PIE Issue 24: The ebook version (The 'Hybrid Conference' Issue)

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THE WORLD’S FIRST FUNKY OPHTHALMOLOGY MAGAZINE

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THE HYBRID CONFERENCE ISSUE

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

The New Face of Ophthalmic Conferences p12

November 2022 piemagazine.org


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

IS IT TIME TO TREAD A DIFFERENT PATH?

OZURDEX® is indicated for the treatment of adult patients with visual impairment due to diabetic macular edema (DME) who are pseudophakic or who are considered insufficiently responsive to, or unsuitable for non-corticosteroid therapy.1 Real world evidence is collected outside of controlled clinical trials and has inherent limitations including a lesser ability to control for confounding factors. 1. OZURDEX® SPC, June 2021. 2. Boyer D et al. Ophthalmology 2014; 121(10):1904-14. 3. Kodjikian A et al. 2018. https://doi.org/10.1155/2018/8289253 Abbreviated product information OZURDEX® (dexamethasone intravitreal implant) Active Ingredient & Strength: Intravitreal implant containing dexamethasone 0.7 mg in the NOVADUR™ solid polymer drug delivery system. Indications: OZURDEX® contains a corticosteroid indicated for the treatment of macular edema following branch retinal vein occlusion (BRVO) or central retinal vein occlusion (CRVO), for the treatment of noninfectious uveitis affecting the posterior segment of the eye, and for the treatment of patients with visual impairment due to diabetic macular edema (DME) who are pseudophakic or who are considered insufficiently responsive to, or unsuitable for non-corticosteroid therapy. Dosage and Administration: • For ophthalmic intravitreal injection only. • The intravitreal injection procedure should be carried out under controlled aseptic conditions. Following the intravitreal injection, patients should be monitored for elevation in intraocular pressure and for endophthalmitis. Contraindications: • Ocular or periocular infections • Advanced glaucoma • Aphakic eyes with ruptured posterior lens capsule • Eyes with ACIOL, iris or transscleral fixated IOLs and rupture of the posterior

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lens capsule. • Hypersensitivity Warnings and Precautions: • Intravitreal injections have been associated with endophthalmitis, eye inflammation, increased intraocular pressure, retinal detachments, and implant migration into the anterior chamber. Patients should be monitored following the injection. • Patients who had a tear in the posterior lens capsule (e.g., due to cataract surgery), or who had an iris opening to the vitreous cavity (e.g., due to iridectomy) are at risk of implant migration into the anterior chamber. • Use of corticosteroids may produce posterior subcapsular cataracts, increased intraocular pressure, glaucoma, and may enhance the establishment of secondary ocular infections due to bacteria, fungi, or viruses. Visual disturbance may be reported with systemic and topical corticosteroid use. • Corticosteroids should be used cautiously in patients with a history of ocular herpes simplex. Adverse Reactions: In controlled studies, the most common adverse reactions reported by 20-70% of patients were cataract, increased intraocular pressure and conjunctival haemorrhage. Full prescribing information

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


IN THIS ISSUE...

Posterior Segment magazine posterior segment • innovation • enlightenment

Matt Young CEO & Publisher

Hannah Nguyen COO & CFO

Gloria D. Gamat Chief Editor

Brooke Herron Editor

Maricel Salvador

07 08 10

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EURETINA 2022 Live Coverage: A Paradigm Shift in Managing Diabetic Macular Edema Experts Lay Out Guidelines for Subthreshold Laser Treatment A History of Discovery: Why AbbVie Focuses on Challenging Eye Care Diseases

Cover Story

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The New Face of Ophthalmic Conferences

Graphic Designer Writers

Andrew Sweeney Hazlin Hassan Joanna Lee Matt Herman Tan Sher Lynn Ruchi Ranga Customer Care International Business Development

Brandon Winkeler Robert Anderson Adam Angrisanio

Innovation

17

18

Enlightenment

Conference Highlights

Tips and Technology in Retinopathy Management

The ABCs of Gene Therapy for Retina

Published by

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Dr. Dhanashree Ratra: Prolific in Perseverance with a Personal Touch

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Presentation Perfection: Highlights from CAKE & PIE Expo 2.0

Media MICE Pte. Ltd.

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

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EURETINA 2022 LIVE Coverage: Real-World Evidence Registries in Ophthalmology Update on Ocular Lymphomas: What's new in the WHO?

We are looking for eye docs who can contribute articles to PIE magazine. Interested? Let's talk! Send us an email at editor@mediamice.com. To place an advertisement, advertorial, symposium highlight, video, email blast, or other promotion in PIE magazine, contact sales@mediamice.com. | November 2022 3


LETTER TO READERS

It’s awesome to be back, APVRS. Dear Readers,

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he pandemic changed the landscape of conferences … and here in ophthalmology – our niche industry – the last two years have seen a huge upgrade in tech in this otherwise, rather traditional market in terms of conducting meetings, events and congresses.

ICE at Team Media M Shanghai. APVRS 2019,

But like the rest of the world, ophthalmic events needed to step up. Though we’ve seen a lot of main congresses canceled or indefinitely postponed at the onset of the pandemic in 2020, virtual congresses were born thereafter. All medical events turned digital and social media platforms became the main “distribution” channels. Then as the pandemic protocols eased up, virtual conferences slowly turned hybrid. From virtual to hybrid. From hybrid to F2F (face-to-face) congresses… Now finally, we’ve all come full circle. Here at the APVRS 2022 in Taipei, Taiwan, the Media MICE team is back. Back on-site! We are exhibiting, we are the official media partner. We are doing the show daily. And yes, we are printing it, including this issue of PIE magazine. It’s been a while since we talked to printers and discussed deadlines and paper quality. Wow, we had it “too easy” … in some ways at least … in the last two years. And then we now have to get back to our network of real people to help us distribute the printed magazines and dailies in the conference halls, yes physically! Ebooks were way too easy indeed… but rest assured, we are getting our groove back. APVRS 2019 in Shanghai, China, was the last “normal” conference we’ve been to. Hopefully starting here at APVRS 2022, we’ll all be back to the (old) normal. But certainly, there are some elements of digitalization and tech in congresses that won’t go back to the old format. This is the new normal after all… and whatever this is, we look forward to seeing you all again in person! Best regards,

Gloria D. Gamat

Chief Editor, Media MICE PIE, CAKE and COOKIE magazines

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Advancing clinical knowledge through collaboration The Barometer Program and the Vision Academy are complementary initiatives supported by Bayer, committed to driving toward optimized, compassionate, patient-focused care for retinal disease. Comprising world-renowned global experts in the fields of retinal disease, vision, diabetes care, and aging, these groups work synergistically to build best practice in patient care. The Barometer Program The Barometer Program is a global initiative to improve the vision health of millions of patients with nAMD, DR, and DME. The Barometer Leadership Coalition, a global group of 23 experts that includes independent clinicians and representatives from the International Federation on Ageing (IFA), the International Agency for the Prevention of Blindness (IAPB), and the International Diabetes Federation (IDF), provides oversight and strategic direction across the program. This flagship advocacy program operates across many workstreams to develop robust evidence and provide meaningful recommendations promoting the patient perspective, such as several peer-reviewed publications on patient-focused clinical management, the “A Chat with Anat” podcast series, and informational materials for ophthalmologists who are interested in improving delivery of care and patient outcomes.

The Vision Academy The Vision Academy is a group of over 100 international ophthalmology experts who, through their collective expertise in retinal disease, provide guidance for best VISION ACADEMY p e op l e | re s e a rc h | e d u c a t i on clinical practice in areas of controversy or with insufficient conclusive evidence. The Vision Academy provides ophthalmic specialists with a forum to share existing skills and knowledge, build best practice, and lead the wider community in the drive toward optimized, compassionate patient care.

Partnerships with NGOs The IFA's mission is to drive the agenda of the world's aging populations to ensure that every older person can live their life to the fullest. The IFA is an invaluable partner through its work in the DR arm of the Barometer Program. They have spearheaded not one, but two, global surveys in recent years, and have recently embarked on formally documenting the referral pathways to specialist vision care for patients with DR in various countries around the world. The IAPB’s objective is to raise the profile of eye care among key international Institutions, policy makers and the public. For the past 8 years, Bayer has been a proud supporter of the IAPB as a World Sight Day Global Partner, where the Love Your Eyes campaign in 2022 saw over 6.5 million people pledging to ‘love their eyes’ by booking a sight test.

Bayer is proud to support these groundbreaking initiatives that bring together expertise and patient advocacy to listen to patients in a meaningful way, and has been delighted to see these collaborations grow from strength to strength. DME, diabetic macular edema; DR, diabetic retinopathy; nAMD, neovascular age-related macular degeneration; NGO, non-governmental organization.

