CAKE Issue 22 - Glaucoma Issue

From Bench to Bedside

With insights from prominent clinicians and researchers, explore the forefront of recent glaucoma research—from groundbreaking trials to emerging trends p16

Rhythm and Views

Celebrating glaucoma progress and challenges

Dear Readers,

It’s the turn of the century—1999. We’re listening to the oracle that is Fatboy Slim , and that track is “Praise You.” Naughty little Norman Cook has lifted the opening lyrics from Camille Yarborough’s 1975 ode to civil rights, “Take Yo’ Praise.” Whoever we want to worship here, the lyrics go:

“We’ve come a long, long way together, Through the hard times and the good. I have to celebrate you, baby, I have to praise you like I should.”

I’ve got to say, in the past few decades—my goodness—those pushing the field of glaucoma forward are due a lot of praise. It’s worth taking stock of how far the field has come—from ‘oh well, the drops failed, so it’s time for a trabeculectomy now,’ to a landscape where there’s a diverse range of options. These range from the subtle and exquisite all the way up to the (relatively speaking) barn door-smashing filtration surgeries of old.

On the pharmacotherapy front, we’ve ditched the preservatives and discovered better drug delivery systems. Although, to my eyes, a lot of that has been about teaching old dogs new tricks.

On the surgical front, there are several laser procedures out there. If there isn’t a stent, shunt, blade, microcatheter, viscodilation device, valve, or similar (or a combination of one or more of them) that can effectively reduce patients’ intraocular pressures (IOPs) to safer levels, then there’s always the option of smashing that barn door to fall back on.

All these developments over the years mean glaucoma specialists now have a toolkit that gives them several options to achieve the desired amount of pressure reduction in the safest and least invasive ways possible. It’s up to you how you want to praise these researchers, engineers, clinicians, surgeons, leaders, and their teams for bringing these options to you—but you should.

I reckon you should simply find them all at the appropriate poster session at ARVO and give them all a hug or a fist bump (you’ll need to judge which is appropriate on a case-by-case basis). How lovely! And yet...

While Fatboy Slim reminds me of the days when I was 20 years old, at the Glastonbury Festival, dancing to the music of the best DJ (who also happened to be a bass player in an indie band from Yorkshire), I’m now aged 46. I live in one of the most expensive cities in the world, Zurich, in one of the richest countries, Switzerland. Life has repeatedly done what it does to most adults over the years: Kicked most of the joy out of it.

But at least Switzerland has one of the best healthcare systems in the world, right? If I were to develop glaucoma, and it progressed to a point where I’d be a good candidate for MIGS, surely I’d be seen quickly, right? After all, I’m paying almost 600 CHF a month to the insurers, right? Wrong.

The health insurers here will only reimburse trabeculectomies.

Unless you’re able to pay more to go private, no MIGS for you. I do not doubt that they have an economic model that shows the cost savings versus health-related quality-of-life outcomes that justify their decision. But I do think those without the means to pay for MIGS out of pocket will experience greater risks and complication rates, and have poorer outcomes than necessary.

I don’t think this reflects well on the insurers or society. I do have the feeling it’s a false economy. And I do believe it’s an affront to the surgeons who could and should be performing the MIGS procedures, as well as to everyone involved in developing the field to the point it is today.

One rich country’s health insurers turning their back on MIGS isn’t going to massively harm the field of glaucoma research (although several Swiss companies do develop MIGS technologies, and it must suck to not be able to capitalize properly on home soil).

Drawing the line between what should and should not be reimbursed is important, as there have to be limits. This is also a ‘first world problem’—there are many countries in the world where most citizens have no access to eye care at all. But from where I’m sitting, the line between reimbursement and “pay it yourself” has been drawn in the wrong place. No praise for you, beancounters!

Cheers,

Mark Hillen, PhD Director of Communications

ELZA Institute, Zurich, Switzerland Editor-At-Large | CAKE

Matt Young CEO & Publisher

Hannah Nguyen COO & CFO

Gloria D. Gamat Chief Editor

Mapet Poso Editor

Matt Herman Associate Editor

Maricel Salvador Graphic Designer

Writers April Ingram Chow Ee-Tan

Diana Truong

Rich Carriero

Tan Sher Lynn

Ruchi Ranga Society Relations & Conference Manager

International Business Development

Brandon Winkeler

Robert Anderson

Sven Mehlitz

Cataract Anterior Segment

Dr.

Dr. Rohit Shetty and Corvis® ST Leveraging the predictive power of biomechanical changes in modern lenticule extraction

Topcon’s Vision for the New Future of Glaucoma Crystallizes at APAO 2024

OCT-A: Glaucoma’s New Ally? Dr. Jacqueline Chua sheds light on the transformative potential of OCT-A in diagnosing and managing glaucoma

Dr. Harvey S. Uy University of the Philippines; Peregrine Eye and Laser Institute, Manila, Philippines harveyuy@gmail.com

Dr. Boris Malyugin S. Fyodorov Eye Microsurgery Institution Moscow, Russia boris.malyugin@gmail.com

Dr. Chelvin Sng Chelvin Sng Eye Centre, Mount Elizabeth Novena Hospital, Singapore chelvin@gmail.com

Prof. Jodhbir S. Mehta Singapore Eye Research Institute (SERI); Singapore National Eye Centre (SNEC) Singapore jodmehta@gmail.com

Dr. George H.H. Beiko University of Toronto; McMaster University, Ontario, Canada george.beiko@sympatico.ca

Dr. William B. Trattler Center For Excellence In Eye Care Miami, Florida, USA wtrattler@gmail.com

Arunodaya Charitable Trust (ACT)

Society Friends

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References: 1. Baudouin C et al. Prog Retin Eye Res 2021:83:100916. 2. Load in Glaucoma Therap. Glaucoma Today. March 2011. 3. Tafotan-S Product Information. Information. 5. Cosopt-S Product Information. 6. European Glaucoma Society Terminology and Guidelines for Glaucoma, 5th Edition. Br J Ophthalmol 2021;105:1-169. Pacific Glaucoma Guidelines. Third Edition. Available at https://www.apglaucomasociety.org/ apgg-asia-paci c-glaucoma-guidelines accessed January 2024.

References: 1. Baudouin C et al. Prog Retin Eye Res 2021:83:100916. 2. Fechtner RD. Reducing the Preservative Load in Glaucoma Therap. Glaucoma Today. March 2011. 3. Tafotan-S Product Information. 4. Tapcom-S Product Information. 5. Cosopt-S Product Information.

6. European Glaucoma Society Terminology and Guidelines for Glaucoma, 5th Edition. Br J Ophthalmol 2021;105:1-169. 7. Asia Pacific Glaucoma Guidelines. Third Edition. Available at https://www.apglaucomasociety.org/ apgg-asia-paci c-glaucoma-guidelines accessed January 2024.

6. European Glaucoma Society Terminology and Guidelines for Glaucoma, 5th Edition. Br J Ophthalmol 2021;105:1-169. Pacific Glaucoma Guidelines. Third Edition. Available at https://www.apglaucomasociety.org/ apgg-asia-paci c-glaucoma-guidelines accessed January 2024.

Santen Pharmaceutical Asia Pte Ltd. 6 Temasek Boulevard, #37-01 Suntec Tower Four, Singapore 038986. Office: +65 6715 7800 © 2024 Santen Pharmaceutical Asia Pte Ltd. All rights reserved.

Santen Pharmaceutical Asia Pte Ltd. 6 Temasek Boulevard, #37-01 Suntec Tower Four, Singapore 038986. Office: +65 6715

7800 © 2024 Santen Pharmaceutical Asia Pte Ltd. All rights reserved.

Santen Pharmaceutical Asia Pte Ltd. 6 Temasek Boulevard, #37-01 Suntec Tower Four, Singapore 038986. Office: +65 6715 7800 © 2024 Santen Pharmaceutical Asia Pte Ltd. All rights reserved.

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Eyeing Big Data

Dr. William Trattler sheds light on big data’s applications in the field of cataract and corneal diseases—among

others

by Tan Sher Lynn

How is big data reshaping eye care? Let’s explore its impact on cataract and refractive surgeries, patient selection, tailored treatment, and the ethical considerations it brings to clinical settings.

Big data has emerged as a transformative force in ophthalmology, reshaping our understanding, diagnosis, and treatment of various corneal conditions. Dr. William Trattler, a respected refractive, corneal, and cataract surgeon from the United States, explored the current applications and promises of big data in the field of cataract and corneal diseases.

Enhancing cataract and refractive surgery outcomes

According to Dr. Trattler, big data has been instrumental in significantly enhancing outcomes in cataract surgery. “Numerous intraocular

lens (IOL) calculation formulas currently available to cataract surgeons leverage big data and artificial intelligence (AI) to enhance the reliability and accuracy of IOL formulas. Notable examples include the Hill-RBF formula by Warren Hill and IOL power calculations developed by ZEISS, as well as Graham Barett’s suite of formulas. With each passing year, IOL formulas continue to improve, leading to better outcomes overall, he noted.

Besides refining intraocular lens calculations, big data has the potential to help surgeons identify the optimal techniques when performing cataract surgeries, such as crunching data on energy usage during phacoemulsification to help optimize the efficiency of

our procedure, according to Dr. Trattler. “Leveraging big data can aid in predicting the most suitable type of intraocular lens for individual patients. One of the major challenges we face is that while we have a very high rate of success when patients choose to receive a range of vision IOLs, there are still a small percent of patients who are not satisfied with their outcome. The hope is that by utilizing big data insights, we can help optimize IOL selection leading to improved patient satisfaction,” he continued.

For refractive procedures, big data is being utilized in laser-assisted in situ keratomileusis (LASIK), photorefractive keratectomy (PRK), and small incision lenticule extraction (SMILE). Companies are aggregating results and employing optimization strategies to refine outcomes in these procedures.

Big data has indeed facilitated significant advancements in LASIK surgery. Dr. Trattler cited an example — Surgivision, a company with an online platform developed by eye surgeon Dr. Guy Kezirian, where practitioners can upload results from their procedures. This aggregated data enables surgeons to make more informed decisions and adjust parameters to achieve the best visual outcomes for their patients.

Data-driven decision making

Dr. Trattler also mentioned that incorporating findings from largescale corneal registries into his clinical decision-making process facilitated more informed patient assessment and treatment approaches. This ultimately improved the quality of care provided to his patients.

“I believe that studies examining data from large patient cohorts provide valuable insights into patient assessment and treatment approaches. A recent study* that caught my attention focused on screening children aged three to 18 to determine the prevalence of keratoconus. This is significant because keratoconus, despite being a treatable corneal disease, is challenging to diagnose at early stages since patients may have no visual symptoms or have any signs on

slit lamp exam,” he explained. “This screening, conducted in Chicago, Illinois, revealed a significantly higher prevalence of keratoconus among children than previously estimated.”

