PIE Issue 33 - January 2025

Next-gen pediatric retina care promises to deliver solutions once deemed out of reach p20

Advancing Vitreoretinal Excellence

Dear Readers,

It is an amazing time in our profession as vitreoretina specialists.

There is so much we have accomplished and so much more to learn and discover.

As Vice President of the European VitreoRetinal Society (EVRS), I am proud to share that EVRS is one of the oldest and most established societies in the vitreoretinal field. From its inception, EVRS has upheld the following core principles:

Inclusivity: Anyone with valuable insights to share is welcome to speak, regardless of cultural background, country of origin or academic position.

Transparency: We uphold a commitment to free and unbiased discourse, accepting only genuine, unsponsored contributions.

Industry Collaboration: While companies play a vital role in our daily practice and educational activities, we maintain transparent and ethical relationships with them.

Education & Mentorship: We place special emphasis on training and fostering strong connections with Young Ophthalmologists worldwide.

EVRS remains dedicated to these values, ensuring a collaborative, open and forward-thinking community for vitreoretinal specialists.

Today, we continue to pursue these goals with the same enthusiasm. We had a great meeting in Budapest a few months ago and are working to organize a new one in Cancun (Mexico) on November 12-15, 2025. In that regard I would like to thank Media MICE who worked with us endlessly to help us make the meeting more interesting and well known, arranging a series of fun and useful events in the best corner of the exhibition area.

In this issue of PIE magazine, be sure to check out the articles on pages 26 and 30, covering key highlights from EVRS 2024.

Once again, thank you to Media MICE and PIE magazine for holding the vitreoretinal field in the highest regard. We appreciate the opportunity to collaborate with you in identifying and addressing unmet needs in this field.

Sincerely,

Barbara Parolini, MD Italy Advisory Board Member, PIE magazine Vice President, EVRS

Posterior Segment

Tackling Retinal Medicine’s Biggest Challenges with ZEISS 06

08

Beyond P-Values

The essential roles of randomized clinical trials, real-world evidence and meta-analysis in advancing retinal healthcare research

Rethinking Retinal Disease Treatment and Management with TOPCON Technology 10 12

The Retina Conundrum Specialists provide new insights into managing critical retinal conditions

Innovation

RGB: New Hues on the Block

The new UWF red/green/ blue modality captures retinal images with natural color, enhancing diagnostic accuracy 18 14

Trials and Tech in Eye Care

Experts share groundbreaking insights into the latest research and technologies in the industry

Cover Story

Glimmers of Hope Next-gen pediatric retina care promises to deliver solutions once deemed out of reach

Empowering Women, Revolutionizing Retina Retinal expert Dr. Jennifer Lim on inclusivity, work-life balance, and the pursuit of excellence in a demanding field

Bridging Perspectives in Eye Care

The Philippine Glaucoma Society’s debut at EVRS 2024 showcases the synergy between glaucoma and retina

Innovation Meets Vision

From mini-telescope implants to breakthroughs in biosimilars, ophthalmologists at EURETINA 2024 showcase cutting-edge retinal treatments

A Meeting of Minds

EVRS 2024 connects global experts in Budapest, setting the stage for continued progress in vitreoretinal care

Dr. Alay S. Banker

Banker’s Retina Clinic and Laser Centre Ahmedabad, India alay.banker@gmail.com

Prof. Gemmy Cheung

Singapore National Eye Centre (SNEC) Singapore gemmy.cheung.c.m@singhealth.com.sg

Dr. Arshad Khanani

Sierra Eye Associates; University of Nevada, Reno School of Medicine Nevada, USA arshad.khanani@gmail.com

Dr. Hudson Nakamura

Bank of Goias Eye Foundation Goiânia, Brazil hudson.nakamura@gmail.com

Dr. Barbara Parolini Eyecare Clinic Milan, Italy parolinibarbara@gmail.com

Dr. Veeral Sheth

University Retina and Macula Associates; University of Illinois at Chicago, USA vsheth@gmail.com

We are looking for eye docs who can contribute articles to PIE magazine. Interested? Let's talk! Send us an email at editor@mediamice.com.

To place an advertisement, advertorial, symposium highlight, video, email blast, or other promotion in PIE magazine, contact sales@mediamice.com.

Matt Young CEO & Publisher

Gloria D. Gamat Chief Editor

Mapet Poso Editor

Matt Herman Associate Editor

Maricel Salvador Graphic Designer

Writers

Diana Truong

John Butcher

Tan Sher Lynn

Contributors

Dr. Paulo Eduardo Stanga

Dr. Perfecto E.O.R. Cagampang III

Hannah Nguyen COO

Travis Plage CFO

Ruchi Ranga Society Relations & Conference Manager

International Business Development

Brandon Winkeler

Robert Anderson

Sven Mehlitz

Published by

Tackling Retinal Medicine’s Biggest Challenges with ZEISS

by Matt Herman

ZEISS welcomed key thought leaders in Asian ophthalmology to discuss optimizing their retinal practices with ZEISS technology, from AI-enabled OCT to the latest in 3D surgical visualization.

The CIRRUS PathFinder can help identify intraretinal fluid outside of the central B scan—even with no significant change on the thickness map, like this [Source: Slide deck of

AZEISS-sponsored symposium at the 17th Congress of the Asia-Pacific Vitreo-Retina Society (APVRS 2024) raised some of the most pressing questions facing retinal ophthalmology—and discussed how ZEISS technology is helping to tackle them.

According to Assoc. Prof. Gavin Tan, session chair and head of Surgical Retina at Singapore National Eye Centre (SNEC), ophthalmologists around the world face myriad challenges in the near future. The need for streamlined workflows and optimizing patient outcomes with surgical precision and speed has never been greater.

Over the course of the symposium, Assoc. Prof. Tan was joined by some

of the region’s biggest names, including Dr. Vivek Dave (India) and Clin. Assoc. Prof. Harvey Uy (Philippines), to see how ZEISS technology is designed to meet the demands of modern retina.

Workflow efficiency with AI and CIRRUS PathFinder

According to Assoc. Prof. Tan, artificial intelligence-enabled tools, like the ZEISS CIRRUS PathFinder deep learning decision support tool, are key to tackling rising patient numbers and the resulting increase in volume of optical coherence tomography (OCT) scans to sift through.

“OCTs are really part of our daily work now, but the need for timely

interpretation of these OCTs presents a barrier,” Assoc. Prof. Tan said.

The solution to this OCT conundrum? AI-enabled tools like the ZEISS CIRRUS PathFinder, which is the first and currently the only AI decision support tool embedded in an OCT machine, according to Assoc. Prof. Tan. “This doesn’t replace you or your diagnosis,” he emphasized, “but it does streamline the review of macular OCT scans by automatically identifying those that may need closer review.”

CIRRUS PathFinder does this by flagging abnormal scans with pathological features. The tool can also detect subtle pathologies that might be missed by human scanners—or flag suspicious scans so that physicians know when to take a closer look, according to Assoc. Prof. Tan.

CIRRUS PathFinder adds up to helping physicians find more pathologies faster and more accurately. “It is impossible for us to scrutinize every single B-scan, but it is easy when we focus on foveal-involving pathologies or subtle lesions in the fellow eye. CIRRUS PathFinder, when it becomes available commercially, will be a very effective tool that can provide accurate identification of abnormalities, allowing you to focus on what’s really pathological,” he said.

“CIRRUS PathFinder can improve your efficiency, reduce the chance of missing pathologies and improve overall physician quality of life not just for retina specialists and more so for general ophthalmologists, glaucoma specialists and optometrists because they would be able to identify what they could have missed. We benefit because the patient can be referred earlier in the pathology where treatment is more likely to be successful in achieving better long-term trajectory outcomes,” Assoc. Prof. Tan concluded.

The power of Retina Workplace and multimodal imaging

ZEISS Retina Workplace image management ecosystem, according

Assoc. Prof. Gavin Tan]

to Clin. Assoc. Prof. Uy, helps him manage his patients with diagnostic accuracy, clinic efficiency and confidence demanded by modern retinal medicine.

One of the keys, he explained, is the effective deployment of multimodal imaging, from ultrawidefield fundus photography to fluorescein angiography, OCT and OCT angiography (OCT-A). “An image management system should be accurate, efficient and give you confidence that your images are telling the truth. The Retina Workplace does all of these,” Clin. Assoc. Prof. Uy said.

Gathering various images into one coordinated scan bears many advantages, according to Clin. Assoc. Prof. Uy. In particular, he pointed to a feature that allows the overlaying of fundus scans. “With the overlay, you can move the crosshair into an area of interest, and then below see what’s happening on the B-scan in that area.”

In addition to its multimodal image analysis features, Clin. Assoc. Prof. Uy also discussed how Retina Workplace facilitates temporal change analysis—correlating treatment with outcomes and planning treatments.

But in the end, it all comes down to the patient—and Clin. Assoc. Prof. Uy believes that one of the Retina Workplace’s greatest contributions to his practice and patient outcomes is how it helps with patient education.

Not only does it free up the time to speak to the patient about their condition and treatment, but it also gives an easy-to-follow visualization of the patient’s condition. “The Retina Workplace provides an accurate assessment of the patient’s disease status and an idea of how they respond to treatment,” he said. “It helps you educate the patient better, improves conversion rates and greatly improves review time efficiency. I think we should all try to get this system into our practice.”

The cutting edge in vitrectomy

Image analysis can go a long way towards improving clinical efficiency, but there is also much that can be

done in the operating theater. Dr. Dave believes that the features of the ZEISS DORC EVA NEXUS are designed to do just that with vitrectomies—and his presentation showed how.

For Dr. Dave, an efficient vitrectomy is all about the interplay of fluid dynamics and instrumentation, with surgical skill being the great coordinator between the two. For fluid dynamics, the DORC EVA NEXUS advantage lies in the successful marriage of venturi and peristaltic pump designs into two modes—vacuum and flow with the VTI pump.

“This ensures you have optimal pressure balance,” he said. “You can toggle between vacuum mode and flow mode depending on your tolerance of fluctuation or turbulence inside the eye on the tissue you are operating on.”

Dr. Dave explained that vacuum mode can be used when more pull on the tissue is required, whereas flow mode can be used when attempting to shave in the retinal periphery or when close to a detached retina.

The second half of the equation is the EVA NEXUS cutter, and Dr. Dave explained how valuable the system’s two-dimensional cutting (TDC) technology is to his surgeries. “The cutter port stays open in both movements of the guillotine, raising the overall efficiency of the probe removing the vitreous because the overall open time increases,” he explained.

Dr. Dave also pointed to another feature of the EVA NEXUS– its Smart IOP function’s utility in maintaining chamber stability. “Smart IOP’s constant pressure monitor ensures that you neither have your anterior chamber collapse nor do you have undue pressure building up and causing corneal edema during the surgery,” he said.

Visualization in the digital OR

The final essential piece for optimizing efficiency and patient outcomes in modern retinal surgery is 3D visualization, and Dr. Dave and Assoc. Prof. Tan wrapped up the session by talking about ZEISS

ARTEVO, and especially the latest ARTEVO 850, a heads-up 3D microscope.

“All the advantages of your DORC system get amplified when your operating platform includes ZEISS ARTEVO,” Dr. Dave said. Besides the myriad advantages gained with ARTEVO’s DigitalOptics™ and the information overlay with AdVision™’s augmented reality display, the real difference for Dr. Dave is intraoperative OCT.

“One of the most important add-ons for this machine is intraoperative OCT, and with more complicated and delicate cases near the macula and fovea, this becomes an invaluable tool in your OR,” he said.

Assoc. Prof. Tan echoed these sentiments in his presentation on the ZEISS ARTEVO 850. Besides intraoperative OCT, Assoc. Prof. Tan put particular emphasis on the utility of ARTEVO 850’s Digital Color Assistance capabilities. “You really get all the color enhancement you need for membranes and tissues,” he said, “ and I think the potential is there to reduce our reliance on stains.”

Overall, each presentation in this session echoed a similar message— that cutting-edge technology from ZEISS empowers clinicians to deliver exceptional patient care and achieve optimal outcomes. As we look to the future, the commitment from ophthalmic companies like ZEISS to innovative solutions that address the challenges faced by ophthalmologists worldwide will undoubtedly drive further advancements in the field of retina.

Disclaimer: Not all products or features are available in all regions. CIRRUS PathFinder is not commercially available yet.

