The Association for Research in Vision and Ophthalmology-

Organizer: Marlies Gijs, PhD, University Eye Clinic Maastricht, School for Mental Health and Neuroscience (MHeNs), Maastricht University Medical Center (MUMC+), Maastricht, The Netherlands

Tear fluid is emerging as a source of non-invasive biomarkers since tear fluid biomarkers are the only way to gather biological information about the eye (and the body) in real time. However, clinical applications of tear biomarkers are not there yet, as the field is facing a lack of standardization and harmonization. Accurate quantification of tear proteins can be improved by standardizing methods to collect and process tear fluid. During this Special Interest Group session, the following themes will be discussed: How to normalize your raw data into clinically meaningful biomarkers?; The need for reference values of commonly investigated tear biomarkers.; How to set up your own tear fluid biobank.; and the need for an open repository of tear proteomics.

Panelists

Suzanne Hagan, PhD, Department of Vision Sciences, Glasgow Caledonian University, Glasgow, Scotland, United Kingdom
Amalia Enriquez-De-Salamanca, PhD, Institute of Applied Ophthalmobiology (IOBA), Universidad de Valladolid, Valladolid, Spain; Networking Research Center on Bioengineering Biomaterials and Nanomedicine (CIBER-BBN), Valladolid, Spain.
Swaminathan Sethu, BDS, MSc, PhD, GROW Research Laboratory, Narayana Nethralaya Eye Foundation, Bengaluru, Karnataka, India
Ashok Sharma, PhD, Center for Biotechnology and Genomic Medicine, Medical College of Georgia, Augusta University, Augusta, GA

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Navigating challenges in AI implementation for retinal disease care: A clinical perspective
June 11 | 9 - 10:30am EDT

Organizers: Rajiv Raman, MS, DNB, Vision Research Foundation, Sankara Nethralaya, Chennai; Maitreyee Roy, PhD, University of New South Wales, Sydney; Rehana Khan, BS, Optometry School of Optometry and Vision Science, University of New South Wales, Sydney

Join our SIG as we delve into the complexities of implementing AI solutions for retinal diseases in clinical care. Retinal diseases demand precision and efficiency in diagnosis and management. This session addresses the hurdles faced in integrating AI into clinical workflows, exploring issues such as data compatibility, regulatory compliance, and clinician adoption. Attendees will contribute to discussions on overcoming these challenges, fostering collaboration between AI developers, clinicians, and healthcare administrators. Let us collectively shape the future of retinal disease care through insightful dialogue and problem-solving.

Discussion themes

Algorithm Selection
- Evaluating criteria for selecting appropriate algorithms for retinal disease diagnosis.
- Balancing sensitivity and specificity: How to choose an algorithm that minimizes false positives and false negatives.
- Considering interpretability and explainability in algorithm selection.
Improving Acceptance Among Clinicians
- Understanding and addressing clinician concerns about AI integration.
- Strategies for effective communication between AI developers and clinicians.
- Providing training and support to enhance clinician confidence in AI-assisted diagnoses.
Tackling Wrong Diagnosis
- Identifying root causes of incorrect AI diagnoses and implementing corrective measures.
- Developing strategies for continuous algorithm refinement based on real-world clinical feedback.
- Establishing feedback loops for clinicians to report and rectify AI-generated errors.
Over referral: Is it a Problem?
- Exploring the impact of over referral on healthcare resources and patient well-being.
- Strategies to minimize over referral without compromising patient safety.
- Balancing the sensitivity of AI algorithms to avoid unnecessary interventions.
Interdisciplinary Collaboration
- Facilitating collaboration between AI developers, clinicians, and healthcare administrators.
- Strategies for creating interdisciplinary teams to enhance the implementation process.
- Encouraging a culture of collaboration and knowledge-sharing in healthcare settings.

