2018, Prof. Vitovska established the annual congress, Ophthalmic Hub, considered the largest Ukrainian ophthalmologists' conference that takes place regularly in the spring. The first congress that took place in Kyiv was highly successful and included over 750 participants and over 80 international speakers. With this congress, Prof. Vitovska set scientific standards comparable to international standards. In the following year, the Ophthalmic Hub already had over 1,200 participants with about 100 international speakers taking part in stimulating programs. Due to COVID-19, the Ophthalmic Hub took place online in 2020 and as a hybrid event in 2021. At the beginning of 2022, plans for the scientific program of this year's congress, scheduled for April 1, 2022, were in full swing. On February 24, 2022, however, everything was rendered obsolete — the war broke out!

Ophthalmic Light The Ophthalmic Light training series is designed as a quarterly regional event, attended by an average of 200 to 400 doctors (https://www.ophthalmic-light. com/).

As early as 2014, she has organized volunteer projects and arranged screenings and care (also in the eastern part of Ukraine) and educational projects for doctors from the regions around Sieverodonetsk, Kramatorsk, Lugansk, and Donetsk. Not only nationally but especially internationally, attention must be paid to ophthalmology and the ophthalmologists in Ukraine. Here, too, Prof. Vitovska is an ambassador for Ukrainian ophthalmology and presents herself and her country at international (online) congresses, such as the recent Indian online meeting, Pan Ophthalmologica, and the International Congress of German Ophthalmic Surgery (DOC) in Nuremberg, Germany.

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Prof. Oksana Vitovska (L) and Dr. Sibylle Scholtz (R)

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Ophthalmic iSchool The Ophthalmic iSchool was started in March 2020 in order to continue to make available scientific training and education. Here, clinical cases are presented and discussed in detail by young ophthalmologists in webinars. This online series was particularly popular during the height of the COVID-19 pandemic, and especially now in the current war situation. A webinar on ophthalmology in wartime took place recently. These Ophthalmic iSchool webinars have been viewed by more than 9,000 people. The webinars can be accessed internationally via the YouTube channel of the Alliance.

The importance of international support and cooperation An essential aspect that describes the high quality and international character of the Alliance is its cooperation with ophthalmological societies. The Ophthalmic Hub is supported by the European Society of Cataract and Refractive Surgery (ESCRS), American Society of Retina Specialists (ASRS), American Academy of Ophthalmology

(AAO), and International Council of Ophthalmology (ICO) with workshops and symposia. Prof. Vitovska maintains close ties with German universities. In 2004, she spent time as a scholarship holder at the University Eye Clinic Heidelberg with Prof. Gerd Auffarth, who became her long-standing mentor and with whom she still has a close friendship and scientific cooperation. She is also working with the Institute for Experimental Ophthalmology at Saarland University on scientific projects. Particularly important for Prof. Vitovska, in the current war situation, is the support from international ophthalmologists and ophthalmological societies, who have extensive experience in the special treatment of war-related eye injuries and blindness. Support is also urgently needed in the rehabilitation of these patients since structures and facilities within Ukraine have been completely destroyed by the war. Using the technologies already available in Ukraine, the international ophthalmological community is now asked to offer Ukrainian colleagues and patients the best possible support within the framework of telemedicine. This is

particularly true for patients in parts of the country that are currently cut off from conventional infrastructure due to the war and who have no access to direct medical care.

What ophthalmology and the world can learn from Ukraine More or less unnoticed, excellent ophthalmological training at the highest level has developed in Ukraine in recent years. Defying COVID-19 and the war, Prof. Vitovska organizes regular and upto-date training. From Frankfurt (Germany) you can reach Kyiv by plane in about two hours. Whenever it will take place again, participation in the next Ophthalmic Hub is definitely worth it — not only to take part in an excellent ophthalmic training event, but also to know a city and a country with its cosmopolitan people, deserving of our friendship and support. Each of us can support Ukraine in our own way!