Editor’s Note

Reporting for this story took place during the 17th Congress of the Asia-Pacific Vitreo-retina Society (APVRS 2024) from 22-24 November in Singapore. A version of this article was first published on piemagazine.org

Beyond

The essential roles of randomized clinical trials, real-world evidence and meta-analysis in advancing retinal healthcare research

by Tan Sher Lynn

Advancing research methodology in the field of retina requires a comprehensive understanding of various study designs, statistical techniques, and the integration of clinical outcomes. At the 24th Congress of the European Society of Retina Specialists (EURETINA 2024) recently held in Barcelona, Spain, retinal experts came together to share invaluable insights.

As clinical trials and real-world evidence (RWE) increasingly inform healthcare decisions, their complementary roles become more evident. Dr. Robyn Guymer, Dr. Nik Tzoumas, Dr. Mark Phillips and Dr. Varun Chaudhary unpack the dynamic relationship between idealized trial data and the messy reality of everyday clinical practice.

Finding a balance between RCTs and RWE

Randomized clinical trials (RCTs) are vital for establishing the efficacy of new treatments, but their controlled settings often differ from real-world practice.

In her insightful presentation, Dr. Robyn Guymer (Australia) highlighted the complementary roles of RCTs and

RWE in healthcare decision-making. While RCTs provide critical proof that an intervention works and is key for drug approvals, they operate under ideal conditions with strict protocols. This can limit their external validity, raising the important question: "Will it be effective for the patient in front of us?”

On the other hand, as Dr. Guymer explained, RWE offers a broader and more heterogeneous perspective, capturing trends in clinical practice and including a wider range of patient demographics.

"Real-world evidence probably represents data that is much more closely aligned with our clinical practice," she noted. However, she cautioned that while RWE provides valuable insights, it is essential

to carefully assess its quality and consider potential biases and limitations in the data sources.

The synergy between RCTs and RWE is key, particularly in evaluating long-term treatment adherence and safety. As Dr. Guymer pointed out, understanding both forms of data helps healthcare professionals better assess impacts and "compare our practice outcomes to those in our communities."

Ultimately, both RCTs and RWE are essential for enhancing clinical guidelines and patient care.

Insights into linear regression

Next, Dr. Nik Tzoumas (United Kingdom) explored the versatility of linear regression in his insightful talk, highlighting its pivotal role in statistical analysis.

"All common tests are approximations or special cases of linear regression," he explained, outlining how this mathematical method predicts outcomes by fitting a straight line through data points. Key components include the intercept, slope and residuals— representing the gap between predicted and actual data.

Dr. Tzoumas emphasized its realworld applications. ”You can use it to predict who will benefit most from a certain drug... or for causal inference,” he noted. Different types of regression models, such as linear, logistic, or Cox, cater to various outcomes, each providing unique estimates of treatment effects.

He stressed the importance of building appropriate models by considering all relevant predictors,

confounders and interactions. "Is the outcome valid? Are the predictors relevant?" he asked, urging analysts to ensure model accuracy.

Additionally, Dr. Tzoumas playfully reminded the audience to inspect their data visually. "You might actually be plotting a regression line through a dinosaur,” he quipped, highlighting the need for thorough data analysis to avoid misleading conclusions.

Interpreting clinical significance in research

Researchers have been using p-values to determine whether the results of an experiment or study are significant. However, Dr. Mark Phillips (Canada) addressed the critical issue of p-value misinterpretation in research, particularly in clinical studies.

"Historically, there's been an overreliance on p-values to determine statistical significance," he noted. According to Dr. Phillips, this reliance stems from the simplicity of interpreting p-values as either

significant or not, which can lead to quick but often flawed conclusions.

He explained that p-values represent the probability of observing a result under the assumption that the null hypothesis is true. However, this probability does not reflect the effect's magnitude. Dr. Phillips cautioned that small p-values in large studies, or non-significant p-values in underpowered studies, do not provide a full picture.

"We can't really conclude that they're actually the same; we just didn’t have a large enough trial to detect any difference," he explained.

To avoid these pitfalls, Dr. Phillips emphasized the importance of contextualizing p-values by considering effect sizes and confidence intervals. He concluded by urging researchers to not let p-values drive clinical decisions.

"P-values are important, but they should not be the driving factor of drawing our conclusions,” he stressed. Instead, understanding

the magnitude and clinical relevance of effects is crucial in research and patient care.

Integrating meta-analysis with patient insights

Meanwhile, Dr. Varun Chaudhary (Canada) pointed out that not all RCTs are well-designed, and some observational studies may lead to results that are “far away from the bullseye.”

Dr. Chaudhary elaborated on the importance of systematic reviews, which involve a thorough selection and critical appraisal of all relevant literature to address a specific clinical question. He described metaanalysis as a statistical technique that combines the results of multiple studies to generate a more precise estimate.

“You need to look for well-done, trustworthy systematic reviews,” he noted, emphasizing that many published reviews lack the rigor needed for credible conclusions.

All in all, Dr. Chaudhary highlighted the importance of integrating metaanalysis with clinical expertise and patient values in the decision-making process. He noted that while metaanalysis provides robust research evidence, it must be combined with insights from patient groups and patient-reported outcomes.

There are gaps in how patient values are currently incorporated into ophthalmology guidelines. The ultimate goal is to transition from evidence to actionable recommendations, ensuring that treatment effects, side effects, and certainty of evidence are considered in making clinical decisions.

Editor’s Note

Reporting for this story took place at the 24th Congress of the European Society of Retina Specialists (EURETINA 2024), held from September 19 to 22 in Barcelona, Spain.

The Retina Conundrum

Specialists provide new insights into managing critical

retinal conditions

by Tan Sher Lynn

Experts at the 24th Congress of the European Society of Retina Specialists Congress (EURETINA 2024) shed light on several critical retinal conditions, including central serous chorioretinopathy (CSCR), pathologic myopia, retinal toxicity from medications and intraocular lymphoma diagnosis— offering fresh insights into treatment and diagnostics.

Leading retinal experts explored a range of often-overlooked aspects of retinal care, providing fresh perspectives into complex retinal conditions that impact vision. Topics included managing the retinal toxicity risks posed by commonly prescribed drugs and navigating the complexities of fluid types in agerelated macular degeneration (AMD).

The discussions highlighted the importance of early detection and personalized treatment strategies— shedding light on the connections between medication, retinal health and disease progression.

Managing chronic CSCR

According to Dr. Camiel J. F. Boon (Netherlands), central serous chorioretinopathy (CSCR) remains mysterious due to its uncertain

causes and unpredictable progression. The condition is characterized by fluid accumulation under the retina, leading to distorted vision.

“Choroidal vascular congestion and leakage are pivotal features of CSCR pathogenesis and are, therefore, important targets for treatment,” he noted.

Dr. Boon found that rare genetic variation in vascular endothelial protein tyrosine phosphatase (VE-PTP) is associated with CSCR, venous dysfunction and glaucoma.

Treatment aims to eliminate the subretinal fluid or leakage to improve vision and reduce or prevent recurrences by addressing the underlying primary problem—the choroid. Treatment options for

chronic CSC include photodynamic therapy (PDT), micropulse laser treatment, conventional laser treatment, anti-vascular endothelial growth factor (anti-VEGF), MRantagonists and β-blockers, among others.

Current evidence strongly suggests that half-dose (or half-fluence) PDT is the treatment of choice for chronic CSC due to its safety and effectiveness. While observation may be the preferred approach for firstepisode acute CSC, treatment should be considered in selected cases.

Choroidal changes in pathologic myopia

Meanwhile, Dr. Kyoko Ohno-Matsui (Japan) discussed the intricacies of choroidal thinning associated with pathologic myopia.

“Thinning begins around the optic nerve in childhood,” she said. “While choroidal thickness is relatively maintained in the fovea and temporal regions, it suddenly disappears nasally to the fovea.” She noted that this abrupt change suggests the thinning is not generalized, indicating that a potential circulatory disturbance may not be the primary cause.

Dr. Ohno-Matsui also emphasized that choroidal changes involve more than just thinning, the entire vascular pattern is altered. “Choroidal vessels undergo constant remodeling, selectively disappearing and leaving large veins across the macula.”

An analysis she conducted 17 years ago showed the selective disappearance of choroidal veins in highly myopic eyes, leading to a large variation in the width of choroidal veins. She compared this phenomenon to baobab trees in desert conditions.

“The remaining ones become gigantic,” she said, which mirrored the stagnation in dilated veins that can result in complications like macular neovascularization.

In summary, Dr. Ohno-Matsui asserted that extreme choroidal thinning is a key feature of pathologic myopia, beginning as a localized process rather than generalized thinning. She then emphasized the

importance of monitoring choroidal vascular patterns for predicting neovascularization risks.

Retinal toxicity risks for common medications

Drugs are often effective in treating diseases, but they can also pose toxicity risks to the retina. Dr. Sarah Touhami (France) examined the retinal toxicity linked to several commonly used medications.

First up was hydroxychloroquine, a drug widely prescribed for autoimmune diseases like lupus. “These drugs are highly efficient, but unfortunately, they can be toxic to the visual cycle and disrupt the phagocytosis functions of the retinal pigment epithelium (RPE),” she explained. This toxicity can lead to an accumulation of damage in the RPE, eventually impairing the outer retina.

Dr. Touhami stressed the importance of regular screening through optical coherence tomography (OCT) to detect early signs of toxicity before patients present symptoms.

She also discussed tamoxifen, a drug used in breast cancer treatment, highlighting its impact on Müller cells and the RPE. “About 10% of [patients] may experience toxic effects when taking more than 20 milligrams per day for over two years,” she shared.

Dr. Touhami further emphasized the effects of mitogen-activated protein kinase (MEK inhibitors), commonly used in cancer treatments. These drugs can induce MEK-associated retinopathy, causing subretinal detachments. Fortunately, this toxicity is often reversible.

She concluded her talk by highlighting pentosan, a drug that can cause flow voids in the choroid, leading to pigmentary changes in the fovea.

Understanding fluid types in AMD

Next, Dr. Elodie Bousquet (France) discussed the complexities of different fluid types found in agerelated macular degeneration (AMD), which include intraretinal fluid (IRF), subretinal fluid (SRF), subretinal hyperreflective material fluid (SHRM), and subretinal pigment epithelium fluid.

Dr. Bousquet stressed the need for careful analysis. She noted that distinguishing between degenerative and neovascular intraretinal fluid can be challenging and emphasized the importance of using OCTA to rule out neovascularization.

The presence of subretinal fluid overlying drusenoid pigment epithelial detachment (PED) is crucial, as it may spontaneously resolve but still indicate underlying RPE dysfunction.

“When you see acquired vitelliform lesions at the top of a drusenoid PED, it means the RPE is dysfunctioning,” she warned.

“We can also find subretinal fluid overlying drusenoid PED. This fluid doesn’t require any intravitreal injections and can spontaneously resolve. However, it’s usually not a good sign, as it indicates that the RPE is dysfunctional,” she added.

Identifying non-neovascular fluid is essential for avoiding unnecessary anti-VEGF injections. “We have to be very careful, and we have to analyze this fluid [in AMD] and try to understand the origin of the fluid, especially in the absence of macular neovascularization. Do not hesitate to repeat OCTA or repeat fluorescein angiography (FA) and indocyanine green angiography (ICGA) to rule out macular neovascularization,” she concluded.

Decoding intraocular lymphoma

Lastly, Dr. Jens Kiilgaard’s (Denmark) talk focused on the complexities of B-cell lymphoma, particularly in the context of intraocular presentations and its systemic nature. He noted that while B-cell lymphoma may initially manifest in the eye, it is fundamentally a systemic disease.

Dr. Kiilgaard discussed how intraocular lymphoma typically resembles a normal germinal center, with characteristic B-cell infiltration that can lead to different survival outcomes based on the type of lymphoma.

He highlighted the distinctions between lymphomas arising from the germinal center and those from peripheral margins. “The germinal

center has a better survival than the activated B-cell from the periphery of the node,” he said.

Additionally, Dr. Kiilgaard discussed the challenges in diagnosing lymphoma through vitreous biopsies, advocating for thorough investigations even when initial results are negative. He stressed the need for vigilance in cases of serous detachment.

“When you have a serous detachment, it’s important to identify the type: Is it rhegmatogenous, tractional, or serous? In the case of rhegmatogenous detachment, you need to locate the retinal hole and close it, either by external or internal surgery,” he explained.