The Barometer Program is managed by clinical leaders in ophthalmology as well as representatives from the IFA, IAPB, IDF and Bayer. The activities of the Barometer Program are funded and facilitated by Bayer where the scientists and representatives from IFA, IAPB and IDF retain decision authority to the research scope, methods, analysis of findings and dissemination of the outputs of the Barometer Program. The Vision Academy is a group of over 100 international ophthalmology experts, who provide guidance for best clinical practice through their collective expertise in areas of controversy or with insufficient conclusive evidence. The Vision Academy is funded and facilitated by Bayer. The opinions and guidance of the Vision Academy outputs are those of its members and do not necessarily reflect the opinions of Bayer. For healthcare professionals only. MA-PFM-OPHT-ALL-1052-1 MA-M_AFL-SG-0375-1 (November 2022)

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ADVISORY BOARD MEMBERS

Dr. Alay S. Banker

Prof. Gemmy Cheung

Dr. Hudson Nakamura

Banker’s Retina Clinic and Laser Centre Ahmedabad, India

Singapore National Eye Centre (SNEC) Singapore

Bank of Goias Eye Foundation Goiânia, Brazil

alay.banker@gmail.com

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

hudson.nakamura@gmail.com

Dr. Kenneth Fong

Prof. Mark Gillies

Dr. Saad Waheeb

OasisEye Specialists Kuala Lumpur, Malaysia

University of Sydney Sydney, Australia

King Faisal Specialist Hospital & Research Centre Riyadh, Saudi Arabia

kcsfong@gmail.com

mark.gillies@sydney.edu.au

saadwaheeb@hotmail.com

SOCIETY FRIENDS

Arunodaya Charitable Trust (ACT)

Asia-Pacific Vitreo-retina Society

Orbis Singapore

Subthreshold Ophthalmic Laser Society

ASEAN Ophthalmology Society

He Eye Specialist Hospital

Retinawesome Retina &

Vitreo-Retinal Society - India

Asia-Pacific Academy of Ophthalmology

Ophthalmology Innovation Summit

Vitreous International

Russian Ophthalmology Society (ROS)

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Young Ophthalmologists Society of India ( YOSI )

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World Ophthalmology Congress


DME TREATMENT

EURETINA 2022 Live Coverage A Paradigm Shift in Managing Diabetic by Matt Herman Macular Edema

POSTERIOR SEGMENT

Questions abound about whether diabetic retinopathy (DR) and its comorbidities like DME can be called inflammatory diseases, and Dr. Zur noted that inflammation is critical in the progression of DR. She then talked about the power of prognostic and diagnostic biomarkers in choosing the right treatment regimen for management of the disease. The multifactorality of DR and DME comes into play here. Though VEGF is an important biomarker, it is just one piece of the puzzle. Inflammatory cytokines also play a role, and tracking and managing these biomarkers can provide clinicians with the knowledge needed to provide more tailored and timely treatments to patients.

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he EURETINA 2017 diabetic macular edema guidelines changed the game. Speakers at a lunch symposium on Day 2 of EURETINA 2022 believe it might be time to move on. Day 2 of the 22nd EURETINA Congress (EURETINA 2022) is in the books, and with it another day of the many things presenters, delegates and press look forward to at conferences of this stature. And though your correspondent, in particular, relishes the deliciously soft double chocolate cookies served at sponsored lunch symposia, it is the academic research, the crystal ball into the future of eye medicine, the case studies and the science that ultimately bring the doctors and delegates to the yard. On this account, EURETINA 2022 delivered once again in unseasonably sunny Hamburg. Beyond delectable chocolatey baked goods, the audience at Day 2’s symposium Evolving Management in Diabetic Macular Edema were treated to two tasty lectures on the shifting landscape of diabetic macular edema treatment.

Of timely treatments and invaluable intervention In 2017, EURETINA made waves when it officially declared the end of an era. Laser photocoagulation was out, and wunderkind anti-VEGF injections were in – and they have remained ever since

as the first-line treatment of choice in managing diabetic macular edema (DME). But five years have passed since then, and the ground is shifting beneath clinicians’ feet once more, according to Dr. Matias Iglicki’s presentation on DME Management: Timely Intervention in Suboptimal Treatment Response. “DME is a multifactorial disease, and VEGF is not a solo player,” Dr. Ignicki stated. “The original guidelines tell us to check after the third anti-VEGF [injection]. But there are plenty of papers supporting the idea of starting with dex[amethasone] in certain patients.” Time is the key factor here, according to Dr. Ignicki. He cited research that shows that by and large, if anti-VEGF doesn’t work, it doesn’t work, and this lost time can be costly in terms of the chance to restore lost visual acuity.

Thinking out of the box As new therapies emerge, it is crucial that clinicians begin to think out of the box, Dr. Zur concluded. Looking at optical coherence tomography (OCT) scans after pharmacological treatment of DME is critical, but it's also important to look at out-of-the-box biomarkers like disorgani­zation of retinal inner layers (DRIL). In the end, the presentations gave way to a lively Q&A on everything from vitrectomy to systemic factor monitoring. But in the end, it is now clear that DME treatment is evolving in exciting ways to deliver more effective, lower burden-of-treatment solutions. Five years after the groundbreaking 2017 EURETINA guidelines, it might be time to take another look at DME treatment regimens.

The inflammation situation

Editor’s Note:

Dr. Ignicki cited inflammation as a key factor in some pathologies of DME, and identifying these cases and treating them with a steroid like dexamethasone in a timely manner is a critical avenue of research. This is where Dr. Dinah Zur picked up the conversation in her talk Emerging Science in Inflammation: Role in Clinical Care.

EURETINA 2022 was held as a hybrid congress in Hamburg, Germany, on 1-4 September 2022. Reporting for this story took place at the event. A version of this article was first published on piemagazine.org.

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POSTERIOR SEGMENT

LASER THERAPY

Experts Lay Out Guidelines for Subthreshold Laser Treatment by Joanna Lee

“Once I see a visible burn, I’ll reduce the power by 50%.” He will then proceed to treat the large areas centered at the peak of the thickened retina (dense pattern as seen on OCT) using a spot size of 160 microns. At 12 weeks, the patient will be re-evaluated using OCT or sometimes autofluorescence. In his practice, the square pattern is often used.

Types of DME suitable for subthreshold laser

“M

any countries are unable to afford continuous unending intravitreal injections for macular diseases,” said Dr. Kenneth Fong. Building the case for the use of subthreshold laser (STL) treatment and its application for retinal diseases, Dr. Fong and two other vitreoretinal doctors presented at a symposium on behalf of The Subthreshold Ophthalmic Laser Society (SOLS) at the recently held CAKE & PIE Expo 2.0 in Da Nang, Vietnam. Having recently published an international guideline for the use of STL in treating diseases of the retina, SOLS is a newly established international protem committee comprising international users of STL. It is currently developing protocols for different laser machines and carrying out research trials for diabetic macular edema (DME), central serous chorioretinopathy (CSCR) and dry age-related macular degeneration (AMD). With about 20% of DME cases unresponsive to anti-VEGF treatments (according to Protocol I of the DRCR Network study), the option to treat with

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STL is a viable exploration. However, the issue remained that visible treatment parameters have been varied in publications, said Dr. Fong. “Some use a 15% duty cycle, some 5% or 10%, so it is hard to compare apples with apples,” he explained. Coupled with that, inexperienced users also tend to undertreat their patients due to fear of using higher laser power. Thus, guidelines are needed. “There is no need to kill the retinal pigment epithelium (RPE) cells in the treatment of DME and CSCR,” he said while explaining how STL works. STL is used to awaken the RPE cells with low levels of laser power to elicit a matrix response in the stimulated zone.

Treatment parameters Dr. Fong uses the optical coherence tomography (OCT) guided (thickness map) at a 5% duty cycle as it is not advisable to go beyond a 10% duty cycle. “It’s important to titrate the laser power,” he said, explaining further how he first starts with a place outside the macular area with a 5% duty cycle burn.

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Subthreshold laser can be used to treat clinically significant extrafoveal edema; it can also be used for treating foveainvolving mild edema (<400 microns thick) with good vision. However, Dr. Fong said that its most common use is in combination treatment in thicker foveas: First, he injects anti-VEGF and then uses subthreshold laser on the residual thickened areas. Showing a few case studies seen on OCT scans, Dr. Fong shared how patients with extrafoveal DME and clinically significant juxtafoveal edema had their conditions resolved. “It takes from 6 weeks (for CSCR) to 12 weeks (for DME) for ST laser to show its effects,” he said. As one gains more confidence using the subthreshold laser, one could treat patients with fovea-involving edema with good vision by moving closer to the fovea. In the case of a patient with a central-involving significantly severe edema, the patient had a good response after an anti-VEGF injection — and after one month and three months, a significant improvement was seen. He noted that it is now more common for the yellow subthreshold 577 (ST 577) nanometer laser wavelength to be used. The PLACE study (2018) using the micropulse 810 wavelength showed there weren’t many differentiations between photodynamic therapy (PDT) and STL. Dr. Lihteh Wu’s retrospective PACORES study, (involving half-dose


PDT compared to ST 577 for central serous chorioretinopathy CSCR) showed how patients treated with STL experienced a 3-line gain from baseline compared to just 19% among PDT patients. “Subthreshold laser is a cost-effective option and should not only be considered in rescue situations,” he said.