For more information Facebook: www.facebook.com/kiev.ophthalmological. society YouTube: www.youtube.com/channel/ UCKgI48EJHQ0U6VLIUWr6bvA Website: ophthalmolog.kiev.ua/

Contributing Doctor Prof. Oksana Vitovska is a professor of ophthalmology at the National Medical University O.O. Bogomolec in Kyiv, Ukraine. From 2014 to 2019, she was the chief physician of the university eye clinic there. Currently, she heads the Ukrainian Alliance of Ophthalmologists. Prof. Vitovska is strongly committed to modern, intensive further training for young ophthalmologists, currently through webinars. Her scientific focus is on glaucoma, uveitis, and biometrics of the eye. In addition, she provides assistance in the care of war-related eye injuries. sibylle.scholtz@gmx.de

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ENLIGHTENMENT

WOMEN IN OPHTHALMOLOGY

Women Who Mean Business As Asian countries roll out innovations amid the ongoing war against COVID-19, women ophthalmologists remain on the frontline by Hazlin Hassan

T

he COVID-19 pandemic has brought more than its fair share of tragedy — but it also saw some triumphs. Among those is the slew of innovations and technology developed in order to tackle the challenges the pandemic has created. The emergence of new tech can be seen in several countries across Asia, including China, Singapore, Malaysia, and South Korea. These countries deployed digital and mobile technologies

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quickly as part of an early response against COVID-19 in Asia, and some of these could help other countries around the world, too.

Track and trace? Appsolutely! Governments around Asia set up trackand-trace systems, often through apps on mobile phones. Among these are MySejahtera (used in Malaysia) and

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TraceTogether (used in Singapore) to track the health and vaccination status of users and to facilitate contact tracing efforts. Although there were some privacy concerns, TraceTogether eventually hit a 92% adoption rate in May 2021. Shopping malls in Malaysia also adopted thermal scanners placed at mall entrances that detected the temperatures of shoppers, while the country’s police force employed the


use of drones to monitor residents’ compliance with lockdowns during festive seasons in case people decided to gather for reunions. Mass testing was crucial when it became clear that the virus was highlyinfectious and potentially fatal. Some countries such as Malaysia launched drive-through testing and vaccination at various hospitals and locations across the country. This reduces direct contact, and drivers do not need to exit their vehicles.

variants BA.4 and BA.5 and new diseases, such as Monkeypox, and the animal-derived Langya virus in eastern China that has infected at least several dozen people, perhaps these innovations are the “new norm” and here to stay. They have certainly done their part to protect lives and livelihoods in Asia. Two renowned women ophthalmologists from Malaysia shared some of their experiences during this challenging period to treat their patients while fighting the good fight against the COVID-19 virus.

Dr. Mae-Lynn Catherine Bastion on the importance of doctors’ protection Dr. Mae-Lynn Catherine Bastion, a professor of ophthalmology (vitreoretina) and senior consultant ophthalmologist at the National University of Malaysia (UKM), operates from two practices in the Malaysian capital of Kuala Lumpur. One is with the busy public service at the governmentrun Hospital Canselor Tuanku Muhriz (HCTM) UKM, where she is a senior consultant ophthalmologist and professor of vitreoretina. The other is at a private practice at the UKM Specialist Center.

The coronavirus outbreak, labeled a pandemic by the World Health Organization (WHO) in 2020, led to lockdowns and international border closures. While many countries have since reopened, it is not yet clear if some of the new technologies and measures used during the pandemic will remain even after the pandemic ends. The situation remains in a state of flux. With the emergence of new COVID

She described some of the problems she faced during the pandemic over the last two years, and how she came up with solutions for them. “Ophthalmologists are particularly susceptible to acquiring the coronavirus due to the need for close proximity to patients when using the slit lamp for eye examinations,” Dr. Bastion noted. Indeed, the first doctor to raise the alarm about the coronavirus in late December 2019 was Li Wenliang, MD, an ophthalmologist working in Wuhan where the coronavirus pandemic originated. The 33-year-old doctor died from the virus in February 2020, having

contracted it from an asymptomatic glaucoma patient in early January. Dr. Bastion added: “Shortages of slit lamp breath shields meant that we had to make our own slit lamp shields.” This involved the simple use of clear OHP plastic covers with holes cut to fit the slit lamp oculars, she explained.