If it’s tractional, it is important to obtain the patient’s medical history; for serous detachment, identifying the cause is essential. “Ultrasound is very effective in distinguishing between inflammation and serous detachment,” he added.

Dr. Kiilgaard pointed out that whenever one encounters a serous detachment and cannot identify the cause, it is important to consider malignant conditions that may lead to such detachment.

“It might not be a malignant tumor, it could also be benign—such as when the whole choroid is congested with choroidal hematoma. Also, be careful when you have treatment-resistant uveitis, as a solid pigmented detachment may not be a true detachment but rather subretinal pigment epithelium deposits. Additionally, if tinnitus is present, it is crucial to consider the possibility of intraocular lymphoma,” he concluded.

Editor’s Note

Reporting for this story took place at the 24th Congress of the European Society of Retina Specialists (EURETINA 2024), held from September 19 to 22 in Barcelona, Spain.

Rethinking Retinal Disease Treatment and Management with TOPCON Technology

by Matt Herman

From dry AMD to diabetic retinopathy and beyond, TOPCON is reimagining the future of retinal medicine with the TOPCON DRI OCT Triton multimodal imaging platform, the IRIDEX PASCAL 577 MicroPulse® subthreshold laser and the Espansione eye-light® LM® LLLT photobiomodulation.

It’s the end of 2024, and TOPCON thinks it might be time to inject new life into how we treat and manage some of the world’s most devastating retinal diseases.

Traditional tools and therapies like optical coherence tomography (OCT) imaging and intravitreal anti-VEGF injections have become synonymous with the subspecialty—but at a TOPCON-sponsored symposium in Singapore at the 17th Congress of the Asia-Pacific Vitreo-retina Society (APVRS 2024), Prof. Ian Yeo (Singapore), Prof. Kelvin Teo (Singapore) and Dr. Giulia Coco (Italy) challenged attendees to look beyond the familiar and into the future.

Rethinking subthreshold laser in the age of antiVEGF

Although subthreshold lasers are not new, Prof. Ian Yeo thinks they have evolved into a major part of the retinal treatment landscape, especially with devices like the IRIDEX PASCAL 577.

“You all come from the generation that only knows about anti-VEGF,” Prof. Yeo said, addressing the audience. “But before anti-VEGF, the laser was the most important tool for managing patients with ischemic retinopathies—and while the PASCAL 577 can do everything a traditional laser can do, it can also do something different with its MicroPulse® subthreshold functionality.”

According to Prof. Yeo, anti-VEGF treatment is not without its flaws, and MicroPulse® subthreshold

laser has a major role to play as both an alternative monotherapy and in conjunction with anti-VEGF treatment.

For starters, anti-VEGF does not treat the underlying causes of exudative retinal disease, according to Dr. Yeo—and there are question marks both in terms of patient compliance, treatment fatigue and recurring treatment cost burden arising from the need for continued injections.

And then there’s the growing subset of patients—including nearly half of those with DME—who don’t respond to anti-VEGF agents.1

“Anti-VEGF has helped our patients see better and faster, so we should end the talk here, right?” Prof. Yeo asked. “But the reality is, it’s not as simple as that. Anti-VEGF doesn’t work for everyone, and those of you who run clinics know that diabetic patients aren’t getting the best treatment possible because there’s always some edema left behind,” he said.

Prof. Yeo believes that subthreshold laser platforms like the PASCAL 577 MicroPulse® can help fill this

gap. “What we have is a useful first-line adjunct therapy together with anti-VEGF treatment, which in my experience at least reduces the number of injections required,” he said. “It can also be used as a primary therapy in patients who are unsuitable for anti-VEGF treatment,” he added.

Dr. Yeo concluded with some useful pearls he uses in his clinic. “One thing I’ve experienced for these patients is that I need really high density [laser spots] and [to] fill up the whole posterior pole as much as possible,” he said. “This is safe and repeatable, but keep in mind to be patient. Results take longer injections—but they will ultimately have longer durability,” he advised.

The shift to multimodal devices

And while subthreshold MicroPulse® laser with PASCAL 577 is adapting— and thriving—in the new post-antiVEGF world, Dr. Kelvin Teo thinks it is time for an even more dramatic change in the way retinal specialists approach imaging: the shift to allin-one multimodal devices like the TOPCON DRI OCT Triton.

“We’ve got a new generation of imaging and retinal diagnosis monitoring available to us now—and we now have new technology from TOPCON that enhances this,” Prof. Teo said.

“The Triton series has been a mainstay in my practice. And what really strikes me about this particular platform is the speed.”

Of all Triton’s advantages, one stands above the rest for Prof. Teo.

“You can see wider and you can see deeper, but the speed is what I’m most impressed with. Patients in the

clinic don’t like to sit still, and any scan takes more than 10 seconds, so speed is essential in getting good quality imaging.”

At the core of the latest Triton is its multimodal imaging prowess, with onboard OCT, fluorescein angiography, color fundus and OCT angiography (OCT-A). The latter, in particular, has been a particular boon to Dr. Teo’s practice. “This is very useful in helping to colocalize where the disease is,” Prof. Teo said.

Where multimodal imaging with Triton also shines is in TOPCON’s postprocessing, including Smart Denoising, image enhancement tools and wider scan lengths. Denoising, in particular—stood out to Prof. Teo for its synergy with the imaging hardware’s speed.

“Denoising is particularly useful when you’re talking about higher speeds,” he said. “In cross-sectional OCT, for example, we don’t need to take average images, so you don’t have to wait for those repeated scans. This makes the platform even faster—on a single B scan, with smart denoise, you can get good, high-quality images.”

In the end, this combination of speed, image quality, multimodality—and TOPCON’s commitment to state-ofthe-art post-processing—is why Prof. Teo continues to rely on Triton in his clinic.

“What is truly exciting is that TOPCON continues to develop these post-processing technologies and help us visualize multiple pathologies better—and having good visualization, qualitatively, is essential for a good retinal practice.”

Photobiomodulation in early dry AMD with eyelight®

Treatments for geographic atrophy (GA), a sight-stealing, late-stage progression of dry AMD, have proven to be one of the hottest topics in retinal medicine. But what if even non-specialists could add a tool in their armamentarium to treat the disease in its earlier form?

This is exactly what photobiomodulation (PBM) with

Month 4

Espansione’s eye-light® aims to do, and Dr. Giulia Coco (Italy) took the audience through the current evidence base for the treatment— and explained how clinicians around the world are already seeing results.

The evidence starts with the Lightwave I trial, where six-month functional and anatomical data have been presented that point to the short-term efficacy of the procedure. In the study, best corrected visual acuity (BCVA) improvements saw 20.3% of PBM-treated patients achieving a gain of 5 or more letters post-treatment, compared to 8.9% in the sham group (p=0.043).2

And this is all done, according to Dr. Coco, with maximum comfort for the patient—which means better compliance, and more consistent treatment effects.

“All patients were fully compliant with the treatment plan, and this is very interesting because this is not a procedure,” she said. “This is not uncomfortable for the patient and there was no dropout rate.”

After presenting a case study with images from a 63-year-old woman with AREDS Category 3 dry AMD who gained 5 letters in BCVA and a marked reduction in drusen volume after one month of treatment.

Dr. Coco concluded her talk by looking at the promising future of PBM with eye-light® LM® LLLT, including early case reports of a

potential response in central serous chorioretinopathy. But for now, the results for dry AMD still coming out are promising enough.

“The preliminary result is that photobiomodulation therapy with eye-light® is safe and well-tolerated for patients with dry AMD, and functional and anatomical data we have analyzed so far have supported the efficacy of the procedure,” she said.

More positive results would be a major step forward in the fight against dry AMD and GA—and like all of the TOPCON technology on display in Singapore during APVRS 2024, another step into the future of retinal disease management.

References

1. Okada M, Mitchell P, Finger RP, et al. Nonadherence or Nonpersistence to Intravitreal Injection Therapy for Neovascular Age-Related Macular Degeneration: A Mixed-Methods Systematic Review. Ophthalmology. 2021;128(2):234-247.

2. Borrelli E, Coco G, Pellegrini M, et al. Safety, Tolerability, and Short-Term Efficacy of LowLevel Light Therapy for Dry Age-Related Macular Degeneration. Ophthalmol Ther. 2024;13(11):28552868.

Editor’s Note

Reporting for this story took place during the 17th Congress of the Asia-Pacific Vitreo-retina Society (APVRS 2024) from 22-24 November in Singapore. A version of this article was first published on piemagazine.org

RGB: New Hues on the Block

The new UWF red/green/blue modality captures retinal images with natural color, enhancing diagnostic accuracy

by Dr. Paulo Eduardo Stanga

Ultra-widefield (UWF) imaging is reshaping retinal diagnostics by providing comprehensive, high-contrast views of the retina. With the introduction of RGB (red/green/blue) imaging technology, clinicians can now capture more natural color representations, enhancing the detection of subtle retinal changes.

UWF imaging is defined by the Widefield Imaging Consensus group as a fovea-centered single (non-montaged) field of view capturing the retina beyond the vortex vein ampullae in all four

quadrants.1 Compared to traditional 30° to 50° fundus photography—or 75° with montaged Early Treatment Diabetic Retinopathy Study (ETDRS) Seven Standard Fields— UWF imaging provides greater

visualization of the retinal periphery. This can be the earliest or the predominant site affected in several retinal diseases.2

UWF imaging, including UWF color fundus, autofluorescence (AF), optical coherence tomography (OCT), fluorescein angiography (FA), indocyanine green angiography (ICGA), and OCT angiography, continues to provide new insights on disease pathophysiology and prognostication and guides ophthalmologists in the early detection, accurate staging, and appropriate treatment of various retinal pathologies.2,3

With short acquisition times and the ability to extensively image the retina through nonmydriatic pupils, UWF imaging is also a promising tool for tele-ophthalmological screening.4

UWF imaging technology

Among the currently available UWF imaging technologies, optomap imaging (Optos PLC; Dunfermline, UK) is based on confocal scanning laser ophthalmoscopy with an ellipsoidal mirror, and is capable of imaging 200° or 82% of the retina in a single capture, covering a greater retinal area in lesser time compared to other UWF cameras.5,6 With the montaging of gaze-steered images, optomap coverage can be further extended to 220° or 97% of the retina for a nearly panretinal view.1

Historically, Optos UWF devices utilized only monochromatic green (532 nm) and red (633 or 635 nm) laser scans to obtain pseudocolor RG (red/green) images that are characterized by a greenish hue due to the absence of a blue channel.5 Recently, the company introduced a color RGB (red/green/blue) imaging modality to its California device that can combine 635-nm red and 532nm green laser scans with a 488-nm blue laser scan to obtain a composite image of the retina with a natural color representation similar to its appearance on fundoscopy.

The updated Optos California device obtains UWF RG and RGB images simultaneously, in addition to sensory red-free and choroidal images. The device is also capable of green and blue laser AF, as well as FA and ICGA.

Figure 1

Figure 2

UWF RG versus UWF RGB imaging: Initial results

At our clinic, optomap imaging is routinely used to assist in disease screening and treatment planning. Therefore, we were interested in assessing if this additional color UWF imaging capability translated to any additional benefits compared to clinically validated UWF RG imaging.

For this, we conducted what was the first qualitative comparison of images captured with the RG and RGB modalities of the Optos California device. One hundred seventy-two eyes of 86 patients were included in a retrospective study at the Retina Clinic London (United Kingdom). UWF RG and RGB image characteristics were compared in a range of retinal conditions.7

The RGB images were characterized by a more natural appearance of the optic nerve and the retina, with the nerve fiber layer and hyaloid reflection being more clearly visible compared to RG images.

This was expected, as shortwavelength blue lasers better visualize the vitreoretinal interface

and superficial retinal structures.8 Thus, subtle epiretinal membranes were more easily detected with RGB imaging.

Vitreous opacities and proliferative vitreoretinopathy (PVR) were more recognizable due to the natural color representation, while the superficial details and complete extent of retinal detachments were more easily visible [Figure 1]

The retinal periphery was more clearly visualized with higher contrast in RGB images, which facilitated the examination of vitreoretinal landmarks and subtle retinal holes, schitic changes and degenerations [Figure 2].