Dr. Trattler continued: “So, as a collective effort in our community, we aim to identify patients with keratoconus at the earliest possible stage to ensure that we can treat their condition before they experience significant vision loss This type of information (provided by the study) has the potential to reshape how healthcare professionals view their patient demographics. Historically, optometrists and ophthalmologists might have waited until patients experienced reduced vision before initiating screening tests. However, this study indicates that conducting this study supports that conducting topography to screen for keratoconus, even in the absence of symptoms or visual impairment, could be beneficial,” he further explained.

When big data and AI work together

Dr. Trattler noted that the essence of AI lies in its ability to unearth solutions to unasked questions, thereby enhancing our ability to achieve better outcomes.

“We have high hopes for the role of AI in delving into big data and uncovering trends and answers to questions we may not have previously considered,” he noted. “By scrutinizing vast amounts of data, AI can identify patterns that may elude human observation, providing deeper insights and enabling us to utilize the findings more effectively. For instance, AI may help surgeons determine which patients are better candidates for EDOF vs trifocal IOLs, based on factors such as preop corneal steepness, preop corneal regularity, anterior chamber depth, axial length, gender, etc. While our current results with range of vision IOLs are quite good, AI can potentially further improve patient satisfaction,” he said.

Moreover, AI has the potential to guide patient selection in ways we may not have envisioned, offering insights into nuanced subsets within larger demographics.

“For example, it may suggest that individuals aged 65 to 85 generally fare well with certain types of range of vision lenses, whereas those aged 85 to 100 may achieve optimal outcomes with a different lens type. Such granular analyses based on big data trends hold promise for improving overall treatment outcomes,” Dr. Trattler elaborated.

Big data and private practice: Bridging the gap

While big data holds immense promise, integrating it into clinical practice presents some challenges. Dr. Trattler highlighted accessibility as a main hurdle.

“While there’s a plethora of studies and analyses available, the crucial step is disseminating this information effectively to surgeons and eye care professionals to enhance patient care. We need to devise better methods for conveying the findings from these extensive data analyses. I believe effective communication is key. With the abundance of emails and text messages we receive daily, it’s about finding a platform that enables doctors to integrate the insights from big data seamlessly into their patient management practices,” he explained.

data is de-identified to prevent bias. “Essentially, we aim to anonymize the data to prevent individuals from being targeted or personally impacted. Additionally, it’s critical to mitigate biases that could unfairly affect particular groups based on factors like ethnicity or religion. The objective is to maintain unbiased data, devoid of any potential harm or discrimination towards specific demographics,” he remarked.

Reference

* Harthan JS, Gelles JD, Block SS, et al. Prevalence of Keratoconus Based on Scheimpflug Corneal Tomography Metrics in a Pediatric Population From a Chicago-Based School Age Vision Clinic. Eye Contact Lens. 2024;50(3):121-125.

Contributor

Dr. Trattler suggested these could involve seminars, webinars, or educational sessions, with both leaders and practitioners playing pivotal roles in educating others and driving implementation.

In terms of understanding the epidemiology or treatment outcomes of corneal diseases with big data, Dr. Trattler believes that we are still in the process of making significant advancements.

“While we haven’t experienced major breakthroughs yet, progress is underway. I anticipate that as researchers analyze data and pose better questions, we’ll see significant developments. Ultimately, the key is determining the right questions to ask when utilizing big data—what information do we need to improve treatments and make a meaningful impact?” he said.

Addressing ethical considerations, Dr. Trattler emphasized that our foremost priority is to ensure that big

Dr. William B. Trattler is a refractive, corneal and cataract eye surgeon at the Center For Excellence In Eye Care in Miami, Florida, USA. He performs a wide variety of cataract and refractive surgeries, including PRK; all laser LASIK; no injection sutureless cataract surgery; as well as laser cataract surgery. He has been an investigator for next generation technologies (like the Tetraflex accommodating intraocular lens) and procedures like corneal collagen crosslinking (CXL). His involvement in the FDA-approval study for CXL led to its approval in 2016. In addition to his private practice, Dr. Trattler is on the Volunteer Faculty at the Florida International University Wertheim College of Medicine, as well as the University of Miami’s Bascom Palmer Eye Institute. He is board certified by the American Board of Ophthalmology and has been an author of several articles and abstracts. In 2016, Dr. Trattler received the Catalyst Award in Advancing Diversity in Leadership from the Ophthalmic World Leaders (OWL), an association of interdisciplinary ophthalmic professionals dedicated to driving innovation and patient care by advancing diversity in leadership.

wtrattler@gmail.com

Dr. Rohit Shetty and Corvis® ST

Leveraging the predictive power of biomechanical changes in

extraction

modern lenticule

by Matt Herman

Since its inception in SMILE, lenticule extraction-based laser vision correction (LVC) has experienced tremendous growth in recent years. Correspondingly, the demand for understanding the impact of this newcomer to LVC on the eye has surged. At APAO 2024 in Bali, Dr. Rohit Shetty delved into his research in this area. He explained why he places his trust in the Corvis® ST (OCULUS Optikgeräte GmbH, Wetzlar, Germany) for assessing corneal biomechanics in both laboratory and clinical settings to optimize surgical outcomes in modern LVC.

Lenticule extraction procedures have truly flourished in modern laser vision correction. However, despite the technology’s rapid success, questions persist regarding the precise effects of these surgeries on the treated ocular structures.

Enter Dr. Rohit Shetty (India), who has directed his research efforts toward unravelling the biomechanical

effects of SMILE and its derivative procedures. During an OCULUS lunch symposium at the 39th Congress of the Asia-Pacific Academy of Ophthalmology (APAO 2024), Dr. Shetty elucidated why the latest advancements in biomechanics are crucial in lenticule extraction procedures—and why the OCULUS Corvis® ST is the tool of choice for this purpose.

Advancing understanding

Dr. Shetty has long recognized that there are gaps in our knowledge of the biomechanical implications of lenticule extraction surgery. His belief that such knowledge is imperative for achieving optimal patient outcomes underpinned his groundbreaking 2017 study on the topic .*

“We realized that surgical outcomes, both intraoperative and postoperative, are heavily influenced by the dynamics of corneal tissue,” Dr. Shetty explained. And understanding these dynamics is now the driving force behind a significant portion of the research coming out of his lab.

Dr. Shetty saw that a more precise, biomechanics-driven approach to corneal tissue dynamics was necessary to advance this understanding. This is due to the inherent variability associated with the subjective, qualitative judgments required in lenticule extraction procedures.

“It’s a completely new dimension of laser surgery, where a lot depends on tactile sensation and the performance of laser spots,” Dr. Shetty explained. “This is why we believe that integrating biomechanics in this era of extensive lenticulebased procedures is crucial. We need the ability to anticipate what is occurring.

Corvis® ST key to early discoveries

The core focus of both Dr. Shetty’s 2017 study and his ongoing research presented at APAO 2024 is to thus harness the power of predictive modelling based on biomechanical insights.

So how can surgeons better comprehend the biomechanical changes during lenticule extraction to facilitate such predictions? The answer involves scrutinizing the relevant biomechanical variables using an appropriate device. For Dr. Shetty, the OCULUS Corvis® ST has emerged as the ideal tool for biomechanical assessments.

In the 2017 study, OCT imaging was utilized to identify biomarkers such as his team’s proprietary Bowman’s

roughness index (BRI) and corneal speckle distribution. However, it was the Corvis® ST, with its corneal stiffness measurement capabilities and more, which played a pivotal role in both the 2017 study and his team’s current endeavours.

“We opted for the Corvis® because of its integration with topography,” he elaborated. “It offers multiple parameters, not just a singular value. It provides stiffness parameters, an aqueous stress index, and elasticity modulus. And I have the flexibility to select the parameters I require.”

In the 2017 study, Dr. Shetty and his team shed light on the current possibilities in making the measurements they needed. “Current in vivo biomechanical assessment options are the Corvis® ST (OCULUS Optikgeräte GmbH, Wetzlar, Germany) and the Ocular Response Analyzer® (ORA) (Reichert Ophthalmic Instruments, Buffalo, NY, USA),” the study authors write.

Crucially, the authors noted that such in vivo measurements were only feasible with the Corvis® ST. “However, correlation between ORA indices and mechanical corneal stiffness is unknown. Using Corvis® ST, we can derive corneal stiffness, specific to the in vivo corneal deformation amplitude waveform.”*

Ultimately, the Corvis® ST’s unique capability to quantify mechanical corneal stiffness unveiled one of the most compelling findings of the 2017 study: corneal deformation at certain force levels indicated a swifter recovery of biomechanical strength in eyes that underwent lenticule extraction.* But this was just the beginning.

The predictive potential of Corvis® ST

Building upon these initial insights, Dr. Shetty’s current research aims to formulate a predictive model for patient outcomes in lenticule extraction. “The primary inquiries were: How does dissection ease correlate with visual quality? And can we forecast this using biomechanical robustness?” he remarked.

Leveraging preoperative biomechanical data from the Corvis® ST—such as corneal stiffness, Corvis Biomechanical Index, thinnest corneal thickness, stiffness parameter A1, and Belin/Ambrosio Enhanced Ectasia Display—Dr. Shetty’s team is now developing a random forest artificial intelligence model to predict the nature of the opaque bubble layer (OBL).

According to ongoing investigations, OBL density demonstrates a positive correlation with dissection difficulty. Consequently, with the aid of the Corvis® ST, it now appears possible to anticipate the characteristics of a given lenticule extraction surgery before it occurs.

“When we fed this small sample into our AI model, it accurately predicted—nearly 80% of the time—the outcomes anticipated by biomechanical analysis,” he noted.

Ultimately, Dr. Shetty contends that the Corvis® ST has been instrumental in realizing the tangible impact of his research on the lives of patients undergoing lenticule extraction. “Without the Corvis® ST, this would have remained a theoretical model—not a practical tool for real patients, which we now possess thanks to the data.”

asserted. “It is immensely beneficial for beginners. It is reliable.”

“It was incredibly straightforward to integrate into practice,” he continued. “It accelerates processes, integrates seamlessly with topography, and furnishes invaluable data that I cannot do without. It enhances my proficiency as a surgeon and augments predictability.”

Ultimately, the Corvis® ST has emerged as the versatile solution Dr. Shetty has sought for his dynamic needs—both in the clinic and for his pivotal research shaping the future of patient outcomes in lenticule extraction-based laser vision correction. Before heading off to deliver his presentation to a packed symposium room at APAO 2024 in Bali, Dr. Shetty had one final thought on the Corvis® ST.

“Familiarize yourself with it. Engage in discussions about it. Its potential exceeds imagination.”

Reference

* Shetty R, Francis M, Shroff R, et al. Corneal Biomechanical Changes and Tissue Remodeling After SMILE and LASIK. Invest Ophthalmol Vis Sci. 2017;58(13):5703-5712.

Contributor

Prof. Dr. Rohit Shetty

For Dr. Shetty, the Corvis® ST’s potential goes way beyond the research laboratory. Despite the specialized role of the Corvis® ST in his groundbreaking work on lenticule extraction, he perceives the device as universally beneficial for all surgeons seeking to immediately enhance their surgical practices.