Guidelines for laser settings revealed There are several reasons for the establishment of guidelines for STL therapy. According to Dr. Chhablani, this therapy has been utilized in clinical practice for more than 30 years with numerous randomized and real-life studies proving its efficacy and safety in various retinal diseases. He and a few other founding members of SOLS have gathered expertise to establish guidelines for the application of STL in retinal diseases.1 The guidelines began with 12 experts, who gathered and deliberated on 43 questions, with the first round of answers gathered anonymously. Subsequently, two virtual meetings were held.

STL’s role in retinal diseases The group of experts determined that there is a role for STL in both centerinvolving and non-center-involving DME in conjunction with or without anti-VEGF therapy. For DME, SOLS recommends

a 5% duty cycle with 200-millisecond pulse duration, and at 150-200 microns spot size without any spaces between laser spots using an integrated pattern system. It was also recommended to titrate with 50% of the threshold power achieved with subthreshold laser. While SOLS experts recommend applying STL to edematous areas, it doesn’t mandate focal treatment of microaneurysm. They don’t recommend any specific structural imaging studies to evaluate laser spots. However, autofluorescence or OCT could be evaluated during follow-up visits for any laser scars, for instance. Follow-up evaluations at six to eight weeks after the STL application are advised, and STL is suggested after two or three months of initial application in case of poor response. STL can also be used for acute and chronic types of CSCR. For acute cases, STL can be applied at one month if there’s no self-resolution. However, for chronic cases, SOLS suggests STL as a first-line treatment, as well as in combination with other therapeutic treatment options. The STL settings and follow-up suggestions and durations are also similar to that for DME. “These consensus guidelines do not suggest management of these diseases but suggest laser application guidelines using different subthreshold laser delivery systems,” said Dr. Chhablani, emphasizing that these guidelines are also general and do not support any particular laser systems. “They are to establish standard

Table 1. Subthreshold laser consensus guideline settings for diabetic macular edema and central serous chorioretinopathy by the Subthreshold Ophthalmic Laser Society (SOLS).

SUBTHRESHOLD LASER SETTINGS

DIABETIC MACULAR OEDEMA

CENTRAL SEROUS CHORIORETINOPATHY

Duty cycle

5%

5%

Pulse duration

200 ms

200 ms

Spot size

150–200 μm

100–200 μm

Spacing between spots

No

No

Titration

Yes

Yes

Titration power

50% of threshold power

50% of threshold power

subthreshold laser applications in clinical practice, and we hope to start future clinical trials to establish level 1 evidence,” he said.

Comparing STL with PDT Dr. Jose Roca from Lima, Peru, was also on hand to talk about his comparative retrospective study involving STL2 as part of the Pan-American Collaborative Retina Study Group (PACORES). The investigation involved 92 eyes using yellow (577 nm) micropulse laser as opposed to half-dose verteporfin photodynamic therapy in eyes with CSCR. It was found that the subliminal (subthreshold) yellow laser produced better visual acuity results than PDT. Both treatments, however, are effective in restoring macular anatomy in eyes with chronic CSCR. It was deemed that STL for CSCR is safe and efficient, with good results and cost-effectiveness. In his personal experience treating CSCR from 2014 to 2016, Dr. Roca found that 60% of his patients (n=62, 95% males) experienced BCVA improvement between 1 to 3 lines after being treated with STL with decrease in choroidal thickness.

References 1.

Chhablani J; SOLS (Subthreshold Laser Ophthalmic Society) writing committee. Subthreshold laser therapy guidelines for retinal diseases. Eye (Lond). 2022;10.1038/s41433022-02136-w. [published online ahead of print]

2.

Roca JA, Wu L, Fromow-Guerra J, et al. Yellow (577 nm) micropulse laser versus half-dose verteporfin photodynamic therapy in eyes with chronic central serous chorioretinopathy: results of the Pan-American Collaborative Retina Study (PACORES) Group. Br J Ophthalmol. 2018;102(12):1696-1700.

Editor’s Note: The symposium on behalf of The Subthreshold Ophthalmic Laser Society (SOLS) was presented at the recently held CAKE & PIE Expo 2.0 in Da Nang, Vietnam. Reporting for this story took place during the event.

Source: Chhablani J, SOLS (Subthreshold Laser Ophthalmic Society) writing committee. Subthreshold laser therapy guidelines for retinal diseases. Eye (Lond). 2022 Jun 23. [Online ahead of print.]

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This is a paid advertorial produced by AbbVie. For Healthcare Professionals Only.

A History of Discovery Why AbbVie Focuses on Challenging Eye Care Diseases

L

ook at the science behind AbbVie’s mission to help prevent vision loss and impairment, a leading cause of disability that affects nearly 30% of the world’s population.1 In 2021, it was estimated that 1.1 billion people around the world live with vision loss and 90% of vision loss is preventable or treatable.2 That’s why AbbVie has set its sights on a future where vision lasts a lifetime, investing in research that aims to improve sight for patients.

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Continuing a long journey of discovery It is the people living with eye conditions around the world that help motivate AbbVie’s eye care scientists to push forward with leading-edge translational research. The company is using new, innovative approaches to investigate some of the major causes of vision loss and impairment, from various stages of glaucoma to retinal diseases and refractive conditions, according to Mayssa Attar, PhD, AbbVie’s vice

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president, research, nonclinical and translational sciences. With over two decades of experience researching eye diseases, Attar leads a team of scientists responsible for the discovery of potential new treatments and the translation of those compounds to clinical trials. Attar and the team are driven by two goals: Bring forward medicines for patients with best-in-class outcomes and reduce the treatment burden. Pursuing


these goals is enabled by an eye care journey that began as Allergan over 70 years ago, bolstered today by AbbVie’s legacy in complex diseases and global scale.

Putting the spotlight on unmet needs A key area of research with great unmet need is retinal disease, driven by degenerative diseases in an aging population, Attar says. Working on retinal diseases presents unique challenges because of the barriers to drug delivery to the retina at the back of the eye. Additionally, researchers are limited in their ability to collect samples for analysis. “These challenges actually speak to how our group is structured and the interdisciplinary approach we take to drug discovery,” Attar says. “Our scientists have become very skilled at using in vitro models and in silico models to close the gap between what we can measure in the lab versus what is operationally feasible in the clinic, which allows us to advance research and test a hypothesis.” Differentiators like having the same state-of-the-art imaging modalities found in an ophthalmologist's office, along with modeling and other digital

technologies, designed to accelerate the translation of science to new medicine that serve the goal of improving patient outcomes and reducing burden on patients. Modeling can help scientists explore other medications aimed at reducing treatment burden through improved efficacy, longer-acting and optimal methods of delivery.

“Our scientists have become very skilled at using in vitro models and in silico models to close the gap between what we can measure in the lab versus what is operationally feasible in the clinic, which allows us to advance research and test a hypothesis.”

driving new areas of science, according to Mike Robinson, MD, AbbVie’s vice president, clinical development, ophthalmology. With a background in academia and many years as a practicing ophthalmologist, Robinson has seen firsthand the great need to elevate the standard of care and continuously improve existing options. While many products exist to treat dry eye, a common condition, there’s still an opportunity to target the inflammation that’s the likely culprit, Robinson says. Another focus is investigating ways to improve vision outcomes over time.

“While there’s no playbook for being a pioneer, we must continue targeting unmet needs and going deep on these diseases.”

— Mayssa Attar, PhD, vice president, research, nonclinical and translational sciences, AbbVie

Illuminating a path for better eye care Strategic collaborations, both inside and outside of AbbVie’s walls, are critical to

— Mike Robinson, MD, vice president, clinical development, ophthalmology, AbbVie

Date of Preparation October 2022 Approval Date November 2022 ALL-ABBV-220402

References

[Image courtesy of AbbVie] (L) Mayssa Attar, PhD, Vice President, Research, Nonclinical and Translational Sciences and (R) Mike Robinson, MD, Vice President, Clinical Development, Ophthalmology.

1.

