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THE WORLD’S FIRST FUNKY OPHTHALMOLOGY MAGAZINE

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THE HAUTE COUTURE ISSUE September/October 2019

magazine

www.piemagazine.org

posterior segment • innovation • enlightenment

Cover Story

IN FASHION

Posterior Segment Trends for

Fall 2019 Page 16


Inside this issue...

Posterior Segment Matt Young

CEO & Publisher

Robert Anderson

page

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Media Director

Hannah Nguyen

Production & Circulation Manager

Gloria D. Gamat Chief Editor

Brooke Herron Associate Editor

Ruchi Mahajan Ranga

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Can Biomarkers in the Aqueous Humor now be used in the Diagnosis, Prognosis or Management of Retinoblastoma?

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To Reuse or Not to Reuse Disposables ... that is the Question!

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Capturing the Essentials with a Navigated Laser Therapy

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The Role of Retinal Photography and Telemedicine in ROP Screening

Advances in DME Treatment Observing the AUC and Treating Early

Project Manager

Travis Plage

Director of Finance

Alex Young

Publications & Digital Manager Graphic Designers

Winson Chua Patalina Chua Writers

April Ingram Gerardo Sison Hazlin Hassan Joanna Lee Olawale Salami Tan Sher Lynn

COVER STORY In Fashion:

Posterior Segment Trends for Fall 2019

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Innovation

www.piemagazine.org

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Surgical Treatment of Advanced Retinopathy of Prematurity: When Less is More

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A New Vision for Treatment of a Rare ROP

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When Fashion Meets Vision

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Out of the Blue: The Zebrafish Animal Model for Ocular Research

Conference Highlights Asia-Pacific Academy of Ophthalmology

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Tackling Sports-related Eye Injuries, Orbital Tumors and Strabismus

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All about the Posters: Highlights from ASRS Top Fashions on the Innovation Runway

Ophthalmology Innovation Summit

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PIE MAGAZINE LETTER TO READERS

Dear Reader, Is it getting ‘haute’ in here? Haute couture, that is.

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n French, haute couture means ‘high fashion’ or ‘high dressmaking’; it refers to bespoke clothing, often made from high-quality fabric and sewn with precision, executed by prestigious fashion houses. The level of skill involved means that each garment is priceless. To be a recognized as a true haute couture designer, fashion houses must adhere to a stringent set of rules set by Chambre de commerce et d’industrie de Paris, like having a workshop based in Paris, employing a certain number of people, producing custom-clothing with one or more fittings, and publicly presenting a collection twice per year. Fresh from the runways of Paris, these public collections help set the trends in fashion each season. To determine if leather is ‘in’, or plaid is ‘out’, all eyes look to Paris and its trend-setting industry experts. And as PIE 11 brings us to Paris – the city of haute couture – we felt it was only appropriate to ‘up’ our fashion game in a nod to the stylish locale. Each quarter, the Vietnam-based PIE Magazine team motorbikes south to Hoi An to design and create conference attire – with each costume tailored to match that particular issue’s theme. From watermelon suits to Mozart costumes, we’ve worn it all . . . and we’re particularly proud to be known for our style (as it were). For the fashionably inclined, Hoi An, Vietnam, is a veritable shopping paradise. Numerous tailors line the streets of the ancient city – and here, anyone can become a fashion designer . . . even the team at PIE Magazine. While we’re admittedly not an acclaimed fashion house, our access to tailors has allowed us to create our own version of high fashion: Congress Couture, with individually tailored suits, colorful shirts and accessories, and stand-out shoes – the complete look for the savvy surgeon for the Fall 2019 Congress Season. The inspiration for PIE 11’s Congress Couture was inspired by apparel fresh from the famous catwalks of Paris. Much like Paris sets the trends in fashion, congresses like EURETINA help establish posterior segment trends through the sharing of knowledge and research. These ‘haute’ posterior segment trends in medical, surgical and innovations are the fabric, needle and thread of treating posterior segment conditions – all with the end goal of improving patient outcomes. In this haute couture-themed issue, the cover story looks at the trends shaping treatment for back-of-the-eye diseases, including new therapies, smaller instruments, the popularity of vitrectomy, and advances in imaging and visualization. In particular, new molecules for treating geographic atrophy due to dry AMD have been top-of-mind for many surgeons, and with recent promising research, it’s possible we might have a therapy for this currently untreatable disease. So, what’s next off the retina runway? Read on, for the hottest ophthalmic fashions of Fall 2019 . . . Fashionably yours, Brooke Herron Associate Editor PIE & CAKE Magazines P.S. This issue also features PIE Magazine’s ‘Congress Couture’ – our first-ever fashion photoshoot, complete exclusive behind-the-scenes photos . . . check out those Media MICE models!

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PIE MAGAZINE ADVISORY BOARD MEMBERS Dr. Gemmy Cheung, MBBS(Lond), FRCOphth(UK) Dr. Cheung currently serves as deputy head and senior consultant of the medial retina service for Singapore National Eye Centre (SNEC), as well as senior clinician investigator for the Singapore Eye Research Institute (SERI). Her research interests include the study of risk factors and clinical features of macular diseases that may be unique in Asian populations. Dr. Cheung has published more than 150 articles, mostly regarding age-related macular degeneration, including polypoidal choroidal vasculopathy, and conducted several clinical trials in anti-vascular endothelial growth factor therapies. Dr. Cheung has also been actively involved in training and education, and has served as an instructor on Asia-Pacific Academy of Ophthalmology (APAO) and American Academy of Ophthalmology (AAO) courses and many other educational programmes. In addition, she is also a volunteer faculty member for the ORBIS Flying Eye Hospital Programme. Dr. Cheung has received a number of prestigious awards, including the Macula Society Young Investigator Award (2017), APAO achievement award (2017), APAO Nakajima Award (2014), APAO Outstanding Service in Prevention of Blindness Award (2013), the Bayer Global Ophthalmology Research Award (2012), the Roper-Hall Medal (2005) and the Elizabeth Hunt Medal (Royal College of Ophthalmologists, UK). [Email: gemmy.cheung.c.m@singhealth.com.sg]

Prof. Mark Gillies, M.D., Ph.D. Dr. Gillies presently holds a number of positions including: director of research and director of the Macula Research Group for the Save Sight Institute; foundation fellow for the Sydney Medical School; professor in the Department of Clinical Ophthalmology at the University of Sydney; head of the Medical Retina Unit at the Sydney Eye Hospital; deputy chair for the Ophthalmic Research Institute of Australia; and director of Eye Associates in Sydney. Dr. Gillies has served as a principal investigator or associate investigator in more than 70 clinical trials, and his research regarding macular degeneration and drug safety and efficacy has been published in 188 journals. He has also received a number of grants to study treatments for age-related macular degeneration, retinal disease and Muller cell dysfunction – among other treatments and studies. Dr. Gillies has also appeared in national media on numerous occasions, including the evening news of all major networks, on ABC radio as a local expert, as well as in print media. His dedication and research has resulted in multiple awards. Most recently, he received Gerard Crock trophies for the best papers at the Royal Australian and New Zealand College of Ophthalmologists (RANZCO) Annual Scientific Meeting (2013 and 2015), an achievement award from the Asia-Pacific Academy of Ophthalmology (APAO) in 2014, and an achievement award from the American Academy of Ophthalmology (AAO) in 2015. [Email: mark.gillies@sydney.edu.au]

Dr. Vishali Gupta, M.D. Dr. Gupta currently serves as a professor of ophthalmology at Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh in India. Throughout her career, she has completed original work in the fields of intraocular tuberculosis, optical coherence tomography, diabetic retinopathy, and fungal endophthalmitis. In addition, she is actively studying vitreoretina and uveitis diseases. She has been published in 65 per-reviewed journals, and has authored 17 book chapters and four complete books. Dr. Gupta also holds a US patent for the development of multiplex PCR for uveitis. In addition, she is a sought after speaker, and has made more than 350 presentations in various national and international meetings. Dr. Gupta has received several awards for her work, including the first JN Pahwa award from the Vitreo Retinal Society of India, the first NA Rao Award from the Uveitis Society of India, and the first NA Rao award from All India Ophthalmological Society (AIOS). [Email: vishalisara@yahoo.co.in]

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POSTERIOR SEGMENT AQUEOUS HUMOR

Can Biomarkers in the Aqueous Humor now be used in the Diagnosis, Prognosis or Management of Retinoblastoma? by April Ingram

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etinoblastoma (RB) is the most common type of ocular cancer in children, and a devastating diagnosis to have to deliver to any family. When a child’s eyes are developing, the retinoblasts (or immature (progenitor) cells) are rapidly dividing to create what will eventually become their retina. Every retinoblast has two copies of the retinoblastoma 1 (RB1) gene. If there is a mutation present in both copies of RB1, the retinoblast cells can grow and divide out of control, forming the tumor we recognize as RB. Despite overall survival rates for RB being approximately 90% in developed countries, preserving the child’s globe and vision still present critical challenges. Typically, the way to manage solid tumors in the body begins with a direct biopsy, but historically, this has not been the practice with RB. Why not? Direct biopsy of the tumor or obtaining any ocular fluid for analysis was contraindicated for fear of causing tumor seeding (where malignant cells are deposited along the tract of the biopsy needle) and dissemination to other tissues. However, while it remains contraindicated to biopsy the RB tumor directly, advancements in therapeutic technique have permitted aqueous humor to be safely extracted from RB eyes undergoing therapy. These tiny samples may hold the key to unlock a unique opportunity for enhanced diagnosis, prognosis and management of RB. Dr. Jesse Berry and her colleagues in the United States agree and conducted a comprehensive review of aqueous humor marker research in RB, that was published in April 2019 in Translational Vison Science

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Jump for joy: New developments could have a real clinical impact on children with retinoblastoma.

& Technology.1 Dr. Berry explains how RB management has changed: “Prior to 2012, it was completely contraindicated to place a needle into an eye with retinoblastoma unless it was enucleated. Francis Munier, MD, changed that paradigm in applying a new safety enhanced mechanism for delivering chemotherapy to the back of the eye.” Munier and colleagues describe the conditions of the RB eye that must be met in order to ensure safety of

the technique: (1) presence of clear medium, (2) absence of invasion of the anterior and posterior chamber on ultrasound biomicroscopy, (3) absence of tumor at planned entry site, (4) absence of vitreous seeds at entry site, and (5) the absence of retinal detachment at the entry site.2 Dr. Munier’s technique has led to the intravitreal injection of chemotherapy (melphalan and/ or topotecan) for seeding in RB being widely accepted and the risk of extraocular spread is considered extremely low, with no reported cases since the implementation of the enhanced safety procedure. The aqueous humor paracentesis is part of the standard protocol for these intravitreal chemotherapy injections. A small volume, 0.1mL, of aqueous fluid is aspirated to induce transient hypotony prior to the intravitreal injection of chemotherapy, not for diagnostic purposes, but as a safety measure, to prevent reflux to the injection site. Dr. Berry describes how aqueous samples had previously been handled as part of that procedure: “Once aqueous is removed from the eye in order to lower the pressure, it was initially tested for cells, which was routinely negative, and then after generally discarded as it had no other value to the procedure.” Dr. Berry and colleagues came up with the idea to test the fluid samples that would have been discarded for tumor DNA . . . which they found! Dr. Berry shares how this discovery has changed the RB landscape: “Not only did this open up a whole new body of research in using the aqueous as a liquid biopsy for retinoblastoma but revived old research as well.


Diagram used by Dr. Berry to show tumor DNA in the Aqueous Humor. Dr. Berry after extraction of aqueous from a child with retinoblastoma.

Previously, scientists had evaluated the aqueous for various clinical markers but because it could only be done AFTER enucleation, so the results had very little clinical value to the patient at that point. Now that it has been shown that aqueous is safe to extract in RB eyes, we can now revisit the clinical impact of this old research – thus, the point of the aqueous biomarkers paper.” They searched, reviewed and summarized all studies that have explored markers in aqueous humor, hypothesizing that these investigations may hold valuable insight into how these biomarkers may correlate with features of the intraocular tumor and provide diagnostic and prognostic value. The key feature is that this analysis is now able to be performed in current patients, not just in enucleated eyes. This means that the work previously done, identifying biomarkers in those enucleated eyes, may now have application to current clinical patients and impact management and diagnosis. Can a 0.1 mL sample be enough volume for analysis? Yes – in 2017 Dr. Berry and colleagues demonstrated that sufficient concentrations of RB tumor DNA was present and available for sequencing and analysis. This early work suggested that aqueous samples

held the potential to be a surrogate to direct tumor biopsy when actual RB tumor tissue was not available, and may even be predictive of aggressive tumor activity, without eyes having to have been enucleated.3 Presently, outside of active research protocols, there are no commercially available clinical tests that are indicated

for any type of diagnostic or prognostic evaluation of eyes with RB. Dr. Berry’s important work continues, “We hope that as we continue to develop the aqueous as a liquid biopsy, these markers will have diagnostic and prognostic significance that make a real clinical impact on these children with retinoblastoma.”