Early adopters of UWF RGB imaging have also described increased clarity and improved visualization of subtle details, as well as more natural color representations of ocular tumors.9

However, this was not to say that the RGB images were always superior. In specific disorders, we found RG and RGB images to better visualize different components of retinal lesions based on their depth in the retina. This is because

Key Takeaways

• In addition to the 635-nm red and 532-nm green lasers used in Optos ultra-widefield RG imaging, the new Optos color RGB modality also utilizes a 488-nm blue laser to obtain retinal images with more natural colors.

• RGB imaging provides better contrast at the periphery due to the natural color representation of retinal holes and degenerations, while the short-wavelength blue laser better images the vitreoretinal interface and superficial retinal findings—such as proliferative vitreoretinopathy, epiretinal membrane, superficial retinal hemorrhages, and neovascularization.

• In comparison, RG imaging better visualizes deeper retinal structures, such as retinal pigment epithelium changes, subretinal fibrosis, deep retinal hemorrhages, and choroidal vessels.

• Ultra-widefield RG and RGB modalities have complementary imaging capabilities, with the adjustment of percentage laser wavelength composition in the OptosAdvance software allowing customization of image presentation for optimal visualization according to the depth of retinal lesions.

long-wavelength red lasers can penetrate the deeper retinal layers and the choroid10 and intermediatewavelength green lasers better visualize the neurosensory retina,11 while short-wavelength blue lasers scan the vitreoretinal interface and the superficial retina.

Thus, deep retinal and choroidal vessels in highly myopic eyes were more clearly visualized with RG images, whereas peripheral retinal atrophy could be better discerned in RGB images [Figure 3]

While drusen in age-related macular degeneration (AMD) were better

Figure 5

Figure 3

Figure 4

characterized with the more natural colors of RGB imaging, areas of geographical atrophy and healthy retinal pigment epithelium (RPE) were better defined in RG images [Figure 4].

In diabetic retinopathy, RGB imaging provided high-contrast visualization of superficial retinal hemorrhages, ghost vessels and neovascularization, while RPE changes and deep retinal hemorrhages were better visualized in RG images. In neovascular AMD, retinal exudates were better demonstrated with RGB images, while RG images provided enhanced visualization of subretinal fibrosis [Figure 5]

A peek into the future of retinal imaging

To summarize, UWF RGB images were characterized by more realistic color representations of the retina that provided greater contrast for the identification of subtle details. Our findings demonstrate that while the RGB modality can better image the vitreoretinal interface and superficial retinal structures, the UWF RG modality enhances the visibility of deep retinal or chorioretinal structures.

Thus, RG and RGB imaging were found to be complementary diagnostic methods. Clinicians may choose between both modalities according to the retinal layer to be visualized in each patient, which will allow accurate detection and objective

References

monitoring of various vitreous, retinal or choroidal pathologies.

Using the integrated OptosAdvance software of the Optos California device, we were also able to manually adjust the percentage wavelength composition of the obtained images to enhance the visualization of different retinal structures. The real-world clinical utility of UWF RGB imaging and the ideal wavelength percentages for the optimal visualization of different retinal lesions will be interesting areas to explore in future studies.

We also anticipate that the clarity and natural appearance of UWF RGB images will improve image interpretability and reduce the rates of ungradable images in artificial intelligence-based automated detection of retinal diseases. In teleophthalmology, this will enable non-specialist health workers to more accurately identify referable cases, allowing for timelier diagnosis and treatment of potentially blinding diseases for improved patient outcomes.

Contributor

Dr. Paulo Eduardo Stanga is the founder, chief medical officer, and vitreoretinal surgeon at The Retina Clinic London in the UK. He is also a professor of ophthalmology at University College London. Financial disclosure: Dr. Stanga is a consultant to Optos PLC.

p.stanga@theretinacliniclondon.com

Figures Legend

All figures courtesy of Ophthalmic Surgery, Lasers and Imaging Retina – Slack Journals. 7

Fig.1. Retinal detachment and vitreoretinal proliferation clearly visualized with more natural color representation on RGB (red/green/ blue) imaging (A) than on RG (red/ green) imaging (B).

Fig.2. Retinal hole, schitic changes and peripheral lattice degeneration are imaged with greater contrast on RGB imaging (A), while retinal pigmentation is better visualized on RG imaging (B).

Fig.3. Eyes with high myopia showing a more natural color representation of retinal atrophy on RGB imaging (A, C) and enhanced visualization of choroidal vasculature and laser retinopexy scars on RG imaging (B, D).

Fig.4. Age-related macular degeneration (AMD) lesions showed better characterization of drusens on RGB imaging (A, C), while retinal pigment epithelium (RPE) changes and transition between geographic atrophy and healthy RPE were better visualized on RG imaging (B, D).

Fig.5. Retinal exudates in neovascular AMD are more clearly visible on RGB imaging (A), while RG imaging better highlights subretinal fibrosis, visible as well-delineated, greenish bands (B).

1. Choudhry N, Duker JS, Freund KB, et al. Classification and Guidelines for Widefield Imaging. Ophthalmol Retina. 2019;3(10):843-849.

2. Kumar V, Surve A, Kumawat D, et al. Ultra-wide field retinal imaging: A wider clinical perspective. Indian J Ophthalmol. 2021;69(4):824.

3. Stanga PE, Valentín-Bravo FJ, Reinstein UI, Saladino A, Arrigo A, Stanga SEF. The role of ultra-widefield imaging with navigated central and peripheral cross-sectional and threedimensional swept source optical coherence tomography in ophthalmology: Clinical applications. Saudi Journal of Ophthalmology. 2024;38(2):101-111.

4. Silva PS, Horton MB, Clary D, et al. Identification of Diabetic Retinopathy and Ungradable Image Rate with Ultrawide Field Imaging in a National Teleophthalmology Program. Ophthalmology. 2016;123(6):1360-1367.

5. Fantaguzzi F, Servillo A, Sacconi R, Tombolini B, Bandello F, Querques G. Comparison of peripheral extension, acquisition time, and image chromaticity of Optos, Clarus, and EIDON systems. Graefes Arch Clin Exp Ophthalmol. 2023;261(5):1289-1297.

6. Chen A, Dang S, Chung MM, et al. Quantitative Comparison of Fundus Images by 2 Ultra-Widefield Fundus Cameras. Ophthalmol Retina. 2021;5(5):450-457.

7. Stanga PE, Bravo FJV, Reinstein UI, Stanga SFE. New 200° Single-Capture Color Red-Green-Blue Ultra-Widefield Retinal Imaging Technology: First Clinical Experience. Ophthalmic Surg Lasers Imaging Retina. 2023;54(12):714-718.

8. Terasaki H, Sonoda S, Tomita M, Sakamoto T. Recent Advances and Clinical Application of Color Scanning Laser Ophthalmoscope. J Clin Med. 2021;10(4):718.

9. Modern Retina Digital Edition. True-to-life retinal imaging with the new ultrawidefield color RGB modality. Available at https://www.modernretina.com/view/true-to-life-retinalimaging-with-the-new-ultrawidefield-color-rgb-modality. Published on June 23, 2024. Accessed on September 9, 2024.

10. Kernt M, Schaller UC, Stumpf C, et al. Choroidal pigmented lesions imaged by ultra-wide-field scanning laser ophthalmoscopy with two laser wavelengths (Optomap). Clin Ophthalmol. 2010;30(4):829-3611.

11. Moon JY, Wai KM, Patel NS, et al. Visualization of retinal breaks on ultra-widefield fundus imaging using a digital green filter. Graefes Arch Clin Exp Ophthalmol. 2023;261(4):935-940.

Outlook Therapeutics’

Bevacizumab Proves Non-inferior to Ranibizumab in 12-Week Trial

After failing to show non-inferiority to ranibizumab at 8 weeks late last year, ONS-5010’s new 12-week data strengthens the case for its upcoming BLA.

Outlook Therapeutics (New Jersey, United States) has announced the completion of the 12-week safety and efficacy analysis for the NORSE EIGHT clinical trial, the second of two studies evaluating ONS-5010 (bevacizumab gamma) for the treatment of wet age-related macular degeneration (AMD).

According to a news release from the company, the 12-week data has shown non-inferiority in ONS-5010 was non-inferior to ranibizumab at week 12, with changes in central retinal thickness, a measure of anatomical response, comparable in both study arms across all three time points.1

In November 2024, the company announced that ONS-5010 did not demonstrate non-inferior BCVA gains compared to ranibizumab at week 8 in the Phase III NORSE EIGHT trial. However, bestcorrected visual acuity (BCVA) data across all study time points showed consistent improvement in vision over time and indicated the presence of biologic activity.

Dr. Julia A. Haller, ophthalmologistin-chief at Wills Eye Hospital (Philadelphia, Pennsylvania, USA) and member of Outlook Therapeutics’ board of directors, commented on the data.

“The 3-month data from NORSE EIGHT provides additional evidence to confirm what retina specialists expected. The clinical trial continues to demonstrate that ONS-5010 injections result in immediate and sustained anatomic efficacy, with steady gains in visual acuity and reliable, consistent safety.”

On the heels of the 12-week data, the company has restated its plans to submit a Biologics License Application (BLA) for ONS-5010 in the first quarter of 2025.

“We believe that the statistically significant 12-week results for ONS5010 in NORSE EIGHT, combined with the complete NORSE EIGHT data set, confirms our successful NORSE TWO pivotal study and will support the resubmission of our BLA in the United States for the treatment of wet AMD,” said Lawrence Kenyon, chief financial officer and interim chief executive officer of Outlook Therapeutics.

Breaking down the data

In the NORSE EIGHT trial, ONS5010 achieved mean visual acuity improvements of +3.3 letters at week 4, +4.2 letters at week 8 and +5.5 letters at week 12. The mean improvement in the ranibizumab arm was +6.5 letters at week 12. The difference in best-corrected visual acuity (BCVA) between ONS-5010 and ranibizumab was -1.009 letters, with a 95% confidence interval of (-2.865, 0.848).

Based on the statistical parameters set forth in the special protocol assessment (SPA) with the U.S.

Food and Drug Administration (FDA), the trial met the noninferiority margin at week 12 (p=0.0043).

The change in central retinal thickness, an indicator of anatomical response, was comparable in both study arms across all three time points.

ONS-5010 demonstrated a reasonable safety profile throughout the NORSE EIGHT trial, with comparable ocular adverse event rates to ranibizumab. No cases of retinal vasculitis were reported in either study arm. The safety results observed in NORSE EIGHT were consistent with previously reported outcomes from the NORSE ONE, NORSE TWO and NORSE THREE trials.2

What’s next for ONS5010?

The therapy has already received regulatory approval in the European Union and the United Kingdom as LYTENAVA (bevacizumab gamma) and is slated for launch in Europe in the first half of 2025.

On the same day, the company also announced that it has entered into warrant inducement transactions anticipated to raise $20.4 million in gross proceeds to strengthen its cash position ahead of its launch in Europe and prospective FDA approval.

With these results, Outlook Therapeutics is positioning ONS5010 as a potential replacement for off-label repackaged bevacizumab, which hasn’t been approved for retinal diseases in the United States.

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

References

1. Outlook Therapeutics Press Release. Available at: https://ir.outlooktherapeutics.com/news-releases/ news-release-details/outlook-therapeuticsrannounces-complete-twelve-week-efficacy Accessed on January 17, 2025.

2. ONS-5010 Clinical Progress. Available at: https:// outlooktherapeutics.com/lytenava-clinical-progress/ Accessed on January 17, 2025.

Trials and Tech in Eye Care

Experts share groundbreaking insights into the latest research and technologies in the industry

by John Butcher

Delegates at the 24th Congress of the European Society of Retina Specialists Congress (EURETINA 2024) explored the future of ophthalmology, unveiling the latest breakthroughs in gene therapy, drug delivery and treatments for macular degeneration.

During the conference, held recently in Barcelona, Spain, retinal experts discussed the latest innovations in ophthalmology, focusing on macular telangiectasia, age-related macular degeneration (AMD) and inherited retinal diseases.

Presenters highlighted promising research, such as the MacTel Study’s progress in macular telangiectasia treatments, new drug delivery systems for AMD and cutting-edge gene therapies like CRISPR for inherited retinal diseases.

Behind the trials

Dr. Tunde Peto, a professor of clinical ophthalmology at Queen’s University of Belfast (Northern Ireland) discussed the MacTel Study, a collaboration between various institutions examining treatments for macular telangiectasia.