WHO (World Health Organization) Blindness and Vision Impairment Factsheet. Available from: https://www.who.int/news-room/fact-sheets/ detail/blindness-and-visual-impairment. Date accessed October 2022.

2.

IAPB (International Agency for the Prevention of Blindness) Vision Atlas. Available from: https:// www.iapb.org/learn/vision-atlas/. Date accessed October 2022.

Contact Krystal Bruno Director International Public Affairs (Eye Care) Krystal.bruno@abbvie.com

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COVER STORY

The New Face of Ophthalmic Conferences by Matt Herman

Ophthalmology and optometry congresses and meetings are back on the menu, and novel opportunities abound.

T

he pandemic daze is over and the halcyon days of in-person meetings and congresses are back in a big way. Doctors, researchers and industry professionals have emerged bleary-eyed from under the COVID-19 rock to jet off to meetings around the globe. Passports have been dusted off. Professional from the waist up has been waylaid, and proper trousers are experiencing a renaissance. Zoom cameras are collecting dust. Mostly. Those of us, including your correspondent, who have been champing at the bit to see friends and colleagues have noticed that things are not quite as they always have been. And not all of the changes can be laid completely at the feet of everyone’s favorite spike-proteined pal. Some developments have predictably been given a shot in the arm by the pandemic. Online meetings have gone from novelty to necessity, for instance.

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But other seismic changes have emerged. And from the test laboratory of the pandemic has emerged a new paradigm for the way ophthalmology creates and shares knowledge and technology.

The true mother of invention An evolution of the ophthalmic space has always been inevitable. Ophthalmology often gets a bum rap for being generally stodgy and slow to change. From a medical standpoint, the eye is delicate and sight vital, and an industry-wide “if it ain’t broke, don’t fix it” credo makes sense when vision is at stake. But just as with the dinosaurs, the time to adapt or perish always comes.

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At the onset of the pandemic, a perishing of sorts was certainly on the table. Research, innovation and communication were stymied across the broader scientific world. A poll conducted by Gao et al. in Nature found that new (non-COVID) publications were down by 9% in 2020 compared with 2019; submissions took a 15% hit, and new collaborations were down by a staggering 35%.* The scientific world at large, and the eye care world along with it, seemed to stop spinning. But life, and the exchange of ophthalmic knowledge, found a way forward through digitization. At this point, everyone is all-too-familiar with online classes, conferences and meetings. According to Dr. Kenneth Fong, president of the upcoming 38th Asia-Pacific Academy of Ophthalmology (APAO 2023) Congress, the switch to digitization would not have taken place sans COVID-19. “Without the pandemic, we wouldn't have hybrid meetings or virtual meetings,” he commented. And for a variety of reasons, the field of ophthalmology is better for it.

A quantum shift Whether the pandemic was the true inflection point or simply an accelerator, the post-COVID conference landscape represents a significant change from the past. For Dr. Oliver Findl, president of the European Society of Cataract “I think the core functions and Refractive Surgeons [of conferences] have (ESCRS), the changed, because early fundamental role in my career, congresses of the conference had one major function — has changed forever.

to meet and discuss, of course, but really, to get information.”

“I think the core functions [of conferences] have changed, because — Dr. Oliver Findl, president of the early in my career, European Society of Cataract and congresses Refractive Surgeons (ESCRS) had one major function — to meet and discuss, of course, but really, to get information,” he noted. Internet databases and online publications are not new, of course, but the pandemic woke the ophthalmic space up to the true power of a constant

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COVER STORY

stream of information. “Now you have a lot of websites out there on demand — information which you always have at your fingertips,” related Dr. Findl. And it is this shift away from conferences being primarily about obtaining new knowledge to something decidedly different that has flipped the script forever.

Watching the watchmen With new research and techniques available at the speed of light through a fiber optic cable, conferences are no longer a one-way conduit of information. Information democratization in the ophthalmic space is in full swing, and it's a good thing. “I remember my first conference really well because I gave a paper on optical biometry,” recalls Dr. Findl, a smile creeping into his face. “Wolfgang Haigis was a chair of the session and he was really into ultrasound biometry. He gave me a really hard time, even though it was one of my first talks.” The faraway look in his eyes abruptly changes to laughter. “That’s a really good memory I have. Well, not a good memory. But a memory.” With the advent of remote discourse, this nerve-wracking trial by fire has gone the way of the horse and carriage. Flamegrilling by authority has become more of an open discussion by consensus, and the ophthalmic world is reaping the benefits of abolishing the gatekeeper. “[Before] there was a sort of fish bowl situation [during presentations]. Now we are looking at more interaction — there’s much more of a discussion happening,” Dr. Findl continued. And when it comes to innovation and advancing the field, more discussion is a good thing. More ideas are heard, new perspectives are gained, and nuance becomes the new norm instead of no’s. “Many years ago in the ‘90s, there were personalities that had issues with each other, and in some cases, there were situations where they were real enemies,” Dr. Findl reflected. With more information out in the open, the days of factional infighting and outsized personalities are going by the wayside, too.

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Balance and tolerance of out-of-thebox ideas without the thumbs up of ophthalmology Caesars are in. Modern conferences are less the exclusive purview of the select few and more forum for all to share in. And when oceans of new ideas can be evaluated more rapidly and on their individual merits more, innovation and adoption of critical new tech are the main byproducts.

“So all a man could win in the conflict between plague and life was knowledge and memories.” — Camus, The Plague

Reckless driving on the information highway But with ophthalmic research traveling further and faster down the information highway than ever before, traffic police are still needed to keep it moving

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along. Quantity over quality is rarely a good thing, especially in science, and Dr. Fong knows this all too well from his experiences organizing APAO 2023. “You need to make sure that only the best are shortlisted and worth people’s time to come and view and discuss,” he commented. At some point, limitations on quality and relevance must be imposed. “You need to curate it. You need to have moderation,” he concluded. But conferences are adapting to the large influx of information in creative and astounding new ways to regulate information streams without suffocating them altogether. Meeting specialization is one way. All-encompassing megameeting marathons on the whole eye are giving way to more specialized meetings split into subspecialties like retina, cataract, refractive, and so on. Digital meetings are also rife with potential for smaller, more targeted fields of knowledge, and Dr. Fong has an idea of what that might look like. “Smaller meetings can transition to


digital versions or try to work together with bigger meetings and have them as satellite meetings,” he suggested. More targeted meetings mean higher participation from both doctors who can contribute the most, and those who need it most. Lectures on critical niche topics like geographic atrophy (GA) might be a poorly attended yawner at a massive meeting. But they get a massive jolt in the arm by going online and attracting more experts around the world who can attend without sacrificing critical time and money to fly to a large conference for just one meeting. And even now, hybrid conferences allow cutting-edge researchers to share their findings with a conference room across the globe through sophisticated teleconferencing capabilities put to the test during the pandemic.

Shorter but sweeter? The implications for such changes on the modern congress landscape are massive in scope and impact. For one, says Dr. Findl, conferences are generally getting

shorter than they were in the past. “Our (ESCRS) congress, for example, used to be four-and-a-half days. Now, it’s essentially three-and-a-quarter, so we reduced it by 20% ... and I think others are doing the same,” he said. On the one hand, this is a massive boon for conference participation. Shorter meetings mean smaller hotel bills, less of a time commitment, and in general, higher participation. This is good news in a world with soaring healthcare costs, increasing appointment wait times, and a notoriously grim work/life balance. “It’s a little more difficult for people to stay away for longer times now,” Dr. Findl observed. “People just can’t take the time off anymore.” And for the vast majority of doctors who are starved for time, shorter in-person meetings with programs reduced to what is absolutely necessary to do in-person are a sorely needed change.

Following the money Conferences, of course, don’t magically

appear from thin air. As doctors trying to find funds for flights, food and lodging know, they run on money and the support of industry. And the place of industry in the conference constellation has also undergone a cataclysmic change for players of all sizes. In days past, titans of industry threw around their weight to distinguish themselves among well-established competition and put their products to the forefront. Lavish parties and raucous entertainment for doctors and purchasing managers were part of a courtship ritual ubiquitous in the business world. The medical device and pharmaceutical industry was certainly no exception. But it is now, and Dr. Fong has seen just how industry mainstays have been challenged by the new look of post-pandemic congresses, resulting in macroeconomic and regulatory headwinds. “There’s a lot less entertainment done by industry because of compliance and things like that,” he said with just the faintest hint of sadness in his voice. “Industry budgets have definitely been affected badly, too. So sponsors are a lot more careful how they spend their money.” And what of small-to-medium enterprises (SMEs)? TJ Waggoner of Waggoner Diagnostics, an independent American company selling all things color vision, knows what it's like for the underdogs of the cutthroat exhibition hall world. “Attending conferences allows doctors to see your devices and organization. It legitimizes the device and the company.” In this sense, the congress story is a tale of two exhibition halls — one where ubiquitous major players compete with one another to be the loudest voice in the room, and one where small players must stand on the shoulders of giants for credibility. Unfortunately, this slight wing-clipping of the great ophthalmic raptors has not allowed smaller birds of paradise like Waggoner Diagnostics to thrive in treacherous skies. At least, not exactly. “With the introduction of resources such as Shopify, Facebook/Google Advertising, etc., it makes it possible for SMEs to compete with the 800-pound gorillas,” said Mr. Waggoner.