References: Ghiam BK, Xu L, Berry JL3. Aqueous Humor Markers in Retinoblastoma, a Review. Transl Vis Sci Technol. 2019;8(2):13. 2 Munier FL, Soliman S, Moulin AP, et al. Profiling safety of intravitreal injections for retinoblastoma using an anti-reflux procedure and sterilisation of the needle track. Br J Ophthalmol. 2012;96:1084-1087. 3 Berry JL, Xu L, Murphree AL, Krishnan S, et al. Potential of aqueous humor as a surrogate tumor biopsy for retinoblastoma. JAMA Ophthalmol. 2017;135:1221-1230. 1

About the Contributing Doctor Dr. Jesse Berry is the associate director of ocular oncology at the USC Roski Eye Institute and Children’s Hospital Los Angeles. In addition, Dr. Berry served as the associate residency program director for the Los Angeles County and University of Southern California Ophthalmology residency program until 2018. She received her undergraduate and medical degree from Harvard University in Massachusetts. Following her ophthalmology residency at the University of Southern California, she was the assistant chief of service at the Los Angeles County Medical Center. She then completed a fellowship in ocular oncology at Children’s Hospital Los Angeles under the mentorship of Drs. Jonathan Kim and Linn Murphree. Dr. Berry is the founder of WOO, Women in Ocular Oncology. Her clinical expertise includes anterior segment, intraocular and external tumors. Her research endeavors are supported by the National Cancer Institute and focus on clinical outcomes of retinoblastoma and choroidal melanoma and use of the aqueous humor to develop of a surrogate tumor biopsy for retinoblastoma. In addition to her work and research, Dr. Berry writes a blog about life in and out of the white coat on instagram as @_moda_md and online at www.modamd.com. She recently had a beautiful baby with her husband Paul Comas: Daphne Linn Comas named in honor of her mentor and wonderful ocular oncologist Linn Murphree, who established the RB program at Children’s Hospital Los Angeles, where she now works. [Email: jesse.berrymd@gmail.com]

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POSTERIOR SEGMENT CLINICAL PRACTICE

To Reuse or Not to Reuse Disposables ... by Hazlin Hassan and Brooke Herron

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hile some surgeons wouldn’t consider reusing disposable tools, others in developing countries are doing so out of potential necessity. This is because reusing single-use instruments may help doctors treat their patients at lower costs. In countries like India, where the nominal per capita income in 2017 was $1850, reducing treatment costs is essential. “In vitreoretinal surgery, the cost of consumables is a significant percentage and consequently drives the patient’s surgical package,” said Dr. Abhishek Kothari, director and chief vitreoretinal surgeon at the Pink City Eye and Retina Institute in Jaipur, India. A package for vitreoretinal surgery in India costs between $500-1200 (USD), while a single-use vitrectomy consumable pack costs around $300400, noted Dr. Kothari. Besides the pack, other items such as forceps and silicone oil may also be used in surgeries, so costs can go up to approximately $500. This can make the

that is the Question!

procedure unviable for the healthcare provider. As such, the ‘reuse’ approach is followed in large scale, Dr. Kothari said, from large high-volume institutes to smaller private practices, to make vitreoretinal surgery more affordable. “Almost every single hospital in Southeast Asia implements this reuse practice, but there is no scientific study or research on its safety,” he said. “Every single hospital in India uses single use consumables more than once, and from what I have gathered from my friends in other neighboring countries like Pakistan, Afghanistan, Bangladesh and Nepal, they all do it. I have visited some African countries, and they do it too. It’s not a choice here, it’s a necessity given the economics.” He said some surgeons in the more affluent west also do this, but the instruments are sent to professional reprocessing units. “When a surgical set is reused, the consumables cost comes down significantly. This enables us to

Reusing disposable instruments could make eye care more accessible to lower income communities.

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provide treatment at affordable costs and gives us leeway in extending the benefit of treatment to socio-economically weaker patients,” explained Dr. Kothari. Reusing tools also reduces waste in many cases – for example, when a surgeon needs to open a complete pack for a silicone oil removal when a cutter is not needed. Reusing instruments also reduces the amount of non-biodegradable plastic waste that is generated for each surgery, thereby saving plastic waste from ending up in landfills or in oceans.

The argument against reuse On the other hand, Dr. Diva Kant Misra, an ophthalmologist at Sri Sankaradeva Nethralaya, India, says: “To state it simply, disposable surgical items are supposed to be disposed after a single use . . so, re-using them goes against the basic principle of ‘disposable’ instruments.”


However, Dr. Misra acknowledges that the financial burden of vitreoretinal procedures is at times unbearable for patient: “Reusing disposable items is a desperate attempt by the treating surgeon to make the procedure affordable for the patients.” And while there are financial advantages to reusing disposables, Dr. Misra says there are also safety disadvantages. “The reuse of instruments always poses a considerable threat to patient’s safety in terms of cross infection, including blood borne diseases,” he explained. “The devices are not designed to be reused; thus, the patient’s safety is also is also threatened by malfunction and breakage linked to reuse.” So, what’s the main concern for reusing disposable surgical tools? According to Dr. Misra, it’s the everpresent risk of endophthalmitis. Therefore, he cautions that the proper sterilization of surgical instruments is vital for safety of these procedures. “Sterilization is a tedious procedure involving collection, cleaning, disinfection, sterilization, packaging, transportation and storage – and this gives a lot of room for damage and loss,” he explained. “Retina surgeries are extremely delicate procedures requiring high degrees of precision and control. The wear and tear occurring due to reuse and repeated sterilization may affect the high quality and precision that is desired from these instruments.” Dr. Misra adds: “Disposable instruments are supposed to save costs and be safer for the patient by doing away with the sterilization process and by removing the risk of suboptimal sterilization.”

A study in sterilization The question remains, however, as to how safe the practice is, and whether there are risks for the patients. “The reuse of disposable surgical instruments is quite prevalent in developing countries like India, so much so that every surgeon that I know regularly reuses disposable instruments,” said Dr. Misra. “Though no peer reviewed published data exists which would guide us in making the best decision, but at times the best decision might be unaffordable to the patient.”

Looking for answers – and for costeffective patient solutions – Dr. Kothari conducted a study* to scientifically assess safety and other issues in reusing single-use tools and disposables in vitreoretinal practice. A typical vitreous surgery includes the use of solid instruments like trocarcannula sets, endoilluminators, laser probes and consumables with hollow tubing and cavities, such as cassettes, vitrectomy probes and connecting tubing. Cassettes and tubing that handle potentially contaminated fluid need to be cleaned thoroughly so that organic matter is not left inside the cavities. These then need to be sterilized with a process that ensures efficient microbial kill on the surface, as well as throughout the inner cavity, along the complete length of the tubing. In the study, trocar cannula sets are subjected to enzymatic and ultrasound cleaning to remove all organic material from the surface. They are then dried and packed before being sterilized by ethylene oxide (EO) sterilization. Endoilluminators, laser probes and diathermy cables are wiped repeatedly with 98 percent alcohol before drying and packaging for EO sterilization. Cassettes and tubing of vitrectomy probe and other tubing are lavaged with 98 percent alcohol to inactivate contaminants and dissolve organic matter, and subsequently lavaged with sterile distilled water. Thorough drying of the cassette and tubing is needed to ensure effectiveness of sterilization and this is achieved by forcing pressurized nitrogen through the tubing to force out fluid, followed by a period of drying before packing and EO sterilization. To ascertain the microbial safety of the instruments, cultures were obtained from the surfaces of trocars, endoilluminators, laser probes, cassettes and vitrectomy probes. Lavage fluid was also obtained from the instruments and subjected to microbiology. “The cultures did not reveal any growth,” noted Dr. Kothari. As the tubing and cavities could be a source of endotoxin despite being sterile, fluid throughputs from them were subjected to bacterial endotoxin testing (BET) by the Limulous Amoebocyte Lysate (LAL) test, which is used to certify endotoxin safety of solutions meant for parenteral use.

Electron microscopy was also used to assess degradation of trocar tips after reuse. The results of the study showed that a total of 25 cultures of both aerobic and anaerobic from instrument surfaces and fluid lavages did not reveal any growth. Endotoxin was not detected in any of the 18 specimens of fluid lavages subjected to BET-LAL testing. Electron microscope imaging of the trocar tips revealed “minimum change in morphology” for two to three uses. The study noted that “there was some degradation and deformation of the trocar tip beyond third use, however, and significant distortion in the tip morphology of the trocars used five times to create sclerotomies”. The study also included cases such as macular holes, epiretinal membranes and vitreous hemorrhage in the clinical chart review. Out of a total of 126 eyes that underwent 23-gauge surgery for the above indications, 35 eyes underwent surgery with new instruments while the rest underwent surgery with reprocessed tools. There was no difference in the incidence of endophthalmitis, or unusual post-operative inflammation, sclerotomyrelated breaks or iatrogenic retinal detachments between the two groups. “However, there was a higher need for sutures to seal sclerotomies in the reuse group,” noted Dr. Kothari. “Thus, standard and meticulously adhered to protocols of reprocessing can ensure the availability of instruments that are safe for reuse.” The performance of most components of a vitrectomy instrument pack does not degrade over three to four reuse cycles, he said. He cautioned however that sharp edges of trocars can wear out with repeated use and may need replacement after two to three uses, or at the first sign of increased tissue resistance. Continuous monitoring of the reprocessing practices and the sterilization technique is crucial to ensure sterility. The degradation of reused instruments, like trocars, is also a concern for Dr. Misra. “We would all want to use high-end cutting-edge equipment to effectively and safely to treat our patients, but that is not always possible,” he shared. “We should

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POSTERIOR SEGMENT CLINICAL PRACTICE adopt a strategy which balances both the worlds: We should limit the reuse of disposable equipment to one or two times, and they should be sterilized using standard and strict protocols.” However, as regulations are continuously becoming more stringent, Dr. Misra advises that uncertain surgeon dispose of items after a single use, wherever possible, as the ideal solution.

Addressing the cost of vitreoretinal surgery It’s critical to counsel patients if they choose to allow surgeons to use reprocessed instruments to reduce their costs. “Though it may be ideal to utilize new sets of consumables for every case, most of us lack such utopian settings,” said Dr. Kothari. “A significant cost reduction can well be achieved without compromising on surgical safety and quality. This can bring down overall surgical costs and increase the affordability of vitreoretinal surgery for the vast majority of our patients.”

For Dr. Misra, he says that a holistic approach should be taken to make treatment more cost-effective for patients. “Correct surgical decision is the very first step toward making vitreoretinal surgery more cost-effective,” he explained. “Whenever indicated, a scleral buckle may be less expensive than a vitrectomy for retinal detachment repair; similarly, a pneumatic retinopexy may be a costeffective option in the right case.” In addition, he says that planning the surgery and aligning the subsequent follow-ups with the patient’s schedule may bring down the financial burden associated with traveling and loss of work hours. Further, Dr. Misra says using indigenously developed instruments and equipment can help lower the cost drastically. “Using them and helping indigenous companies in refining their products is a worthwhile investment for future cost-cutting,” he concluded. * Kothari, AR. Re-using disposables in vitreoretinal practice. Newsletter of the Vitreoretinal Society of India, March 2018. pg 24-26

About the Contributing Doctor Dr. Abhishek R. Kothari, MS, FMRF, FICO, FRCS, completed his undergraduate medical education from Coimbatore Medical College and ophthalmology residency from S.M.S. Medical College, Jaipur. He completed a fellowship in vitreoretinal surgery at Sankara Nethralaya, Chennai and worked at the world renowned Aravind Eye Care System in India. He has presented several research papers and has won prestigious awards at national and international fora (including The All India Ophthalmologic Society Academic Research Committee Award 2007, S Natarajan All India Ophthalmologic Society award for best paper in Retina in 2009, the International College of Ophthalmology Merit Award 2009, the Best paper in the All India Ophthalmologic Society Retina 2010, The Natarajapillai Award 2010, Asia Pacific Vitreoretinal Society Merit award 2010, the Rajasthan Ophthalmic Premier League Award 2012 and many others). He has also delivered numerous presentations in various national and international conferences. Dr. Kothari has published several papers and is the chief editor of a textbook on vitreoretinal surgery (Principles and Practice of Vitreoretinal Surgery, Jaypee Brothers, New Delhi), besides having authored several chapters in other textbooks. He is actively working on automated image recognition in OCT images using artificial intelligence/deep learning techniques, and has interests in the economization of high quality healthcare. He has trained several Indian and overseas vitreoretinal fellows. [Email: dr.a.kothari@gmail.com] Dr. Diva Kant Misra, DO, DNB, MNAMS, FVRS has completed his long term Vitreo-Retina Surgery fellow from Sri Sankaradeva Nethralaya. He holds the post of General Secretary, Young Ophthalmologists Society of India & Chief Editor, Young Ophthalmologists Times. He is the recipient of various Ophthalmic awards like, APAO Achievement Award, Bangkok 2019, Best of IJO Award 2017-18, Ophthalmic Hero of India 2017 & 2018, KOS International Travel Grant 2019, Busan, The Yasuo Tano Award from Asia Pacific Academy of Ophthalmology, Singapore in 2017 and The APVRS Tano Award 2018, Malysia and other national & state level awards. He has published extensively (26 publications (Indexed & Non Indexed) and book chapters) and has presented in conferences held at various and has presented in conferences held at various international and national forums. He has been an invited faculty in various international forums like EURETINA, APAO & AAO. [Email: divakant@gmail.com]

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Learn more about Navilas® EURETINA booth 210 www.od-os.com


POSTERIOR SEGMENT LASER THERAPY

Capturing the Essentials with a Navigated Laser Therapy by Olawale Salami and Brooke Herron

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reating diabetic macular edema (DME) with anti-VEGF monotherapy has significantly improved visual outcomes in clinical studies. However, in the real world, the injection burden of such a treatment regimen can sometimes lead to poor patient compliance. One alternative to secure durable outcomes is combining anti-VEGF with navigated laser therapy (i.e. Navilas® 577s Retina Laser, OD-OS GmbH, Teltow, Germany), which optimizes the effect of intravitreal injections by directly decreasing retinal leakage and swelling. As a consequence, the injection burden decreases significantly without compromising therapeutic success.* A 2019 paper by Menzler et al., compared results from three studies to review the clinical efficacy of Navilas. The authors found that in all studies, Navilas (in addition to anti-VEGF) reduced retinal thickness and improved visual acuity (VA). “Moreover, the number of antiVEGF injections is reduced without affecting the physiologic and functional outcome,” noted the authors. “Lowresponders to anti-VEGF therapy are expected to benefit from Navilas as a second-line therapy option.”

A New Wave of Visualization and Documentation The Navilas laser system has been a game changer in the laser management of patients with DME by allowing direct visualization of the fundus and more accurate focal laser photocoagulation of microaneurysms, which is performed based on preplanned treatment locations with the real-time fundus image. The Navilas 577s enables physicians to digitally pre-plan the entire laser therapy on fundus images – as well as on thirdparty diagnostic images like fluorescein

Achieve peak patient outcomes with Navilas.

angiography (FA), indocyanine green angiography (ICGA), optical coherence tomography (OCT) or OCT angiography (OCTA) – and to precisely document and execute this therapy plan with the help of computerized image guidance. Dr. Pradeep Prasad, chief of the ophthalmology division at Harbor-UCLA Medical Center, says: “One of the challenges when applying subthreshold laser is that when you don’t have visual feedback to know where you’ve administered laser. So, with the Navilas documentation, it’s nice, because you can be sure of where you’re applying the laser.” And now, OD-OS has released a new software update for Navilas 577s: A multimodal export wizard that retina specialists can use to flexibly generate high resolution images of their focal and peripheral treatments in different configurations. This allows for advanced, transparent documentation for all purposes and records. Furthermore, it facilitates knowledge sharing in different scenarios – with colleagues in talks and in publications, with residents and students for teaching purposes, and with patients for education on the treatments performed.