“[This study] taught us so many lessons in approaching a clinical trial for something we knew very little about,” she shared.

According to Prof. Peto, MacTel is a bilateral condition that leads to vision loss, affects both genders, is typically diagnosed after the fourth decade

and shows subtle early signs and symptoms. This rare disease is more common than previously thought.

The MacTel Study, which began in mid-2004, is a major global project with multiple components, including a natural history study, a genetics study, laboratory science, a donor eye program and clinical trials, she said.

Among the key lessons learned from the study, she added, was that reaching the clinical trial stage requires both deciding on a trial endpoint and having something you can measure. These elements are important for running a trial that is efficient, fast and safe.

“If you have something measurable

going into a clinical trial and you can track how quickly that changes, then you’ll be able to establish how much of that change can potentially be influenced by a drug, as well as establish the normal level of change. Once you have this information, you can start thinking about your sample size, the duration of the study and the requirements for the trial,” explained Prof. Peto.

What’s next in sight for nAMD?

Dr. Nicole Eter, a professor of ophthalmology and chair of the department of ophthalmology at the University of Muenster (Germany), discussed new therapies for the treatment of age-related macular degeneration.

“I think we have already come a long way in the treatment of neovascular AMD (nAMD), and right now, we have a variety of anti-VEGF treatment options,” Dr. Eter said, presenting a slide that highlighted milestones in nAMD treatment.

She then ran through a variety of those treatments, as well as those currently under clinical investigation, before discussing the potential future breakthroughs in the field of ophthalmology.

According to Dr. Eter, there are four ways nAMD treatment could progress. These include improvements in current anti-VEGF therapy, long-acting port delivery systems, tyrosine kinase inhibitors and gene therapy. In all areas, she added, there are studies and trials currently underway that show promising results.

“There are various approaches to drug therapy for neovascular AMD and geographic atrophy, including long-acting devices and multi-target developments. And we will hear a lot more about these in the coming years,” she said.

A new hope for AMD treatment

Dr. Timothy Jackson, a consultant ophthalmic surgeon and professor of retinal research at King’s College London (United Kingdom), talked about the role of VEGF-C and VEGF-D inhibition in the treatment of age-

related macular degeneration.

According to Dr. Jackson, almost half of patients don’t achieve significant gains, around 60% experience persistent fluid and 25% will suffer further vision loss over the first 12 months.

“We need to do better,” he told the audience, before posing the question: Why might VEGF-C and VEGF-D be potential new targets?

“We are learning more and more about VEGF-C, but it is already well established that it stimulates retinal angiogenesis,” he said. “It is also known to increase vascular leakage and permeability, and there are elevated levels of VEGF-C and its receptors, VEGFR-2 and VEGFR-3, in nAMD clinical specimens. So, it certainly looks like a viable culprit,” he continued.

Several companies are paying attention to this and developing treatments accordingly, he added. He then highlighted sozinibercept (OPT302; Opthea, South Yarra, Australia) combination therapy as the most advanced in terms of clinical testing.

Next, he talked about the results of a Phase IIB trial for sozinibercept, which he described as “particularly promising in terms of the result.”

Conducted at 109 sites across 10 countries, the trial found that a higher dose of the drug showed subretinal fluid reduction, fewer intraretinal fluid cysts and a shrinkage of the mean lesion area.

There were “structural and functional benefits” at a two-milligram dose, he said, with no obvious safety signals.

Dr. Jackson noted that the next step for the drug is a Phase III trial involving almost 2,000 patients, which has recently completed recruitment.

“Several treatments are being developed to target VEGF-C and give a broader inhibition to the VEGF family,” he said. “It’s going to be an exciting time to see these trials as they emerge.”

The future of gene therapy

Dr. Robert Maclaren, a professor

of ophthalmology at the University of Oxford (United Kingdom) and honorary consultant vitreoretinal surgeon at Oxford University Hospitals NHS Foundation Trust, presented the latest developments in gene therapy for inherited retinal disease.

He predicted three changes ahead, including robust anatomical endpoints using advanced imaging, improved subretinal surgical delivery using robotic systems and increased gene therapy options with clustered regularly interspaced short palindromic repeats (CRISPR) gene editing. “[The latter] was the way forward for most inherited retinal diseases in the future,” he said.

Dr. Maclaren showed slides demonstrating the effectiveness of gene therapy in reversing degenerating peripheral vision, resulting in “dramatic improvement.” He followed his presentation with a demonstration of a robotic system advancing a needle into the subretinal space of a patient’s eye.

“You can see the injection is incredibly slow and controlled. The retina is detaching very slowly. And this controlled manner means there is very limited, if any, retinal stretch, allowing us to deliver the sub-retinal gene therapy vector safely and efficaciously,” Dr. Maclaren shared.

Subretinal injections are difficult, he added, but robotic systems provide a potential solution to this challenge.

He then proceeded to describe CRISPR, a bacterial vaccination, which he said was “very exciting technology.”

“CRISPR is a system that exists in bacteria to protect themselves against bacterial viruses known as bacterial phages. A phage would infect a bacterium, and if the bacterium survives, it will make a copy of the phage DNA and store it within a library within its genome,” he explained.

“Within this library, we also have genes that are able to read these unique bacteria phage sequences called CRISPR-associated genes,” he added. This provides a “very primitive but nevertheless very effective immune system against the bacterial

viruses,” Dr. Maclaren continued.

Harnessing this gene editing power, he concluded, provides the opportunity not just to replace a missing gene but also to deliver the CRISPR system itself—with the ability to protect against disease.

Port delivery system for nAMD and DME

Dr. Patricia Udaondo, co-founding director and head of the Retina Division of Aiken Ophthalmological Clinic and a professor at University and Polytechnic Hospital La Fe (Spain), introduced the port delivery system for the treatment of nAMD and DME—which she said had advantages over monthly injections.

The port delivery system works by passive diffusion of anti-VEGF therapy inside the eye, maintaining a continuous dose of treatment, Dr. Udaondo explained. While monthly injections of anti-VEGF have shown “fantastic results” they also lead to fluctuating drug levels, she added.

“With this new approach, we can use the benefit of a treatment that works in patients, but without this reduced concentration in the eye. By maintaining a continuous level of VEGF suppression, we could better control the disease,” she said.

Dr. Udaondo also noted that trials showed patients had high levels of satisfaction with the treatment delivered via the port delivery system, with the majority preferring to switch to it over monthly injections.

Addressing the issue with the septum inside the device dislocating, she explained that this had been resolved through updates to both the implant and the refill needle.

Editor’s Note

Reporting for this story took place at the 24th Congress of the European Society of Retina Specialists (EURETINA 2024), held from September 19 to 22 in Barcelona, Spain.

Glimmers of Hope

Next-gen pediatric retina care promises to deliver solutions once deemed out of reach

by Diana Truong

Relentless innovation, global collaboration and dedicated specialists are driving a promising future for pediatric retina care, bringing solutions once thought impossible within reach. However, ensuring equitable access and bridging the gap between innovation and implementation remain crucial for realizing this potential for every child.

The parents of a three-monthold baby girl had all but given up hope for her left eye. Born with a condition called persistent fetal vasculature (PFV), the vessels within her eye, which typically vanish at birth, remained stubbornly intact, forming a dense white membrane that obscured her vision. To complicate matters, her eye was unusually small, leading even seasoned ophthalmologists to deem it unsalvageable.

In a last-ditch effort, the child’s parents sought help from Prof. Wai-Ching Lam, a pediatric retina specialist from Canada. While hope for the child’s eye was dim, Prof. Lam saw a glimmer of possibility, thanks to recent technological advancements.

“Ultrasound biomicroscopy (UBM) allows us to scan the anterior part of the eye, including the iris and immediately behind it,” Prof. Lam explained. “This is critical in cases like this one because the retina can sometimes develop in aberrant positions. When we go in to clean it

up, we might inadvertently create a retinal tear leading to retinal detachment.”

With careful planning and the precision afforded by proper assessment, Prof. Lam was able to identify the areas at risk and successfully remove the obstructive membrane.

“Now, the child is patched and fitted with a contact lens to get some vision in that eye,” he shared. While the restored sight isn’t perfect, it’s functional—providing the small patient with a future her parents never thought possible. “Otherwise, the eye would have been lost, and maybe it would end up having to be removed,” Prof. Lam said.

This case highlights the intricate balance between innovation and expertise in pediatric retina care—a field fraught with unique challenges. For patients like this baby, early and accurate diagnosis is critical, yet it remains one of the most formidable hurdles in managing pediatric retinal conditions.

Diagnosis in a blink

Diagnosing retinal conditions in young children can feel like grueling detective work, especially with squirming little ones. But thanks to advancements in wide-field imaging technology, things have become a bit easier. Clinicians can now capture high-quality retinal images in just a quarter of a second—faster than the blink of an eye.

This leap in technology has also opened doors to early detection.

of a child’s retina can be uploaded to the cloud, where the AI system swiftly analyzes them and provides an almost instant assessment.

“AI nails down the diagnosis, and the patient can be referred in a timely fashion with less delays,” noted Prof. Lam. Parents, too, benefit as they no longer endure prolonged periods of uncertainty.

In resource-limited settings, these advancements are particularly transformative. Telemedicine platforms combined with portable fundus cameras enable technicians in rural areas to photograph a baby’s retina and send the images to experts miles away. “They allow us to document changes and share information much more efficiently,” Prof. Lam said. “Before, we had to rely on hand-drawn illustrations, which were quite inaccurate a lot of times.”

Swift and accurate diagnosis lays the groundwork for timely intervention, a critical factor in preventing vision loss in young patients. Early detection means clinicians can choose from an expanding array of treatment options, tailoring care to the child’s unique needs and the specific condition.

From gold standard to game changers

“Retinal screening for neonates can pick up serious conditions like tumors or optic nerve defects that were difficult to pick up before.”

“Retinal screening for neonates can pick up serious conditions like tumors or optic nerve defects that were difficult to pick up before,” Prof. Lam explained.

Artificial intelligence (AI) is now revolutionizing this process further, adding speed and precision to neonatal screening. By integrating AI into diagnostic workflows, images

Treating retinal conditions in children is a delicate dance between established techniques and groundbreaking innovations. Today’s clinicians have an expanding arsenal, from tried-and-true therapies like laser photocoagulation for retinopathy of prematurity (ROP) to emerging therapies that push the boundaries of possibility.

Laser photocoagulation, which ablates the peripheral avascular retina, remains the gold standard for managing ROP, halting abnormal blood vessel growth, and preserving vision in preterm infants. However, “children can get quite stressed with

lasers and they can go into cardiac arrest,” said Prof. Lam. “About 15 years ago, people started using the anti-vascular endothelial growth factor (anti-VEGF) injections as an alternative treatment to retinopathy and found very successful management.”1

Anti-VEGF drugs like ranibizumab (Lucentis®; Genentech; California, USA) have demonstrated effectiveness in managing aggressive ROP and other vascular conditions. It is less invasive than laser treatment and spares more peripheral retina, which is crucial for a child’s developing vision.

That said, these treatments come with challenges, such as the potential for systemic absorption, which could impact overall development in children. As a result, careful monitoring of patients after treatment is essential to ensure safety and efficacy.1

Surgical interventions for retinal detachment in children have also evolved, driven by innovations in tools and techniques. Pediatric eyes, with their smaller size and developing structures, present unique challenges that traditional instruments cannot address.

“Imagine using the large-sized instruments designed for adults on very small eyes. Your treatment and your efficiency are limited.” Prof. Lam explained. Instruments like 27-gauge vitrectomy tools, compared to traditional 20-gauge ones, allow for precise maneuvers in the smallest of eyes, reducing trauma during surgery and enabling safer, more effective outcomes.2

For complex cases, such as retinal detachment involving proliferative vitreoretinopathy (PVR), surgeons can now employ advanced techniques like scleral buckling combined with pars plana vitrectomy (PPV). These procedures are more refined and tailored to pediatric anatomy, improving the success rates of retinal reattachment in children.3

Beyond surgical and pharmacologic solutions, gene therapy is transforming the landscape of

pediatric retina care. This cuttingedge treatment offers the potential for curing inherited retinal diseases (IRDs), not just managing them.

“Until five years ago, there wasn’t any treatment for those individuals,” Prof. Lam noted. “Now we can actually replace defective genes and even reverse damage.”