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COVER STORY

But while the digitization decentralization coursing through the veins of ophthalmic exhibition halls may trickle down to the industry landscape, Mr. Waggoner thinks these effects are limited. “I never expect the ‘good ole days’ of doing business to go away … dinners and entertainment are a triedand-true method of selling devices and pharmaceuticals,” he lamented. But in the end, he does think the newfound post-pandemic spirit of innovation of opportunity shows some promise. “The old tactics will stick around but the companies that are nimble and innovative will always come up with solutions to get the attention of decision makers.”

The times, they are (kind of) a-changing In the end, ophthalmic conferences have a distinctly different flavor from the days of old. Congresses have seen a change in the way people think about

research, what research is shared, and how doctors around the world access it. A healthy dose of flexible, innovative thinking enabled and fostered by the technological wizardry emerging from the ashes of the pandemic is the main result, and patients and the industry as a whole is better. But for many things, the song remains the same, and that’s not necessarily a bad thing. The pillars of industry undergirding research have shown cracks in the face of regulatory and macroeconomic forces of nature. Damaged as they are, however, Dr. Fong doesn’t see any radical changes to the status quo on the horizon. “Ophthalmology in particular is very focused on technological advances, pharmaceutical advances,” he argued. “You need to interact with industry to drive innovation.” And despite worldwide hysteria around the creeping permanence of the workfrom-home movement, neither Dr.

Fong nor Dr. Findl thinks that in-person conferences are ever going to be fully off the table. “We need the face-toface component because there are so many things that colleagues discuss outside the meeting hall, during the coffee breaks or dinner time, or in a hotel lobby,” noted Dr. Fong. “[In these situations], doctors are actually more free, able to discuss things more easily because they're not weighed down by work or being at home.” Dr. Findl concurs. “I don't think inperson conferences are going to be replaced. That's what I thought at the beginning of COVID," he admitted. “But I think we learned very quickly within a year, year-and-a-half, that people just don’t want to sit in front of their computer all the time.”

Reference *

Gao J, Yin Y, Myers KR, et al. Potentially longlasting effects of the pandemic on scientists. Nat Commun. 2021; 12: 6188.

Contributing Doctors Dr. Kenneth Fong is recognized as an ophthalmologist in the United Kingdom, Australia and Malaysia. He graduated with a medical degree from the University of Cambridge in 1998 and trained to be an eye surgeon in London. Dr. Fong then spent two more years training in the U.K. and at the Royal Perth Hospital in Australia to subspecialize in retina. After 18 years of working in the U.K. and Australia, he returned to Malaysia in 2009 to serve as associate professor, consultant ophthalmologist and retinal surgeon at the University of Malaya in Kuala Lumpur. He is currently the managing director of OasisEye Specialists in Kuala Lumpur. Dr. Fong is the president of the Malaysian Society of Ophthalmology and serves as a council member for the APVRS. kcsfong@gmail.com

Prof. Oliver Findl, is a professor of ophthalmology and chairs the Department of Ophthalmology at the Hanusch Hospital, Vienna, Austria. He founded and heads the Vienna Institute for Research in Ocular Surgery (VIROS). Prof. Findl’s research fellowship at Children’s Hospital in Boston was followed by residency and an anterior segment surgery fellowship at the Medical University of Vienna. He was a consultant ophthalmic surgeon at Moorfields Eye Hospital, London, UK, for several years. His research interests are in the fields of optical biometry, presbyopia correcting IOLs, posterior capsule opacification and the pathogenesis of myopia. Dr. Findl has authored over 350 articles in international peer-reviewed journals and is currently the president of the European Society of Cataract and Refractive Surgeons (ESCRS) as well as the treasurer of the Austrian Ophthalmological Society. oliver@findl.at

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Terrace L. Waggoner Jr. (who goes by TJ), has been developing medical devices for approximately 10 years. T.J. Waggoner has an undergraduate degree in psychology, a master’s in Business Administration, and a master’s in industrial/ organizational psychology from the University of West Florida. T.J. has completed his coursework for a PhD in organizational behavior but he continues the painful process of checking all the boxes to finally obtain his PhD from Claremont Graduate University. You may be wondering how T.J. fell into ophthalmic medical devices, and he owes the pleasure to his awesome father, Dr. Terrace Waggoner. T.J. believes that not having an educational background in engineering or medicine has allowed him to think outside the box and create devices where other individuals saw too many constraints. tj@waggonerdiagnostics.com


GENE THERAPY

The ABCs of Gene Therapy for Retina by Matt Herman

INNOVATION

Gene therapy challenges abound While we’ve come a very long way in a short amount of time, Dr. Bainbridge noted, obstacles abound for the science behind gene therapy. Dosing, efficiency, and specificity remain difficult to pin down and fine tune. Delivery vectors are also problematic. Immunogenicity issues like inflammation and atrophy are inevitable when introducing any foreign substance into the body. Inflammations can be sidestepped using immunosuppression, but the risk of harm is still great. Atrophy is another hazard lurking in the shadows, and the potential for resultant long-term harm must be addressed.

Dr. James Bainbridge gave RANZCO 2022 attendees a crash course on developments from the cutting edge of gene therapies.

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he anonymous-sounding Great Hall 2 at the 53rd Annual Scientific Congress of the Royal Australian and New Zealand College of Ophthalmologists (RANZCO 2022) host venue Brisbane Convention & Exhibition Centre is not your average lecture space. Presenters spoke from a pit to doctors from around the world lining the rafters of the cavernous conference hall. This epic fish-bowl feel has led your correspondent to refer to the hall as the “Thunderdome” from the Aussie postapocalyptic Mad Max series of films. But unlike the grim dystopian wasteland of Mad Max, Dr. James Bainbridge of the prestigious Moorfield’s Eye Hospital (London, United Kingdom) gave audiences a wildly utopian view of the future of retinal medicine with his overview of gene therapies on Day 2 of RANZCO 2022. And instead of gladiatorial battles to the death, awe-inspiring glimpses of hope for some of ophthalmology’s most villainous diseases poured out of the Thunderdome pit.

Look what we can do! Dr. Bainbridge’s lecture, entitled Gene

Therapy - Opportunities and Challenges, began with an overview of the current state of the retinal gene therapy space. Disease-causing gene defects, he explained, are currently approached in three ways – supplementation, silencing (or blocking), and editing. Supplementation, he explained, is currently the most widely-used gene therapy. This therapy involves providing synthetic gene copies to the cells that need it. Silencing is the opposite of supplementation, Dr. Bainbridge continued. In this strategy, toxic protein production that induces harmful gains of function is ‘silenced’ by blocking translation via RNA interference. The final, and by far most complex and novel of the three, is gene editing. CRISPR-Cas, developed by Drs. Jennifer Doudna and Emmanuelle Chapentier, is the most common form of this gene therapy subtype. Gene editing involves actually fixing the underlying defect by directly editing DNA, and is the most promising type for one simple and powerful reason. Successful gene editing therapy can cure some of the planet's most menacing ailments.

The safety and scalability of delivery is also a key field in need of improvement. Intravitreal injection, subretinal injections via various approaches like transvitreal/transretinal, transscleral/ transchoroidal, and suproachoroidal/ transchoroidal all have their positives and negatives, and further investigation is needed to ensure safe and scalable efficacy. Beyond the medical nitty gritty, efforts also must be made to optimize gene therapy trial design. Dr. Bainbridge concluded his talk by pointing out specific areas of improvement here, including the identification of relevant and reliable outcome measures, establishing valid comparators, and improving efficiency for more timely outcomes.

Editor’s Note: A version of this article was first published in CAKE & PIE POST, 53rd RANZCO 2022 Edition, Issue 3.

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INNOVATION

RETINOPATHY

Tips and Technology in Retinopathy Management by Tan Sher Lynn

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arious techniques and pearls to manage retinopathy were shared by retina experts during a symposium session at the CAKE & PIE Expo 2.0 in Da Nang, Vietnam. Here are some of the highlights...