“We must dispel the notion that [Corvis® ST] is solely for highly specialized individuals,” he

DNB, FRCS, FWCRS, FACS, PhD (Netherlands) is the chairman of Narayana Nethralaya (Bangalore, India), clinical and translational scientist at GROW Laboratories and faculty at the Department of Ophthalmology of Maastricht University (The Netherlands). Dr. Rohit is a cornearefractive surgeon and a clinician and translational scientist with a keen interest in refractive surgery, dry eye, keratoconus and corneal ectatic disorders. He has been practicing high-volume refractive surgery for 20 years. Dr. Shetty obtained his FRCS in Glasgow, Scotland, United Kingdom, in 2006 and is currently an FRCS examiner. He is the Chief Mentor for the Dual Academic Program (PhD & Clinical Fellowship) at Narayana Nethralaya Eye Institute and Maastricht University.

drrohitshetty@yahoo.com

OCULUS Corvis® ST

Topcon’s Vision for the New Future of Glaucoma Crystallizes at APAO 2024

by Matt Herman

New developments in glaucoma diagnosis and treatment have changed the way ophthalmologists approach and manage the disease. For some of the Asia Pacific region’s most eminent glaucoma experts, Topcon’s suite of cuttingedge tools are bridging the gulf between these innovations and everyday use in the clinic.

The treatment paradigm for glaucoma is changing. A day hardly passes now when one of the most vexing pain points for glaucoma disease detection and management hasn’t been conquered in the lab.

Topcon Healthcare (Topcon; Tokyo, Japan) has made the translation of these critical innovations into reality its sole mission through its suite of modern glaucoma

tools, like Triton™ OCT, Maestro2, and the IRIDEX Cyclo G6® Glaucoma Laser System and MicroPulse P3® Delivery Device.

Moderated by Prof. Widya Artini Wiyogo (Indonesia), a recent symposium at the 39th Congress of the Asia-Pacific Academy of Ophthalmology (APAO 2024) focused on what the fruits of the latest research are bearing in the clinic, with eminent specialists Prof. Victor Koh (Singapore), Dr. Eun Ji Lee (South Korea) and Dr. Virna Asrory (Indonesia) on the podium reporting on their experiences.

These top names in glaucoma covered a wide range of applications, from understanding glaucomatous disease genesis, to monitoring and predicting optic nerve damage and treating it — and how they use

Topcon’s offerings to unlock it in their clinics.

Hood reports with Triton and Maestro2 OCT

One of the promises of modern glaucoma research has been the usage of new tools like swept-source optical coherence tomography (SS-OCT) for earlier detection of glaucoma and treatment guidance.

With her turn at the podium, Dr. Asrory explored the practical usage of the Hood Report and where it fits into her practice.

The Hood Report report uses Topcon’s Triton and Maestro2 SSOCT to look at the retinal nerve fiber layer (RNFL) and coordinate structural damage and functional information from tests like visual field perimetry.

“It aids the decision-making process when determining which areas of the visual field should be examined for agreement between structural and functional loss,” Dr. Asrory said.

But why do glaucoma physicians need this aid when they have tools like visual field testing at their disposal? Dr. Asrory’s answer was simple: Visual field tests can be unreliable at best, and even misleading in extreme cases.

Patients, she said, get fatigued— especially when the test is being performed on the second eye. There is also a learning curve, which can cause issues for those with undetected glaucoma who have never taken a visual field test. This, and many other factors, can cause reliability problems in the form of false positives and negatives.

These problems can be addressed with the Hood report, which uses

OCT images from Topcon’s Triton and Maestro2 by boosting the meaning of visual field data points. By comparing probabilities against a reference database the report is able to pinpoint problem areas warranting further investigation.

“The Hood Report compares structural and functional data to support management decisions, particularly if insufficient historical data is available.”

Dr. Virna Asrory

This is an example of a Hood Report. Photo Credit: Topcon

“The Hood Report compares structural and functional data to support management decisions, particularly if insufficient historical data is available,” Dr. Asrory said.

Historical data, she concluded, likely to be absent in newer patients more likely to encounter problems with visual field tests. In other words, patients who are more likely treatment naive or with undetected glaucoma that need accurate screening the most.

Another key feature of the report is the arrangement of the circumpapillary RNFL scan (cpRNFL) into a nasal-superior-temporalinferior-nasal (NSTIN) arrangement, as opposed to the traditional temporal-superior-inferior-nasaltemporal (TSINT) order.

“This positions the structures most vulnerable to glaucomatous damage in the center of the graph,” explained Dr. Asrory. “The traditional TSINT format splits these vulnerable areas.”

In the end, Dr. Asrory asserts that the Hood Report functionality on Topcon’s Triton and Maestro2 adds up to a new, powerful tool in the fight against glaucoma in the stages that it is most needed. “All of the essential elements affected by glaucoma are on one page,” she said.

“Because of these characteristics of the structurevascular relationship, [OCT-A] can be used to monitor glaucoma.”

Dr. Eun Ji Lee

“The Hood Report is a single widefield OCT analysis that aids in detecting glaucomatous damage, especially for early screening. It increases confidence for glaucoma management for our patient based on structural and functional analyses,” she concluded.

The OCT-A advantage

Translational medicine again took center stage when Dr. Eun Ji Lee, one of South Korean and Asian glaucoma’s most recognizable names, took the stage. She tackled translating research in OCT angiography (OCT-A) and glaucoma into clinical practice.

According to Dr. Lee, one of the immediate benefits of the OCT-A capabilities of Triton and Maestro2 in glaucoma is the ability to look at the vasculature around two retinal layers—the RNFL and the ganglion cell inner plexiform layer (GCIPL). Localized loss of deep retinal vasculature in these layers, she noted, is correlated with loss of structure in the retinal.

“Because of these characteristics of the structure-vascular relationship, [OCT-A] can be used to monitor glaucoma,” Dr. Lee said. “As glaucoma progresses, there is a gradual decrease in vascular density, and the location of the glaucomatous damage is also shown in the vascular map.”

Dr. Lee also noted that OCT-A presents unique advantages when it comes to the so-called ‘floor effect’, where limits in the dynamic range of OCT images make it difficult to measure glaucomatous damage and progression in more severe cases.

This is not the case with OCT-A. “Because OCT-A does not measure thickness, it should be more free from the ‘floor effect’, she said. “A study compared OCT-A and OCT to see the visual field damage, and compared the structural function and vascular function relationship. [The study] found that this vascular function relationship performed better in eyes with severe visual field damage.”1

Dr. Lee went over further advantages of OCT-A immediately applicable to the clinic, including her own research on using choroidal OCT-A in detecting choroidal microvascular dropout for prediction of glaucoma progression.2

“We can use OCT-A in glaucoma,” she said. “It can be used in diagnosis, especially in highly myopic eyes or eyes with pathologic myopia—and it could potentially also be useful in advanced glaucoma.”

Most importantly, though, is the view that OCT-A gives into the future of glaucomatous disease. “It can also be used to predict the prognosis by the presence of microvascular dropout by predicting rapid progression in adjacent areas.

“In the future, I hope that OCT-A can be used to tailor treatment in individual patients to determine whether the patient needs further IOP lowering or not,” Dr. Lee concluded.

Dr. Eun Ji Lee

Dr. Virna Asrory

New frontiers in MicroPulse TST and cataract

Prof. Victor Koh, head of the department of ophthalmology at National University Hospital and National University of Singapore, brought the session to a close with his presentation on his research with combined MicroPulse transscleral laser therapy and cataract surgery.

Using the IRIDEX Cyclo G6 Laser and the MicroPulse P3 delivery device, Prof. Koh’s work compares combined MicroPulse TLT and phacoemulsification cataract surgery with phacoemulsification with iStent and phacoemulsification with endoscopic cyclophotocoagulation.

After reviewing the importance of patient selection, Prof. Koh first gave the guidelines he uses in his own MicroPulse TLT practice. This includes patients not suitable for incisional or prolonged glaucoma surgery, those who have had prior incisional glaucoma surgery to lower IOP, those who have just had incisional glaucoma surgery, or those who have uncontrolled IOP in eyes with a poor prognosis and need a reduction in medication burden.

This indicates a long list of potential patients for what Prof. Koh ultimately believes is an invaluable and versatile procedure. His results in the iStent study speak to this, as

well. Patients receiving TLT with phacoemulsification saw an IOP reduction to 14.0±2.2 and 14.5±2.2 at 6 and 12 months postoperatively from 16.8±3.5, compared to the iStent group, which went from 16.6±3.6 at baseline to 14.4±3.6 and 15.7±3.1, also at 6 and 12 months, respectively.

“I think combined cataract surgery with MicroPulse laser is effective and safe. This is a viable option for patients with both cataract and mild glaucoma.”

— Prof. Victor Koh

For medication decrease, Prof. Koh was enthusiastic. “There was also a significant reduction in the number of medications after surgery, and this was sustained up to one year, where the majority of them are off medications” he said, noting the importance of how patients were selected for TLT.

These results were echoed in the second study, where phacoemulsification with TLT and with endoscopic photocoagulation were compared. “There is a higher

rate of success and a higher rate of survival for patients who underwent phaco and MicroPulse laser,” he said.

Ultimately, the conclusion for MicroPulse TLT for Prof. Koh was clear. “I think combined cataract surgery with MicroPulse laser is effective and safe. This is a viable option for patients with both cataract and mild glaucoma,” he said.

“I now also use this procedure if I’m not sure of the visual deficiencies of this patient. Someone, for example who might be elderly with dense, wide massive cataract,” Prof. Koh continued.

“The other group of patients that might benefit are patients with more advanced PACG, who don’t have too much pressure and just want to do a cataract surgery. And lastly, if you have someone with a cataract and a request to have the burden of medications after surgery lowered, this is something to consider as well.”

With Triton OCT, Maestro2 and MicoPulse TLT leading the way, patient-tailored and optimized glaucoma screening, diagnosis, prediction and management are here. This is what Topcon technology is all about, and the presentations by these three glaucoma experts have showcased how these cuttingedge solutions are now ready to be incorporated into everyday practice for improved quality of care.

References

1. Moghimi S, Bowd C, Zangwill LM, et al. Measurement Floors and Dynamic Ranges of OCT and OCT Angiography in Glaucoma. Ophthalmology. 2019;126(7):980-988.

2. Lee EJ, Kim JA, Kim TW, Kim H, Yang HK, Hwang JM. Glaucoma-like Parapapillary Choroidal Microvasculature Dropout in Patients with Compressive Optic Neuropathy. Ophthalmology. 2020;127(12):1652-1662.

Editor’s Note

The 39th Congress of the AsiaPacific Academy of Ophthalmology (APAO 2024) was held from 22 to 25 February in Bali, Indonesia. Reporting for this story took place during the event.

Prof. Victor Koh

Prof. Widya Artini Wiyogo

Eye Banking in Focus

APAO 2024 highlights the crucial role of eye banking in advancing eye care

by Tan Sher Lynn

Emphasizing the importance of eye banking, experts at APAO 2024 stressed the need for specialized research donation programs, explored the influence of donor corneal properties on graft survival, and presented innovative methods to boost donor retrieval rates after the pandemic. To say the least, collaborative efforts among eye banks, healthcare institutions, and regulatory bodies are crucial for ensuring fair access to eye care and continuing advancements in the field.