“The Navilas 577s system was also designed with teaching the next generation of laser surgeons in mind,” said Dr. Winfried Teiwes, managing director at OD-OS. “Thanks to the digital pre-planning functionality, supervisors can review laser plans of their residents prior to treatment and monitor treatments on a computer screen in real-time. Now the multimodal export function adds to its real-time teaching capabilities so that supervisors can more easily perform post-treatment evaluations and share knowledge in teaching scenarios and academic lectures.” Source: OD-OS Press release, Available at https://www.od-os.com/latest-news/detail/asrs2019-multimodal-reporting-made-easy-withthe-navilas-577s-retina-laser/ * Menzler J, Neubauer A, Ziemssen F. Navigated laser in diabetic macular edema: the impact of reduced injection burden on patients and physicians-who wins and who loses? Int J Ophthalmol. 2019; 12(2): 342–345.

Editor’s Note: To learn more watch this video, https://www.od-os.com/navilaslaser-systemr/multimodal-reports/.

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POSTERIOR SEGMENT TELEMEDICINE

The Role of Retinal Photography and by April Ingram

Telemedicine in ROP Screening

R

etinopathy of prematurity (ROP) continues to be a leading cause of treatable childhood blindness worldwide. This vasoproliferative disease affects the smallest (low birth weight), most fragile and those who were born early (low gestational age). In order to monitor progression and provide appropriate intervention during the critical period of advanced ‘referral warranted’ disease, regular (often weekly) screening examinations are required. Typically, it is skilled ophthalmologists that perform these exams, largely by indirect ophthalmoscopy. This translates into many examinations, for an increasing number of premature infants, by very few ophthalmologists with ROP expertise – if there is one available in the area at all. Notably, fewer than 10 percent of examined infants with any ROP will require treatment. Advancements in the capabilities of retinal imaging over recent decades have aimed to improve and streamline the process of screening and detecting severe ROP, addressing challenges related to accessing care, providing specialized training in ROP, and creating appropriate documentation of disease progression. As explained by Dr. Igor Kozak from Moorfields Eye Hospital Center in Abu Dhabi, United Arab Emirates: “Teleophthalmology is a rapidly evolving field which combines available technology, image analysis and clinical experience to provide (mostly) diagnostic services in the absence of ophthalmologist in situ. It is applicable in areas with discrepancy between a high number of patients and an insufficient number of specialists.” A recent review published in Seminars in Perinatology from Dr. Graham Quinn, Children’s Hospital of Philadelphia and University of

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Telemedicine puts ROP screening at newborns' fingertips.

Pennsylvania, U.S., and Dr. Anand Vinekar, Narayana Nethralaya Eye Institute, Bangalore, India, weighs in on important developments in retinal photography and telemedicine in ROP. They discuss important studies that have enhanced our understanding of the pros and cons of using retinal imaging as a tool to ensure timely care for the increasing number of infants at risk for ROP blindness around the world.1 They summarize the methods and findings from eight key ROP telemedicine projects conducted over the past two decades, using several different approaches to imaging, (i.e. retinal imaging performed by ophthalmologists, nurses or specially trained non-physicians) and screening and diagnosis of ROP, some dating back to the early 2000s. Dr. Quinn has been fundamental to the development of ROP screening and treatment programs around the world, assisting eye care and neonatal teams with the emerging and growing demands of caring for premature infants. He explained where digital imaging may play a key role in meeting the needs of ROP screening: “Telemedicine is most likely to be easily implementable is those regions with low levels of ophthalmologist availability, whether due to limited numbers of ophthalmologists or distance from service, he said. “In

regions with high density of service, there may be less of an urgency to use ROP telemedicine, but I expect that this will change over time as more data are developed for implementation and costs, and as demand for detection increases with the increasing population of premature infants.” Dr. Kozak confirms this variability of acceptance and uptake of telemedicine screening programs for ROP: “In spite of increased sensitivity and specificity of teleophthalmologic screening, the current recommendation by the American Academy of Ophthalmology (AAO) is that that ‘telemedicine is an useful adjunct but not a replacement for binocular indirect ophthalmoscopy’.2,3 However, in countries with low/middle income and with a fewer number of trained specialists per population, this approach has increased availability of service.” Dr. Vinekar has vast experience with the implementation of these program. He leads the Karnataka Internet Assisted Diagnosis for Retinopathy of Prematurity (KIDROP) program in India, which uses a modified wide-field camera for automatic uploading of images that are reviewed by a specialist.4 An impact assessment of KIDROP showed that in the 10 high-risk ROP states (a population of 680 million), more than 35,000 infants


would be detected with ROP with 1,200 of those needing treatment annually. This means KIDROP is a significant “blind-person-year” saver, estimated at $108 million (USD).5 Dr. Vinekar described the value of telemedicine in ROP (or tele-ROP): “It is emerging as a powerful and pragmatic solution to deliver ROP screening in the rural outreach and underserved areas of several middle-income nations, where there are millions of infants and a handful of specialists to carry out the service alone.” “Besides non-physician certified imagers, nurses in these remote neonatal units can be trained onsite and remotely (like in India) to obtain images and even report them with an initial decision-based algorithm: refer for treatment, follow-up or discharge triage,” explained Dr. Vinekar. “Even nations with adequate human resources are adopting image-based screening because of its medico-legal advantage in documenting disease and outcomes after treatment. With the availability of new, more affordable wide-field cameras, the field is only expanding. In countries like India, these cameras are already being used for universal eye screening.” As treatments for ROP and techniques for retinal imaging technology continue to evolve and improve, Drs. Quinn and Vinekar caution that conclusions and recommendations for digital image evaluation in ROP cannot be set in stone. They leave readers with a series of important questions to consider, raised by these changing paradigms: “Should quantitative measures be used to assess disease severity? What other imaging modalities should be considered? Should studies of optical coherence tomography or fluorescein angiography be conducted to determine greater detection of potentially serious disease? Should only images of the posterior pole, which are easier to obtain, be considered? What is the utility of examining mosaicked images versus single images? How might image evaluation need to respond to changing indications for treatment over time?”1

Dr. Vinekar shares his enthusiasm and optimism for the advancements that are on the horizon in ROP, noting: “Artificial intelligence in ROP may hold promise in handling large number of images as the number of adopters increase.” Dr. Kozak adds his impression of teleophthalmology and its potential for the future: “Teleophthalmology seems to be a feasible alternative to improve

services in the physical absence of health care providers. Improvements in imaging and data transfer technologies have allowed for creating functional networks of outreach clinics directing data to reading centers. While mostly diagnostic in nature at the moment, there seems to be a potential for teleophthalmology to become therapeutic modality using image-based laser systems.”6

References: Quinn GE, Vinekar A. The role of retinal photography and telemedicine in ROP screening. Semin Perinatol. 2019;pii: S0146-0005(19)30070-9. 2 Fierson WM, Capone A Jr. American Academy of Pediatrics Section on O, American Academy of Ophthalmology AAoCO. Telemedicine for evaluation of retinopathy of prematurity. Pediatrics. 2015;135:e238–e254. 3 Quinn GE, Ells A, Capone A Jr., et al. Analysis of discrepancy between diagnostic clinical examination findings and corresponding evaluation of digital images in the telemedicine approaches to evaluating acute-phase retinopathy of prematurity study. JAMA Ophthalmol. 2016;134:1263–1270. 4 Vinekar A, Jayadev C, Bauer N. Need for telemedicine in retinopathy of prematurity in middleincome countries: e-ROP vs KIDROP. JAMA Ophthalmol. 2015;133:360–361. 5 Vinekar A, Mangalesh S, Jayadev C, et al. Impact of expansion of telemedicine screening for retinopathy of prematurity in India. Indian J Ophthalmol. 2017;65:390–395. 6 Kozak I, Payne JF, Schatz P, et al. Teleophthalmology image-based navigated retinal laser therapy for diabetic macular edema: a concept of retinal telephotocoagulation. Graefes Arch Clin Exp Ophthalmol. 2017;255(8):1509-1513. 1

About the Contributing Doctors Anand Vinekar, MD, FRCS, PhD currently serves as a clinical and research Professor at Narayana Nethralaya Eye Institute, Bangalore, India. He heads the department of Pediatric Retina and is the Founder and Program Director of KIDROP – a tele-ROP model that was pioneered in India since 2008. Dr. Vinekar serves as a technical member of India’s National ROP Task Force and served as a member of the Queen Elizabeth Diamond Jubilee Trust, UK, for the ROP program in India. He was the principal clinical investigator of government funded low cost, wide-field ROP camera that was developed in India. His recent work has focused on ROP biomarkers in tears, online ROP education and augmented reality based training for laser treatment. [Email: anandvinekar@yahoo.com] Graham Quinn, MD, MSCE, is an attending surgeon in the Division of Ophthalmology at The Children’s Hospital of Philadelphia. He is also a Professor Emeritus of Ophthalmology at the University of Pennsylvania. Dr. Quinn’s interest areas are retinopathy of prematurity (ROP) and visual and ocular development in children. He was a principal investigator and member of the executive and editorial committees of the landmark CRYO-ROP study and PI of the Philadelphia Center and worked with Velma Dobson, PhD in the Vision Testing Center for ETROP. He served as a member of the original group that developed the International Classification of ROP and chaired a “revisiting” of the classification in 2005. He has participated in a large number of international conferences and workshops on ROP prevention and treatment in countries with rapidly developing neonatal care systems. Recent work has concentrated on early markers identifying at risk babies and also telemedicine in ROP. [Email: quinn@email.chop.edu] Igor Kozak, MD, PhD, MAS is a fellowship-trained vitreoretinal and uveitis specialist with interest in clinical research. He is currently clinical lead at the Moorfields Eye Hospital Center in Abu Dhabi. He has published extensively in the top ophthalmic scientific journals and participated in numerous clinical trials. He is a frequent presenter at international ophthalmology conferences. [Email: igor.kozak@moorfields.ae]

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POSTERIOR SEGMENT DME TREATMENT Advances in DME Treatment

Observing the AUC and Treating Early

by Joanna Lee

A

s the prevalence of diabetic retinopathy (DR) increases in Asia-Pacific countries, so has the proportion of patients with severe visual loss or blindness. For patients with diabetes, the loss of sight is one of the most concerning complications. So, when clinical results from the VIVID and VISTA studies show five-letter visual gains, it offers doctors and patients a promising avenue to mitigate this growing threat. Some of these therapies for DR were discussed during the recent AsiaPacific Academy of Ophthalmology (APAO) Congress, in a symposium titled ‘Advances in DME Treatment’. According to Dr. Paisan Ruamviboonsuk, who chaired the session, one strategy for determining a treatment’s long-term efficacy is by observing the area under the curve (AUC). He said this is important because it provides key insights into the day-to-day visual experiences of patients over time, rather than only examining letter gains or losses at pre-specified time points during clinical studies. By monitoring AUC, physicians can also catch disease progression and treat early (with aflibercept, for example) – and thus, reduce the amount of time patients experience poor vision, while increasing the opportunity for meaningful final vision gains. Early and intensive treatment with aflibercept was also explored, with data from the VIVID and VISTA studies showed rapid and increasing visual acuity (VA) gains at year one. These results were relayed by Dr. Voraporn Chaikitmongkol, assistant professor of ophthalmology at Chiang Mai University, Thailand. Investigators found that at 52-weeks, patients who received aflibercept gained ≥10 letters from baseline – and these improvements could be sustained for three years. Another study covered by Dr. Chaikitmongkol was the DRCR. net Protocol T, which compared the efficacy of different anti-VEGF agents

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Don't hit snooze! Early and intensive treatment help achieve rapid VA gains for patients with DME.

for visual impairment due to DME. This study also showed how early, intensive treatment in the first year can make a significant reduction in the treatment burden thereafter. In examining the differences between anti-VEGF agents, Protocol T results show that at week 52, patients treated with aflibercept gained more letters than those treated with bevacizumab and ranibizumab. Meanwhile, post-hoc analysis of the Protocol T study showed that lower HbA1c, younger age and patients with no history of pan retinal photocoagulation (PRP) are associated with better 2-year visual outcomes. Dr. Chaikitmongkol also noted that emerging data from real-world studies like APOLLON are also showing good visual gains with aflibercept in DME management, with improvements of approximately 8 letters after 6 months of treatment. Dr. Neil Bressler, a professor from Johns Hopkins University’s School of Medicine, USA, discussed another realworld study – Protocol V, a randomized, multi-center clinical trial. He presented results from the trial and again mentioned the important of the AUC. He also asked the gathered crowd: “Does it matter which anti-VEGF drug you use?” In his answer, he says that sometimes it matters, and sometimes it doesn’t. To explain, he pointed to a subgroup in Protocol V, which could have contributed to the differences in the trial’s results: In this subgroup, patients with a VA or 20/50 or worse (which was half the subgroup driving the overall results),

were the ones who experienced the most superior visual outcomes with aflibercept over two years, compared with those using other agents. However, for those with VA of 20/30 or 20/40, the results comparing the three anti-VEGF agents weren’t as pronounced. Thus, aflibercept seems clinically effective for patients with lower VA. Dr. Bressler also discussed how they calculated the AUC: Investigators took each subject’s AUC and looked at the change in baseline VA, plotted out against the x-axis of weeks. The AUC for each subject was then calculated by approximating the sum of a series of geometric figures seen on the graph. He also mentioned the study showed the subjects’ vision remained stable even after 6 months in both VA gained and actual VA, showing little loss of vision – even if the edema persisted beyond two years. Dr. Bressler concluded his session by saying that “the regimen does lead to a reduced number of infections,” adding that those interested could access the slides and studies on this topic at DRCR.net. Editor’s Note: A version of this article first appeared in APAO 2019 Show Dailies Day 3 issue published at APAO 2019 Congress in Bangkok, Thailand (page 4). The APAO Show Daily is the official conference news of Asia-Pacific Academy of Ophthalmology congress, published by PIE and CAKE Magazines. Reporting for this story also took place at APAO 2019 Bangkok, where Media MICE was the Official Media Partner..


th The 35 Congress of Asia-PaciďŹ c Academy of Ophthalmology th

in conjunction with

The 25th Congress of Chinese Ophthalmological Society

Celebrating our Diamond Jubilee (1960~2020)

(852)3943-5827 secretariat@apaophth.org http://2020.apaophth.org/ HOSTS:

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COVER STORY

IN FASHION

Posterior Segment

Trends for Fall 2019 by Brooke Herron

S

tylish physicians aside, ophthalmology is typically not associated with haute couture – however, like fashion, it is an industry that plays close attention to trends, be it in innovation, medical or surgical technique. So, as we kickoff the ‘Fall 2019 Congress Season’ at EURETINA in Paris – the home of high fashion – PIE Magazine got the scoop on what’s ‘haute’ on the minds of posterior segment doctors. Below, trend-setting vitreoretinal specialists from the U.S. and India, discuss the fabrics, needles and threads shaping patient outcomes for back-of-the-eye conditions.