Luxturna® (voretigene neparvovec; Spark Therapeutics, Inc., Pennsylvania, USA), the first FDAapproved gene therapy for retinal conditions, targets RP65 mutations associated with Leber congenital amaurosis (LCA). According to Prof. Lam, its approval has opened a floodgate, propagating therapies for other IRDs.

Innovations that inspire

What made Luxturna so revolutionary wasn’t just its ability to treat LCA, but the innovative use of adenoassociated virus (AAV) as a delivery system. AAV, known for its ability to infect retinal cells with minimal immune response, opened the door to a wave of new therapies targeting a wider array of genetic retinal conditions.4

AAV vectors are now being explored in clinical trials for a variety of pediatric retinal diseases, such as Stargardt disease and X-linked retinoschisis. Researchers have discovered that AAV2 can effectively reach the inner retina, while AAV8 has shown promise in transducing photoreceptors when delivered subretinally. This ability to target specific retinal cells makes AAV an ideal vehicle for gene therapy, particularly for conditions like retinitis pigmentosa (RP), achromatopsia, and choroideremia.4

One promising development is botaretigene sparoparvovec (botavec; Janssen Pharmaceuticals; Beerse, Belgium), an investigational gene therapy designed to tackle X-linked RP. This treatment delivers functional copies of the RPGR gene to the retina, aiming to restore a stable gene sequence in both rod and cone photoreceptors.5

Recognizing botaretigene sparoparvovec’s transformative potential, regulatory bodies have granted the therapy prestigious

designations, including Fast Track and Orphan Drug status from the US Food and Drug Administration (FDA), as well as Advanced Therapy Medicinal Product and Orphan designations by the European Medicines Agency (EMA). Botaretigene sparoparvovec is currently being evaluated in the Phase 3 LUMEOS trial.

In addition to AAV gene therapies, other cutting-edge technologies like clustered regularly interspaced short palindromic repeats (CRISPR) are being explored to repair defective genes directly within the retina. This gene-editing approach has the potential to fix the root cause of genetic retinal diseases at the DNA level.6

Meanwhile, another area of advancement involves gene therapies designed to deliver anti-VEGF treatments. Instead of repeated injections, a single gene therapy like 4D-150 (4D Molecular Therapeutics; California, USA) could enable the eye to produce its own therapeutic agents, effectively transforming it into a self-sustaining ‘drug factory.’7

In other antiVEGF news, novel agents and delivery methods aim to enhance both efficacy and safety. Longacting anti-VEGF formulations like Eylea® HD (Regeneron Pharmaceuticals; New York, USA) and sustainedrelease implants are in development to reduce the frequency of treatments, a critical advancement for pediatric patients where frequent injections pose risks.

therapies in conditions like RP and Stargardt disease. Although largely experimental, early results suggest that stem cells could not only halt disease progression but potentially reverse damage in certain cases.9,10

Retinal implants, sometimes referred to as ‘bionic eyes,’ are offering a glimpse into a future where even severe vision loss can be partially restored. These devices, such as the Argus II (Second Sight Medical Products; California, USA) retinal prosthesis system, work by translating visual information into electrical signals that stimulate the remaining retinal cells.

While current implants are limited to providing basic visual functions, like distinguishing light and dark or detecting motion, advancements in microelectronics and bioengineering aim to deliver more detailed visual experiences in the coming years.11

The fight for equity

As science pushes the boundaries of possibility, novel therapies are becoming more accessible, sparking hope in families worldwide. But an unsettling question lingers: Are they truly reaching all children who need them?

“Retinopathy of prematurity is probably one of the more common eye conditions affecting children, particularly causing preventable blindness.”

For all the groundbreaking progress, the uneven patchwork of global healthcare infrastructure often leaves those in resource-limited settings waiting in the shadows, unable to access these life-changing treatments.

Stem cell therapies are another beacon of hope, aiming to regenerate damaged or degenerated retinal tissue. Induced pluripotent stem cells (iPSCs) and retinal progenitor cells are being explored for their ability to replace lost photoreceptors or support retinal health by restoring retinal pigment epithelial (RPE) cells.8

Clinical trials are underway to test the safety and efficacy of these

This inequity is starkly evident in the burden of pediatric retinal conditions in developing countries. Here, ROP, trauma-induced retinal damage and untreated congenital disorders cast long shadows over the futures of countless children. These challenges are not merely medical—they are stories of interrupted potential and deferred dreams, underscoring the urgency of delivering solutions to the places where they’re needed most.

“Retinopathy of prematurity is probably one of the more common eye conditions affecting children, particularly causing preventable blindness,” said Prof. Lam. He explained how improving healthcare in low- and middle-income countries has led to what is known as the ‘third epidemic of ROP.’

“These countries were able to keep more premature babies alive, but they didn’t have experience managing this condition before, as they previously didn’t have children surviving,” Prof. Lam noted.

International collaborations are pivotal in addressing these challenges. Organizations like FOCUS Inc. (Illinois, USA) provide training programs and fellowships to empower local specialists. However, sustaining these efforts requires more than just education. Equipment, infrastructure and ongoing support are crucial to creating long-term impact.

Bridging the gap between innovation and implementation

The future of pediatric retina care is one of promise and perseverance—a journey fueled by relentless innovation, global collaboration and the unwavering commitment of specialists like Prof. Lam. Each breakthrough, whether in advanced imaging, portable diagnostic tools, or gene therapy, edges us closer to a world where no child’s sight is written off as a lost cause.

“In a country where the GDP is low, the question is: How can resources be adequately distributed? Even for well-funded countries, keeping up with the cost of new equipment and advancements is a challenge.”

But the road ahead demands more than scientific triumphs. It calls for equitable access, creative solutions in resource-limited settings and a collective effort to bridge the chasm between innovation and implementation.

The stakes are high, but so is the reward: A child’s ability to see the world, and with it, the limitless possibilities that vision brings.

Contributor

Prof. Wai-Ching Lam is the head and medical director of the Ophthalmology Department of Vancouver General Hospital and the University of British Columbia Hospital. Between 2016 and 2022, he was the clinical professor and Albert Bing-Ching Young Professor of Ophthalmology at the University of Hong Kong, and the chief of service of Ophthalmology at HKU-Shenzhen Hospital and Queen Mary/Grantham Hospital, Hong Kong. Prof. Lam has held various leadership positions at the University of Toronto from 1996 to 2016. He is currently a board member of the Canadian Retina Society, previously a council member of the Asia-Pacific Vitreoretina Society, and an editorial board member of the Asia-Pacific Journal of Ophthalmology. A vitreoretinal surgeon of adult and pediatric retinal diseases, Prof. Lam has published over 110 peer-reviewed articles and authored seven book chapters. His clinical and scientific work has been recognized with the Achievement Award by the American Academy of Ophthalmology, Asia-Pacific Academy of Ophthalmology, and Fellow of the American Society of Retina Specialists.

dr.waiching.lam@gmail.com

“Training somebody is one thing. Supporting them and providing them with the necessary equipment is another,” Prof. Lam highlighted. “In a country where the GDP is low, the question is: How can resources be adequately distributed? Even for well-funded countries, keeping up with the cost of new equipment and advancements is a challenge.”

The global community must also grapple with the broader implications of emerging treatments like gene therapy. “Luxturna, for instance, costs about one million [USD] per dose,” said Prof. Lam. While its potential is transformative, he acknowledged the risk of creating greater inequities. “The excitement of gene therapy is there, but I worry that it will create a greater separation between the haves and have-nots,” he cautioned.

References

1. Wu KY, Wang XC, Anderson M, et al. Innovative use of nanomaterials in treating retinopathy of prematurity. Pharmaceuticals. 2024:17(10);1377.

2. Khan MA, Kuley A, Riemann CD, et al. Long-term visual outcomes and safety profile of 27-gauge pars plana vitrectomy for posterior segment disease. Ophthalmology. 2018;125(3):423-431.

3. Topcu H, Erdogan G, Alagoz C, et al. The effect of combining scleral buckle surgery with pars plana vitrectomy for treatment of recurrent retinal detachment secondary to proliferative vitreoretinopathy. Beyoglu Eye J. 2023;8(2):91-96.

4. Ghoraba HH, Akhavanrezayat A, Karaca I, et al. Ocular gene therapy: A literature review with special focus on immune and inflammatory responses. Clin Ophthalmol. 2022;16:1753-1771.

5. Sladen PE, Naeem A, Adefila-Ideozu T, et al. AAV-RPGR gene therapy rescues opsin mislocalisation in a human retinal organoid model of RPGR-associated X-linked retinities pigmentosa. Int J Mol Sci. 2024;25(3):1839.

6. Abdelnour SA, Xie L, Hassanin AA, et al. The potential of CRISPR/Cas9 gene editing as a treatment strategy for inherited diseases. Front Cell Dev Biol. 2021;9:699597.

7. She K, Su J, Wang Q, et al. Delivery of nVEGFi using AAV8 for the treatment of neovascular age-related macular degeneration. Mol Ther Methods Clin Dev. 2022;24:210-221.

8. Radu M, Brănișteanu DC, Pirvulescu RA, et al. Exploring stem-cell-based therapies for retinal regeneration. Life (Basel). 2024;14(6):668.

9. Park SS, Bauer G, Fury B, et al. Phase I study of intravitreal injection of autologous CD34+ stem cells from bone marrow in eyes with vision loss from retinitis pigmentosa. Ophthalmol Sci. 2024;5(1):100589.

10. Moghadam Fard A, Mirshahi R, Naseripour M, et al. Stem cell therapy in Stargardt disease: A systematic review. J Ophthalmic Vis Res. 2023;18(3):318-327.

11. Chuang AT, Margo CE, Greenberg PB. Retinal implants: A systematic review. Br J Ophthalmol. 2014;98(7):852856.

Empowering Women, Revolutionizing Retina

Retinal expert Dr. Jennifer Lim on inclusivity, work-life balance, and the pursuit of excellence in a demanding field

by Tan Sher Lynn

Dr. Jennifer Lim, a trailblazer in retinal care, combines her passion for medical innovation with a dedication to advancing diversity in ophthalmology. Through her groundbreaking work and advocacy for women in leadership, she aims to shape a more inclusive and dynamic future for both the field and the profession.

Dr. Jennifer Lim’s fascination with retinal care was sparked by the unique connection between systemic diseases and their manifestations in the retina.

“Medically, I was captivated by the fact that systemic disease had retinal manifestations. Surgically, I was drawn to the intensity and complexity of retinal surgery, particularly the non-elective nature of most retinal surgeries,” shared Dr. Lim, the director of Retina Service at the University of Illinois Chicago (UIC). This dual appeal of intellectual challenge and urgent, impactful surgery laid the foundation for her remarkable career.

Fostering work-life balance

As a woman advancing in ophthalmology, Dr. Lim encountered a lack of female role models in her field. Balancing her professional aspirations with family responsibilities presented additional challenges to her career journey.

“I sought to emulate both women and men who exemplified characteristics that I admired,” Dr. Lim said. “I asked them for advice, joined WIO (Women in Ophthalmology), and co-founded Women in Retina. I sought advice about family and work balance from WIO members.”

She also developed a strong sense of discipline—staying focused and using her time wisely. “For example, I would play, read or do homework with my child when she was awake, and then I would dedicate time to computer work after she was asleep,” she shared. “I complete all patient-related charts and phone calls at work. I am highly focused during my clinic and OR days, and I make sure to teach my trainees and provide them with immediate feedback.”

Dr. Lim even uses her one-hour commute to listen to audiobooks or catch up on phone calls. “At home, I prioritize self-care and family time, making sure to have dinner with my family every night unless I have a work meeting,” she continued.

When her daughter was younger, Dr. Lim made quality time with her a priority. She dedicated the hours until bedtime to her daughter, and reserved work for after-hours. Even now, family connections remain central to her routine. “We have a daily FaceTime call with our daughter at 9 pm,” she said.

She also limited professional travel, particularly international trips, unless her family could join her. “I try to adhere to my goal of not having more than one work-related trip per month, and I do not travel during the holidays,” she stressed.

Dr. Lim credited her success in part to her mentors Dr. Mort Goldberg and Dr. Julia Haller. Dr. Goldberg’s mantra, “Prior proper preparation prevents poor performance,” became Dr. Lim’s guiding principle.