Adapting safety practices beyond COVID-19 “These precautions really should be kept in place even after the pandemic is over as it can prevent acquiring other respiratory illnesses such as flu from patients,” she noted. One of the main places where innovations were necessary was the operating theater at HCTM, she added. “For instance, during cataract surgery, it was noticed that a distinct aerosol could be seen, confirmed by fluid condensation on the eye drapes, produced during the phacoemulsification step. In order to reduce this, to prevent transmission of the virus in the aerosol, the operating field was covered with a transparent sterile drape that included the undersurface of the microscope through which wrist holes were cut,” she further explained. “Since there are no such custom-made ophthalmic drapes for this purpose, we had to look to the orthopedic and Ear, Nose and Throat (ENT) departments for this,” Dr. Bastion shared. “Fortunately, these specialties routinely use sterile transparent drapes for their operating microscopes.” As it fortuitously turned out, the one used by orthopedic surgeons, in particular, had an elastic band that could be easily fitted onto the microscope. “This allowed a barrier to be created between the OT environment and the aerosolization that occurred during the procedure. This highlights how tools can be shared across specialties in times of need such as the pandemic,” she explained. Another practice innovation to reduce aerosolization and contamination with ocular fluids was to ensure that vitrectomy surgeries were small gauges

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ENLIGHTENMENT

WOMEN IN OPHTHALMOLOGY

matters. These patients prefer to drink holy water or water which has had prayers chanted over them, in the hope that the water alone will cure them. “I am willing to compromise and have them run concurrently if they are prayer water and not an actual medication that may contain steroids and other harmful ingredients. But the traditional healers usually advise them against mixing the two together,” she shared. This can lead to disastrous effects, including ultimately the eventual permanent loss of vision, which could have been avoided if the patients had been more aware and compliant. “So patients lose precious time that can lead to permanent blindness. This applies to those with cancer as well,” Dato’ Dr. Haslina added. Needless to say, it is crucial to create a higher level of awareness among these patients before they endanger their vision. and performed using valved ports. The valves prevented fluid egress when instruments were taken out of the ports, she said.

Dato’ Dr. Haslina Mohd Ali advocates patient education For Dato’ Dr. Haslina Mohd Ali, a vitreoretinal surgeon at Hospital Sultanah Bahiyah, her problems are a different kettle of fish entirely.

with new appointment dates, there were remarks made that it is alright if they keep missing appointments as the department would keep calling them! Another obstacle she faces in her practice is the belief among some patients that “traditional medicine” trumps modern treatment, sometimes to their detriment. Some Malaysians believe in traditional medicine — many consult traditional healers or sometimes “bomohs” (witch doctors in Malay) on physical or spiritual

Based in the rural and conservative northern Malaysian states of Kedah and Perlis, her challenges can sometimes stem from her patients’ beliefs and a lack of compliance and awareness. “Patients' awareness and educating them effectively are of utmost importance. We need to change their mentality and involve them actively in their own management,” said Dato’ Dr. Haslina. “We used to contact diabetic patients with moderate and serious eye changes, who failed to turn up for their follow-up and treatment, using a phone designated for this. Some came, some did not,” she lamented. When the patients were contacted again

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Not only that, but during the COVID-19 pandemic, many patients were also fearful and wary of going to the hospital for their appointments and surgeries due to the risk of catching the virus. “Patients were afraid of coming to the hospital. The uncertainty and our lack of understanding of COVID, plus the initial vaccination limitations caused us to decrease follow-up appointments and surgeries,” she noted. The hospital contacted patients needing


treatment and those who warranted a follow-up appointment, but the calls were ignored because of a spike in scams all over Malaysia. “Our challenge was that they refused to pick up their phones, maybe because they thought it could be from scammers.” Scammers have become increasingly commonplace across Asia, including Malaysia, particularly during the pandemic. The latest is a so-called COVID-19 assistance scheme purported to be from the Malaysian government offering cash aid. At least three Malaysians have been cheated of almost RM5,000 (USD1,200) in July after they received a message via SMS offering them a special assistance of RM500 to be credited into their bank accounts after filling in their personal details through the given link. Instead, they discovered that their money went missing from their accounts. While scammers deploy a wide range of ideas and technologies to extract one’s hard-earned money, this is an example of how innovations can be abused.

Putting digital solutions to good use However, technology is also put to good use during the pandemic, such as transforming how ophthalmologists carry out lessons and meetings. Having to shift these to virtual platforms allowed them to continue these sessions safely. "The surge and progress in digital solutions have and will continue to change the way we approach things,” enthused Dr. Haslina. “More could participate without decreasing disruptions in service apart from adhering to lockdowns.” Teleconferencing is also used to discuss the management of patients, especially about diabetic retinopathy, the top cause of blindness among the working population in Malaysia, she added. "What used to be slow and disruptive has improved tremendously," she shared. The interpretation of fundus photographs is also set to improve

with artificial intelligence, while the classification of diabetic retinopathy is expected to become less operatordependent, she added. Each country has faced its fair share of challenges and utilized numerous innovations in its battle against the coronavirus. Some are new and some were adapted to be used during the pandemic.