The second day of the 39th Congress of the Asia-Pacific Academy of Ophthalmology (APAO 2024) highlighted the pivotal role of eye banking in driving eye care forward. Insightful discussions focused on the significance of tissue donation in research advancement, factors impacting corneal graft survival, and strategies for enhancing donor rates at eye banks.

Eye bank’s role in supporting research

Eye banks play a crucial role in supporting research alongside providing tissue for transplantation,

emphasized Ms. Heather Machin (Australia), an ophthalmic nurse and head of the Lions Eye Donation Service.

“By supplying tissue for research, eye banks contribute to advancing knowledge of the eye and its connections to other body parts, developing prevention programs, future therapies, medical devices, and improving access to services,” she said.

However, the current system is primarily focused on transplantation, resulting in a lack of routine availability and planning for research tissue.

Ms. Machin also highlighted disparities in how research donors are treated compared to transplant donors, stressing the need for a dedicated research donation program. Such a program would allow for planned and coordinated tissue allocation, expand donation opportunities for individuals ineligible for transplantation, and enhance accountability.

In addition, she emphasized the importance of sharing corneas among research groups to maximize donation impact.

Factors affecting corneal graft survival

Corneal endothelial cell density (ECD) gradually decreases over the long-term postoperative period and can sometimes lead to the failure of transplanted corneal grafts. As such, Dr. Koji Kitazawa (Japan) and his colleagues set out to assess the biological properties of donor corneas to determine if they affect ECD.

Postoperative ECD was assessed according to the maturedifferentiated human corneal endothelial cell (HCEC) contents, categorized into three groups: highmaturity (> 70%), middle-maturity (10% to 70%), and low-maturity (< 10%).

Results showed that at three years post-op, the mean ECD significantly decreased to 911 (388) cells/mm2 in the low-maturity group, compared with 1604 (436) cells/mm2 in the highmaturity group. The low-maturity group significantly failed to maintain ECD at 1500 cells/mm2 at three years postoperatively. Additional ECD analysis for patients who underwent Descemet’s stripping automated endothelial keratoplasty (DSAEK) alone displayed a significant failure to maintain ECD at 1500 cells/mm2 in the low-maturity group.

Dr. Koji observed that none of the donor factors such as age, sex, diagnosis, or diabetes affected postoperative ECD. However, he noted the presence of dead cells in the donor corneal endothelium before transplantation.

Concluding his study presentation, Dr. Koji highlighted that the reason

The panel of experts on Day 2 of APAO 2024 in Bali, Indonesia, provided insights and inspiration on the next generation of eye banking

for the decline in postoperative ECD after transplantation remains unknown. However, he suggested that the biological properties of donor corneas influence graft survival. He emphasized the importance of future evaluations focusing on cellular senescence to enhance the understanding of cell maturity.

Increasing donor retrieval post-COVID

Meanwhile, Dr. Ma. Dominga B. Padilla, president of the Eye Bank Foundation of the Philippines, shared the center’s experience in boosting donor retrieval post-COVID.

“The very difficult situation of COVID-19 has changed the mindset of society and forced hospitals and our eye bank to do things differently,” she said.

“As the world opened up in 2022, our eye bank had a few challenges to deal with. Many medico-legal officers who used to support us had resigned or were on study leave,” she continued. “Hospitals that had already

developed corneal retrieval programs had lost momentum, and there was a huge spike in patients with corneal diseases who needed a transplant.”

But despite these challenges, there was a silver lining. “More hospitals, especially government hospitals under the Department of Health (DOH) started to enter into serious Memorandum of Agreements (MOAs) with the eye bank. And the DOH finally made deceased donor donation and transplant one of the key performance indicators (KPIs) for the hospitals,” she said.

In addition, Dr. Padilla highlighted the importance of satellite retrieval centers, which significantly increase tissue yield. She expected that this would only get better due to ongoing efforts to establish more centers nationwide.

In conclusion, she noted that key strategies to enhance donor retrieval rates involve aligning with the DOH to prioritize deceased donor donation and transplantation as a key performance indicator, maintaining

ongoing engagement with hospital partners nationwide, and offering incentives to hospitals and their procurement transplant coordinators (PTCs).

The importance of eye banking in ophthalmology cannot be overstated, as it serves as a cornerstone for both clinical practice and scientific progress in the field. On a global scale, collaborative efforts between eye banks, healthcare institutions, and regulatory bodies are essential to ensure equitable access to eye care and to facilitate ongoing advancements in the field.

Editor’s Note

The 39th Congress of the AsiaPacific Academy of Ophthalmology (APAO 2024) was held in Bali, Indonesia, from February 22 to 25. Reporting for this story took place during the event. A version of this article was first published on cakemagazine.org.

BIOMECHANICS MEETS TOMOGRAPHY

HEY CORVIS ST I just took a look at the tomography. These values call for caution.

I don’t think I would operate.

HI PENTACAM The biomechanics looks good, though. The cornea is very stable. I don’t see any problem with operating.

O.K. TOGETHER NOW Tomography and corneal biomechanics together make the decision easier: Surgery could be an option.

Corvis® ST meets Pentacam®: Combined measurement results for a safe decision on surgery

Benefit from the combination of biomechanical data from the Corvis® ST and tomographic data from the Pentacam®. Provide surgical care to more patients safely!

From Bench to Bedside

With insights from prominent clinicians and researchers, explore the forefront of recent glaucoma research—from groundbreaking trials to emerging trends

by April Ingram

In our pursuit to provide optimal care for glaucoma patients, research plays a pivotal role. This article explores the latest advancements and perspectives from top experts, shedding light on impactful studies and future directions in glaucoma care.

Without research, we cannot advance in our quest to provide the best possible care and outcomes for our patients. Fortunately, we live in an era of rapid advancement, witnessing significant shifts in the way we can provide care for our glaucoma patients. By uncovering new targets and earlier detection and intervention, we aim not only to halt deterioration but also to restore vision.

Current landscape of glaucoma clinical trials

The hot topic in glaucoma for decades now has been all about minimally invasive glaucoma surgeries (MIGSs). MIGS has become an essential modality for glaucoma management, fulfilling the promise of safe and efficacious early interventions for mild-to-moderate

More recently, researchers are revisiting MIGS, exploring ways to further enhance outcomes. Combined MIGS procedures, whether targeting the same aqueous outflow mechanism or a different one, have faced challenges due to limited high-quality evidence supporting their effectiveness and associated costs. Of course, having more options to offer patients increases the opportunity to find the best therapeutic option to meet their individual needs.

presented promising results in early trials and great potential for clinical application.

Despite our focus on controlling elevated IOP as our primary modifiable risk factor, we recognize glaucoma as a multifactorial neurodegenerative disease. Researchers are now looking at targeting those neurodegenerative processes that occur at the retinal ganglion cell level, leaning into neuroprotective strategies directed at the degenerative mechanisms, metabolism, insulin signaling, mTOR, axon transport, apoptosis, autophagy, and neuroinflammation.

Despite exciting and interesting initial results, the variability and complexity of glaucoma have highlighted the need for strict phenotyping of patients to translate current preclinical findings into a clinical setting.

Devices, interventions, and therapeutics—numerous clinical trials are ongoing at every phase of development, while others have overcome regulatory hurdles and are now in prime time, available at clinics near you.

Expert perspectives on recent and future glaucoma studies

We asked expert clinicians, who are also deeply engaged in research, to share their opinions and key insights about the studies they are most excited about and those they see as among the most impactful to glaucoma care—both recently and in the years to come. glaucoma patients, leaving them with minimal trauma and enabling rapid recovery.

The latest exciting innovations to limit vision loss in glaucoma patients are the minimally invasive micro sclerostomy (MIMS) and trabeculotome tunneling trabeculoplasty (Triple-T), which have

Dr. Steven J. Gedde, a professor of ophthalmology and vice chair of education at the Bascom Palmer Eye Institute, as well as an investigator in numerous clinical trials, recognizes the importance of well-designed randomized studies.

“Several recent multicenter randomized clinical trials have provided valuable information to guide the care of patients with glaucoma,” Dr. Gedde shared. “Randomized clinical trials are considered the gold standard for evaluating therapies. The process of randomization is designed to produce comparison groups that differ only by the treatment received.”

Importantly, we also wanted to be sure that we understand the challenges encountered when implementing new therapies, technologies, or policies into practice.

Dr. Jason Bacharach is the medical and research director at North Bay Eye Associates and co-director of Glaucoma Service in the Department of Ophthalmology at the California Pacific Medical Center and Pacific Vision Eye Institute. He has been at the forefront of clinical trials for decades.

He shared that with every completed trial and presentation of data, there are things that should be carefully considered. “The question of translation from trials to practice is key. Look at the conduct of the trial. How long were the subjects followed? How large was the trial? Was there a control wing?” he said.

He added that the enrolled patient population may differ from many

of the patients currently sitting in the waiting room. “One important factor is to ensure the representative population in the trial is reflective of the patients you care for,” he added.

Perspectives on the PTVT study

Dr. Gedde provided his thoughts on three clinical trials that hold great potential and opportunity for the future of glaucoma care. The first is the Primary Tube Versus Trabeculectomy (PTVT) Study, which compared the safety and efficacy of tube shunt implantation and trabeculectomy with mitomycin C (MMC) as an initial glaucoma surgical procedure.1

“The trial enrolled 242 patients with medically uncontrolled glaucoma and no previous incisional ocular surgery,” Dr. Gedde shared. “They were randomly assigned to treatment with a tube shunt (350-mm2 Baerveldt glaucoma implant) or trabeculectomy with MMC (0.4 mg/ml for 2 minutes).”

This trial followed patients for up to five years. “Primary tube shunt surgery had a higher failure rate than primary trabeculectomy with MMC throughout five years of follow-up, but the difference was only statistically significant at one year but not at three years or five years. Mean IOPs were lower in the trabeculectomy group than the tube group, and this superior IOP reduction was achieved with significantly fewer medications,” he said.

“Early postoperative complications were more common after trabeculectomy with MMC compared with tube shunt surgery, but both procedures had similar rates of late postoperative complications and serious complications requiring reoperation to manage the complication and/or producing vision loss,” Dr. Gedde continued. “An inverse relationship was seen between preoperative IOP and surgical failure in the tube group; patients with lower preoperative IOP had higher failure rates, and those with higher preoperative IOP had lower failure rates. The success of trabeculectomy with MMC was less influenced by preoperative IOP.”

Dr. Gedde shared the impact of the PTVT study and the importance of patient selection. “This study highlights the importance of considering preoperative IOP when deciding between primary trabeculectomy with MMC and primary tube shunt surgery,” he noted.