The Fabric When creating a new design, selecting the right fabric is crucial – you wouldn’t want a summer dress made from wool, or a winter jacket made from chiffon! Like fabrics are chosen to fit the season, drugs are designed to fit the condition or disease pathway. And although we’re not dressing eyeballs for the catwalk, determining the right ‘fabric’ is key for patient’s visual

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In medical, newer molecules targeting pathways other than VEGF are trending. – Dr. Alay Banker

outcomes . . . and this season, new molecules are trending. Evidence of this trend was found at the Ophthalmic Innovation Summit (OIS) held recently in Chicago, where a collection of upcoming therapies – including potential new drugs for dry age-related macular degeneration (AMD) – modelled their benefits to a decidedly stylish crowd. [Ed. Note: See page 41 for more OIS highlights!] Dr. Brett Foxman, the chief of the Division of Ophthalmology at Shore Medical Center in New Jersey, USA, has also noted that new molecules are in vogue: “Intravitreal therapies with new mechanisms of action and classes of chemicals are currently trending – as well as those targeting

different diseases and those decreasing treatment regimens.” From India, Dr. Alay Banker, the director and chief vitreoretinal surgeon at Banker’s Retina Clinic, in Ahmedabad, agrees that newer molecules, which target pathways other that VEGF – as well sustained delivery devices, including nano and suprachoroidal delivery systems – are popular in medical. In particular, therapies to treat dry AMD with geographic atrophy (GA) – a condition with no current cure – are in style. “It looks like there are new meds on the horizon to treat dry AMD with geographic atrophy that may actually increase visual acuity – not just slow progression,” said Dr. Foxman.


G

enerally speaking, ophthalmology isn’t usually associated with fashion. However, at PIE Magazine, we’ve always interwoven the two. Over the years, we’ve worn watermelon suits, dressed as flight attendants, retina monsters, bakers and race car drivers – and these costumes tie directly to the theme of each posterior segment magazine. So, now that we’re at EURETINA in Paris, it’s natural that we embrace our inner fashionistas, and present you with ‘Haute Couture’. Below, some of our catwalk-ready models reveal their favorite fashions and trends.

Hannah Nguyen, Production & Circulation Manager (PIE and CAKE Magazines), COO & CFO (Media MICE).

As an avid jet-setter herself, Ms. Nguyen’s favorite congress fashion harks back to Hawaii (also her favorite conference destination), where she flew the friendly ophthalmic circuit in a flight attendant costume. When she’s not pointing out the nearest exit, you’ll find her behind the camera, computer or smart phone, keeping Team Media MICE flying along at mach speed.

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COVER STORY One such therapy noted by Dr. Foxman – and fresh from the OIS and the American Society of Retina Specialists (ASRS) runway – is elamipretide, which targets mitochondrial dysfunction. Results from a recent study1 – which assessed the safety, tolerability and efficacy of elamipretide in dry AMD – were displayed fashionable in a poster at ASRS 2019. Specifically, the investigators studied the effects of the elamipretide on leakage-independent vision loss in fellow, non-study eyes with neovascular age-related macular degeneration (nAMD) in the ReCLAIM study. They found that that the mean change in standard BCVA in fellow eyes with nAMD was +6.3 ± 5.0 letters (p<0.001) – resulting in a ≥6-letter BCVA gain in 54% of fellow eyes, and a ≥10-letter BCVA gain in 31%. Meanwhile, the mean change in LLVA (low luminance visual acuity) in fellow eyes with nAMD was +6.4 ± 4.8 letters (p<0.001) – also resulting in a ≥6-letter LLVA gain in 54%, and ≥10-letter LLVA gain in 31%. They concluded that subcutaneous administration of elamipretide for dry

Another trend in surgery is not new . . . away from scleral buckles and toward vitrectomy. I agree with the trend, but it’s led to less buckle experience with newer surgeons.

– Dr. Brett Foxman AMD was associated with improved vision in fellow, non-study eyes with nAMD. Another promising drug is APL-2, a complement factor 3 inhibitor, which has shown to reduce GA growth in a phase 2 trial (Filly).2 Dr. Foxman says: “[APL-2] is a new type of molecule for use in the eye to inhibit a pathway (that has not yet been treated by intravitreal injection) for a condition that, so far, we don’t have a treatment for.” The Filly trial enrolled 246 patients with GA at more than 40 clinical sites in the U.S., Australia and New Zealand. Patients received monthly or every other month (EOM) intravitreal injections of APL-2 for the first 12

Matt Young, CEO & Publisher. Mr. Young

doesn’t need a reason to dress up – and in fact, it’s his unique sense of style that started it all. That said, his favorite congress attire goes back to the basics – when PIE was just starting, and the trend of orange, banana and watermelon suits were taking Southeast Asia by storm. When he’s not working the conference circuit, Matt spends his spare time dreaming up new costumes and internally debating a career in fashion design.

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months and then received no treatment up to month 18. At 12 months, patients with monthly injections had a 29% reduced GA growth rate, while those on EOM treatment were reduced by 20%, compared to sham. From 12-18 months, patients received follow-up, but no treatment – and during this period, GA lesions in both treated groups grew at a rate similar to the sham group: Patients previously receiving monthly treatment showed only a 12% reduction, while those in the EOM group decreased to 9%.3 Additional phase 3 trials are scheduled, with results in the next few years. Dr. Foxman also mentioned two up-and-coming drugs for targeting


nAMD: brolucizumab and faricimab, noting the HAWK and HARRIER, and STAIRWAY trials, respectively. HAWK and HARRIER were similarly designed phase 3 trials that compared brolucizumab with aflibercept to treat active choroidal neovascularization due to nAMD in 1,817 patients. It was found that “brolucizumab was noninferior to aflibercept in visual function at week 48 . . . and while overall safety was similar between the two drugs, anatomic outcomes favored brolucizumab over aflibercept.4 Next on the runway is STAIRWAY5: A 52-week study that assessed two extended dosing regimens of faricimab (6.0mg at every 16- or 12-weeks), compared to ranibizumab (0.5mg every 4 weeks). In the two faricimab groups, the mean improvement from baseline was 11.4 letters in the 16-week group and 10.1 in the 12-week group. The mean improvement for patients in the ranibizumab group was 9.6 letters. The authors found the three treatment regimens were similar in terms of patients gaining, or a avoiding a loss of, more than 15 letters. The safety profile of faricimab was also consistent with other intravitreal anti-VEGF therapies. Of course, there are many fabrics to choose from in fashion. Likewise, there are numerous molecules in the drug development pipeline other than those highlighted here – all with their own distinct pattern of targeting, and thereby treating, sight-threatening conditions like wet and dry AMD . . . making this a trend worth following.

The Needle Performing eye surgery is like a weaving a needle through delicate fabric – for success in both, care and precision must be taken to avoid complications (although a detached retina is much worse than a missed stitch!). And indeed, a tailor without a needle is much like a surgeon without instruments. For the past few years, surgical instruments have been riding the “smaller is better” wave, with 27-gauge (27G) pars plana vitrectomy

Rob Anderson, Director of Media. If you ask Mr.

Anderson, his favorite congress theme – by far – was our racing theme, complete with fire-proof race suits and helmets. His enthusiasm for this particular fashion stems from his love of impersonating race car drivers, watching Talladega Nights (‘shake ‘n bake!’) and pushing his scooter to its limits along the roads in Vietnam.

(PPV) topping the ophthalmic in-style charts. The potential to improve patient outcomes is the driving force behind this 27G trend, and the goal of making successful PPV procedures less invasive and safer, with a quicker recovery. A 2019 study in the Journal of Ophthalmology notes that in the beginning, 27G PPV was considered for less complex cases – however, surgeons have advocated for its use in more complicated procedures recently. That said, 27G vitrectomy also has some potential drawbacks when compared to its earlier versions, 23G

and 25G, including: a reduction in the flow rate (which could influence the efficiency of the procedure), increased instrument flexibility (especially during anterior maneuvers), and the potential to underfill tamponade.6 According to Dr. Foxman, 27G PPV has been a hot trend for a while, and though instrumentation has improved, it hasn’t been revolutionary. To zoom in on the details of this trendy instrument, numerous studies have been conducted on its safety and efficacy. A 2018 study7 by Li et al., evaluated the safety and efficacy profile

Elamipretide is a new drug with the potential to improve vision.

– Dr. Brett Foxman

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COVER STORY

Travis Plage, Director of Finance. Mr. Plage is a

newer addition to Team Media MICE, and as such, this is his first time rocking the congress runway – and lucky for him, this is our most dapper theme yet. When he’s not managing the company finances, he spends a lot of time lamenting his decision not to wear a belt with his suit and debating (mostly with himself ) if brown shoes match grey pants.

A 2019 article9 found that “there are no reliable data to prove whether SB surgery or vitrectomy is more advantageous, and a standard treatment is still lacking, generally leaving surgical treatment options to be selected according to the experience of the attending doctors”. Dr. Foxman says that he agrees with the trend, but that it’s led to less buckle experience with newer surgeons. Dr. Banker has also noted the popularity of vitrectomy machines, along with newer vitreous substitutes and technology cutters. Innovations in surgical technology, like in PPV, have certainly provided more options for both patients and doctors – and time will tell which trends stick. Plus, instrumentation aside, a new trend in surgical viewing systems may also thread together additional benefits . . .

The Thread of 27G pars plana vitrectomy (PPV) for treating vitreoretinal diseases, including: rhegmatogenous retinal detachment (RRD), full-thickness macular hole, diabetic retinopathy, vitreous hemorrhage, Eales disease, pathological myopia-related vitreous floater and macular epiretinal membrane. The authors found that 27G PPV was safe and effective for the various vitreoretinal diseases but cautioned that “surgeons may encounter a learning curve and should gradually expand surgical indications from easy to pathologically complicated cases”.

Looking at longer-term rates (minimum of 1-year follow-up), another 2018 study8 found that 27G PPV was well tolerated, “with low rates of postoperative complications across varied surgical indications”. Using smaller instrumentation for vitrectomy has helped usher in another trend: The shif t from scleral buckling (SB) and toward PPV in cases of RRD. In the community, opinions vary widely on the advantages and disadvantages of each.

In imagining, automated wide-angle imaging, combining color, FFA, ICG and OCT in one machine, is trending. – Dr. Alay Banker

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Thread is a vital component to creating clothing, just as imaging and visualization systems are crucial for diagnosis, as well as pre-, intra- and postoperative disease and patient management – and the latest iterations have been getting some attention. In fact, the ASRS 2019 Global Trends in Retina Survey10 included topics like the use of 3-D visualization, intraoperative OCT (iOCT), OCT angiography (OCTA) and swept source OCT (SS-OCT) in its questionnaire. [Ed note: See infographic on page 22 to see how these four fashionable systems rank around the world.] Dr. Foxman has also noticed this focus on innovation: “There’s a trend toward digital surgical viewing systems, like Alcon’s NGENUITY, as well as intraoperative OCT,” he said. “However, these will be slow to reach the typical community retinal surgeon’s operating room due to cost and uncertain increased value in a very cost-conscious era.” According to Dr. Banker, threedimensional heads-up microscopes (3DM) are trending in the operating


room. That’s because PPV with 3DM is more comfortable for surgeons – plus, they don’t pose a greater risk of complications. In addition, 3DM surgery helps to significantly improve both the teaching and the learning of intraoperative surgical procedures.11 In imaging, Dr. Foxman says that there’s been a strong trend toward ultra-widefield photography. But with a caveat: “The cost is high . . . to the degree that a small practice will probably not recoup the increased cost over a standard fundus camera,” he said, adding that however, it does appear to have value and many retina docs have decided it’s worth the cost. The use of OCTA – and its value – is another trending topic. “OCT angiography is also a trend, but its value is not really clear . . . it’s one of those items that you like if you have it, but you may not go out and buy this feature outright,” explained Dr. Foxman. He said that in his practice it just happened: Several of the older OCTs needed replacement, so when forced to upgrade, they chose to add OCTA to two of the three new machines. As far as imaging, Dr. Banker adds that OCT machines combining indocyanine green with angiography (ICG), automated wide-angle imaging and fundus fluorescein angiography (FFA), are also gaining attention. Meanwhile, emerging technology in the autointegration of artificial intelligence (AI) systems and less expensive phone-based imaging devise (using applications with AI) are garnering enthusiasm and are definitely ‘looks’ worth watching in the upcoming season’s shows.

The Final Garment At the EURETINA 2019 Congress in Paris, we expect all of these trends to walk down the metaphorical catwalk: From the fabrics of disease-targeting agents, to the needle of surgical instruments and new techniques, sown together by the threads that create visualization pre-, intra- and postoperatively.

And through research, study and practice, surgeons will continue to design ‘haute couture’ procedures, using the latest (and trending) innovations to continue improving patient outcomes for posterior segment conditions.