Meanwhile, she learned from Dr. Haller the importance of confident, efficient and poised leadership. “I also aim to be outspoken, efficient and yet kind and caring,” Dr. Lim enthused.

Optimistic about the future of retina care

As for the groundbreaking advancements in retina, Dr. Lim is particularly excited about artificial intelligence (AI), gene therapy and cell-based therapies.

“AI has the potential to revolutionize patient care,” noted Dr. Lim. “Currently, AI can assist in diabetic retinopathy screening—we were involved in the pivotal clinical trial that led to FDA approval for one of these AI systems. In collaboration with the outstanding UIC Engineering Department, we are developing algorithms to use AI for classifying disease severity and aiding treatment decisions,” she shared.

Dr. Lim envisions a future where home-based imaging systems and personalized medicine would enable patients to present for treatment only when necessary.

“Home imaging devices, such as home-based optical coherence tomography (OCT), could transform patient management by enabling personalized medicine,” she said. “This would allow patients to seek treatment as needed, rather than undergoing routine monitoring, particularly for intravitreal injections in cases of diabetic macular edema (DME) and neovascular age-related macular degeneration (AMD).”

Gene therapy, she added, will offer cures for hereditary retinal diseases and enhance treatment durability for conditions like neovascular AMD and diabetic macular edema (DME).

“Moreover, drugs with novel mechanisms of action will assist us in achieving enhanced efficacy and durability in treating retinal conditions, such as neovascular

AMD. And cell-based therapies, designed to replace lost factors or damaged cells, will restore or prevent loss of function,” Dr. Lim explained.

An advocate for diversity and inclusivity in ophthalmology

As the vice chair for Diversity and Inclusion at UIC, Dr. Lim is dedicated to fostering an equitable and inclusive environment, advocating for diverse representation in ophthalmology.

The increasing representation of women in leadership roles within ophthalmology reflects a positive shift towards greater diversity and inclusion— something Dr. Lim is proud of.

“Throughout my career, I have witnessed more women be elected or appointed to leadership roles in retina societies, departments of ophthalmology, and other professional organizations,” she shared.

With that said, Dr. Lim also emphasized the critical role men play in this progress, alongside the collective effort of women striving for equity. “Women need to continue to strive for these positions, which they will achieve by their hard work and support of each other. There needs to be continued awareness of the importance of diversity and inclusion,” she added.

She also encourages aspiring female ophthalmologists to pursue their goals with determination. “Go for it and aim high! Your drive and passion will carry you forward. Lean on your ‘sisters’ in the field and reach out—those who have gone before you want to help you succeed. I love it and would do it over again,” she enthused.

Looking ahead, Dr. Lim sees a future where the ophthalmology profession is more diverse and inclusive, ultimately benefiting patients and practitioners alike. “In the future, I hope that our field will reflect the diversity of the general population. Patients would see doctors who look like them, increasing trust and compliance,” she concluded.

The transformative power of passion and dedication

Dr. Lim’s journey is a testament to passion, discipline and resilience. She has forged a path that balances a rewarding career with personal commitments—all while driving innovation and championing equality in medicine.

By highlighting the transformative power of dedication and a clear vision for the future of retinal care, Dr. Lim inspires both women and men to strive for excellence in the field of retina.

Contributor

Dr. Jennifer I. Lim holds the Marion H. Schenk Chair in Ophthalmology at the University of Illinois Chicago, where she is a distinguished professor, vice chair for Diversity and Inclusion, and director of Retina Service. She earned her MD with Distinction from Northwestern University (AOA) and completed her residency at UIC, followed by retina fellowships at the Wilmer Eye Institute, Johns Hopkins. She holds various leadership positions, including president of The Retina Society, associate editor for JAMA Ophthalmology, deputy editor-inchief for EyeWiki , UIC councilor for AOA, and co-founder of Women in Retina. Dr. Lim leads in clinical and translational research and holds an R01 grant. She has received numerous awards and authored over 380 publications and 30 book chapters and books, including AgeRelated Macular Degeneration (Third Edition) and Case Studies in Medical Retina: A Diagnostic Approach (2024)

jennylim@uic.edu

Bridging Perspectives in Eye Care

The Philippine Glaucoma Society’s debut at EVRS 2024 showcases the synergy between glaucoma and retina

by Diana Truong

Last year, the grand halls of the Budapest Congress Center hosted a momentous convergence of culture and expertise, as the 21st European VitreoRetinal Society Meeting (EVRS 2024) welcomed a groundbreaking new inclusion—the Philippine Glaucoma Society (PGS).

For the first time in its history, the annual EVRS meeting featured a dedicated session on glaucoma led by a dynamic team from the Philippines, the Philippine Glaucoma Society. These milestones not only marked the society’s debut but also emphasized the critical intersection of glaucoma and retina specialties in modern ophthalmology.

Pride and excitement were palpable among the PGS delegation. “We’re very proud to be the first glaucoma society and the first Filipino society presenting in a retina meeting. It’s just so exciting,” reflected Dr. Catherine Nasol, who delivered a lecture on combined pars plana vitrectomy and glaucoma drainage device insertion during the PGS session.

Adding to the significance, the event celebrated the appointment of Dr. Perfecto E. O. R. Cagampang III as the first Filipino EVRS Ambassador. In this pivotal role, Dr. Cagampang bridged Filipino expertise with the international ophthalmology community, ensuring that glaucoma’s often-overlooked relationship with retinal diseases received the spotlight it deserves.

“We’re very proud to be the first glaucoma society and the first Filipino society presenting in a retina meeting. It’s just so exciting.”

- Dr. Catherine Nasol

PGS President Dr. Maria Margarita Lat-Luna expressed heartfelt gratitude. “On behalf of the Philippine Glaucoma Society, we extend our deepest appreciation to Dr. Perfecto E. O. R. Cagampang III—it was you who turned the key to open the door for the Philippine Glaucoma Society,” she said.

The interconnected worlds of glaucoma and retina

The synergy between glaucoma and retina care is undeniable. These two areas are deeply interconnected, both structurally and functionally, with complications in one often triggering issues in the other.

Dr. Cesar Perez, Jr., who presented on the incidence of ocular hypertension following pars plana vitrectomy with silicone oil injection, highlighted this relationship. “The optic nerve lies beside the retina, and so certain glaucoma conditions are better controlled by relieving the retina conditions of patients. Bridging glaucoma and retina gives the best care to our patients,” he shared.

Advancements like anti-fibrotic agents for glaucoma have inadvertently increased the incidence of vitreoretinal complications, creating the need for shared expertise.

“About a third of patients undergoing retina procedures develop glaucoma,” explained Dr. Cynthia Verzosa, who

discussed the use of anti-VEGF in managing neovascular glaucoma secondary to diabetic retinopathy. “It’s a good idea to share what we do with retina patients who eventually end up in our clinic. It’s also a good way to inform everyone that they need to be monitoring eye pressure, too.”1

Shared expertise for better outcomes

The collaboration between retina and glaucoma specialists is vital for ensuring comprehensive care.

For retina specialists encountering intraocular pressure spikes following retinal procedures such as pars plana vitrectomy or intravitreal injections, Dr. Verzosa shared practical advice. “In general, you can start giving medications that are easily accessible to ophthalmologists… eye drops or tablets. You can also do some initial laser treatment. And when all else fails, call your favorite glaucoma specialist to help you out.”1

Dr. Nasol added a personal perspective, noting how her marriage to a retina specialist has enhanced her work. “It’s very convenient for me to be married to a retina specialist because we have a lot of glaucoma procedures that need retina consults. He’s just a call away all the time,” she shared.

Opening doors to global collaborations

The PGS’s presence at EVRS has paved the way for promising collaborations, setting a precedent

for other subspecialties in Philippine ophthalmology to gain international recognition.

“We aim to set up and strengthen new networks,” noted Dr. Lat-Luna. “We are usually confined to our colleagues in the United States and counterparts in Asia, but this experience with EVRS is a giant leap for us. It has opened a lot of opportunities not just for the Philippine ophthalmology system but for the Philippine Academy of Ophthalmology as well.”

Honoring the legacy of Dr. José Rizal

It’s impossible to discuss Filipino ophthalmology without evoking the name of Dr. José Rizal, the national hero whose multifaceted life continues to inspire.

Born in 1861, Dr. Rizal was a polymath and political activist, best known for his writings that fueled the Philippine revolution and led to his execution in 1896. Yet, fewer may know that Dr. Rizal was also an accomplished ophthalmologist, driven by a deeply personal mission: To restore his mother’s failing eyesight.2

At a time when ophthalmology was emerging as a distinct specialty, Dr. Rizal pursued rigorous training in Europe. He began under the renowned French ophthalmologist Louis de Wecker, whose innovative techniques in cataract and glaucoma surgeries influenced Dr. Rizal’s budding career.

Later, he continued his studies under Otto Becker at the University

of Heidelberg, gaining advanced knowledge that solidified his expertise. Along his journey, he met scientific luminaries like Ernst Fuchs and Rudolph Virchow, encounters that further honed his skills and reputation.2

Dr. Rizal’s dedication bore fruit when he successfully performed cataract surgeries on his mother, first in Hong Kong and later in Dapitan in the Philippines, where he was exiled. His work was nothing short of transformative, drawing patients from far and wide and earning him a reputation as a “miracle worker” who could restore sight.2

Today, Dr. Rizal’s legacy as a healer and visionary endures, embodied in modern milestones like the Philippine Glaucoma Society’s debut at EVRS 2024. This moment was more than a showcase; it was a tribute to Dr. Rizal’s ideals—a fusion of global knowledge and local expertise aimed at progressive medicine.

From Dr. Rizal’s pioneering days to the PGS’s strides on the global stage, the Philippines continues to bridge gaps and build meaningful connections in the world of ophthalmology, shining brightly as a beacon of innovation and dedication.

References

1. Sahoo NK, Balijepalli P, Singh SR, et al. Retina and glaucoma: Surgical complications. Int J Retin Vitr. 2018;4:29.

2. Ravin TB. Jose Rizal: Philippine national hero and ophthalmologist. Arch Ophthalmol. 2001;119(2):280-284.

Editor’s Note

Reporting for this story took place at the 21st European VitreoRetinal Society Meeting (EVRS 2024), held from November 14 to 17 in Budapest, Hungary. Dr. Perfecto E. O. R. Cagampang III contributed to this story.

Innovation Meets Vision

From mini-telescope implants to breakthroughs in biosimilars, ophthalmologists

at EURETINA 2024 showcase cutting-edge

retinal treatments

by John Butcher

The recently concluded 24th Congress of the European Society of Retina Specialists (EURETINA 2024) highlighted several key innovations in the field of retinal care—offering new hope for patients with conditions like age-related macular degeneration (AMD) and proliferative diabetic retinopathy (PDR).

Presentations included cuttingedge treatments such as the minitelescope IOL SING for geographic atrophy (GA), large inferior retinotomy techniques for retinal redetachment and the efficacy of FYB201 biosimilar ranibizumab. Experts also discussed the role of GLP-1 receptor agonists in reducing the risk of AMD and innovative approaches to restoring vision in dry AMD patients.

Changing lives, one eye at a time

Prof. Nicole Eter, a professor of ophthalmology and chair of the

department of ophthalmology at the University of Muenster (Germany), started the session with a presentation on the minitelescope IOL SING from Samsara Vision (Editor’s Note: SING IMT received a CE mark for the European Union in 2020 and is not currently FDA approved) for patients with geographic atrophy. She described the device as a “smaller incision new generation implantable miniature telescope” with a magnification of 2.7.

The only Galilean telescope designed to improve visual acuity and quality of life, it features ultra-precision wide-angle micro-optics designed to create a magnifying telephoto effect to reduce the impact of the scotoma associated with AMD.

The device works as a preloaded system surgically placed into the eye, which projects images onto the retina. “It is only implanted into one eye, which is then used for detailed tasks like reading, while the other

eye is used for peripheral vision,” she said.

Improving outcomes for retinal detachments

Dr. Andre Marcelo Gomes, director and president of the Lens Ophthalmology Group (Brazil), spoke about large inferior retinotomies for proliferative vitreoretinopathy (PVR) in silicone oil-filled eyes.

According to Dr. Gomes, recent advances in vitreoretinal surgery tools and visualization systems offer an opportunity to improve surgery outcomes. He presented a singlecenter, retrospective, interventional case series analysis of 18 patients with retinal detachment due to PVR, which developed inferiorly after a primary pars plana vitrectomy (PPV) and silicone oil implantation for a previous retinal detachment.