Insights from the EAGLE trial

Next, Dr. Gedde shared his insights into the Effectiveness in AngleClosure Glaucoma of Lens Extraction (EAGLE) Trial, which compared clear lens extraction and laser peripheral iridotomy (LPI) as initial treatment for primary angle-closure disease.2

“The study recruited 419 patients age ≥ 50 years with newly diagnosed primary angle-closure glaucoma or primary angle closure with IOP ≥ 30 mmHg. Enrolled patients were randomized to clear lens extraction or LPI,” Dr. Gedde shared.

Nearly all outcome measures favored the clear lens extraction group after three years, including quality of life, IOP, use of glaucoma medications, and visual acuity.

“A cost analysis was performed based on patients recruited at centers in the United Kingdom,” he said. “The initial cost was higher among patients who underwent clear lens extraction relative to LPI, but lens extraction was more cost-effective after 10 years due to lower medication usage and fewer subsequent ocular procedures.”

Dr. Gedde also provided his impression of the EAGLE trial. “This important trial demonstrated the benefit of early lens extraction in a subset of patients with primary angle-closure disease, i.e., those with primary angle-closure glaucoma and primary angle closure with marked IOP elevation.”

This shift, we noted, where interventional glaucoma, including laser treatment, surgery, and innovative drug delivery systems to lower IOP, should no longer be thought of as an aggressive approach or a last resort. Instead, it should be seen as an opportunity to minimize the treatment burden for

patients and enhance their long-term outcomes.

This opportunity for first-line intervention was highlighted by Dr. Gedde as he shared his thoughts on the recent Laser in Glaucoma and Ocular Hypertension (LiGHT) Trial. This multicenter randomized clinical trial compared eye drops and selective laser trabeculoplasty (SLT) as first-line treatments for reducing IOP.3

A total of 718 patients with newly diagnosed, untreated open-angle glaucoma and ocular hypertension were randomly assigned to treatment with 360 degrees of SLT or topical glaucoma medications.

Dr. Gedde described the key results of the LiGHT Trail. “Nearly 80% of patients maintained IOP control with only SLT during years of follow-up, and a significant cost benefit of SLT over drops was observed,” he shared. “There was no significant difference in quality of life between the drop group and SLT group, and this was the primary outcome measure in the study. An extension study continued the follow-up of patients from the LiGHT Trial for six years. The rate of glaucomatous progression and need for trabeculectomy surgery was significantly higher in the drop group compared with the SLT group,” he explained.

His final thought: “This landmark trial supports the use of SLT as an initial treatment for open-angle glaucoma and ocular hypertension.”

AI in glaucoma: A work in progress

The wave of artificial intelligence (AI) and its applications are permeating many aspects of our lives, some of which we don’t even realize. AI has established itself as a valuable tool across many specialties within ophthalmology, holding the potential to standardize and improve disease detection for earlier diagnosis and intervention. It can also play a crucial role in monitoring therapeutic outcomes and improving access to screening.

Dinah Chen and colleagues recently published a review of AI and deep learning applications in glaucoma.

They found that, while interesting and promising, more work is needed before this research study is ready to roll into our clinics. Specifically, they noted that most of the algorithms are limited by their focus on a single imaging modality, fundus photos or optical coherence tomography, and the lack of a consensus in diagnostic criteria.4

Chen and colleagues also felt that an AI algorithm predicting treatment response was still a gap that needed to be addressed. These are all crucial issues, given the complexities inherent in the multimodal and variable nature of glaucoma. For now, we will categorize AI under ‘to be continued.’

There never seems to be a shortage of glaucoma patients in our waiting rooms each day, with the burden of delivering timely and quality care always top of mind. The experience of the pandemic may have spurred it on, but virtual glaucoma clinics have taken a significant step forward in recent years. And why not? They hold the potential to increase healthcare capacity while easing the disease burden of glaucoma for both patients and physicians.

Yi Fang Lee and colleagues in Singapore published an evaluation of the outcomes of their asynchronous virtual glaucoma clinic after three years of experience.5 More than 3,400 patients had their visual acuity, intraocular pressure (IOP), and visual fields or optic nerve head imaging recorded, followed by a virtual review by an ophthalmologist. They found that overall, this model

was safe, time-efficient, and cost-effective, with patients experiencing low rates of glaucoma progression.

A guiding principle in glaucoma innovation

Advancements are indeed exciting, often launched at flashy events during conferences. However, it is important to ask how they will fit into our daily practice, workflow, and for our staff and patients.

Dr. Bacharach raises some key things for pharma and device companies to consider when introducing something new into the glaucoma space, hoping for uptake into practices. “Ask, what is the value proposition of the intellectual property (IP)? Will the IP be disruptive, create new revenue streams, have a billable code or at least make fiscal sense if approved?” he said.

But most importantly, he added, the question to always keep top of mind when moving from experimental and into clinical practice is, “Will it improve the quality of life of patients?”

Traditionally, glaucoma has been managed primarily as a medical disease, with surgical intervention considered only when things start to deteriorate. However, there is a paradigm shift happening. The idea of harnessing technology, combined with advancements in therapy and exploration of new targets, has led us to an exciting time for clinicians and a hopeful time for patients.

Contributors

Dr. Steven J. Gedde , MD, is a professor of ophthalmology and vice chair of education at the Bascom Palmer Eye Institute. With an extensive national and international lecturing experience, Dr. Gedde has authored and coauthored more than 400 articles, book chapters, and abstracts. He is the editor of the second edition of Curbside Consultation in Glaucoma: 49 Clinical Questions and has served on the editorial boards for Ophthalmology, Journal of Academic Ophthalmology, EyeNet, Ocular Surgery News, Ophthalmology Management, and EyeWorld . Dr. Gedde has served on the board of directors of the American Glaucoma Society and the American Board of Ophthalmology . He is the chair of the Glaucoma Preferred Practice Pattern Panel. He is a study chairman for the Tube Versus Trabeculectomy (TVT) Study and Primary Tube Versus Trabeculectomy (PTVT) Study.

sgedde@med.miami.edu

References

1. Gedde SJ, Feuer WJ, Lim KS, Barton K, Goyal S, Ahmed II, Brandt JD; Primary Tube Versus Trabeculectomy Study Group. Treatment Outcomes in the Primary Tube Versus Trabeculectomy Study after 5 Years of Follow-up. Ophthalmology. 2022;129(12):1344-1356.

2. Mitchell WG, Azuara-Blanco A, Foster PJ, Halawa O, Burr J, Ramsay CR, Cooper D, Cochran C, Norrie J, Friedman D, Chang D. Predictors of long-term intraocular pressure control after lens extraction in primary angle closure glaucoma: results from the EAGLE trial. Br J Ophthalmol. 2023;107(8):1072-1078.

3. Gazzard G, Konstantakopoulou E, Garway-Heath D, Adeleke M, Vickerstaff V, Ambler G, Hunter R, Bunce C, Nathwani N, Barton K; LiGHT Trial Study Group. Laser in Glaucoma and Ocular Hypertension (LiGHT) Trial: Six-Year Results of Primary Selective Laser Trabeculoplasty versus Eye Drops for the Treatment of Glaucoma and Ocular Hypertension. Ophthalmology. 2023;130(2):139151

4. Chen D, Ran Ran A, Fang Tan T, Ramachandran R, Li F, Cheung CY, Yousefi S, Tham CCY, Ting DSW, Zhang X, Al-Aswad LA. Applications of Artificial Intelligence and Deep Learning in Glaucoma. Asia Pac J Ophthalmol (Phila). 2023;12(1):80-93.

5. Lee YF, Chay J, Husain R, Wong TT, Ho CL, Lamoureux EL, Chew ACY. Three-year Outcomes of an Expanded Asynchronous Virtual Glaucoma Clinic in Singapore. Asia Pac J Ophthalmol (Phila). 2023;12(4):364-369.

Dr. Jason Bacharach , MD, is the medical and research director at North Bay Eye Associates in Sonoma County, California, USA. He is also the co-director of Glaucoma Service in the Department of Ophthalmology at the California Pacific Medical Center and Pacific Vision Eye Institute in San Francisco, California. He has been involved in research for over 20 years and has been the principal investigator in over 140 Phase II-IV pharmacology and device studies in an effort to increase the effectiveness of glaucoma management as well as numerous other ocular diseases. Dr. Bacharach was also the first doctor in the Western United States to implant the Glaukos iStent, the first micro-invasive glaucoma surgical device, known as MIGS, to treat intraocular pressure.

jbacharach@northbayeye.com

OCT-A: Glaucoma’s New Ally?

Dr. Jacqueline Chua sheds light on the transformative potential of OCT-A in diagnosing and managing glaucoma

by Rich Carriero

OCT-A has garnered attention for its ability to track blood flow in the retina, offering unprecedented insights into retinal vasculature. In an interview with CAKE Magazine, Dr. Jacqueline Chua, a respected authority in ocular imaging, emphasized OCT-A’s potential to revolutionize glaucoma management, unlocking breakthrough potential for the disease.

Optical coherence tomography angiography, or OCT-A, is the (relatively) new kid on the OCT block—and it’s starting to attract buzz in surprising places.

OCT-A tracks blood flow in various layers of the retina to produce three-dimensional scans of the microvasculature in the back of the eye. Unsurprisingly, its debut has led to a cascade of research, showcasing the technology’s significant promise in screening for, managing, understanding, and treating a host of retinal diseases.

Glaucoma, then, might seem like a surprising place for OCT-A to show up. But Dr. Jacqueline Chua, an associate professor at Duke-NUS Medical School and clinicianscientist specializing in ocular imaging at the prestigious Singapore Eye Research Institute, believes

that OCT-A has breakthrough potential for the disease.

Dr. Chua, who authored a recent review1 summarizing why OCT-A might be beneficial for glaucoma, commented for this publication on the evidence supporting its role in the disease.

“Currently, OCT-A is positioned as a promising and valuable tool in the diagnosis and monitoring of

glaucoma,” she shared. “It offers reliable differentiation between glaucomatous and healthy eyes, with good repeatability and reproducibility. The technology has advanced to the point where it provides valuable insights, particularly in advanced glaucoma cases,” she continued.

Providing access to powerful biomarkers

“OCT-A plays a crucial role in the treatment journey for glaucoma by offering a non-invasive and highresolution assessment of retinal vasculature. It aids in early detection and provides insights for treatment planning and extended monitoring, particularly in advanced stages where traditional methods face limitations,” Dr. Chua explained, summarizing recent findings in eye care.

OCT-A’s utility in glaucoma lies in its ability to distinguish a number of powerful biomarkers. These include optic nerve head and peripapillary vessel density, macular vessel density, and a variety of choroidal parameters, such as choroidal microvascular dropout.

Notably, OCT-A scans of glaucoma patients reveal reductions in blood vessel profusion around the optic disc and macula in the superficial layers, along with capillary loss at the choroidal level. These biomarkers align closely with OCT-A structural scans and visual field maps.2

Dr. Chua also believes that OCT-A offers particular advantages for advanced glaucoma cases. Unlike changes currently tracked in cupto-disc ratio and nerve fiber layer thinning, density loss in retinal microvasculature correlates with disease progression through moderate and even advanced stages.