References: Mettu PS, Allingham MJ, Cousins SW. “Effects of the Mitochondria-Targeted Drug Elamipretide on Leakage-Independent Vision Loss in Fellow Eyes with Neovascular AMD in the ReCLAIM Study. Poster at the 2019 American Society of Retina Specialists; 2019 July 26-30; Chicago, United States. 2 Kassa E, Ciulla TA, Hussain RM, Dugel PU. Complement inhibition as a therapeutic strategy in retinal disorders. Expert Opin Biol Ther. 2019;19(4):335-342. 3 Nebbioso M, Lambiase A, Cerini A, et al. Therapeutic Approaches with Intravitreal Injections in Geographic Atrophy Secondary to Age-Related Macular Degeneration: Current Drugs and Potential Molecules. Int J Mol Sci. 2019; 20(7):1693. 4 Dugel PU, Koh A, Ogura Y, et al. HAWK and HARRIER: Phase 3, Multicenter, Randomized, Double-Masked Trials of Brolucizumab for Neovascular Age-Related Macular Degeneration. Ophthalmology. 2019;pii: S0161-6420(18)33018-5. 5 Khanani AM, et al. Simultaneous Inhibition of VEGF and Ang-2 with Faricimab in Neovascular AMD: STAIRWAY Phase 2 Results. Presented at the 2018 American Academy of Ophthalmology (AAO) Annual Meeting; 2018 Oct 26; Chicago, United States. 6 Veritti D, Sarao V, Lanzetta P. A Propensity-Score Matching Comparison between 27-Gauge and 25-Gauge Vitrectomy Systems for the Repair of Primary Rhegmatogenous Retinal Detachment. J Ophthalmol. 2019;2019: 3120960. 7 Li J, Liu SM, Dong WT, et al. Outcomes of transconjunctival sutureless 27-gauge vitrectomy for vitreoretinal diseases. Int J Ophthalmol. 2018;11(3):408-415. 8 Khan MA, Kuley A, Riemann CD, et a;. Long-Term Visual Outcomes and Safety Profile of 27-Gauge Pars Plana Vitrectomy for Posterior Segment Disease. Ophthalmology. 2018;125(3):423-431. 9 Li Liao, Xiao-Hua Zhu. Advances in the treatment of rhegmatogenous retinal detachment. Int J Ophthalmol. 2019; 12(4): 660–667. 10 Singh RP, Stone TW, Hahn P, eds. 2019 Global Trends in Retina Survey: Chicago, IL. American Society of Retina Specialists; 2019. 11 Romano MR, Cennamo G, Comune C, et al. Evaluation of 3D heads-up vitrectomy: outcomes of psychometric skills testing and surgeon satisfaction. Eye (Lond). 2018;32(6):1093-1098. 1

About the Contributing Doctors Dr. Brett Foxman has been the chief of the Division of Ophthalmology at Shore Medical Center in New Jersey, USA, since 2008 and a retina specialist at Retinal and Ophthalmic Consultants, P.C. since 1992. He completed his ophthalmology residency and retina fellowship at the University of California, Los Angeles (UCLA), Jules Eye Institute. Dr. Foxman is active in various societies and has served on the board of the American Society of Retina Specialists (ASRS) and the American Retina Foundation. He’s given numerous lectures and published papers, and is actively involved in research, with interests in therapies for posterior segment conditions like dry AMD. In 2019, he received a United States patent for a scleral depressor which makes small changes, but advances to retinal surgery. [Email: bfoxman@retina.com] Dr. Alay S. Banker is the director of Banker’s Retina Clinic, Ahmedabad, Gujarat and chief of Gujarat Telemedicine ROP Project (Honorary Services). After completing MS from Gujarat University, he completed a vitreoretinal fellowship at Medical Research Foundation, Sankara Nethralaya, Chennai. Following that, he was a clinical instructor and fellow of vitreoretina and uveitis at University of California, San Diego, USA. He has won awards from societies including the American Academy of Ophthalmology (AAO), the American Society of Retina Specialists (ASRS), and the AsiaPacific Academy of Ophthalmology (APAO). Dr. Banker is a member of the International Uveitis Society Group (IUSG) and the Chief Liaison leader for Asia-Pacific Region to the International Affairs Committee of ASRS. He has published 48 papers in international and national peer-reviewed journals and has written eight book chapters. He has given more than 500 guest speaker presentations and over 100 instruction courses at national and international conferences. [Email: alay.banker@gmail.com]

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HAUTE TRENDS In Imaging & Visualization An excerpt from the ASRS Global Trends Survey 2019

Do you have access to OCT-A? Yes, and find it useful in clinical practice

Asia/ Pacific

No, I do not have access

58% 25%

United States

Europe

58.8% 25.9%

27.1% 53%

Do you have access to SS-OCT? Yes, and find it useful in clinical practice

No, but plan to have access soon

60

60

60

50

50

50

40

40

40

30

30

30

20 10

34.1

10

15.6

United States

Asia/ Pacific

17.2

21.3

58.3

10

48.2

United States

35.8 24

Europe

25.0

0

0

Asia/Pacific

35

20

20

45.8

0

42.6

No, and do not plan to have access soon

Europe

What is your experience with, and assessment of, 3-D heads-up visualization systems? Have not used 3-D in the OR, but plan to Have used 3-D in the OR and do not think it is helpful Have used 3-D in the OR and it has been helpful

What is your opinion of intraoperative OCT? Have not used intraoperative OCT

75.7%

Asia/Pacific

77.2%

United States Europe

69.3% Singh RP, Stone TW, Hahn P, eds. 2019 Global Trends in Retina Survey: Chicago, IL. American Society of Retina Specialists; 2019.


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INNOVATION ROP SURGERY

Surgical Treatment of Advanced Retinopathy of Prematurity When Less is More by Olawale Salami

Microincision vitrectomy surgery (MIVS) along with wide angle viewing systems allow surgeons to effectively manage ROP surgeries while at the same time reducing complication rates in infantsâ&#x20AC;&#x2122; eyes.

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etinopathy of prematurity (ROP) is one of the most common causes of visual loss in infancy and can lead to lifelong vision impairment and blindness. It primarily affects newborn babies who weigh 1,250 grams or less, or are born before 31 weeks of gestation. Landmark trials such as CRYOROP and ETROP (Early Treatment Retinopathy of Prematurity) have provided deeper understanding of the natural history of the disease and established management guidelines. Currently, in developing countries like India, there are several important barriers to early treatment initiation in extremely premature infants with ROP. These include lack of awareness, lack of availability of specialized care, and low access to timely screening service in the immediate post-natal period. An important complication of ROP is tractional retinal detachment (TRD) and once that occurs, surgical intervention in the form of vitrectomy

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Take a bite out of ROP with MIVS.

is necessary. Vitrectomy relieves the traction, eliminates the scaffold for further fibro vascular growth and can remove the excessive levels of vascular endothelial growth factors (VEGF). Micro-incision vitrectomy surgery (MIVS) has the advantage of minimal ocular surface disruption. It increases the surgeonâ&#x20AC;&#x2122;s ability to access between tight retinal folds and reduces surgical trauma, resulting in faster and better postoperative recovery. MIVS is used almost universally for most vitreoretinal procedures. In a paper titled, Surgical outcomes of microincision vitrectomy surgery in eyes with retinal detachment secondary to retinopathy of prematurity in Indian population*, Dr. Parveen Sen and colleagues from the Department of Vitreoretinal Services, Shri Bhagwan Mahavir Vitreoretinal Services, Sankara Nethralaya, Chennai, reported anatomical outcomes of MIVS for Stage 4 and 5 ROP in Indian Infants.

Their findings were published in the June 2019 edition of the Indian Journal of Ophthalmology. Between January 2012 and April 2015, Dr. Sen and colleagues reviewed medical records of 202 eyes of 129 premature children undergoing MIVS for Stage 4 or 5 ROP. The primary outcome measure was the proportion of eyes with anatomical success (defined as attached retina at the posterior pole at last follow-up). Furthermore, complications associated with MIVS were noted and an analysis of risk factors associated with poor anatomical outcomes was performed. The infants were monitored for an average period of 32 weeks. At the end of follow-up, Dr. Sen and colleagues observed that 102 eyes (50.5%) had achieved anatomical success, including 74% eyes in Stage 4a and 4b, and 33% in Stage 5. Complications were documented in some infants, including intraoperative break formation in


ROP is largely a preventable cause of childhood blindness. If premature babies are screened within the first four weeks of birth and treated appropriately, surgical intervention can be prevented in most cases. – Dr. Parveen Sen

19% of infants, postoperative vitreous hemorrhage in 28%, raised intraocular pressure in 12.7%, and cataract progression in 2.4% of infants. Based on the study results, the authors concluded that “MIVS along with wide-angle viewing systems allow surgeons to effectively manage ROP surgeries, while at the same time reducing the complication rate in these eyes, which have complex pathoanatomy and otherwise grim prognosis”. Dr. Sen provided a narrative of some of the key challenges faced today by surgeons in the management of advanced ROP. She explained that “ROP is largely a preventable cause of childhood blindness. If premature babies are screened within the first four weeks of birth and treated appropriately, surgical intervention can be prevented in most cases”. “Once the child needs surgical intervention, a highly competent

and experienced team comprising a pediatric retina specialist, pediatric anesthesiologist and a pediatrician is necessary to handle the baby during surgery and provide the essential postoperative care. Such a team very often may be available only in tertiary care centers,” she added. According to Dr. Sen, surgery itself for ROP is a typical example where less is more. “Astute preoperative planning and precise execution are the keys to success,” she emphasized. For stage 4 ROP surgery, a vitrectomy through the pars plicata (since pars plana is not well developed in very small babies) with MIVS is the most widely accepted surgical approach at present. In addition, the limbal approach, which avoids the pars plicata is the popular approach in cases of stage 5 ROP. “It allows adequate surgical maneuvering as well as decreases the rate of complications associated with this surgery. Regular follow-up of these babies is a must for adequate visual rehabilitation,” explained Dr. Sen.

On surgical outcomes, Dr. Sen clarified that “surgery itself is extremely demanding and unforgiving, needing high degree of precision and accuracy. In spite of best efforts, the success rate of surgery in the most advanced stage (stage 5) of ROP may be about 30 percent due to the complex nature of these retinal detachments”. Furthermore, Dr. Sen gave important advice on the best ways to prevent ROP: “Prevention by timely screening and treatment is the best approach. To meet the challenge of preventing visual loss from ROP and screening all premature babies (about 3.5 million premature babies are born annually in India), ophthalmologists, neonatologists, gynecologists and government institutions must take collaborative efforts.” * Sen P, Bhende P, Sharma T, et al. Surgical outcomes of microincision vitrectomy surgery in eyes with retinal detachment secondary to retinopathy of prematurity in Indian population. Indian J Ophthalmol. 2019;67(6):889-895.

About the Contributing Doctor Dr. Parveen Sen was born in 1971 in India. She is a trained vitreoretinal surgeon and did her fellowship at Sankara Nethralaya in 2000. Since then she has worked as a vitreoretinal surgeon at the Department of Vitreoretina at Sankara Nethralaya, a tertiary care ophthalmic center in Chennai, India. She has been practicing for the last 19 years and is an experienced surgeon with large number of complicated vitreoretinal surgeries to her name. She heads the Retinal Electrodiagnostics Services at Sankara Nethralaya. Her special areas of interest are pediatric retinal Imaging, pediatric retinal surgery, especially surgery for retinopathy of prematurity, as well as other pediatric retinal detachments (PFV, FEVR, Coats and Trauma), velectrophysiology, genetic disorders of the retina, AMD, polypoidal choroidal vasculopathy and retinal imaging. Dr. Sen has more than 72 publications in the peerreviewed indexed journals and has made many presentations at national and international conferences. She has been actively involved in the teaching and training of vitreoretinal fellows and guided them through their research work. She has co-authored three books and has written several book chapters. Dr. Sen is also a reviewer for several national and international journals. [Email: parveensen@gmail.com]

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INNOVATION ROP TREATMENT

A New Vision for Treatment of a

Rare ROP

A diamond in the rough: Finding treatments for rare diseases.

by Gerardo Sison

T

reatments for retinopathy of prematurity (ROP) have become a growing focal point for vulnerable populations, especially in Asia-Pacific. Although quite rare, ROP is among the leading causes of childhood blindness. In Asian countries, preterm infants often develop ROP at higher birth weights compared to those reported in the West. Successful treatment depends not only on screening premature babies, but also on the type of treatment used. Most cases of ROP have been treated with laser therapy, considered the standard of treatment until recently. Still, unique cases of ROP have occurred, notably one case of aggressive posterior retinopathy of prematurity (APROP) where diode laser photocoagulation was used in a preterm child with APROP and ocular albinism.1

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Below, Dr. Alay Banker, director of Banker’s Retina Clinic, Ahmedabad, Gujarat, India – one of the first practitioners to use anti-VEGF therapy for ROP – sheds some insight on this case and the use of different treatment methods available today.

APROP with Oculocutaneous Albinism “In ocular albinism, patients do not have pigments in their retina,” said Dr. Banker. “The primary way the laser works when you do laser therapy [is that] it’s taken up by the pigments in the retina to cause coagulation. So, that’s why, in this case, where there is no pigment in the eye, it’s very difficult to get a laser reaction.” Oculocutaneous albinism is distinguished by the complete or partial lack of melanin in the retinal pigment

epithelium (RPE). This can prove to be rather challenging when treating with laser therapy due to the difficulties in visualizing retinal tears and effectively using an endolaser. According to the report from the Indian Journal of Ophthalmology1, diode laser photocoagulation was implemented at higher parameters in a preterm female child with zone 2 APROP and hypopigmentation of the RPE and choroid. The baby was given topical anesthesia and did not experience any complications such as retinal tear or choroidal hemorrhage. Other cases of ROP in similar infants found challenges with laser therapy and had to complete treatment with cryoablation of the retina. However, diode laser set for deeper choroid penetration resulted in successful treatment.


“Diode laser affects the choroid and is usually more effective in cases which have less pigments,” Dr. Banker commented. “The ideal case would be to use anti-VEGF treatment first, and then laser therapy after a few weeks. This way you can have vessels growing into the periphery where the retina is relatively seen with more pigments and thus, see the laser reaction more clearly.”

Treatment Options: Laser vs. Anti-VEGF Therapy Although successful, it would not be right to say that researchers in this case study did not have other treatment options. Other than argon-green or diode laser photocoagulation, antiVEGF therapy has been established as a viable option to treat ROP types. For instance, anti-VEGF medications have shown effectiveness in treating severe zone 1 ROP and APROP. “One problem with using the diode laser extensively is that, since you’re treating the choroid more, there is a risk of swelling or choroidal detachment,” said Dr. Banker. “With anti-VEGF, the retina is able to undergo more normal peripheral vascularization, so you just have to do laser treatment in the remaining avascular retina.” High VEGF levels can cause abnormal development of retinal blood vessels in premature infants. Therefore, anti-VEGF medications can combat structural irregularities before they cause extensive damage. Anti-VEGF medications are typically injected into the eye while the infant is under brief general anesthesia. Drugs like bevacizumab, ranibizumab, aflibercept and pegaptanib have shown clinical success with preterm infants at high risk of vision loss. The RAINBOW study2, in particular, has shown promise as an ongoing trial evaluating the use of ranibizumab vs. laser therapy in ROP. “While the standard of treatment is the laser when it comes to treating APROP, or any severe ROP in zone 1 disease, using laser therapy destroys 70 to 80 percent of retinal peripheral area, which causes severe field restrictions

as the child grows up,” explained Dr. Banker. “Now, the majority of experts are supporting anti-VEGF as a firstline therapy. They can then follow-up with the babies and go on to add laser therapy at a later stage.” According to Dr. Banker, preterm infants already have a lot of risks. “Doing laser treatment at the start of therapy will take around 35 to 45 minutes, which may be more harmful,” he said. “Instead, we can do minor laser treatment when the baby is healthier and more stable. The procedure will be shorter with less anesthesia needed.” Dr. Banker further explained: “Anti-VEGF therapy allows vascularity to grow into zone 2 [which extends to the edge of the retina on the side of the eye toward the nose] so that we can then laser the remaining 30 percent of the avascular peripheral retina. This way we are minimizing any destructive effects of therapy.” Despite its advantages, anti-VEGF therapy has a higher rate of recurrence of ROP with a longer mandatory followup procedure. “Laser therapy is a more finite treatment. Babies who have had laser therapy often require less

number of follow-ups,” said Dr. Banker. “It’s important to assess the patient to determine the method of treatment.”