Macular hole repair The session kickstarted with Dr. Jay Chhablani (USA), who discussed various macular hole repair techniques, including flap surgeries and autologous retinal grafts. The various flap surgeries available nowadays include autologous lens capsular flap, inverted flap and inverted internal limiting membrane (ILM) flap technique, which involves the use of Muller cell fragments to induce gliosis. “These cell fragments act as a scaffold and promotes proliferation, thus repositioning the photoreceptors,”

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explained Dr. Chhablani. However, he noted that complications may arise with this method, such as “disinsertion of the flap from the hole margin”, and “complete removal of the flap with a cutter while trimming”. To prevent these complications, he advised surgeons to be very gentle when manipulating the flap, use scissors to trim the flap and turn off the infusion port to reduce fluid currents. As for the free ILM flap technique – which is Dr. Chhablani’s favorite – it can be used in primary ILM peeling surgery or in failed macular hole. Nevertheless, this method has its own challenges as well, such as displacement of the flap during fluid air exchange, which he said, can be prevented by using a slightly larger graft than the size of the hole. On the other hand, to prevent the flap from floating in the viscoelastic, he suggested tucking the graft in the macular hole edges.

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For the autologous neurosensory retinal graft technique, he advised using a soft tip cannula or forceps to separate the graft, perfluorocarbon liquid (PFCL) to ease transportation of the retinal graft, and slow fluid air exchange to avoid graft displacement. “There are novel techniques with good anatomical results for large, recurrent or chronic macular holes. Nevertheless, the long-term functional outcome needs to be further analyzed,” he concluded.

Choroidal hemorrhage management Meanwhile, Prof. Dr. S. Natarajan from India shared tips on managing expulsive choroidal hemorrhage. “The key to preserving an eye with an intraoperative suprachoroidal hemorrhage is early recognition and prompt action prior to the expulsion of intraocular contents,”


he said, noting that the signs and symptoms include a sudden onset of severe intraoperative pain, excessive iris movement or prolapse, forward movement of the lens and darkening/ loss of red reflex. “If a suprachoroidal hemorrhage is suspected, immediate closure of the wound should elevate the intraocular pressure (IOP) sufficiently to tamponade the suprachoroidal bleeding. Ideally, close the wound with 8-0 sutures. If there is no time to place sutures, approximate the wound edges with digital pressure or toothed forceps,” Prof. Natarajan advised. In some cases, surgery may be needed. Indications for surgical management and choroidal drainage include a central retinal apposition that does not resolve within one to two weeks, shallow/flat anterior chamber with secondary IOP elevation, hypotonic, persistent flat anterior chamber and intractable eye pain.

Holistic care for diabetic macular edema Next, Dr. Diva Kant Misra from India shared how we can manage diabetic macular edema (DME) in a holistic manner. The steps include firstly performing a systemic evaluation (of blood sugar, blood pressure, renal profile, lipid profile, etc.), followed by a clinical evaluation (e.g. fundus imaging, optical coherence tomography (OCT) imaging and classification, size of cystoid spaces, subretinal fluid, choroidal biomarkers, etc.) and finally

strategizing an evidence-based therapy, such as anti-VEGF drugs and lasers. “According to the Indian guidelines, we can start with anti-VEGF and use steroids to sustain it, or in nonresponding cases after a minimum of three injections,” he said, adding that in such cases, corticosteroid helps to stabilize the blood retinal barrier (BRB), down-regulate VEGF expression and inhibit the production of prostaglandins and pro-inflammatory cytokines. Dr. Misra also mentioned that if the patient’s condition worsens even with anti-VEGF treatment, the surgeon should switch to a better anti-VEGF or steroid, and if doing so still doesn’t help, vitrectomy should be considered. Nevertheless, if a patient with DME came in with a good vision, he can be safely observed first, as anti-VEGF injections should only be scheduled if vision deteriorates, as proposed by the DRCR.net Protocol V clinical trial.

AI-based screening and smartphone imaging Advanced technology such as deep learning and smartphones are playing an increasingly important role in ophthalmology. According to Prof. Paisan Ruamviboonsuk from Thailand, Thailand is one of the few countries with an established screening program for diabetic retinopathy (DR). It started with a retrospective study on the validation of an artificial intelligence

(AI) model in 2018 where more than 12,000 retinal images of Thai diabetic patients across 13 regions were collected for analysis. Then, during the prospective study stage where AI was is deployed in a clinical setting (20182020), over 7,900 Thai diabetic patients underwent real-time screening for DR/ DMEW using AI across nine community hospitals. And beginning October this year, the country started to integrate deep learning into its National DR Screening Program. “Deploying AI in clinical practice may be the last but difficult step in translational medicine. AI algorithm should at least be prospectively validated for robust performance before deployment. The success of deployment may rest on factors beyond accuracy parameters, such as the implementation into current clinical workflow or adherence to referrals,” said Prof. Ruamviboonsuk. On a different note, Dr. Ashish Sharma from India said that smartphone imaging devices with software can produce images that are identical to those produced by high-end fundus cameras. “The advantage of smartphone-based handheld imaging device is that you can easily take images of the peripheral fundus, a difficult task to do unless you have wide-field imaging,” he said, noting that nevertheless, there are challenges with such devices in terms of stability, the presence of a learning curve and image artifacts. “To date, the smartphone-based fundus camera was used as an imaging tool rather than a screening tool. And wide-field imaging is possible even up to ora serrata with some learning curve,” he noted.

Editor’s Note: CAKE & PIE Expo 2022 (C&PE 2.0) was held as a hybrid event in Da Nang, Vietnam, on 20-21 August 2022. Reporting for this story took place at the event.

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ENLIGHTENMENT

WOMEN IN OPHTHALMOLOGY

Dr. Dhanashree Ratra

Prolific in Perseverance with a Personal Touch by Joanna Lee

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edicated, diligent and determined might be three words that best describe Dr. Dhanashree Ratra, senior consultant at the Department of Vitreoretinal Diseases of the renowned Sankara Nethralaya Medical Research Foundation in Chennai, India. Having been working there for 26 years, Dr. Ratra has managed to fill the years with an enviable, prolific string of achievements in her medical, teaching and research career while raising a family. Her work at Sankara Nethralaya has seen her set up and manage vitreoretinal (VR) departments in the earlier part of her career at various Indian cities like Jalna and Kolkata, and Colombo in Sri Lanka. She had also been a senior consultant in Shenzhen, China, in 2014. What’s more, she has also published over 90 peer-reviewed papers and won many recognition and accolades for some of them. In addition, she has also given close to 200 lectures at different ophthalmological conferences worldwide while also being an editor and reviewer for various ophthalmic journals. Dr. Ratra traces her passion for medicine and ophthalmology back to the days when she was pursuing her MBBS at the Mahatma Gandhi Institute of Medical Sciences, Sevagram, under Nagpur University. It was there in an institution set up based on Gandhi’s principles of non-violence that the spark of her passion for helping the blind was ignited, especially when she was posted to a leprosy colony. “We had to adopt villages and look after the members of four families in each village throughout our MBBS. Many patients would have eye problems due to leprosy, and I thought, we must do something for these less fortunate people,” she said.

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Her early years spent adapting to various school situations, including impoverished ones and getting used to language differences due to her engineer father’s transfers around India have helped shaped her resilient and positive outlook in life. Later, when witnessing vitreoretina (VR) surgery for the first time during medical training, Dr. Ratra admitted that she was smitten. “I fell in love with it. It was so awesome that you could see the retina and do microsurgery in it. It was like out of this world,” she recalled with excitement. From then on, her path in ophthalmology was sealed.

Pushing past hard work and loneliness Besides the challenge of securing a medical seat in universities during her time, she also faced tests of perseverance during her training years. “When I chose the vitreoretinal branch, there were not many women pursuing this field. It was also thought that women perhaps could not do as good a job, perhaps because it was a rigorous grind with tough training. Some days, we worked continuously from 5am to 12 midnight where we couldn’t get food by then. Her rigorous training did not stop at school. As a junior doctor, she

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was called to do emergency cases in the operation theater almost every night. Yet, she persevered. There were times in her work, for instance, when she was pioneering the VR department in Jalna when she felt alone. “There was no support staff. Instead, I had to train the nurses who didn’t know about retinal surgery. I had to do everything myself, like the fluorescein angiography, injecting the dye, taking the photos,” she recounted. “I was very young then, and being a woman, many times the patients would not believe that I could do something. So, I had to convince them. Luckily, I did


good cases and the patients had good results. Only then was the trust built up, and they started to believe in me.”

Achievements doubled in value Dr. Ratra is very aware of the struggles that women doctors have to often overcome. “I think women have to work twice as hard as men. So, any woman’s accomplishment, even though it is a small one, carries a much higher value, I would say,” she shared. At the same time, having her parents and in-laws who were a great support to her and her doctor husband, Dr. Vineet Ratra, during the early years was invaluable. Her daughter is currently a second-year medical student. “It’s not possible to do everything alone. Sometimes, you want to become a superwoman and do everything yourself, but that’s quite impossible. So, it’s good to have some help and support around. Men have many things going much easier, but for a woman to achieve that, she has to work very, very hard. So, you should not take lightly any achievement which you have made, because any small achievement is also great,” Dr. Ratra said.