He noted that all patients involved in the study underwent secondary surgery with large inferior retinotomy and silicone oil re-implantation, with subsequent analysis of anatomical success, functional improvement and post-op complications.

Using slides to demonstrate the results, he said the retina was re-attached in close to 90% of the eyes, with only two eyes remaining detached after six months.

The anatomical success rate was almost 90% (16 of 18 patients), although some complications did occur—including hypotony in one case, optic disk atrophy in two cases, epiretinal membrane in two cases and cystoid macular edema in three cases.

In conclusion, he said PPV with large inferior retinotomy and silicone oil tamponade may result in a significant anatomical and functional success rate for retinal re-detachment with inferior PVR cases by relaxing the shortened retina.

Understanding biosimilars

Dr. Ashish Sharma, a consultant at the Lotus Eye Hospital and Institute (India), presented on FYB-201 biosimilar ranibizumab’s efficacy and safety in clinical settings.

“Our group, the International Retina Biosimilar Study Group, has been

working to understand biosimilars and their various aspects, including real-world data, perception and differences in trial designs,” he said.

The group carried out a retrospective, interventional, uncontrolled, multi-center study to understand early experiences surrounding ranibizumab biosimilar (FYB 201) from data collected at five centers—across the United Kingdom, Spain and the United States.

The primary outcome measure used was visual results after ranibizumab biosimilar FYB 201 injections at the end of the last follow-up, with the secondary outcome measure being adverse events after ranibizumab biosimilar FYB 201 injections (to check whether there were any safety issues).

Dr. Sharma noted that early real-world data from this limited series suggests that FYB 201 is an efficacious and safe ranibizumab biosimilar.

A new ally against AMD?

Dr. Aleksandra Rachitskaya, a vitreoretinal surgeon and associate professor of ophthalmology at the Cleveland Clinic Cole Eye Institute (USA), discussed the impact of GLP-1 receptor agonists on non-exudative age-related macular degeneration.

“It’s been shown in animal models that GLP-1RAs are protective against retinal ganglion cell loss. In fact, there’s been a recent publication suggesting that the use of these drugs is also associated with reduced risk of developing glaucoma after three years,” she shared.

She then introduced a study showing the impact of GLP-1RAs on the risk of ocular diseases in an at-risk population. Involving more than 7,000 patients, the study found that GLP1RAs were associated with a reduced risk of non-exudative AMD compared to metformin and insulin after five years.

Dr. Rachitskaya noted that this significant reduction appeared after two years compared to metformin and insulin. GLP-1RAs also significantly reduced the risk of exudative AMD and glaucoma compared to insulin but not

compared to metformin after five years. Usage of GLP-1RAs showed no significant impact on the risk of cataract formation.

“Currently, we are working on prospective trials looking at the role of GLP-1RAs in different stages of AMD,” she concluded.

The art of retinal rescue

Dr. Nassim Abreu, associate professor in the Retina Department at Hospital Dr Elias Santana (Dominican Republic), shared insights into the current understanding of surgery for proliferative diabetic retinopathy (PDR).

Showing slides of severe PDRs, Dr. Abreu said: “The condition could be really hard to approach when trying surgery, especially when the patient has the same condition in both eyes.”

He added that there is “robust information” on the advantages of anti-VEGF during diabetic retinopathy (DR)

“We know that it halts the progression of diabetic retinopathy; it helps to regress neovascularization from the retina and the fibrovascular tissue,” he said. Dr. Abreu noted that it is important to know the status of the hyaloid in these cases, especially in the most severe ones.

He then turned his attention to the latest instruments and visualization tools available to treat these cases, including pneumatic handpieces, which can be used singularly or as a pair.

“I like this approach because, on one hand, it helps you with tremors, especially in cases that take up too much time and our hands get tired. And on the other hand, it helps with more controlled maneuvers. Eventually, bio-manual techniques for these cases are mostly needed most of the time,” he said.

He ended his session with a series of take-home messages. Tractional retinal detachment (TRD) can become very complex, he said, and complete removal of the hyaloid should be the goal of the diabetic vitrectomy to stabilize the disease better.

The era of neuroenhancement

Prof. Baruch Kuppermann, director at the UCI Health Gavin Gerbert Eye Institute (USA), shared about reversing vision loss in dry agerelated macular degeneration using neuroprotection and neuroenhancement.

“We are currently in the era of neuroprotection and trying to edge into the era of neuroenhancement,” he said.

Neuroprotection slows the progression of deterioration by making RPE and photoreceptors more resistant to injury—stopping or delaying cell death and stabilizing loss of function, he continued.

Neuroenhancement, however, could not only slow the rate of cell death but also make the remaining damaged cells function better, allowing for visual improvement and effectively reversing the degeneration.

Dr. Kuppermann focused on dry agerelated macular degeneration (dAMD) and AMD-associated GA. But he said a range of diseases with unmet needs could benefit from neuroprotection and neuroenhancement advances, with multiple pathways undergoing exploration.

He noted that restoration of functional vision appears to be achievable in dAMD patients with more anatomical integrity using new approaches, including mitochondrial stabilizing drugs, macrophage repolarization and Fas ligand binding. This suggests that early treatment of dAMD is warranted to reverse vision loss.

Editor’s Note

Reporting for this story took place at the 24th Congress of the European Society of Retina Specialists (EURETINA 2024), held from September 19 to 22 in Barcelona, Spain.

A Meeting of Minds

EVRS 2024 connects global experts in Budapest, setting the stage for continued progress in vitreoretinal care

by Dr. Perfecto E.O.R. Cagampang III

The 21st European Vitreo-Retina Society Congress (EVRS 2024) delivered a vibrant program of scientific exchange, international collaboration and celebratory moments, culminating in the announcement of Cancun as the next host city.

From the warmth of their successful 2023 meeting in picturesque Cappadocia, Turkey, the European Vitreo-Retina Society moved to the colder climate of Budapest, Hungary, to host its 21st Congress from November 14 to 17, 2024.

Close to 500 delegates convened at the Novotel City Hotel and Budapest Congress Center for four days of cutting-edge retinal lectures.

A blend of science and sociability

Superb social events complemented the program, including a welcome dinner on the first day and a delightful river cruise on the Danube on the second. The cruise featured an authentic Hungarian cultural show, a DJ and a cocktail dinner, which attendees thoroughly enjoyed.

Global perspectives in retinal care

Daytime programs featured symposia from the Egyptian Society of Retina, EuroLam, the Middle East African Council of Ophthalmology (MEACO), the Indian Society of Retina and the Philippine Glaucoma Society.

In a spirit of collaboration and knowledge sharing, the EVRS Congress presented spectacular talks on prevalent retinal diseases, including diabetic retinopathy, macular holes, retinal detachment and glaucoma.

Discussions of treatment strategies showcased innovative surgical procedures from various surgeons, as well as future directions in the field. These included new diagnostic and surgical equipment for retinal procedures, along with novel

treatment approaches for both gene therapy and laser technologies.

Celebrating excellence

The 21st EVRS Congress also celebrated outstanding contributions through several awards, recognizing excellence in various formats of scientific communication.

Notably, this year marked a historic moment as all competition winners hailed from India. The following were recognized for their exceptional work: Subhadra Jalail - Poster Contest, Rajiv Gandhi - Photo Contest and Sangeet Mittal - Video Contest.

In addition to these awards, the distinguished EVRS Ambassador Award 2024 was presented to two distinguished personalities: David Martin de Fonseca and Sangeet Mittal.

This year, Sangeet Mittal commemorated a significant moment by making history at EVRS, becoming the first person to receive three awards: First place in the video contest, second place in the photo contest and the EVRS Ambassador Award.

Looking ahead to Cancun

Over four days, EVRS 2024 became a vibrant hub, connecting professionals from all corners of the globe. The event truly highlighted the Society’s role as a vital platform for sharing knowledge and promoting collaboration within the field of vitreoretinal health.

The announcement of the 22nd meeting taking place in Cancun, Mexico, perfectly embodies this international spirit.

Editor’s Note

Reporting for this story took place at the 21st European VitreoRetinal Society Meeting (EVRS 2024), held from November 14 to 17 in Budapest, Hungary.

Oculis’ OCS-05 Shows 43% Improvement in Retinal Structure in Acute Optic Neuritis

Oculis’ Phase II trial showcases a novel neuroprotective approach to acute optic neuritis.

The future of acute optic neuritis (AON) could be moving away from focusing on inflammation.

Oculis (Zug, Switzerland) announced positive results for the Phase II ACUITY trial evaluating OCS-05, an investigational neuroprotective therapy for the disease.

This novel treatment showed significant improvements in both retinal structure and visual function, offering hope for patients with AON, a condition currently lacking targeted neuroprotective therapies. According to trial results, OCS-05, an advanced peptidomimetic small molecule, demonstrated a 43% improvement in ganglion cell-inner plexiform layer (GCIPL) thickness compared to placebo at 3 months, with the benefits sustained at 6 months.

The results position OCS-05 as a potential first-in-class neuroprotective treatment for acute optic neuritis and other neuroophthalmic conditions.

“These positive safety and efficacy results from ACUITY represent a significant milestone in bringing the first potential neuroprotective treatment in ophthalmology to patients,” said Dr. Riad Sherif, chief executive officer of Oculis. “The improvement in vision is especially encouraging, and the consistent improvement in retinal structure highlights the therapeutic potential of OCS-05 across multiple ophthalmic and neurological conditions.”

Key trial results and highlights The ACUITY trial, a double-blind, placebo-controlled study, enrolled 36 patients with acute optic neuritis of demyelinating origin. Patients received OCS-05 intravenously alongside standard steroid therapy.

OCS-05 showed a 28% improvement in retinal nerve fiber layer (RNFL) thickness by 6 months and significant visual function gains. Patients treated with OCS-05 (3 mg/kg/day) combined with steroids showed a favorable improvement in LCVA mean change from baseline, with patients gaining approximately 18 letters at 3 months and 15 letters at 6 months compared to placebo plus steroids. The results were statistically significant, with p-values of 0.004 at 3 months and 0.012 at 6 months.

The trial met its primary endpoint with no clinically significant differences in cardiac safety (electrocardiogram parameters) between OCS-05 and placebo groups. Adverse events were mild, transient, and non-clinically significant.

A shift in managing acute optic neuritis

AON is characterized by inflammation and demyelination of the optic nerve, often leading to vision loss.

Steroids are the current standard treatment, reducing inflammation in the optic nerve—but they fail to prevent long-term structural damage and visual impairment. OCS-05 is designed to go beyond inflammation, directly protecting the optic nerve and retinal structure.

Dr. Mark Kupersmith, an expert at the Icahn School of Medicine at Mount Sinai Hospital in New York, added: “These groundbreaking results represent an important advancement for acute optic neuritis patients. Steroids have been used to treat the inflammation seen in acute optic neuritis, but don’t prevent persistent visual impairments or reduce structural loss.`

“There remains a critical unmet need for neuroprotective therapies to preserve vision and the potential neuroprotective properties of OCS05 observed in the ACUITY trial and

its impact on visual function could offer significant hope for patients. These results, if replicated in larger clinical trials, could have profound implications, not only for this condition, but potentially for MS and other optic nerve disorders as well as glaucoma.”

Future development and expansion

The U.S. Food and Drug Administration (FDA) has cleared OCS-05’s Investigational New Drug (IND) application, which paves the way for clinical development in the U.S. Oculis also holds orphan drug designations for OCS-05 in both the U.S. and Europe, underscoring its potential to address this rare condition.

The company is planning additional studies to explore OCS-05’s applications in other neurodegenerative conditions, including multiple sclerosis, glaucoma, and optic nerve disorders.

Prof. Pablo Villoslada, chair of the Department of Neurology at Hospital del Mar, Pompeu Fabra University in Barcelona, Spain, and Oculis scientific advisory board member, said: “I am excited to see that the ACUITY results are consistent with the robust effects observed in animal models of neuroinflammation and neurodegeneration in the prevention of retinal ganglion cell damage and that OCS-05 has shown promising results in the improvement of vision. I look forward to the additional studies that can now be initiated for acute optic neuritis while further exploring the full potential of this promising neuroprotective candidate in both ophthalmology and neurology indications.”

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