It is interesting to see the ingenious applications that resulted from existing technologies and those that were invented due to necessity during the outbreak. In time, there may be better, more efficient, and effective inventions to fight the latest virus just lurking and waiting to emerge from the shadows.

Dato’ Dr. Haslina Mohd Ali graduated from the National University of Malaysia (UKM) in 1989 and obtained her Master’s in Ophthalmology at UKM in 1999. She completed her fellowship in Vitreoretina at the Royal Liverpool University Hospital in the United Kingdom from January 2004 to April 2005. She is the only vitreoretinal surgeon in the north Malaysian states of Kedah and Perlis. She has been instrumental in treating patients in the state general Hospital Sultanah Bahiyah in the Kedah state capital of Alor Setar, and has also collaborated with other hospitals around Malaysia. She was head of the Ophthalmology Department at the hospital from 2013 until 2020 and also provided VR services in Sarawak state on Borneo Island for two years until July 2020. She has collaborated with non-governmental organization Yayasan Sultanah Bahiyah to provide mobile screening services in Kedah. She has initiated a series of courses conducted by World Sight Foundation based in the United Kingdom. This includes courses on orthoptics, ocular oncology, and neuro-ophthalmology that were carried out in several states in Malaysia. Having served the government sector for 31 years, she is also an active member of the government’s National Prevention of Blindness and Cataract Outreach Committee. She has trained fellows in VR and postgraduate students. She is the recipient of the AsiaPacific Academy of Ophthalmology (APAO) Outstanding Service in Prevention of Blindness Award in September 2021.

Professor Dr. Mae-Lynn Catherine Bastion graduated from the University of Sydney, Australia, with an MBBS (First Class Honours) in 1999. In 2003, she received a fellowship in Ophthalmology from the Royal College of Surgeons of Glasgow. The following year, she received a Doctor of Ophthalmology postgraduate degree from the National University of Malaysia (UKM). In 2007, she completed her clinical fellowship in vitreoretinal surgery at The Eye Institute, Singapore. She is currently the head of Vitreoretinal Services, Department of Ophthalmology, UKM. In 2009, she became the head of the Department of Ophthalmology, for which she served two terms. She was appointed UKM Professor of Ophthalmology (Vitreoretina) in 2014 and received the Academy of Medicine (AMM) Fellowship in 2015. She is the Postgraduate and Fellowship Coordinator of the UKM Ophthalmology Department. She teaches undergraduate and postgraduate ophthalmology while maintaining a private practice at UKM Specialist Centre. She has trained six fellows in Vitreoretinal Surgery since 2010. Dr. Bastion currently serves on the Malaysian Universities Conjoint Committee of Ophthalmology, is Chairperson of the Vitreoretinal Chapter of the College of Ophthalmologists, and Treasurer of the Malaysian Society of Ophthalmology. She was the founding chairperson of the UKM Ophthalmology Researchers’ Society. Her research interests are in vitreoretinal diseases and vitrectomy, vitreolysis, diabetic keratopathy, and stem cell therapy. She has several ongoing research grants with over 70 peer-reviewed publications.

haslina.eye@gmail.com

maelynnbdr7@gmail.com

Contributing Doctors

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CONFERENCE HIGHLIGHTS

AOS 2022

Of Bubbles, Tumors and…

Sushi?

Uncovering some medical mysteries in vitreoretina by Joanna Lee

O

nce in a while, ophthalmologists come across diagnoses that appear puzzling. Several Asian doctors who shared case studies at the 5th ASEAN Ophthalmology Society Virtual Congress (AOS Virtual 2022) held last month showed that while some precedents could be found, they were rare for each diagnosis. The more is known, perhaps, the earlier and more accurate the intervention could be in case one of these situations is encountered.