Panelists

Gavin S. Tan, MBBS, FRCSEd, PhD, Singapore National Eye Centre, Singapore Eye Research Institute, Singapore, Republic of Singapore
Paisan Ruamviboonsuk, MD, Department of Ophthalmology, College of Medicine, Rangsit University, Rajavithi Hospital, Bangkok, Thailand
SriniVas R. Sadda, MD, FARVO, Doheny Eye Institute, University of California - Los Angeles
Daniel SW Ting, MD, PhD, Department of Ophthalmology and Visual Sciences, Duke-National University of Singapore Medical School, Singapore, Singapore
Gyan Prakash, PhD, Associate Director, International Programs, National Eye Institute

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Beyond the brain: The impact of neurological diseases on ocular health
June 11 | Noon - 1:30pm EDT

Organizer: Nienke van de Sande University Eye Clinic Maastricht, School for Mental Health and Neuroscience (MHeNs), Maastricht University Medical Center (MUMC+), Maastricht, The Netherlands

Explore the intersection of neurology and ophthalmology in our Special Interest Group, "Beyond the Brain: The impact of Neurological Diseases on Ocular Health". In this session, four expert panelists will discuss the latest research regarding the effect of neurological diseases on the eye. The discussion will span a spectrum of topics, ranging from the potential of tear fluid biomarkers as minimally invasive diagnostics for various neurological conditions, to changes observed in retinal examinations. We will also explore more fundamental questions, including communication and fluid routes between the eye and the brain. Participants are invited to actively engage with our panelists throughout the discussions. Share your clinical experiences, pose questions, and contribute to the discussion. We hope you will join us at the crossroads of neurology and ophthalmology.

Panelists

Marlies Gijs, PhD, University Eye Clinic Maastricht, School for Mental Health and Neuroscience (MHeNs), Maastricht University Medical Center (MUMC+), Maastricht, The Netherlands
Umur A. Kayabasi, MD, D- NO Visual Center, Uskudar University, lstanbul, Turkey
Sarah F. Hamm-Alvarez, PhD, FARVO, Department of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, Los Angeles, CA; and Department of Ophthalmology, Roski Eye Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA.
Nicholas J. Ashton, PhD, Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Gothenburg 405 30, Sweden Department of Old Age Psychiatry, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK. Centre for Age-Related Medicine, Stavanger University Hospital, Stavanger, Norway. NIHR Biomedical Research Centre for Mental Health and Biomedical Research, Unit for Dementia at South London and Maudsley, NHS Foundation, London, UK

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Eye movements as a window to ophthalmic diagnostic decision-making
June 11 | 6 - 7:30pm EDT

Organizer: Kaveri A. Thakoor, PhD, Columbia University Irving Medical Center, NY, NY, USA

The goal of this significant interest group (SIG) is to launch awareness of the potential wealth of information embedded in the eye movements of expert ophthalmic clinicians as they view ophthalmic images for disease diagnoses. Such eye movements have the potential for aiding in understanding of mechanisms behind expert diagnostic decision-making (from a neuroscience perspective), for aiding in medical education/training, and for training of AI systems to perform with higher accuracy and interpretability (already has shown some promise in radiology). This SIG will include talks from an ophthalmology residency program director, a visual neuroscientist, and an AI-in-ophthalmology engineer who will share their newest initiatives and latest results toward using eye movements to inform multiple fields from visual neuroscience and AI to medical education. The target audience is everyone at ARVO from ophthalmologists (the experts themselves) and ophthalmologists-in-training to AI engineers and visual neuroscientists – anyone interested in the role of eye movements in informing our understanding of medical-expert decision-making and how this information can be harnessed to help create more explainable automated diagnostic systems and more objective medical education.