Guiding the next generation Known as a good teacher and well sought-after mentor, Dr. Ratra is most satisfied with her work having guided and mentored 34 postdoctoral fellows for specialization in vitreoretinal surgery in the last 25 years. She is also involved in teaching post-graduate students, conducting regular classes, seminars, and symposia. “When I know that my students are out there doing such good work and gaining good names for themselves, and they speak of their gratitude for my teaching, I’m happy that I have achieved something in life," enthused Dr. Ratra.

Not forgetting the personal touch While having taught many students, she also learned one of the greatest lessons

through her patients. She describes this case as one of the high points in her life. It was the story of one of her patients in Calcutta whom she passed off as just another case. “He was a one-eyed patient who had developed retinal detachment and I operated on him. Two or three years passed, and one day, I got a call from my boss saying a patient wanted to see only me and no one else. He waited for me and I was in another complex at that time. I was wondering why he didn’t want to see my boss who was known as the best VR surgeon in India,” shared Dr. Ratra. It turns out the one-eyed patient had been diagnosed with prostate cancer and only had very few days to live. “Before he died, he wanted to come see me. He told me I was the only one who saved his eyesight because no one else had diagnosed his other eye prior to my surgery on him. He said he was very grateful to me and had only wanted to meet me. I was very touched by his gesture that he would consider me worthy to come all the way despite his bad health,” said Dr. Ratra. With seeing so many patients daily, most doctors treat each patient just like another case. “We don’t even look at them as a person, or consider their personal problems. I just said okay, it’s a case of retinal detachment. Just operate and forget it,” she said. “Now I tell my students to think of the patient as a person who has come to you for help. When you give them the personal touch, it can really help the patient overcome his or her problem. It’s because we say 50% of medicine is faith. If you have faith, and if you believe in the doctor, 50% of your disease is cured. So, the rest of the 50% is the surgery and the drugs, etc,” explained Dr. Ratra.

What keeps her going A self-confessed workaholic, Dr. Ratra said her love for doing VR surgeries is what keeps her going. She hopes her researches might churn out a landmark study as well. “I want to focus on perhaps newer methods to treat retinal diseases, as many are untreatable like

diabetic retinopathy and congenital retinal diseases; or newer methods of drug delivery to the eyes,” she shared. Deep within, her beliefs have propelled her career the most, something she had developed during her MBBS years. “It’s inculcated in our minds, that it is not just work, but that we’re duty bound to help others. When you get to be birthed a human, your life should not be wasted; so you must do something good to serve others. Fortunately, I’m in a profession where I can directly serve people. When we do our work, it is like serving God,” she concluded.

Contributing Doctor Dr. Dhanashree Ratra (MS, DNB, FRCSEd) is a senior consultant for Shri Bhagwan Mahavir Vitreoretinal Services at Sankara Nethralaya, Chennai, India. The renowned vitreoretinal surgeon with 25 years of experience is also a beloved teacher. Her achievements and awards include Best Lady Fellow award (1997), Best Associate Consultant (2003), Best Scientific Paper (JM Pahwa Award, 2008), DB Chandra Award for the Best Scientific Paper (2010), Best Poster Award in the annual meeting of the American Academy of Ophthalmology (2011), Best Poster (International Uveitis Conference 2016), Best Clinical Research Award (IERG 2018), Award for Best Research Women In Ophthalmology 2019, Best of IJO Award 2019, Best Paper - Vitreoretinal Diseases (AIOC 2020), IJO Peer Review Honour Award 2021 and IJO Gold award 2022. She is actively involved in clinical and basic sciences research projects, being also the principal investigator for several clinical trials. She is also section editor for retina in Indian Journal of Ophthalmology, review editor in Frontiers in Ophthalmology and reviewer of Indian and several international ophthalmology journals with over 90 peer-reviewed publications, 12 chapters in books, and 125 invited lectures, including three keynote addresses in international conferences. drdad@snmail.org

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CONFERENCE HIGHLIGHTS

C&PE 2.0

Presentation Perfection

Highlights from CAKE & PIE Expo 2.0 by Andrew Sweeney

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ookies and milk, a bacon sandwich with brown sauce, ketchup with french fries … there are so many things in our lives that just wouldn’t be the same, or as good, without something else complementing them. I mean imagine a world where you couldn’t buy popcorn when you go to the cinema, or attend an ophthalmology conference without being able to peruse through fascinating panel discussions and presentations. When the Media MICE team was putting together the CAKE and PIE Expo (C&PE) 2.0, we knew we had to attract the very best ocular care talent and get them to bring their conference game.

of the most perfectly perfunctory presentations one could hope to enjoy at a conference, and we’re sure many attendees went on to pontificate about some of the things they learned to their patients and peers. The subjects covered in these reports ranged from topics that are commonly encountered at ophthalmology events right now as well as those of a more novel nature. All the sessions remain available to view on demand, so if you want to delve even deeper into them then we highly recommend you do so.

Wicked VKHD

insights into a retinal disease that was unfamiliar to some of the most seasoned Media MICE staffers: Vogt Koyanagi Harada Disease (VKHD). This segment was presented by Dr. Kshitij Raizada, a vireoretina specialist at the eponymous Dr. Raizada Eye Center in Bareilly, India, and he reported that VKHD is a form of bilateral granulomatous panuveitis that can occur with or without extraocular manifestations. It is most commonly encountered in females aged between 20-50 years of age, people of Hispanic and Asian backgrounds, and have a T-cell autoimmune reaction against melanin, melanocytes, and retinal pigment epithelium.

The session – PIE Symposium: Posterior Segment and Beyond – included some

The first presentation was of a more novel nature as it offered considerable

Symptoms of VKHD usually begin to manifest in the prodromal stage and

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include headaches, fever, orbital pain, nausea, dizziness, and light sensitivity, combined with neurological and auditory hallucinations, which can last for three to five days. Once the disease reaches the uveitic stage, the patient may experience blurred visual acuity in both eyes (which may be asymmetric) as well as anterior chamber inflammation, hyperemia, edema of the optic disk, and multiple serous retinal detachments. If a patient presents themselves with these symptoms at your clinic, Dr. Raizada recommends checking for granulomatous anterior segment inflammation, and using optical coherence tomography (OCT) and color fundus photo to achieve a diagnosis.

Finding a safe port Bridging the gap between the new and the established was Novel and Emerging Retinal Therapeutics, presented by Dr. Errol Chan, a consultant ophthalmologist at the Singapore Medical Group. This report highlighted what he called the high burden of monitoring visits and intravitreal infection treatments, as well as novel treatments that can be deployed in the near future. These include faricimab, a bispecific antibody that’s designed to target both the VEGF-A and the Ang-2 pathways to reduce neovascularization, and will be applied in the treatment of diabetic macular edema (DME) and age-related macular degeneration (AMD), as well as the ranibizumab port delivery system. This investigational delivery system is based on a customized formulation of

ranibizumab, is surgically implanted at the pars plana in the operating theater, and is subject to in-clinic refill exchange procedures. The device enables continuous drug delivery into the vitreous and is mediated by passive diffusion along a concentration gradient, and has been shown to be effective in the treatment of neovascular age-related macular degeneration (nAMD). In one study that lasted for 24 weeks, patients who were administered ranibizumab via the port delivery system enjoyed slightly improved baseline best corrected visual acuity, and overall, it was found “noninferior and equivalent to the application of ranibizumab in monthly doses”.

Patients, front and center One of the most classic presentation formats that we enjoy is the case study, as it’s always important to remember the impact of ocular care on individual patients. Instructive Cases in DR by Dr. Apoorva Ayachit, a vitreoretinal surgeon at the M. M. Joshi Eye Institute in Hubballi, India, was a report that included a number of interesting case studies. One of the most intriguing was one involving a 65-year-old patient who was diagnosed with bilateral vitreous hemorrhage secondary to proliferative diabetic retinopathy (PDR), who was ‘posted for vitrectomy’ surgery. During the procedure, Dr. Ayachit and her team noticed a number of thick blood clots across all quadrants of the eye and once they were cleared, they noticed white-centered clots as well, which led them to investigate further as

this was not typical of PDR. As a result, the patient was found to have chronic myeloid leukemia, characterized by a high white blood cell count with 50,000 myeloblasts found in a peripheral smear, as well as deep hemorrhaging and dehemoglobinized blood adherent clots. Dr. Ayachit then reported that his HB A2 was found to only be 6%, leading her to diagnose him with beta thalassemia trait, which negatively affects the hemoglobin in the red blood cells. These are just a few of our highlights from the session, and other case studies remain available to view at your convenience, along with a number of other events that took place during C&PE 2.0. If you do decide to go online and check out footage from our conference, then make sure to drop a comment on our social media pages and let us know what you think. And remember, the best sauce for fries is not just ketchup … combine it with mayonnaise.