The Future of ROP Treatments When asked about what’s next for ROP treatment, Dr. Banker mentioned that there are some innovative practices in store: “We’re going to use AI and deep learning to develop an algorithm where we’ll be able to predict babies who have been treated with anti-VEGF and identify babies at high risk of recurrences,” he said. “We can then identify their response to treatment and advise those babies to come for earlier, more frequent follow-ups.” In effect, treatment methods for ROP are not limited to certain cases as reflected by this case report. With successful treatment of APROP with ocular albinism, laser photocoagulation still encompasses an effective treatment for ROP even in challenging cases. Still, according to experts like Dr. Banker, anti-VEGF therapy is a major element in treating ROP, while peripheral damage and follow-up treatments remain a concern with laser therapy.

References: Gangwe AB, Parchand SM, Azad RV, et al. Successful treatment of aggressive posterior retinopathy of prematurity with diode laser in ocular albinism: A case report. Indian J Ophthalmol. 2019;67(6):962–964. 2 RAINBOW Study: RAnibizumab Compared With Laser Therapy for the Treatment of INfants BOrn Prematurely With Retinopathy of Prematurity. Available at: https://clinicaltrials.gov/ct2/ show/NCT02375971. Published March 3, 2015. Accessed August 23, 2019. 1

About the Contributing Doctor Dr. Alay S. Banker is the director of Banker’s Retina Clinic, Ahmedabad, Gujarat and chief of Gujarat Telemedicine ROP Project (Honorary Services). After completing his MS from Gujarat University where he won the Gold Medal, he did a vitreo-retinal fellowship at Medical Research Foundation, Sankara Nethralaya, Chennai. He then served as a clinical instructor and fellow of Vitreo-retina and Uveitis at University of California, San Diego, USA. Some of his achievements include the International Scholar Award and International Education Award from American Academy of Ophthalmology (AAO), Senior Honor Award and Honor Award from American Society of Retina Specialists (ASRS), APAO Achievement Award 2014, the Late Dr. Piyush Patel Award for Social Service from Ahmedabad Medical Association, Gold Medal from All India community Ophthalmology Society for Community project on ROP and Dr. R. N. Mathur Oration from Gujarat State Ophthalmological Society, 2012. He has also won many Best Paper and Best Poster awards at AAO, USI, VRSI, State meets and AIOS including the Col. Rangachari Award for best paper at AIOS 2013. He is amongst a select few to be invited as a faculty to both the Uveitis and Retina Subspecialty Meets by AAO and to the Vail Vitrectomy Meet. He is a member of the International Uveitis Society Group (IUSG) and the Chief Liaison leader for Asia-Pacific Region to the International Affairs Committee of ASRS. Dr. Banker has published 48 papers in International and national peer-reviewed journals and has written eight book chapters. He has given over 500 guest speaker presentations and over 100 instruction courses at national and international conferences. [Email: alay.banker@gmail.com]

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ENLIGHTENMENT FASHION

When Fashion Meets Vision by Tan Sher Lynn

Dr. Arun C. Gulani, dubbed “the Da Vinci of Eye Surgery”, talks about how he threads ophthalmology and fashion together. . .

D

r. Gulani is an ophthalmologist specializing in advanced KeratoLenticulo-Refractive (i.e. the full spectrum cornea and lens-based surgeries), which includes all versions of LASIK, premium cataract surgeries and corneal surgeries, to provide patients with spectacle independence. Originally from India, he completed his postgraduate in ophthalmology and earned the coveted gold medal. While still a junior resident ophthalmologist, he wrote the first textbook on Color

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Doppler for eye tumors, which attracted the attention of renowned eye surgeons and universities from all over the world. And at the young age of 25, he was invited to receive the Becton Dickinson Career achievement award in Philadelphia, where most of the competing candidates were in retirement age. “Having received numerous invitations from the U.S., I proceeded with refractive surgery while it was still in its infancy, and was even called ‘Buccaneer Surgery’,” he said. According to Dr. Gulani, he was naturally attracted to ophthalmology when he was exposed to it during surgical rotations in medical school. “Not only was it a combination of surgical artistry at its highest form, it also provided for my desire for

innovation, along with near-immediate gratification from patient’s visual outcomes,” he said. In 2003, he founded the Gulani Vision Institute at the Southpoint area of Jacksonville, Florida, based on his philosophy of a “High-Tech” and “High-Touch” approach to patient care. The institute soon grew into a globally acclaimed ophthalmology center, receiving patients and students from all over world.

An Eye for Fashion Impeccably dressed, even in the slightest details, Dr. Gulani’s love for high fashion is evident in his practice. To him, it is important to be welldressed as it reflects his pride in his work and his desire to impart elegance wherever he can. “Fashion is my parallel passion, just like eyes are. In my practice, my penchant for colors, symmetry, beauty and elegance are always the driving factor to bring out the best in each and every person as I custom-treat each and every eye to fulfill my patients’ best vision potential,” he shared.


In 2017, Dr. Gulani launched his fashion line – Gulani Fashion. “My fashion line is as unique as my practice is. In fact, my tagline for Gulani Fashion is “For Those Who Have Arrived” – for people who aspire to look their very best. Once again, just like my eye surgeries, I don’t offer choices. I will decide what is best for my clients based on each person’s unique characteristics – their background, desires, body type and what I feel should be the colors and cuts that would suit them best, for both men and women. Then, I celebrate their looks just like how I celebrate their vision,” he said. In fact, his artistic sense can be felt and seen in his everyday life. For instance, he uses colors in full range from suits to scrubs to the lighting in his surgery suite and colors of medical instruments. “One surreal observation is that somehow (without knowing it), I always seem to be wearing the color that coincides with the color of the theme of the conference at which I am speaking,” he noted.

A Fulfilling Life Dr. Gulani believes that each one of us is born with our internal GPS, and it is this GPS which he has allowed to unfold throughout his life, creating beautiful, unique outcomes that the world is able to regale in today. Even though he has received numerous national and international awards and recognition, to him, his best achievement is his family and the fact that he was able to help so many patients around the world. “My proudest achievements are my family and the blessing that I have gathered from so many patients from all over the world for nearly three decades, and from having mentored so many to achieve the best of their potential. My passion for eyes and fashion has never allowed me to feel that I am working at all, and when my patients celebrate their outcomes with me there is nothing higher or greater that I can look forward to,” he said.

Fashion is my parallel passion, just like eyes are. In my practice, my penchant for colors, symmetry, beauty and elegance are always the driving factor to bring out the best in each and every person as I custom-treat each and every eye to fulfill my patients’ best vision potential.

– Dr. Arun C. Gulani When he is not busy with fixing eyes or designing clothes, Dr. Gulani loves to spend time with his family, and indulge in his other passions, namely modeling, sports, travel, Porsche-racing, as well as eating ice-cream and candies. As a sought-after mentor and speaker, he constantly encourages eye surgeons to stop talking about technology and in-the-box thinking, but to rise beyond and accept the artistry of eye surgery in delivering vision beyond 20/20 in every patient. “It is a constant pleasure to share my work with colleagues worldwide,

and despite how exciting our progress in the eye care industry may be, I am dedicated to change the mindset of eye care providers to believe that no patient should be wearing glasses or contact lenses, as they are a mark of disability whose time of extinction has already passed,” he said. “They say imitation is the best form of flattery and I must say I am gratified to see lately, doctors dressing up, allowing pictures with patients and even using my ‘thumbs up’ sign tradition, which I introduced nearly three decades ago,” he quipped.

About the Contributing Doctor Dr. Arun C. Gulani is a world-renowned LASIK cataract, and corneal surgeon and performs the entire spectrum of advanced vision surgeries to reduce dependence on glasses and contacts, customising vision correction surgery to meet each patient’s unique goals. He has extensive experience in a wide variety of eye surgery techniques and technology. He was formerly the Chief of Cornea and Assistant Professor of Ophthalmology in the University of Florida’s School of Medicine before founding the Gulani Vision Institute in 2003, where he receives a global clientele and acts as a consultant to eye surgeons and the eye care industry as well. With an eye of an artist, his passion is to make people see and with his no-hype, one-on-one personalized care, he has turned Jacksonville, Florida into a vision destination for the world.[Email: gulanivision@gulani.com]

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ENLIGHTENMENT EYE RESEARCH

Out of the Blue The Zebrafish Animal Model for Ocular Research by Gerardo Sison

V

isual impairment and blindness affects millions of people worldwide each year. And, as the general age of the population increases, rates of vision loss are not getting any better. Despite our knowledge of these visual conditions, there is still a lack of understanding on how these visual problems arise. The question then becomes: How can we better treat them? With such an important question to be answered, there is a growing need for animal models in research. One particular application for zebrafish has evolved in the study of retinal pigment epithelium (RPE) as it relates to prevalent diseases, such as agerelated macular degeneration (AMD). By understanding critical points of pathogenesis, researchers may be one step closer to unlocking new treatment modalities.

Zebrafish as a Model Organism According to Dr. Jeffrey Gross, PhD, director of research at the Department of Ophthalmology, University of Pittsburgh School of Medicine, zebrafish are an ideal model for studying visual developments. “Zebrafish provide a robust system for modeling human diseases,” said Dr. Gross. “Since cell types are similar and the architecture is the same, they are valuable for understanding mechanisms of disease.” Zebrafish are a type of freshwater fish belonging to the minnow family. Native to South Asia, zebrafish have become widely used specimens in research and drug development.

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Fish animal models are ‘in’ this season. (Zebrafish not pictured)

Compared to mice, the eyes of zebrafish develop at a faster rate with features that more closely resemble those of human eyes. “Compared to mice which have a rod-rich retina, zebrafish have a conerich retina similar to the human retina,” share Dr. Gross. “The zebrafish retinal structure is arranged in the same way as that in humans, so you’re modeling the same process.” As a useful animal model, zebrafish are easy to care for without incurring high laboratory costs. Because they can produce up to 200 eggs for every mating, zebrafish can provide a large sample size needed for identifying structures of interest and other potential mutant variations. “We can look at 10 to 20 embryos at a time versus a much smaller sample in mice,” said Dr. Gross. “Along with other factors, this makes zebrafish useful for developmental biology, imaging, and genomics.” Zebrafish utilize vision as a defense mechanism against predators. Their resourceful vision system and 360-view allows them to remain alert to predator shapes while also detecting potential food sources. Additionally, because of their regenerative abilities within their ocular systems, zebrafish

have opened many doors for new treatment methods.

Regenerating Zebrafish RPE after Genetic Ablation As a specialized, pigmented monolayer of cells, the RPE separates the retina from the choroid and acts as a critical component of vision. The dysfunction and degeneration of the RPE is believed to play an important role in the pathology of diseases, notably AMD. In AMD, RPE dysfunction and degeneration can result in the loss of cone photoreceptors and eventually, the loss of vision. In one of his recent studies1 published this year, Dr. Gross and his team examined the mechanisms of RPE regeneration in zebrafish. They studied this mechanism by developing a transgenic model that implemented ablation of mature RPE. Using this model, they found for the first time, that stimulating endogenous RPE regeneration may provide a possibility for treating RPE degenerative diseases in humans. “We sought to understand how the RPE regenerates in order to see how regeneration may be stimulated


Compared to mice which have a rod-rich retina, zebrafish have a cone-rich retina similar to the human retina. The zebrafish retinal structure is arranged in the same way as that in humans, so you’re modeling the same process.

– Dr. Jeffrey Gross in a human eye,” explained Dr. Gross. “We want to see whether the strategies it employs could be used to keep RPE functioning in diseased eyes to retain vision longer. We could then identify genes, pathways and potential compounds which could help preserve and restore vision.” Interestingly, compared to other models for RPE regeneration, their zebrafish model more closely resembles the degeneration and loss of visual function seen in late-stage AMD. Other models use non cell-specific injury methods such as debridement or laser photocoagulation. However, the zebrafish model produces RPE and photoreceptor degeneration which may provide a more applicable clinical picture for evaluating RPE regeneration in mammals.

Making Waves for Research in Ocular Disease Several studies have used zebrafish models to explore the therapeutic potential of new drugs for pathological conditions from cardiovascular disease to infectious diseases. In recent years, studies in ocular diseases have shown an even stronger potential with zebrafish. Similar disease phenotypes have been replicated in zebrafish, mirroring several human vision conditions such as glaucoma, cataracts and diabetic retinopathy. One study in the Human Genetics

and Human Mutation journal found a crystalline gene mutation using zebrafish animal models.2 The protein crystalline, is known to influence refractive power by regulating lens and cornea transparency. Mutations of the CRYBA2 and CRYGC gene were ultimately found to be linked to the formation of cataracts in humans. Other studies, such as the one found in Human Molecular Genetics, examined the genetics of glaucoma. Experts later found a link between a FOXC1 gene mutation and increased intraocular pressure in zebrafish. Anterior segment defects and severe myopia were also exhibited due to mutations in the FOXx1 gene, predominantly expressed in the periocular mesenchymal cells.3 Lead investigator, Bo Chen, PhD, , an associate professor of Ophthalmology and Director of the Ocular Stem Cell Program at the Icahn School of Medicine at Mount Sinai, found that zebrafish could repair retinal damage within a few days. Dr. Chen and his colleagues explored evidence for vision restoration as a result of Müller glial cell derived regeneration.4 Due in part to Müller glial cells, the freshwater fish can replenish damaged retinal nerve cells

and essentially repair vision. While Müller glial cells do not possess regenerative properties in the human retina, these cells may provide deeper insight for future research in retinal degeneration. Plus, with the additional understanding of RPE regeneration provided by Dr. Gross’s study, the framework behind photoreceptor degeneration may be further laid out.