Bubbling trouble: A case of rapid ascent What happens when decompression illness (DCI) causes problems for the eyes? Dr. Maria Joan Van Loy from the Philippines dove deeper into the subject when a 38-year-old female professionally

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certified open water recreational diver came in with some “visual field defect” in the right eye. When the upper eyelid was lifted, it was noted that the patient had a warped vision in the superotemporal visual field and, later, a superior arcuate scotoma was noted in the same eye when blinking in a welllighted room.

times even in past dives. Thus, nitrogen could have accumulated in her system.

Because of the increase of pressure outside the body, nitrogen bubbles go from the lungs to the blood and into the tissues. “As a rule [in diving], never ascend faster than 10 meters per minute to allow the nitrogen to diffuse from the blood and the tissues to the lungs,” Dr. Van Loy said. “Fast ascends could cause decompression illness,” she further cautioned.

She was given 100% oxygen inhalation at the emergency room while waiting for her COVID-19 and lab test results.

Electronic diving records showed the patient had ascended fast quite a few

HBOT reduces the amount of nitrogen bubbles in the bloodstream, allowing

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This latest sudden event occurred right after the patient’s third dive, with Dr. Van Loy assessing she had suffered from arterial gas embolism (AGE, perfusion blockage caused by gas bubbles in the arterial circulation) in the right eye.

Immediately after that, she was scheduled for a hyperbaric oxygen treatment (HBOT), 24 hours after her last dive. “The rule is to continue treatment until symptoms are resolved,” Dr. Van Loy explained.


reperfusion. It reduces neutrophil and edema while decreasing bubble size and forces the remaining gas outside the circulation. “DCI or Caisson disease should be suspected if it occurs within 24 hours after diving,” said Dr. Van Loy, noting that the condition is more prevalent among commercial rather than recreational divers

DCI risk factors and precautions One of the symptoms of AGE is blurring of the vision. Ophthalmic manifestations of DCI are quite rare although they do appear as nystagmus, visual field defects, scotomas, or homonymous hemianopsia. In a study, fluorescein angiography (FA) among divers showed up as retinal pigment epithelium (RPE) abnormalities. “Some changes were similar to that of choroidal ischemia,” Dr. Van Loy said. Risk factors for DCI include body fat, previous DCI, being female, dehydration, and presence of patent foramen ovale (PFO), along with repetitive diving, postdive exercises, increase in temperature, and high altitude exposure. To avoid DCI, some important safety reminders were to perform safety stops (three to five minutes at five meters), have a minimum of four hours before flying, stay hydrated,

use a dive computer, and be aware of the ascending rate. Prognosis of DCI includes future recurrence. “Yes, you can still dive, but with safety precautions,” Dr. Van Loy warned.

Tumor mystery: Abnormality above RPE Dr. Kelvin Teo, consultant in the Medical Retina Department, Singapore National Eye Centre (SNEC), recounted a puzzling case of a 55-year-old man who was referred to SNEC for suspected early or intermediate age-related macular degeneration (AMD) after RPE pigmentation and potential drusen were noted on the fundus. However, Dr. Teo noticed there was an abnormality above the RPE which was described as a confluent

hyper-reflective subretinal band. In comparison, the RPE area of a regular AMD patient is relatively intact, while his referred patient showed discrete subretinal nodule and irregular RPE. “It’s definitely not something seen in patients with early or intermediate AMD,” he said. Another interesting clue was a focal subretinal deposit on the optical coherence tomography (OCT), something absent in patients with intermediate AMD. There were other abnormalities that added to the puzzle — for instance, the confluence of subRPE deposits. After blowing the image up a little, diffused intraretinal deposits were seen above the focal sub-RPE nodule (deposit). Coincidentally, the patient experienced weakness in the limb just as he was sent for further investigation, prompting a magnetic resonance imaging (MRI) scan, which showed lesions that were central nervous system (CNS) B cell lymphoma. Three months into the treatment, the OCT scan through the fovea showed the pigment epithelial detachment (PED) subsiding and irregularities on the temple side slowly fading away. The

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CONFERENCE HIGHLIGHTS

fundus showed significant reductions in the RPE lesions as well.