All of these factors contribute to OCT-A overcoming what Dr. Chua terms the ‘floor effect’ with current structural measurements. “Unlike OCT metrics, vessel density does not exhibit a measurable floor value, providing a potential avenue for continued monitoring in advanced cases,” she said.

Machines of the future

Dr. Chua sees such research revelations about OCT-A as a game

changer for glaucoma. “OCT-A is likely to be seamlessly integrated with structural measurements, providing a comprehensive understanding of both vascular and structural changes in the retina. This holistic approach can offer a more complete picture of glaucoma pathology and aid in treatment decision-making,” she continued.

For Dr. Chua, the future of OCT-A in glaucoma is all about breaking through limitations in current standard-of-care imaging. “The capability of OCT-A to overcome the ‘floor effect’ in advanced glaucoma, particularly in monitoring perifoveal vessel density, could enhance the monitoring of disease progression. This continuous monitoring may provide valuable data for assessing the effectiveness of treatments and making timely adjustments,” she added.

The process of integration is already underway. Doctors can now analyze structural and microvascular changes side-by-side to make a surer diagnosis. However, mastering this art is not easy.

“[Eye care practitioners] should be familiar with the capabilities and limitations of OCT-A in glaucoma assessment. Proficiency in interpreting vessel density metrics and considering the impact of various factors on OCT-A measurements is essential for their effective use in future clinical practice,” Dr. Chua noted.

No matter how adept the clinician is, manual comparison is a laborious process. The solution, she said, lies in the promise of artificial intelligence (AI) and machine learning.3

“AI is expected to play a significant role in enhancing the capabilities of OCT-A in glaucoma assessment. Its anticipated role includes the analysis of OCT-A multilayer images, enabling efficient processing of large datasets,” Dr. Chua explained.

“This is especially beneficial in clinical settings where time is a critical factor. Automation reduces the workload on clinicians, allowing for quicker and more standardized evaluations, ultimately leading to improved efficiency in glaucoma assessment,” she added.

Roadblocks in OCT-A adoption

However, despite the promise of OCT-A in glaucoma, it’s not a plugand-play solution—yet. Obstacles slowing the full implementation of OCT-A fall under two categories: Technical and regulatory.

Visual artifacts are one common tech complaint. Onboard software is designed to compensate for routine imaging issues like patient motion. Nevertheless, eye blinks, vitreous floaters, and overlying blood vessels can still cast shadows on the final scan, affecting the reliability of the resulting images.

Segmentation errors, which involve discrepancies in measured versus observed scan depth, are another common problem. “Providing comprehensive training to operators and clinicians to recognize artifacts and emphasizing the importance of obtaining high-quality scans can minimize their impact,” explained Dr. Chua.

Segmentation errors are not always the fault of the machine or the operator. Each OCT manufacturer has its own scheme for demarcating and labeling the various retinal layers, resulting in a lack of standardized roadmaps for navigating the retina.4

Confidentiality concerns present another regulatory hurdle. The inability to create large-scale scan databases for research purposes hampers both demographic studies and effective AI training.

protocols, including acquisition parameters, scan patterns, and device-specific settings. Collaboration among manufacturers, researchers, and regulatory bodies can contribute to standardization efforts,” she concluded.

References

1. Hong J, Tan SS, Chua J. Optical coherence tomography angiography in glaucoma. Clin Exp Optom. 2024:1-12.

2. Rao HL, Pradhan ZS, Suh MH, Moghimi S, Mansouri K, Weinreb RN. Optical Coherence Tomography Angiography in Glaucoma. J Glaucoma. 2020;29(4):312-321.

3. Li C, Chua J, Schwarzhans F, et al. Assessing the external validity of machine learningbased detection of glaucoma. Sci Rep. 2023;13(1):558.

4. Patel PJ, Chen FK, da Cruz L, Tufail A. Segmentation error in Stratus optical coherence tomography for neovascular age-related macular degeneration. Invest Ophthalmol Vis Sci. 2009;50(1):399-404.

Editor’s Note

A version of this article was first published on cookiemagazine.org.

Contributor

Recent innovations in imaging and diagnostics, such as retinal fluid monitors and polygenic risk assessment for glaucoma, have shown that scientists and regulators can develop diagnostic software algorithms based on large sets of patient data without compromising privacy and security. Given the immense potential for OCT-A, it’s only a matter of time before these retinal scans will be similarly accessible.

Dr. Chua argues that cooperation and standardization are key to these issues: “One potential strategy is establishing consensus guidelines and standards for OCT-A imaging

Dr. Jacqueline Chua is a clinician-scientist at the Singapore Eye Research Institute and a practicing optometrist in a primary eye care setting at the Singapore National Eye Centre. Dr Chua graduated with a Bachelor of Optometry degree from the University of Melbourne and a PhD from the University of Auckland. Upon completion of her doctorate, she undertook a five-year stint in optometric academia. She has also attained a clinical fellowship from the American Academy of Optometry. She was recently awarded the Transition Award, an early career talent development fund for clinician-scientists to improve the detection of glaucoma using new imaging technology.

jchua@duke-nus.edu.sg

A Vision For Reform

A passionate advocate for change, Dr.

Ma. Dominga

Cecilia B. Padilla spearheads impactful initiatives in eye banking and healthcare advocacy in the Philippines

by Chow Ee-Tan

Meet Dr. Ma. Dominga Cecilia B. Padilla, whose illustrious career as an ophthalmologist, politician and corneal transplant advocate spans decades. From her humble beginnings to her groundbreaking achievements in medicine, Dr. Padilla’s story is one of passion, dedication, and unwavering commitment to serving others.

Dr. Ma. Dominga Cecilia B. Padilla, more popularly known as Minguita in her homeland, the Philippines, is an accomplished ophthalmologist who wears many hats.

Among her most notable contributions to the field of medicine is the establishment and operation of the Eye Bank Foundation of the Philippines (EBFP), a humanitarian NGO that has made corneal transplants accessible to blind Filipinos from all walks of life since 1995.

In addition to her active practice as an eye surgeon at St. Luke’s Medical Center Global City, Dr. Padilla also held various leadership roles, including head of the Committee on Ethics and Discipline, head of the Ocular Tissue Transplant Service, and member of the President’s Advisory Board.

Dr. Padilla believes that divine intervention led her to become an ophthalmologist.

“Since I was young, I wanted to be many things: A concert pianist, an actress, a lawyer, a diplomat, among others,” she recalled. “It was after the mandatory spiritual retreat in my senior year in high school that I decided to become a physician.”

Then came the decision about specialization. Her first options were endocrinology, and then plastic surgery. However, her father’s vision started to deteriorate rapidly due to pathologic myopia and myopic macular degeneration. Her decision to become an ophthalmologist became a no-brainer. She wanted to help her father continue working as a lawyer, so she pursued ophthalmology.

Navigating a maledominated profession

In the late 1980s, ophthalmology wasn’t considered a woman’s field. Most renowned clinicians and ophthalmic surgeons were men. The most prominent female ophthalmologist at the time was primarily recognized as an academic rather than a clinician. Apart from herself, there was perhaps only one other female who was starting to establish herself clinically.

Since she began her residency more than three decades ago, Dr. Padilla has witnessed a significant shift in women’s roles in medicine, particularly in ophthalmology. Today, there is gender parity among ophthalmologists, marking a substantial change from previous years.

“In my residency interview, I was asked a lot of questions about my relationship status, such as whether I had a boyfriend and if I had plans to marry. When I started practicing, I had no practice to inherit—I had to start from scratch!” recalled Dr. Padilla.

“My very first patients were Filipino construction workers preparing to work overseas in the Middle East. I used to go to an overseas employment office, bringing with me my portable instruments because the office lacked ophthalmic equipment,” she shared. “I examined them before their departure, certifying those who were fit for work. They formed my initial core patients. Eventually, when they were able to send money home, their family members became my patients at the Makati Medical Center,” she continued.

Among her first significant breakthroughs was performing surgery on an expatriate’s son who had been injured by a sharp pencil in the eye.

“I knew that initially the father did not trust me to do the surgery because of my gender and age. I found out a few months later that the reason he eventually let me do the surgery was because he inquired about my competence from our chairman, Dr. Carlos Sevilla. Dr. Sevilla assured him that his son couldn’t be in better hands. I owe a lot to Dr. Sevilla,” she shared.

Advocacy and commitment

The decision to specialize in cornea and establish an eye bank was another calling for Dr. Padilla. During her residency, ophthalmologists in the Philippines had to live with the stark reality that they could not help those who were corneal blind, many of whom were children or productive adults. This was primarily due to the lack of corneal tissue. The occasional

tissue the Philippines could get was donated from other countries. Recognizing this urgent need, efforts had been ongoing since the 1950s to establish an eye banking system.

“One thing led to another, and the right people came into my life, to whom I owe much for helping to establish the eye bank,” reflected Dr. Padilla. “The road has not been easy, and the system of eye banking, or organ and tissue donation in general, still has much room for improvement. However, the eye bank is still standing and continues to serve individuals in need of corneal transplants, regardless of their background.”

The Eye Bank Foundation was established on March 17, 1994, and the Santa Lucia International Eye Bank of Manila, the physical medical eye bank facility, was inaugurated on October 16, 1995.

Dr. Padilla’s tireless contributions to the ophthalmology fraternity have earned her multiple accolades and awards, both locally and internationally.

When asked which of her many awards means the most to her, Dr. Padilla cited the Jose Rizal Memorial Award given by the Philippine Academy of Ophthalmology (PAO). This award, given by her peers, holds special significance as it represents the highest honor the PAO can give for lifelong contributions to ophthalmology.

Another deeply meaningful award for Dr. Padilla is the Association of Eye Banks in Asia Award, recognizing her profound and lifelong contribution to eye banking in Asia. Additionally, an award for her service to the community during the COVID-19 pandemic also means a lot to her.

According to Dr. Padilla, among the most satisfying aspects of being an ophthalmologist is transforming the lives of those whose eyesight has been restored, as well as those of their loved ones.

“As the founder of the eye bank and currently its ambassador-at-large, I am committed to working towards the goal of truly institutionalizing cornea donation in the country so that we will have the tissue we need, when and where we need it,” she enthused.

Together with the eye bank staff and officers, they go around the country, setting up eye tissue retrieval centers, and training healthcare professionals in the art and science of eye banking and, counseling. “I would also like to see the Philippines more involved in research, especially in regenerative ophthalmology and stem cells, among others,” she added.

A vision for change

Despite all that she had already done, Dr. Padilla felt a strong calling to do more for her country. This call was especially strengthened by the

Dr. Padilla with Filipino national scientist, teacher and mentor for universal health care, Dr. Ernie Domingo and his wife

Dr. Padilla with her two nieces

Dr. Padilla with her husband Dr. Victor Lopez and their pug Maxi

pandemic, during which she actively helped out in the country’s COVID-19 response. She played a key role in making COVID testing accessible and affordable, for which she received the Exemplary Makatizen Makahero Award from the government of Makati, recognizing her sacrifice and heroism in serving the city’s residents and aiding its recovery from the pandemic.