The Future of Zebrafish Retinal disease is a growing problem that can only be tackled with greater understanding of the underlying mechanisms of disease. With an increased need for adequate studies comes the need for effective animal models. Because of their similar anatomical eye structure to the human eye, zebrafish can provide a new lens into the pathology behind ocular conditions. Zebrafish are easy to maintain, relatively quick to generate and display rapid retinal development. With several studies already replicating human vision disorders in zebrafish, the zebrafish model can only gain more traction moving forward.

References: Hanovice NJ, Leach LL, Slater K, et al. Regeneration of the zebrafish retinal pigment epithelium after widespread genetic ablation. PLoS Genet. 2019; 15(1): e1007939. 2 Reis LM, Tyler RC, Muheisen S, et al. Whole exome sequencing in dominant cataract identifies a new causative factor, CRYBA2, and a variety of novel alleles in known genes. Hum Genet. 2013;132(7):761–770. 3 McMahon C, Semina EV, Link BA. Using zebrafish to study the complex genetics of glaucoma. Comp Biochem Physiol C Toxicol Pharmacol. 2004;138(3):343-350. 4 Yao K, Qiu S, Wang YV, et al. Restoration of vision after de novo genesis of rod photoreceptors in mammalian retinas. Nature. 2018;560(7719):484-488. 1

About the Contributing Doctor Dr. Jeffrey Gross is the E. Ronald Salvitti chair in ophthalmology research in the Department of Ophthalmology, University of Pittsburgh School of Medicine, and the vice chair and director of research. He is also the director of the Louis J. Fox Center for Vision Restoration and of Ocular Development, Disease and Regeneration Laboratory at the University of Pittsburgh School of Medicine. Dr. Gross earned his PhD in biology at Duke University and has served as a professor at the Department of Molecular Biosciences, Institute for Cellular and Molecular Biology & Institute for Neuroscience, University of Texas. Dr. Gross contributes as a member of the Society for Developmental Biology, the Genetics Society of America, the American Association for Vision and Ophthalmology, and the International Society for Eye Research. He is also associate editor of BMC Developmental Biology and editorial board member of Developmental Dynamics. [Email: grossjm@pitt.edu]

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ENLIGHTENMENT WOMEN IN OPHTHALMOLOGY

Living Her Destiny by Tan Sher Lynn

Vitreoretinal specialist Dr. Judy Kim – the first KoreanAmerican to be elected into the American Ophthalmological Society – pursues her passions with faith and perseverance, and her numerous achievements attest to her accomplishments.

D

r. Judy Kim comes from a closeknit South Korean family who believes in giving their children the best. When she was 9-years-old, her entire family moved to Japan, and then to the United States when she was 11. Her parents have always been a strong influence. “My parents did not distinguish between their two daughters and two sons when choosing a career path, unlike many Asian parents of that generation. In fact, a big factor in my parents’ decision to immigrate to the United States was to allow the best opportunities, even for his daughters. My mother, a career woman as a

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pharmacist, was a role model for me. And my father often said his inheritance to his children is education and faith, both of which cannot be taken away by anyone or anything,” shared Dr. Kim.

Finding Her Purpose After graduating from the University of Chicago, Dr. Kim attended the Johns Hopkins University School of Medicine. During the second year of medical school, she was selected for the Howard Hughes-NIH Research Scholar Program, which provided housing at the National Institutes of Health campus. She found her purpose there, where she worked daily to solve questions that could benefit people in the future. “What can I do to help others and make a meaningful contribution to the society? This is the question that drives me until today. I want to be a part of the solution. I want to be a change-maker. The things I learned while learning to do research – the importance of collaboration, being open minded, asking the hard questions, thinking

analytically as well as creatively, being open to guidance, valuing data and objectivity, as well as gut instinct, staying inquisitive, and giving my best, have all helped me greatly throughout my career,” she said. When she returned to John Hopkins, Dr. Kim took an elective in ophthalmology in hopes of easing into clinical clerkships. This step changed her career trajectory from becoming an immunologist to an ophthalmic surgeon. “While at Bascom Palmer as a resident, and Medical College of Wisconsin as a vitreoretinal fellow, I had many great teachers and mentors with whom I still interact closely. I cannot thank them enough for their generosity in time and sponsorship, both in the field of ophthalmology and in leadership opportunities. I am also blessed with amazing friends and colleagues. Through my observations and interactions with them, they have been my mentors, helping me to improve in my various roles. I try to pay back by mentoring and helping others.”


A Rewarding Career “I became an ophthalmologist, more specifically a retinal diseases and vitreoretinal surgery specialist in academic medicine, because it perfectly fits my interests. I enjoy working with my hands, solving complex problems, teaching and mentoring, and interacting with and helping people of all ages and all walks of life. The field has seen numerous exciting technological and pharmacological advances and continues to do so, which fuels my curiosity and pursuit of knowledge,” said Dr. Kim. “I appreciate the opportunity to assist in moving the field forward through research, clinical trials, teaching and leadership in various organizations,” she said, adding that it has been rewarding to initiate and lead a successful teleophthalmology program – TeleEye Health Collaborative – with her community partners to prevent vision loss in their community. “Of all the senses, people value sight the most,” she continued. “How lucky am I then to be able to preserve sight on a daily basis, while training the next generation of bright ophthalmologists and collaborating with like-minded colleagues around the world to benefit our patients, communities and societies . . . it is too much fun and rewarding to be called a job!”

I became an ophthalmologist, more specifically a retinal diseases and vitreoretinal surgery specialist in academic medicine, because it perfectly fits my interests. I enjoy working with my hands, solving complex problems, teaching and mentoring, and interacting with and helping people of all ages and all walks of life. – Dr. Judy Kim “AOS is the first specialty society in the United States and the members have influenced virtually every facet of ophthalmology. I am grateful to be a member, since it is not only an approval by exceptional peers as having achieved a distinction in the art and practice of ophthalmology, but also because one had to write a thesis that had to be accepted!” “I am also the first KoreanAmerican to be elected in the Board of Trustee of AAO and to have served on the board of all three American retina societies (ASRS, Macula and Retina). I am only the second woman to be on the executive committee of ASRS and will become the president of the largest retina society in the world. I have grown through these and other leadership opportunities, learned from exceptional

leaders, and have enjoyed leading various organizations with vision and strategic implementation,” she said. Dr. Kim believes that the key to her accomplishments is treating other people with respect and compassion, listening to others, working hard beyond the expectations of others, forgiving herself when she fails and learning from it, and staying positive and persevering. Given her background, she believes she tends to have a global view and strives to be a bridge between the East and West. “Honestly, I did not strive to be the first Korean-American in these areas, but they happened while I pursued my passion. I do not think about being a woman or Asian-American or being ‘vertically challenged’ (except when the circumstances take me there).

The Key to Success While Dr. Kim has received many awards and honors, including: appearing on the Best Doctor list annually since 2003; being inducted into the Retina Hall of Fame as an inaugural member; receiving the Honor Award and Senior Honor Award from the American Society of Retina Specialists (ASRS) and the American Academy of Ophthalmology (AAO); and giving named lectures. She is especially proud of being the first Korean-American to be elected into the American Ophthalmological Society (AOS). Dr. Judy Kim (left) and her family

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ENLIGHTENMENT WOMEN IN OPHTHALMOLOGY However, I often think about becoming the best human being that I can be, while helping others to achieve the same. I am still a work in progress and under construction,” she said.

Family Matters Dr. Kim attributes her achievements to her family who supported her all the way. “I am where I am not only because of my mentors and friends, but because of my family. While my children were younger, I always felt guilty that I was not spending enough time with them. Now my daughter, a resident in obstetrics and gynecology, and my son, a Naval Academy graduate currently training to be a Marine pilot, say that they are glad that I was a full-time career mom, since my work allowed them to be spared from my constant attention!” “I give special credit to my husband, who has been my partner in life, best friend, cheerleader, confidant, and advisor . . . who keeps me grounded and shares many of the household chores. He jokes that he had to cook in order not to starve while waiting for me to come home! While my work has been all consuming, my family makes it worthwhile as they cheer in my successes and encourage me in times of adversities,” said Dr. Kim. “My husband and I enjoy traveling to international conferences, medical missions, gardening and singing in the choir. While work and children are important,

I advise young couples to invest in the relationship with their spouses. Because once the children grow up and are out of the house, you will be left with your spouse. A happy spouse equals to a happy house!” she said.

Hopes and Advice As the landscape of ophthalmology continues to evolve, Dr. Kim wishes that there will be improvements in screening and early diagnosis, lower costs and a reduced treatment burden. “Perhaps incorporating artificial intelligence will make much of this possible, but we need some changes in policy,” she commented. To ophthalmologists starting out in their career, she says: “Have fun! We are working in an amazingly rewarding field that is also constantly changing. Changes bring challenges but also opportunities. Be prepared for these opportunities and take a chance on yourself. You might like it! Also, do some soul searching to identify your strengths, weaknesses and your source of fulfillment in life. Work toward your goals, not what others expect of you. There are more female colleagues in our field than ever, and we should support each other. Good mentors can be found in women as well as men, you just need to reach out and ask. Most importantly, have fun while collaborating and improving lives!”

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About the Contributing Doctor Judy E. Kim, MD, is a graduate of the University of Chicago, Johns Hopkins University School of Medicine, and Howard Hughes Medical Institute-National Institutes of Health Research Scholars Program. She completed her ophthalmology residency training at Bascom Palmer Eye Institute and vitreoretinal fellowship at the Medical College of Wisconsin. Currently she is a professor of ophthalmology at the Medical College of Wisconsin. Dr. Kim has received numerous awards and honors, including being named in the “Best Doctors in America” annually since 2003 and is included in the US News & World Report Best Doctor listing. She has received the American Academy of Ophthalmology Achievement Award and Senior Achievement Award, as well as the American Society of Retina Specialists Honor Award. She has been elected to many regional and national leadership and committee positions and serves on the review boards of a number of peerreviewed journals. Dr. Kim has published extensively and is a sought after lecturer and presenter nationally and internationally. She is actively involved with Diabetic Retinopathy Clinical Research Retina Network and has served as a Principal Investigator in a number of multicentre clinical trials related to vitreoretinal diseases and surgery. Her research interests include clinical trials, diabetic retinopathy, age-related macular degeneration, surgical retinal diseases, telemedicine and ocular imaging. [Email: jekim@mcw.edu]

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CONFERENCE HIGHLIGHTS APAO 2019 COVERAGE

Tackling Sports-related Eye Injuries, Orbital Tumors and Strabismus by Hazlin Hassan

S

trabismus, a condition where the eyes fail to align and work together, can be caused by orbital floor fractures from blunt trauma or sports-related injuries. Statistics show that every 13 minutes, an emergency department in the United States treats a child with a sports-related eye injury. While strabismus can be treated at any time, experts agree that an early and thorough diagnosis enables more effective treatment for the patient. Other causes of strabismus are congenital or hereditary, the result of an illness, or long-sightedness or due to a lesion on the cranial nerve. And sometimes it can occur postoperatively. “We see strabismus postoperatively as well, and a lot of time the question is: Do we wait, or do we refer them immediately for strabismus evaluation?” said Dr. Srinivas S. Iyengar, San Diego Eyelid Specialists, San Diego, California, during a session on Pediatric Ophthalmology and Strabismus at the APAO Congress in Bangkok, Thailand, in March 2019. Dr. Iyengar, who specializes in oculofacial plastic surgery and has served as part of the medical staff for professional sports teams including the San Diego Chargers and the Detroit Tigers, also talked about implant selection for orbital floor fractures. Citing a study from December 2018 involving 88 patients on “Permanent Versus Bioresorbable Implants in Orbital Floor Blowout Fractures,” he noted that bioabsorbable and permanent implants were found to be equally safe and effective for isolated orbital floor fractures. He presented several cases with iatrogenic causes of strabismus and orbital fractures. The first was that of a truck driver with hyperglobus at three months, with

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A punch in the face is one case of strabismus. Ok, not really.

a porous polyethylene implant with titanium placed by a general plastic surgeon. In this case, he noted that implant should be removed. The second case was that of a lawyer who suffered an orbital fracture while surfing. “We see them a lot of the time because the surfboard comes back and hits them in the eye,” he said.  The patient wanted to return to work as soon as possible and underwent surgery.  The fracture then resolved very quickly. In a third case, a professional baseball player suffered an orbital floor fracture after he was struck by a ball. “People wanted to operate on him. I told him he didn’t need surgery and we would observe him. I was kind of nervous because this was the first time

my name was in the press, which was kind of stressful for a young surgeon,” joked Dr. Iyengar. He noted that in cases of orbital floor fractures in high profile athletes, it was important to review the mechanism of fracture, indications for surgery, issues with patients who may be hit again, and the risk of globe rupture. “Depending on what job they do, there is some value in deciding which implant to use, if they are likely to be struck again, whether or not certain implants are safer,” he said, adding that a softer implant may be better than a rigid implant as it would absorb the force of a hit better. In conclusion, he said that most patients with an orbital floor fracture do not need surgery and can be observed.


Orbital wall injuries can involve the floor, medial wall or multiple walls. It could be a direct muscle injury, isolated muscle injury, combined injury, nerve damage, muscle circulation or muscle belly injury.