Presentations

Educational insights derived from resident vs. expert eye movements
Royce WS Chen, MD, Columbia University Irving Medical Center, NY, NY, USA

Eye movements of trainees vs. experts show significant differences in terms of quantity and location; these differences can serve to aid in medical education and quantification of skills progression in exciting new ways.
What small eye movements reveal about internal states
Susana Martinez-Conde, PhD, State University of New York, Downstate Health Sciences University, Brooklyn, NY, USA

To maintain our perception of a stable world, our oculomotor system must calibrate how much our eyes must move when we fixate. Too little movement can lead to visual fading, and too much motion to blurred and unstable vision. Central and peripheral pathologies can disturb this fine balance. Determining how normal fixation differs from pathological fixation has the potential to aid early and differential diagnosis of neurological and ophthalmic disease, as well as the quantification of its progression and response to treatment.
Creating an expert–AI team for eye disease detection driven by expert gaze data
Kaveri A. Thakoor, PhD, Columbia University Irving Medical Center, NY, NY, USA

We are using the power of Vision Transformers (built from the same natural language processing-inspired transformer backbone behind ‘ChatGPT’) to learn the eye movement trajectories of ophthalmologists as they view optical coherence tomography data. Just as transformers learn the grammar of a language, our models learn the ‘grammar’ of a clinician’s eye movement trajectory across OCT images, creating more accurate, efficient, and interpretable AI ‘teammates’ for medial experts in the ophthalmic clinic.

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Unravelling the causes of reticular pseudodrusen in age-related macular degeneration: Genetics, stem-cell modelling and immune regulation
June 11 | 6 - 7:30pm EDT

Organizers: Carla J. Abbott, BOptom, PhD, Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, Melbourne, Victoria, Australia; Robyn H. Guymer, MBBS, PhD, FRANZCO. Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, Melbourne, Victoria, Australia

Reticular pseudodrusen (RPD; aka subretinal drusenoid deposits) are a critical age-related macular degeneration (AMD) phenotype, associated with a high risk of progression to sight-threatening late-stage disease. However, much is still unknown about their underlying cause, genetic associations and pathophysiology. The RPD Consortium was formed to solely investigate RPD and has combined and harmonized phenotyping and genotyping data from 15 international research groups for the purposes of conducting a meta-analysis of a genome-wide association study for RPD in the setting of AMD. Our group has also targeted key areas of basic research into improving our understanding of their pathogenesis and impact, through further deeply phenotyping patients, including generating stem cells from RPD patients, investigating immune regulation from RPD patients and deriving mouse models that recapitulate aspects of RPD biology. These disease models have the potential to improve our understanding of the cause of RPD and in doing so, identify novel therapeutic targets for treating AMD with coexistent RPD and prevention of vision loss from late-stage disease.

Presentations

A genome-wide association study of reticular pseudodrusen in age-related macular degeneration
Samaneh Farashi, PhD, Walter and Eliza Hall Institute, University of Melbourne, Melbourne, Victoria, Australia.

Several genes known to associate with AMD are reportedly associated with RPD, including the ARMS2/HTRA1 loci, however, there are inconsistent findings. Revealing genetic risk factors of RPD is not straightforward given the difficulty of detecting RPD via standard clinical examination and color fundus photos. Our Reticular Pseudodrusen Consortium aims to obtain the largest cohort of well-phenotyped RPD and genotype data and perform a genome-wide association study (GWAS), to determine the genetic risk factors of RPD. The presentation will discuss the approach to the multi-cohort GWAS and post-GWAS analyses and advanced bioinformatics methods to tease out the genetic risk factors of RPD.
Using stem cells to help our understanding of reticular pseudodrusen
Alice Pébay, BSc (Psych), PhD, University of Melbourne, Melbourne, Victoria, Australia

A hallmark of age-related macular degeneration pathogenesis is the accumulation of drusen underneath the retinal pigment epithelium, a biological process also observable in vitro. The accumulation of drusen is able to predict the progression to advanced AMD, making accurate characterisation of drusen in vitro models valuable in disease modelling and drug development. Reticular pseudodrusen (RPD) deposits above the retinal pigment epithelium in the subretinal space is a critical AMD subtype that is high risk for AMD progression. The talk will describe a semi-automated pipeline for quantifying the presence of drusen-like deposits in vitro, using cultures derived from patient-specific induced pluripotent stem cells (iPSCs). High-throughput confocal microscopy and 3D reconstruction can be used to quantify the drusen-like deposits including location and composition and whether the deposits are on the apical or basal surface of the retinal pigment epithelial cells. The application of in vitro iPSC modelling in understanding AMD and RPD pathophysiology will be discussed.
The immune system and reticular pseudodrusen
Erica L. Fletcher, PhD, University of Melbourne, Melbourne, Victoria, Australia