In October 2021, Dr. Padilla made a bold move by filing her certificate of candidacy for the Senate. She took this last-minute leap of faith despite recognizing the slim odds of victory.

“While victory may have evaded me for that particular race, I know I ran a very good campaign that resonated with a lot of people, especially the youth. I don’t think I have any plans now to run for the 2025 election. I’m taking a break for a while, but I know I can’t say never.”

Her platform comprised 12 parts, half of which were health-related. These included the proper implementation of the UHC Act, reforming the Philippine Health Insurance Corporation (PhilHealth) by addressing the systemic problems plaguing the GOCC; safeguarding the welfare of healthcare workers; addressing mental health issues, especially among youth; institutionalizing tissue and organ donation; and fixing the supply chain management problem for medicines to ensure they reach those in need instead of rotting in warehouses—a longstanding issue in the country yet to be addressed.

“While victory may have evaded me for that particular race, I know I ran a

very good campaign that resonated with a lot of people, especially the youth. I don’t think I have any plans now to run for the 2025 election. I’m taking a break for a while, but I know I can’t say never,” she quipped.

Of faith and service

Dr. Padilla is married to renowned ophthalmic plastic surgeon Dr. Victor Lopez and has a stepson in the United States. When not working, she enjoys playing the piano, singing, dancing, cooking, and watching sports on TV, especially women’s volleyball and soccer. She even has a few song recordings that can be viewed on her YouTube channel!

If and when this happens, then we will have a much better chance of a responsive, efficient, and compassionate healthcare system,” she concluded.

Contributor

She has written numerous sociopolitical and medical commentaries published in major broadsheets in the Philippines, and continues to occasionally contribute when she feels the need to share her views on certain topics affecting the public.

At the core of all she does is Dr. Padilla’s faith in God. She visits the Blessed Sacrament as often as she can and has been serving in the music ministry as a song leader at her Parish since the age of 14.

Looking ahead, Dr. Padilla hopes to see her country treat its healthcare workers with the respect they deserve.

“I would like to see universal healthcare take root, especially in terms of access to regular, basic check-up packages covered by PhilHealth, particularly in geographically isolated and depressed areas. We also need to utilize information technology and even artificial intelligence (AI) effectively to reach as many of our people as possible, despite the challenge of a dwindling health human resource pool,” she explained. “This will require the integration of various government departments. Preventive healthcare should be our main focus, and this cannot happen without integration and efficient networking.”

Last but not least, she said, “We need our leaders to view healthcare as sacred. It is a right, not a privilege. Hence, it should not be held hostage by political patronage and corruption.

Dr. Ma. Dominga Cecilia ‘Minguita’ B. Padilla , MD, FPAO, FPCorS, is the founding president/CEO of the Eye Bank Foundation of the Philippines, a humanitarian NGO that made corneal transplants accessible to blind Filipinos. Currently its ambassador-at-large, Dr. Padilla is also a founding council member of the Asia Cornea Society (ACS) and the current head of the Association of Eye Banks in Asia (AEBA). She is an active consultant at the St. Luke’s Medical Center, where she is also the head of the Ocular Tissue Transplant Service. Other current positions include membership in the Commission on Legislation of the Philippine Medical Association and the Sector Skills Development Group of the Unilab Foundation. She was a clinical associate professor at the University of the Philippines College of Medicine from 2008 to 2021 and chaired the Committee on Ethics and Discipline at the St. Luke’s Medical Center from 2015 to 2021. She was the head executive staff of the Philippine Health Insurance Corporation from 2015 to 2016 and then became the spokesperson for the Universal Healthcare (UHC) Study group of the University of the Philippines. She is an author and co-author of various published papers on ophthalmology as well as socio-political essays. Her interests include eye banking, dry eye, ocular infections, keratoprosthesis, public health, and good governance. Dr. Padilla is a recipient of multiple awards for her work in eye banking, prevention of blindness, community service, curbing health insurance fraud, and service during the time of the COVID-19 pandemic.

minguita@gmail.com

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The Atropine Conundrum

Experts offer valuable insights into the disparities between research findings and real-world outcomes in atropine use

by Diana Truong

As myopia rates continue to rise globally, atropine offers hope in curbing its progression. However, recent studies have presented conflicting evidence regarding its effectiveness. Experts weighed in on this debate, shedding light on the disparity between research findings and clinical practice.

Amidst the rising tide of global myopia rates, atropine has emerged as a promising new treatment modality, aiming to wrest control over the axial length growth that marks myopia’s relentless march. Sort of.

Foundational studies like 2006’s Atropine for the Treatment of Myopia (ATOM)1 and its longer-term 2016 successor, ATOM22 , established atropine, and especially low-dose atropine (generally regarded as concentrations of 0.01-0.05%) as a much-needed tool in the myopia specialist’s toolkit. However, other studies have painted a much different picture.

Most recently, data from a landmark 2023 study funded by the National Eye Institute and conducted by the Pediatric Eye Disease Investigator Group (PEDIG) in the United States have cast doubt on the efficacy of low-dose atropine. The study concluded that low-dose atropine (.01%) provided no benefit over placebo.3

care practitioners scratching their heads.

So what’s behind this minefield of mismatches, and how can the modern practitioner make actionable decisions based on these seemingly irreconcilable findings?

Clinical realities vs. research constraints

A lot—according to pediatric myopia expert Dr. Sun Chen-Hsin, a clinicianengineer at Singapore’s National University Hospital. With Singapore possessing one of the world’s highest myopia rates, his clinic sits at a critical hotspot in the myopia epidemic.

As a proponent of the promise of atropine, Dr. Sun was alarmed by the PEDIG group’s disappointing verdict on the drug. Nevertheless, he believes that a closer look at the existing research reveals a skewed reflection of real-world atropine results.

This bombshell assertion has ignited a long-simmering controversy surrounding atropine for myopia,

bringing it to a full boil. Nuances ranging from concentration to treatment duration, and even race, have produced wildly different efficacy results—leaving many eye

For him, treatment methodology plays a significant role in explaining the discrepancy between the research findings and the real-world results observed in his clinic and those of his colleagues.

Dr. Sun pointed out that many of the previous studies, including the PEDIG and ATOM studies, involved an abrupt halt in the treatment of the drops.

“That’s not what we do in real life—we continue to follow up,” Dr. Sun said.

“We never stop the atropine, like in the clinical studies, because we know they are going to rebound. The higher the concentration, the more pronounced the rebound,” he noted, referring to the apparent myopic increase observed in some clinical trial patients following the abrupt cessation of the drug.

According to Dr. Sun, practical clinicians opt for a more gradual tapering approach to mitigate these rebound effects and ensure the slowing of myopia progression. Atropine levels are decreased or increased, and treatment intervals are lengthened over extended periods based on individual patient responses.

These time scales, however, are not practical in clinical trials like the PEDIG study. “It’s a very long, drawnout process,” he explained. “It’s really difficult to design this kind of trial to run for five or seven years.”

ATOM2 and its five-year clinical trial length corroborate this statement by more closely (though not perfectly) reflecting the real-world use of atropine. The study lasted five years, with the treatment phase spanning 24 months, followed by a 12-month cessation period. Those exhibiting myopia progression during this break were subsequently reintroduced to atropine 0.01% for an additional 24 months. ATOM2 revealed that this 0.01% concentration, when reintroduced to prevent rebound, exhibited the highest efficacy in myopia control with fewer side effects.2

Understanding formulation variability

Dr. Sun also believes that variations in the formulation of atropine have led to inconsistencies in results across numerous studies.

He referenced the work of Dr. Greg Ostrow, a former chemist turned pediatric ophthalmologist, whose presentation at the Brazilian Academy of Myopia Control and Orthokeratology’s World Congress on Myopia Control revealed the chemistry behind atropine drops as a potentially significant variable.

In his presentation, Dr. Ostrow scrutinized the formulation of atropine drops and found that the compound’s bioavailability is inversely proportional to its acidity. However, stability and shelf life also play a crucial role—more stable solutions tend to have a longer shelf life.

This duality poses a quandary. To achieve FDA approval, atropine solutions must maintain stability for two years, which requires an acidic pH of four. However, this acidic pH hinders optimal absorption into the eye.

The effects this has on children may be another source of study variability. “Firstly, this stings the eye. Children will have more tearing and will squeeze more drops out of the

eye as they put them in,” commented Dr. Sun on Dr. Ostrow’s findings. “Secondly, lower pH reduces the absorption of atropine into the eye itself,” he said. “When you have more acidity, it simply doesn’t penetrate the eye.

Pupil size as a key indicator

For Dr. Sun, the crux of the matter lies in the challenge of comparing atropine strength across diverse studies. Each study employs atropine manufactured differently, leading to variations in bioavailability and effectiveness. As such, it is inherently difficult to draw concrete conclusions due to these disparities in atropine formulations

However, Dr. Sun looked underneath the hood of these studies and found a possible way of evaluating the absorption of atropine. “One thing that can give you a surrogate marker of how much atropine there is—is the pupil size of the children,” Dr. Sun said.

A change in pupil size could thus indicate atropine absorption, as it is also a mydriatic agent. He observed that critically, in studies with positive efficacy data like ATOM2 and 2019’s LAMP, a notable increase in pupil size was observed.2 ,4

In the PEDIG study, Dr. Sun noted that although pupillary size was not measured, there were no complaints about increases in photophobia—a telltale sign of an atropine-induced increase in pupil size. For him, this all suggests poor absorption of the drug.

Dr. Sun also recalled his observation about the potentially inverse relationship between formulation acidity and efficacy in the PEDIG trial. “In PEDIG, both the placebo group and the treated group had eye irritation, perhaps from the higher acidic carrier vehicle,” he said.3

Though these inferences from the studies are far from concrete, they could suggest further avenues for research. “This is, of course, all speculative,” Dr. Sun noted. “But this could be an answer to

the question of why there is so much variability in these studies.”

“The number outside the bottle might not be a consistent measure of how much of the drug is getting into the eye. I think in order for there to be standardization, there should be a standardization of pupil change across studies to see how much of the atropine actually went into the eye,” he concluded

Racial disparities in atropine response

Besides stoppage-related rebounds, methodology discrepancies, and formulation variation, differences in testing populations—specifically, race—also play a vital role. And one of the leading voices putting forth this explanation comes from a perhaps unexpected source.

Reflecting on the negative PEDIG study results, which found that low-dose atropine did not impede myopia progression, lead co-author Dr. Michael X. Repka emphasized the potential racial differences in treatment response.

“The absence of a treatment benefit in our US-based study, compared with East Asian studies, may reflect racial differences in atropine

response,” Dr. Repka said in a statement on the study results.

“The study enrolled fewer Asian children, whose myopia progresses more quickly, and included Black children, whose myopia progresses less quickly compared with other races,” he continued.