“However, those with entrapment, hypoglobus, large floor fractures and iatrogenic cases require surgery,” he said, adding that postoperative imaging is warranted in patients with persistent strabismus. Furthermore, Dr. Faruk H. Orge, professor of ophthalmology and pediatrics at Case Western Reserve University School of Medicine in Cleveland, Ohio, USA, presented on “Orbit-related Strabismus – Myths and Facts: Tackling Strabismus after Orbital Floor Fractures.” “Orbital trauma-related strabismus can come in many shapes. The more you practice, the more you see bizarre stuff,” said Dr. Orge. Orbital wall injuries can involve the floor, medial wall or multiple walls. It could be a direct muscle injury, isolated

muscle injury, combined injury, nerve damage, muscle circulation or muscle belly injury. “It’s sometimes difficult to see what’s going on,” he said, citing an example of a boy who hid a floor fracture injury from his mother by covering it with his hair after falling from a tree. “For orbital floor fractures, sometimes treatment options include doing nothing at all,” said Dr. Orge. Some people choose to patch one eye, use glasses such as bifocals with prisms, or fog their lenses with scotch tape, which he described as ‘a simple cure’. However, Dr. Orge cautioned that these injuries can be complicated. There are several types of strabismus, from vertical, horizontal, torsional, combined, restrictive and fixed globe. “In summary, the history of the event, a thorough examination and surgical timing are important. You have to really understand what you’re dealing with. Some of them are straightforward, some of them are not. The expectation of the patient has to be in the core of the discussions in surgical planning. You have to let them know it may take multiple surgeries. You have to underline that complications can occur, I cannot emphasize it enough,” he said. On the other hand, Dr. Peter J. Dolman, Clinical Professor from the University of British Columbia, Vancouver, Canada, spoke about orbital tumors and strabismus: “While we think of tumors often as benign or malignant neoplasms, we should keep in mind it could also be lymphoproliferative disorders like lymphomas or IgG4-

related disease, vascular anomalies such as cavernous or lymphatic malformations, and inflammatory masses like Wegener’s Disease.” According to Dr. Dolman, these mass lesions often present with proptosis or displacement, palpable mass, pain or discomfort, vision blurring, diplopia or strabismus, and a misalignment of the visual axis, which could be constant or intermittent. Tumors can be analyzed using CT or MRI scans, both of which can show its location, borders and invasiveness. In the acute phase, cases are often managed with radiotherapy and IV or oral corticosteroids to suppress the immune inflammation. Dr. Dolman shared the case of a patient with intraconal lesions and soft-tissue lymphoma with strabismus, which responded to radiotherapy and combined chemotherapy. Another case he presented on was a patient with inflammatory lesions, granulomatosis with polyangiitis. She developed an inability to move the left eye and became progressively frozen. A CT scan showed the destructive lesion of vasculitis. She was treated with immunosuppressive therapy. In summary, Dr. Dolman noted that most benign lesions do not cause strabismus, rather infiltrative or cicatrizing malignancies and inflammations may cause it. Editor’s Note: The APAO 2019 Congress was held in Bangkok, Thailand, on March 6-9, 2019. Reporting for this story also took place at APAO 2019. Media MICE Pte Ltd, PIE Magazine’s parent company, was the Official Media Partner at APAO 2019.

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CONFERENCE HIGHLIGHTS ASRS 2019 COVERAGE

All about the Posters

Highlights from ASRS

by Brooke Herron

P

osters are always a big draw at any congress – and at the recent American Society of Retina Specialists (ASRS) annual meeting in Chicago, they took center stage with scientific discovery and investigation. Below we share details from a couple that caught our eye at PIE . . .

Can IOP be predicted by changes in CST? “In patients with ME due to retinal vascular diseases, early anatomical response was significantly correlated with IOP change after intravitreal DEX.” Elevated intraocular pressure (IOP) occurs in 1/3 of patients receiving an intravitreal dexamethasone (DEX) implant (Ozurdex, Allergan Inc., Irvine, CA, USA). Therefore, Dong Yoon Kim, MD, PhD, and colleagues investigated whether IOP changes could be

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predicted by early anatomical response in macular edema (ME) due to retinal vascular diseases treated with the intravitreal DEX implant. Their results were presented in a poster titled “Association between intraocular pressure change and early anatomical response after dexamethasone implant”. They conducted retrospective review involving patients with diabetic macular edema (DME) or ME due to retinal vein occlusion (RVO), who underwent intravitreal DEX implantation and 3 months follow-up. Eyes were divided into increase (IIOP) or nonincrease (nIIOP) of IOP, as well as good (GAR) versus poor anatomical response (PAR). Best corrected visual acuity (BCVA), IOP and central subfield thickness (CST) at baseline, 1 week, 1 month and 3 months were compared between the two groups. A total of 49 eyes (29 with DME and 20 with ME due to RVO) were

included in the study. In total, 18 eyes experienced IIOP, while 31 did not. There was a significant difference in the mean CST reduction at 1 week from baseline between the two groups (-207.11 ± 85.48 in the IIOP group; -140.29 ± 86.19 in the nIIOP group, p = 0.012). Twenty-two eyes were classified as GAR and 27 eyes were PAR. There was a significant difference in the mean IOP elevation at 1 week from baseline after DEX between the two groups (4.00 ± 4.54 GAR, 1.33 ± 2.43 PAR, p = 0.012). The amount of CST reduction from baseline at 1 week had a statistically significant correlation with the amount of IOP change from baseline at 1 week and 1 month after DEX implant (r = 0.443, p = 0.001; r = 0.122, p = 0.001). These results led the investigators to conclude that “patients with good early anatomical response after DEX should be carefully monitored for IOP elevation”.


Vitrectomy for TRD: Get the timing right for better visual outcomes “The most common reason for delay was medical risk stratification.” What is the optimal timeframe for better visual outcomes in patients undergoing vitrectomy for diabetic tractional retinal detachment (TRD)? And what are the reasons for delays? These are the questions Kathleen A. Regan, MD, from the University of Wisconsin, Department of Ophthalmology and Visual Science, along with colleagues from the University of Florida, Department of Ophthalmology, explored in a poster titled: “Causes and Consequences of Surgical Delay to Vitrectomy for Diabetic Tractional Detachment”. While waiting to perform vitrectomy for diabetic TRD has been associated

with worse visual outcomes, it’s unknown what the ideal timing is for repair. In fact, it’s known that waiting 3 months results in 25% of eyes losing vision. To investigate contributing factors, and clinical outcomes of surgical delay, a retrospective case series of 130 eyes from 105 patients was conducted. It was found that the primary reasons for delay included: medical risk stratification (n=18); patient preference (n=7); and prior treatment (n=7). Other factors were noted as: loss to follow-up, financial, medical illness, OR scheduling and family/ride. Dr. Regan utilized a multivariable regression analysis to determine that this delay was associated with a worse visual outcome. Meanwhile, surgical timing of 1-14 days was associated with a better visual outcome than from 15-28 days (p = 0.02). This led the investigators to conclude that vitrectomy within two weeks from the decision for surgery was associated with better visual outcomes. In addition, they found that surgical timing was associated with the patients’ medical complexity, (including elevated hemoglobin A1C, endocrinology involvement and hemodialysis), and noted that surgeons might consider expedited referrals for better preoperative medical management.

Do patients treated with antiVEGF for nAMD suffer from increased RRD? With a reported rate of 0-1%, rhegmatogenous retinal detachment (RRD) is a rare complication from intravitreal anti-VEGF agents – and to date, no study has explored characteristics associated with RRD in patients receiving anti-VEGF treatment for neovascular age-related macular degeneration (nAMD). Therefore, Danny A. Mammo, MD, from the University of Minnesota

Department of Ophthalmology and Alexander Ringeisen, MD, and D. Wilkin Parke III, MD, from Vitreoretinal Surgery P.A. in Minneapolis, hypothesized that “RRD in patients undergoing anti-VEGF treatment for nAMD may experience an increased rate of detachments in the area of the injection site, as well as a decrease in postoperative injection frequency due to the presumed increased anti-VEGF clearance in the virectomized eye”. Their results were presented in a poster called “Rhegmatogenous retinal detachment in active neovascular agerelated macular degeneration”. The investigators conducted a single-center retrospective, consecutive review of all nAMD patients with RRD while receiving bevacizumab, ranibizumab or aflibercept between 1/1/2014 to 30/10/2018, with outcome measures including the quadrant of the retinal break(s), visual acuity (VA) at the time of RRD and final follow-up, as well as pre-op and post-op injection frequency. They found that the superotemporal quadrant was the most frequently involved in known retinal breaks; while the 21.1 days was the average between last injection and RRD onset. The average VA at time of RRD was 20/230, and at last follow-up at 34 months it was 20/220. Additionally, 64.7% of patients either increased their injection interval or required no post-op injections (n=4), while 5 patients had decreased injection intervals and one patient maintained similar intervals. This led Dr. Mammo and colleagues to conclude that “the quadrant involved in patients with RRD while receiving intravitreal injections for nAMD does not seem to differ from the normal reported distribution of retinal breaks in in all eyes with RRD”. Additionally, this study found that the majority of nAMD patients required fewer injections postoperatively, which may be due to increased oxygenation of the vitreous after PPV, which reduces VEGF expression.

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CONFERENCE HIGHLIGHTS ASRS 2019 COVERAGE Surgical outcomes of 23-gauge PPV after phaco: Is smaller better for outcomes? “Findings of this study suggest that managing post-cataract surgery retained lens fragments with 23-gauge PPV is safe and efficient.” Dislocated lens material into the vitreous cavity is a well-recognized complication of phacoemulsification surgery – and pars plana vitrectomy (PPV) remains the sole effective strategy to definitively eradicate the lens matter. In the past 25 years, major studies have reviewed the outcomes of PPV for dislocated lens fragments performed with 20-gauge instruments . . . however, surgical outcomes of 23-gauge PPV remain uncertain. Therefore, Elizabeth Yang and colleagues from Moorfields Eye Hospital, London, United Kingdom, explored outcomes and predictive

factors of 23-gauge PPV in a poster titled: “Visual Outcomes and Prognostic Factors of 23-Gauge Vitrectomy for Retained Lens Fragments after Phacoemulsification”. A retrospective, non-interventional cohort study including 291 consecutive eyes of 291 patients with dislocated lens material managed with PPV from 2012 to 2017 at Moorfields Eye Hospital was conducted. The investigators collected baseline demographic and clinical data, intraoperative factors and postoperative complications, including BCVA. They used univariate and multivariate logistic regression to characterize the impact of clinical factors on achieving better than 20/40, or worse than 20/200 vision. They found that from 0.73 ± 0.70 (before cataract surgery), logMAR VA improved to 0.46 ± 0.63 (p < 0.001). At 6 months, 183 (62.9%) achieved BCVA better than 20/40, while 45 patients (15.5%) had a BCVA worse than 20/200. Final VA of 20/40 or better

was associated with better pre-cataract surgery VA, age <75 years and absence of diabetic or persistent CME (p < 0.05). Meanwhile, poorer VA before cataract surgery, a delay of more than 2 weeks before PPV and aphakia, were the only factors predictive of 20/200 or worse VA at 6 months (p < 0.05). Results also showed that the most frequent complications were de novo ocular hypertension (10%) and transient cystoid macular edema (CME; 8.6%); the retinal detachment rate was 3.1%. These findings led the investigators to conclude that managing postcataract surgery retained lens fragments with 23-gauge PPV is safe and efficient. They also suggested that VA outcomes were not adversely affected, as long as PPV is performed up to two weeks after cataract surgery. Timing or technique of the IOL placement also did not affect outcomes. In addition, the investigators noted that appropriate and prompt management of CME may improve outcomes.

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CONFERENCE HIGHLIGHTS OIS@ASRS 2019

Top Fashions on the

Coming soon: New therapies

AsclepiX Therapeutics, a best-inclass agent that inhibits VEGF and activates Tie2 as a monotherapy. CEO Wendy Perrow says that with AXT107, potentially only one intravitreal injection per year is needed . . . which would dramatically reduce the treatment burden. Another company is also developing an anti-VEGF: Kodiak Sciences is designing ophthalmic Antibody Biopolymer Conjugates (ABCs) for increased durability and efficacy. Jason Ehrlich, MD, PhD, chief medical officer & chief development officer for Kodiak, highlighted KSI301, an anti-VEGF ABC that optimizes both molecular weight & formulation strength, with encouraging Phase 1a clinical study results. “It’s well-tolerated at all dose levels with rapid-onset, highmagnitude responses sustained to 12 weeks,” he explained. Another drug has been found to not only be well-tolerated – but it also has the potential to improve vision and treat earlier stage AMD – differentiating it from other approaches. Because AMD is characterized by marked mitochondrial defects Stealth Biotherapeutics’ lead product candidate, elamipretide, stabilizes cristae architecture and electron transport chain structure during oxidative stress by binding to cardiolipin in the inner mitochondrial membrane. CEO Reenie McCarthy says that in ReCLAIM, a 40-patient Phase 1 trial, they found that elamipretide therapy improved regular and lowlight vision in drusen and geographic atrophy cohorts. Of course, these are just some of the highlights – there are many more innovations coming to retina, all in the name of improving diagnostics, workflow and treatment to the benefit of both the patient and physician.

Numerous companies walked their latest therapies down the metaphorical runway at OIS. These novel molecules show promise for improving patient outcomes for some of the most stubborn posterior segment conditions. One development extends the duration of anti-VEGF: AXT107 from

Editor’s Note: The OIS@ASRS 2019 was held in Chicago, Illinois, USA, on July 25, 2019. Reporting for this story also took place at OIS@ASRS 2019. Media MICE Pte Ltd, PIE Magazine’s parent company, is an Official Media Partner at all OIS conferences alongside ASRS, AAO and ASCRS.

Innovation Runway by Brooke Herron

T

o continue improving patient outcomes, innovation is paramount. And at the recent Ophthalmology Innovations Summit (OIS) alongside the American Society of Retina Specialists (ASRS) annual meeting in Chicago – or OIS@ASRS – attendees were privy to some of the top technologies and therapies coming down the posterior segment pipeline. From artificial intelligence (AI) to new molecules, below we detail some the upcoming developments in vitreoretinal diagnostics and treatment.

Take me to your leader . . . Leaders in AI, that is. Nah, we’re not talking about science fiction, like robots with feelings, we’re talking about the AI that could revolutionize the way ophthalmologists screen and diagnose patients. “AI, to me, is a novel advance going forward. Ophthalmology – and retina in particular— is uniquely situated for AI . . . and the impact is going to be huge,” said Timothy Murray, MD, founding director and CEO of Miami Ocular Oncology & Retina (MOOR).

One area of potential impact is in vision screening for newborns. Daruis Moshfeghi, MD, is the co-founder of Pr3vent – a company using AI and deep learning to provide this screening for up to 4 million babies in the U.S. annually. As Dr. Moshfeghi noted, screening that many babies would take a lot of doctors . . . or just one good algorithm. Another focus is on biomarkers. Shelley Boyd, MD, is the president and CEO of Tracery Ophthalmics – a biomarker-driven, AI-powered, technology stack for precision drug development. According to her: “In ophthalmology, we rely on images and image-based biomarkers . . . and this is true for some of the biggest healthcare challenges we face. Biomarkers are measures of disease, of health, of treatment efficacy and of safety. They drive clinical decision with the promise of personalized medicine.” At Carl Zeiss Meditec, they have their own vision for AI: To enhance the doctor’s ability to provide care. Niranchana Manivannan, PhD, senior staff scientist, clinical research & analytics development for Zeiss explained: “Instead of clinicians going through all 128 b-scans, with AI, we can automatically highlight the scans of interest so clinicians can start from that particular point . . . and that would improve the workflow. Clinicians would have more time to spend with patients and see more patients.”

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