Reticular pseudodrusen (RPD) are a risk factor for the progression of age-related macular degeneration, however the mechanism by which they develop are unknown. Potential systemic changes in the immune system may be linked to RPD pathophysiology. This talk will discuss how the phagocytic function of human peripheral blood monocytes and serum cytokine changes can be assessed. Immune system findings in participants with AMD both with and without reticular pseudodrusen compared to healthy controls will be discussed, along with the role of systemic immune factors in RPD pathogenesis. Disclosures Robyn H. Guymer, MBBS, PhD, FRANZCO Roche Genentech (C) Apellis (C) Novartis (C) Bayer (C) Belite (C) AbbVie (C) Janssen Complement Therapeutics (C) Alice Pébay, BSc (Psych), PhD PYC Tx (C) All other participants reported no relationships to disclose.

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Harmonizing big data and building research networks for AI applications: A global perspective
June 11 | 9 - 10:30pm EDT

Organizers: Sally L. Baxter, MD, MSc, University of California San Diego; Michelle Hribar, MS, PhD, National Eye Institute, Oregon Health & Science University; Kerry E. Goetz, MS, National Eye Institute

Advancements in computational tools and data have provided researchers with increasing ability to discover patterns, improve risk stratification, and predict patient outcomes. Data standardization is necessary for harmonization and analysis of data from different sources. The OMOP Common Data Model (CDM) is a widely used data model, including in the All of Us Research Program and the National COVID Collaborative (N3C), that standardizes and harmonizes data from multiple institutions. The OMOP CDM has supported both centralized data repositories and distributed research networks. These are crucial for big data analytics and AI applications. This SIG will convene an international group of experts to share their experiences developing or using data sources that leverage common data models. Speakers and moderators include experts from the All of Us Research Program, the European Health Data Evidence Network, the NIH Bridge2AI Consortium, the National Eye Institute, and the OMOP Workgroup in Eye Care & Vision research. Attendees will learn about recent advances and ongoing initiatives, and they will have an opportunity to engage in active discussion to help inform future efforts.

Presentations

Common data models and data harmonization in All of Us
Andrea Ramirez, MD, MS, National Institutes of Health, All of Us Research Program

Andrea Ramirez is the Chief Data Officer for the NIH All of Us Research Program. In this talk, she will discuss how the program has harmonized data from hundreds of enrollment sites across the US to produce a nationwide repository of data from diverse populations who have been traditionally under-represented in biomedical research.
Enabling international collaboration through the European Health Data Evidence Network (EHDEN) and Data Analysis and Real World Interrogation Network (DARWIN EU®)
Maxim Moinat, MS, Erasmus University Medical Center

Maxim Moinat is a data engineer who has been a long-time collaborator with the Observational Health Data Sciences and Informatics (OHDSI) and EHDEN communities. He will discuss the development and use of the EHDEN/DARWIN research networks, which have been pivotal in generating real-world evidence in Europe.
The importance of data standards in AI: best practices from the NIH Bridge2AI Consortium and the AI-READI Data Generation Project
Aaron Lee, MD, MSCI, University of Washington

Aaron Lee, MD, MSCI, is the lead PI for the AI-READI Data Generation Project (DGP), one of 4 DGPs in the NIH Bridge2AI Consortium. He will discuss how the Bridge2AI Consortium is promoting adoption of data standards and the importance of standards and FAIR (Findable, Accessible, Interoperable, Reusable) principles for AI.

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Mathematical and computational ophthalmology
June 20 | 9 - 10:30am EDT

Organizers: Paul A. Roberts, MMath (Oxon), DPhil (Oxon), Centre for Systems Modelling and Quantitative Biomedicine, University of Birmingham Peter Woodward-Court, BSc, MBBS, MRes, University College London, Moorfields Eye Hospital This SIG will serve 3 purposes: 1) to bring together quantitative/biomedical scientists & clinicians using quantitative methods in ophthalmology; 2) to summarise the current state of affairs; 3) to clarify future directions & foster new collaborations.