Editor’s Note: CAKE & PIE Expo 2.0 was held as a hybrid event on August 20-21, in Da Nang, Vietnam. Reporting for this story took place during the event.

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CONFERENCE HIGHLIGHTS

EURETINA 2022

EURETINA 2022 LIVE Coverage Real-World Evidence Registries in Ophthalmology by Hazlin Hassan

DR and anti-VEGFs The study looked at 12-month treatment outcomes of ranibizumab versus aflibercept for macular edema in central retinal vein occlusion in routine clinical practice. Its aim was to compare 12-month treatment outcomes of eyes receiving aflibercept or ranibizumab for macular edema secondary to central retinal vein occlusion (CRVO) in routine clinical practice. The Swedish Macula Register (SMR) is a register for the treatment of AMD established in 2003. New modules for the treatment of diabetic macular edema (DME) and retinal vein occlusion (RVO) in the SMR were registered between 2019 and 2021, said Dr. Inger Westborg of Uppsala University Hospital, Sweden.

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he emergence of large digital databases of health records – which enables the collection and analysis of data – is revolutionizing how specialists diagnose and treat patients. Real-world data (RWD) on treatment pathways, clinical outcomes and characteristics of patients with retinal diseases are useful for conducting real-world studies in the field of ophthalmology. RWD comprises findings from various observational study types and can provide vital information about the effectiveness of a treatment in clinical practice. RWD sources consist of diverse cohorts of patients, including those that are normally excluded from randomized controlled trials (RCTs), and can therefore provide insight into the clinical effectiveness of a treatment in various subgroups of patients in a real-world setting. Evidence from RWD sources may provide a better understanding of the long-term safety, effectiveness in clinical practice and utilization patterns of antiVEGF therapy. Experts from around the world shared some of the current RWD available, containing information on patients with retinal diseases, on Day 2 of the 22nd EURETINA Congress (EURETINA 2022) in Hamburg, Germany.

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Big data and AMD Big data can lead to new insights in age-related macular degeneration (AMD), according to Dr. Aaron Lee, a retina specialist at the University of Washington, USA. Big data is useful to store and analyze datasets that are otherwise too large and complex to be studied with traditional tools. The Intelligent Research in Sight Registry (IRIS Registry) by the American Academy of Ophthalmologists (AAO) can be used to measure environmental risk factors for the disease. It can provide early risk prediction, differential diagnosis, and treatment optimization. IRIS was started in 2014 and has over 70 million unique patients. It is the first comprehensive eye disease clinical registry in the United States and keeps the records of patients, provider locations, age, gender, race, insurance, smoking and phakic status. Data from the Fight Retinal Blindness! Project used in a study showed that both aflibercept and ranibizumab improved visual acuity in routine clinical practice, with aflibercept showing greater improvements in this comparative analysis, said Dr. Daniel Barthelmes, director of the Eye Clinic at the Universitats Spital Zurich, Switzerland.

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A total of 6,595 eyes in 4,506 patients were registered for diabetic retinopathy treatment. In 2021, there were 791 new treatment-naive eyes registered. There was a diagnosis of diabetic macular edema in 88% of patients. Men made up 60% of patients and women 40%. Treatment choice is anti-VEGF in most cases, noted Dr. Westborg. A total of 501 eyes in 4885 patients are registered for the retinal vein occlusion module. In 2021, there were 959 new treatment-naive eyes registered. Men comprised 53% of patients, and women 47%. Anti-VEGF was the first treatment choice in most cases. As more countries start collecting data on patients and treatments, the future of big data and RWD looks bright, as the large quantum of data available may help doctors to diagnose and treat patients better in the future.

Editor’s Note: EURETINA 2022 was held as a hybrid congress in Hamburg, Germany, on 1-4 September 2022. Reporting for this story took place at the event. A version of this article was first published on piemagazine.org.


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CONFERENCE HIGHLIGHTS

53rd RANZCO 2022

Update on Ocular Lymphomas

What's new in the WHO? by Joanna Lee

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he World Health Organization (WHO)’s classification of tumors of the eye (WHO Classification of Tumours of the Eye, WHO Classification of Tumours, 4th Edition, Volume 12) is considered as the gold standard for diagnosing tumors. Giving an update on its latest edition, Prof. Sarah Coupland, George Holt Chair in Pathology and Honorary Consultant Histopathologist at the University of Liverpool (United Kingdom), unpacked to the audience of the recently held 53rd RANZCO 2022

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congress in Brisbane, Australia, how the new WHO classification of ocular lymphomas will influence the future of identification and treatment of these diseases. Lymphomas are divided into Hodgkin’s and non-Hodgkin’s lymphoma types with further subclassifications according to where they occur. Lymphomas in and around the eye are extranodal lymphomas. The WHO’s classification of lymphomas incorporates as much

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as possible information derived from clinical studies, immunophenotypes, histomorphology and molecular genetics. “Revolutions are occurring in more areas of medicine including in the area of molecular diagnostics,” Prof. Coupland said. “As a result, the new WHO classification is not only including genetics, but also transcriptomics, proteomics and epigenetics as well.”


Besides being on the editorial board, Prof. Coupland was also involved in the classification efforts through WHO’s updated Hematolymphoid Blue Book, a body of work involving 380 authors comprising pathologists, molecular biologists, hemato-oncologists, pediatric oncologists and radiation oncologists from across 31 countries. The updated volume will be released this coming November.

the Leukemia journal1-2 in July 2022. Focusing on intraocular lymphomas, she revealed some of the changes that the new volume has captured. For instance, there is a new umbrella term of classification called “Diffuse Largecell B-cell Lymphoma of an immuneprivileged site” under which are found three lymphomas. Essentially, both VRL and CNS lymphomas now come under this new umbrella term.

“Revolutions are occurring in more areas of medicine including in the area of molecular diagnostics, as a result, the new WHO classification is not only including genetics, but also transcriptomics, proteomics and epigenetics as well.”

The advantage of placing these lymphomas together is that besides being able to compare and differentiate between the two, “it can initiate collaborations between centers to fast-track research in these areas”. Treatment for VRL can then be according to the site of the occurrence, whether it is ocular, ocular and CNS or if it is systemic. These would also be helpful when reporting the diseases under progressively global registries, such as the International VR B-Cell Lymphoma Registry.

— Professor Sarah Coupland, Honorary Consultant Histopathologist at the University of Liverpool, UK The overview of the updated classifications has been published in

Prof. Coupland also discussed ocular lymphomas, particularly highlighting the low-grade B-cell lymphoma (extranodal marginal zone B-cell lymphoma or EMZL), which is significantly rarer. “However, it is important to distinguish between the choroidal lymphomas and the vitreoretinal lymphomas because

patients with choroidal lymphomas really have a good prognosis,” she said. Previously termed uveal pseudotumor, uveal lymphoid hyperplasia, or uveal lymphoid neoplasia, these lymphomas only affect the uveal tract. Primary choroidal lymphomas are lowgrade EMZL similar to ocular adnexal MALT lymphomas. The new WHO Blue Book indicated that MALT lymphomas have a range of locations. “Interestingly, according to their locations, they have differing genetic alterations,” she said. “As a traditional pathologist, I believe morphology and immunophenotyping are the gold standards for making diagnoses for lymphomas in whatever body sites. The WHO classification is continually revising and incorporating important information which helps us understand the biology of disease and design clinical therapies. Molecular tests (including NGS and metagenomic sequencing) do make unequivocal diagnoses. Some of these tests are freely available and their costs are decreasing so they could be used in lower socioeconomic situations," concluded Prof. Coupland. Most importantly, concerted international efforts like registries and shared bioresources are important to improve outcomes through the use of artificial intelligence and multi-center clinical trials.

References 1.

Alaggio R, Amador C, Anagnostopoulos I, et al. The 5th edition of the World Health Organization Classification of Haematolymphoid Tumours: Lymphoid Neoplasms. Leukemia. 2022;36(7):1720-1748.

2.

Khoury JD, Solary E, Abla O, et al. The 5th edition of the World Health Organization Classification of Haematolymphoid Tumours: Myeloid and Histiocytic/Dendritic Neoplasms. Leukemia. 2022;36(7):1703-1719.

Editor’s Note: A version of this article was first published in CAKE & PIE POST, 53rd RANZCO 2022 Edition, Issue 4.

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