The 2023 study Myopia Outcome Study of Atropine in Children (MOSAIC), echoed these comments on the role of race. This study was the first to be conducted on a primarily white European population, whereas previous studies had predominantly focused on Asian populations.5

MOSAIC saw mixed results for atropine in spherical equivalent refraction (SER) but positive results for slowing axial elongation in this population. In the conclusion of the study, the authors noted issues with the generalizability of previous studies due to their relatively ethnically homogenous patient populations.5

The impact of participants’ age

This unexpected result could potentially point to another factor influencing the inconsistency in the major atropine studies—the age range of the participants.

Myopia exhibits a unique trajectory. At around age 15, approximately half of the children experience stabilization in their myopia, and this trend continues, with more achieving stability as they transition into their early 20s.6

As myopia progression typically slows with age, the age range of research participants has emerged as a crucial factor in assessing atropine’s effectiveness. This was another key observation of MOSAIC, which involved European children with an age range extending up to 16. The study authors noted that many Asian studies have limited participant age to 12, potentially introducing an influencing factor on research outcomes.

Dr. Repka, the lead author of the PEDIG study, concurred. In recent public comments on the PEDIG study, he emphasized the probable impact of age on the outcome and stressed the importance of administering treatment during the phase of peak progression to optimize its benefits for patients.

From conundrum to clarity

Atropine began as a beacon of hope for myopia control, but now it stands as a multifaceted puzzle, instigating a quest for answers.

The once-clear path has become a complex web of considerations— from study duration and ethnicity differentials to age nuances and atropine formulations. Each facet introduces layers of intricacy, teasing researchers and clinicians with more questions than answers.

strategies have a synergistic effect?” asked Dr. Michael Chiang, director of the NEI, when commenting on the PEDIG results.

“Could we develop other approaches to treatment or prevention based on a better understanding of what causes myopia progression?”

In the end, though potential explanations are coming into focus, uncertainty persists. Yet within this uncertainty lies the heartbeat of progress. These conflicting results are not roadblocks but rather signposts, urging the community to delve deeper, question assumptions, and refine hypotheses.

“The overall mixed results on lowdose atropine show us we need more research. Would a different dose be more effective in a US population? Would combining atropine with other Editor’s Note

this article was first published on cookiemagazine.org.

Contributor

References

1. Chua WH, Balakrishnan V, Chan YH, et al. Atropine for the treatment of childhood myopia. Ophthalmology. 2006;113(2):2285-2291.

2. Chia A, Lu QS, Tan D. Five-Year Clinical Trial on Atropine for the Treatment of Myopia 2: Myopia Control with Atropine 0.01% Eyedrops. Ophthalmology. 2016;123(2):391-399.

3. Repka MX, Wise KK, Chandler DL, et al.; Pediatric Eye Disease Investigator Group. Low-Dose 0.01% Atropine Eye Drops vs Placebo for Myopia Control: A Randomized Clinical Trial. JAMA Ophthalmol. 2023;141(8):756-765.

4. Yam JC, Jiang Y, Tan SM, et al. Low-concentration atropine for myopia progression (LAMP) study: A randomized, double-blinded, placebo-controlled trial of 0.05%, 0.025%, and 0.01% atropine eye drops in myopia control. Ophthalmology. 2019;126(1):113-124.

5. Flitcroft I, Kobia-Acquah E, Lingham G, et al. Myopia outcome study of atropine in children (MOSAIC): Two-year results of daily 0.01% atropine in a European population. Invest Ophthalmol Vis Sci. 2023;64(8):1963.

6. Walline JJ, Berntsen DA. Atropine, 0.01%, for Myopia Control. JAMA Ophthalmol. 2023;141(8):766-767.

Dr. Sun Chen-Hsin is a clinician engineer at Singapore’s National University Hospital. He graduated from Johns Hopkins University in 2008 with a Bachelor of Biomedical Engineering and a Master of Science in Electrical and Computer Engineering in 2009. In 2013, he received a Doctor of Medicine (MD) from Duke-NUS Graduate Medical School. After completing his ophthalmology residency and clinician-scientist training in 2019, he was accredited by the Specialists Accreditation Board as a specialist in ophthalmology by the Ministry of Health of Singapore. As an expert in managing progressive myopia in children and an engineer, he has developed a wearable device for tracking outdoor time and near reading, and is currently developing an ambulatory biometer for more precise measurements of axial elongation in myopic children.

cfssch@nus.edu.sg

The Tales Ocular Tissues Tell

Experts at ARVO 2024 discuss current and future directions in biomechanical research

by Matt Herman

Advances in biomechanical analysis are opening up enticing new avenues in tissue research. During a symposium at ARVO 2024, experts in the field showed the promise—from screening to treatment—that a deeper understanding of these structures may bring.

The eye plays host to a complex array of structures and tissues that researchers are only beginning to unravel and understand. Much-needed progress on understanding the component structures and materials that make up the eye and their properties has been steady but slow.

The barriers to a comprehensive understanding of the biomechanical

properties of ocular tissues are many. The eye and its components are small. There isn’t much, if any, tissue to spare. And in vivo studies are sensitive due to the essential role of sight in human life and the complex, easily disrupted web of structural interactions that enable it.

But researchers gathered for a symposium at the 2024 Annual Meeting of the Association

for Research in Vision and Ophthalmology (ARVO 2024) believe that might be changing. Technologies like optical coherence elastography (OCE), Brillouin microscopy and more are blossoming—and with them, a whole host of new insights, novel biomarkers, and head-turning possibilities for screening, treatment and beyond.

Novel methods for seeing—and measuring— the eye

Manual tissue palpation is one of the oldest forms of medicine, and Dr. Kirill Larin (University of Houston, USA) is at the forefront of those trying to bring it to the modern age for use in the eye.

After tracing tissue palpation back to its roots in Ancient Egypt and Greece, Dr. Larin described his vision for OCE, a modern method for, in a way, palpating the tissues of the eye to discover the secrets latent in their biomechanical properties.

In OCE, force is applied to a tissue, which is then imaged and measured to understand properties like elasticity, as well as relative hardness and softness. “It’s embarrassingly simple,” Dr. Larin said.

“You take standard OCT imaging and apply a force. When you apply a force, if you measure the area and divide by change in the tissue structures, you can deduce its mechanical properties because if you have stiffer material, it’s going to deform less,” he said.

According to Dr. Larin, one key observation that has propelled OCE forward is the ability to use natural variations in IOP (when the heart beats, for example) as a way to induce and measure deformation. The resulting lack of a need to apply external force has opened many doors for OCE.

As a result, this technology is seeing a rush of possible new applications across ophthalmology. In LASIK, for example, the softness of the cornea can be measured preoperatively in an attempt to predict the possibility of post-LASIK corneal ectasia.

Dr. Larin also mentioned research on using OCE measurements in corneal

injuries and keratoconus. He’s even used it to measure the limbus and the eye globe itself. “It allows you to do 3D imaging of tissue, and this can give you highly localized mechanical information. I personally believe there’s great promise for the future detection of different diseases and therapeutics,” he concluded.

Dr. Giuliano Scarcelli (University of Maryland, USA) spoke next about how he’s breathing new life into Brillouin microscopy, another method for imaging ocular tissue for biomechanical evaluation.

With this technique, interactions between light waves and sound waves are measured to provide useful information on the hidden structures within the eye. Dr. Scarcelli’s work on Brillouin microscopy has been gathering steam over the last few years, yielding promising results.

Similar to Dr. Larin’s work with OCE, Dr. Scarcelli sees great potential for the technology in corneal ectasia and keratoconus, among others. Direct and accurate measurements of the cornea with high spatial resolution that can be performed in vivo are a holy grail of sorts in corneal biomechanics. According to Dr. Scarcelli, Brillouin microscopy just might be the ticket.

Deep dives on the lens and mechanobiology of glaucoma

After these scintillating new tools and their potential were put on display, the spotlight shifted to advancements in our current knowledge of the biomechanics of the eye and its tissues. Dr. Catherine Cheng (Indiana University Bloomington, USA) presented her work on understanding the nuanced, deep structures of the lens in mouse eyes.

Dr. Cheng’s group focused on determining factors in lens stiffness and resilience. They found that the complexity of interdigitations between fiber cells, cytoskeletal networks such as the f-actin networks and intermediate filament networks, and the integrity of the lens capsule were key contributors to lens stiffness.

On the other hand, the contributors to lens resilience were different. According to Dr. Cheng, cytoskeletal networks like f-actin may be involved, and there could be a correlation with lens nucleus size, although further research is needed. The lens capsule also might be involved, though Dr. Cheng said this depends on the severity of the defect.

One of her findings, however, sparked significant interest. “Most importantly, we found that the Y-suture actually plays a really important role in lens elasticity,” she said. “In fact, the mispatterning of cells and the misalignment of the Y-suture cause the lens to be more resilient.”

For Dr. C. Ross Ethier (Georgia Institute of Technology, USA), it is glaucoma that has drawn the kind of specialized attention that Dr. Cheng’s group placed on lens biomechanics. His presentation was full of insights into the mechanobiology of the apparent self-regulation of IOP homeostasis in the human eye.

Dr. Ethier’s lab* has taken full advantage of technologies such as the aforementioned Brillouin microscopy and OCE, along with atomic force microscopy (AFM), to reach some fascinating conclusions.

He has found that the outflow pathway tissues, such as the trabecular meshwork and the inner wall of the endothelial monolayer lining Schlemm’s canal, are stiffer in glaucomatous eyes—although the mechanobiology of the outflow pathway remains complex. However, the regulatory system for maintaining IOP homeostasis in healthy eyes holds perhaps the most promise for Dr. Ethier.

“We have a very complex mechanobiologic regulatory system with redundancy and multiple pathways,” he explained. “This is great because it offers a lot of opportunities for therapeutic intervention, hopefully leading to pressure control.”

The promise of modern biomechanical analysis

The final speaker of the day, Dr. Christine Wildsoet (University of California at Berkeley, USA), brought

home the most crucial theme of the session, carried over from Dr. Ethier. In the end, it’s all about helping patients, and she explained how scleral biomechanics might be opening new doors for interventions in one of the world’s most pressing areas: Myopia.

Dr. Wildsoet surveyed a large amount of research on the influence of the sclera in myopia. Among these, she revisited the role of the sclera in IOP and the potential benefits of using an agent like latanoprost to control myopia.

She also discussed research on hydrogel drugs delivered to the sclera as a potential alternative to the unpopular and highly invasive scleral buckle in failing sclera in myopic eyes. However, her overall message and point of emphasis were much more general, providing a fitting end to the session.

“I think translation is a two-way street,” Dr. Wildsoet began. “We’ve got to be jumping between the clinic and basic science and back again to inform one another. Having cross-disciplinary collaboration is really valuable for getting us to think outside the box,” she concluded, pointing to the immense potential on display throughout the symposium for the integration of engineering and biomechanical evaluation into potentially life-changing innovations in ocular tissue research.

Reference

* Georgia Tech. Ethier Lab. Available at https:// ethier.gatech.edu/. Accessed on May 7, 2024.

Editor’s Note

The Annual Meeting of the Association for Research in Vision and Ophthalmology (ARVO 2024) was held from May 5 to 9 in Seattle, Washington, USA. Reporting for this story took place during the event. A version of this article was first published on cakemagazine.org.

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