A cancerous confirmation Finally, the culprit was confirmed as primary vitreoretinal lymphoma. Dr. Teo highlighted a study1 that showed the frequency of OCT features that characterize this group of patients. In reference, the study also identified OCT features similar to the ones seen by Dr. Teo, such as the discrete nodules and confluent band, hyper-reflective infiltration in the inner layers of the retina, sub-RPE deposits, undulation of the RPE, and hyper-reflective foci in posterior vitreous. Another study2 suggested that the “development of intraretinal deposits could be an important early indicator of disease progression or recurrence.” In summary, primary vitreoretinal lymphoma (PVRL) or CNS lymphoma could be a difficult diagnosis to make but the OCT is a useful tool, even though the signs may be subtle. There needs to be a careful study of the OCT, especially of the presence of hyper-reflective bands above the RPE while intraretinal involvement shows progression.

Sushi-like manifestation? The mystery continues in the next case. A rare diagnosis of retinal images came Dr. Paolo S. Silva’s way at the Joslin Diabetes Center, Harvard Medical School, USA. The first case involved a 63-year-old man with type 2 diabetes mellitus (DM) with hypertension. An ultra-widefield (UWF) image of his right eye showed a diffuse, creamy pinkish discoloration of the retina with the left eye being similar. There was also creamy, white discoloration of the peripheral retinal vessels where the vessels were difficult to visualize.

AOS 2022

When magnified, the cream-colored vessels from the mid- to far periphery appear light on red-free imaging, while the normal vessels appear dark. The magnified view of the superotemporal quadrant showed a yellowish hue of the retina with creamcolored vessels blending into the fundus background. Similar findings were seen in the inferior temporal periphery. In the left eye, there were gradual color changes to the vessels moving toward the periphery, and this was also visible in the inferior nasal periphery.

A rare case of lipemia retinalis Dr. Silva’s second case was also a male patient, a 43-year-old type 2 DM patient with hypertension. The ultra-widefield image of the left eye also showed a diffused creamy discoloration together with a whitish discoloration of the peripheral retinal vessels. However, different from the previous patient, there were white patches on the retina. These were later discovered to be “fat deposits” in the retina related to the revealed disease. On the red-free imaging, the retinal vessels and retinal lesions appear white. “This is in stark contrast to how retinal vessels and lesions turn dark on red-free imaging,” he said. Furthermore, OCT imaging for the patient showed hyper-reflective dots in the inner retinal layer with retinal vessels appearing engorged with hyper-reflective material that causes posterior shadowing. The two patients’ laboratory test results showed a marked increase in triglycerides and cholesterol levels.

retinalis. It is a rare but important ocular finding in severe hypertriglyceridemia. It can remain undetected until triglyceride levels rise above 2,500mg/dL.3 Its classic appearance is salmon cream-colored retinal blood vessels which are the result of oversaturation of plasma with triglyceride-laden chylomicrons, causing light scatter.4 It doesn’t usually affect visual acuity. UWF imaging or careful peripheral clinical examination is important for the early detection of lipemia retinalis.5 This disease may start at the periphery before reaching the posterior pole. Fortunately, the disease is reversible with weight reduction, diet, exercise, and reduction of alcohol intake. Although no treatment is required for it, physicians should still be alert to its signs and symptoms.

Editor’s Note: The 5th AOS Congress was held virtually on March 26-27, 2022. Reporting for this story took place during the event. A version of this article was first published on piemagazine.org.

Finally, the mysterious diagnosis was uncovered: The patients have lipemia

References 1.

Barry RJ, Tasiopoulou A, Murray PI, et al. Characteristic optical coherence tomography findings in patients with primary vitreoretinal lymphoma: a novel aid to early diagnosis. Br J Ophthalmol. 2018;102(10):1362-1366.

2.

Yang X, Dalvin LA, Mazloumi M, et al. SPECTRAL DOMAIN OPTICAL COHERENCE TOMOGRAPHY FEATURES OF VITREORETINAL LYMPHOMA IN 55 EYES. Retina. 2021;41(2):249-258.

3.

Cypel M, Manzano R, Dos Reis FA, et al. Lipemia retinalis in a 35-day-old infant with hyperlipoproteinemia: case report. Arq Bras Oftalmol. 2008;71(2):254-256.

4.

Zahavi A, Snir M, Kella YR. Lipemia retinalis: case report and review of the literature. J AAPOS. 2013;17(1):110-111.

5.

Silva PS, Gupta A, Ajlan RS, et al. Ultrawide field scanning laser ophthalmoscopy imaging of lipemia retinalis. Acta Ophthalmol. 2018;96(5):e643-e646.

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