Presentations

Mathematical and computational modeling of ocular hemodynamics: From theory to clinical applications
Giovanna Guidoboni, PhD, Dean, Maine College of Engineering and Computing, University of Maine, Orono, ME, USA Professor, Electrical and Computer Engineering, University of Maine, Orono, ME, USA

In this presentation, the advantages and disadvantages of mechanism-driven and data-driven modeling will be discussed. Examples of how their combination is beneficial in ophthalmology will be presented in the context of ocular hemodynamics.
Computational approaches to AMD research: Opportunities and challenges
Tiarnan D.L. Keenan, MD, PhD, Stadtman Tenure-Track Investigator, National Eye Institute, National Institutes of Health

This SIG talk will discuss the great opportunities afforded by computational approaches to research in age-related macular degeneration (AMD), together with some important challenges. • This will include a discussion of diverse applications of artificial intelligence in AMD research, together with their strengths and weaknesses – from deep learning approaches to automated diagnosis, severity classification, prognostic risk prediction, and retinal fluid quantification, to machine learning applications such as cluster analysis to understand AMD subtypes and genotype-phenotype relationships. • The opportunities and challenges of advanced statistical techniques will also be discussed, including mediation analysis to dissect complex causal relationships between AMD disease features, genotype, and progression. • In the topical domain of analyzing geographic atrophy progression, the complexity but importance of analyzing proximity-based progression, alongside area-based progression, will be discussed, using the example of recent AREDS1/2 data.
Computational and mathematical modeling of IOP homeostasis and aqueous humor drainage
C. Ross Ethier, PhD, FARVO, Georgia Institute of Technology & Emory University

Aqueous humor outflow resistance is generated and homeostatically regulated by multiple, complex signaling processes. This presentation will give an overview of mathematical and computational models that relate the microarchitecture of the outflow pathway to its ability to generate flow resistance, and important signaling loops that maintain this resistance.

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Secondary glaucoma: Bridging metabolomics to develop potential disease-specific therapies
June 20 | 9 - 10:30am EDT

Organizers: K'Mani Khimoii Blyden, BS, Medical College of Georgia, Augusta University, Augusta, GA, United States; Omar Badla, MBBS, Bascom Palmer Eye Institute, University of Miami, Miami, FL, United States

During this session, we aim to explore the role of metabolomics in developing disease-specific interventions for common causes of secondary glaucoma, such as pseudoexfoliative (PEXG) and pigmentary glaucoma (PG). Currently, there are no disease-specific interventions available for the treatment of either disease, resulting in a significant overlap in the treatment of these conditions and primary open-angle glaucoma/Glaucoma. Recent advances in metabolomic and molecular research have highlighted various pathways and molecules that play crucial roles in the pathophysiology of these diseases. These findings could serve as potential targets to create treatments that are specific to PEXG and PG. Our aim is to foster discussions among experts from various fields of ophthalmology to share insights and enhance our understanding. Through these collaborative efforts, we hope to encourage a multidisciplinary approach to better develop strategies addressing this issue.

Panelists

Dongfeng Chen, MD, PhD, Massachusetts Eye and Ear Infirmary and Schepens Eye Research Institute, Harvard Medical School, Boston, MA.
Ursula Schlötzer-Schrehardt, PhD, Department of Ophthalmology, University Erlangen-Nürnberg, Erlangen, Germany.
Sunee Chansangpetch, MD, Glaucoma Research Unit, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Thai Red Cross, Bangkok, Thailand.
Tin (Ed) Aung, FRCS, MD, PhD, FARVO, Singapore Eye Research Institute, Singapore National Eye Centre, Singapore
Sanjoy K. Bhattacharya, M.Tech., PhD, FARVO, Bascom Palmer Eye Institute, University of Miami, Miami, FL, United States.

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Beyond the eye: Insights into Cerebral/Cortical Visual Impairment (CVI)
June 20 | 6 - 7:30pm EDT

Organizers: Kerry E. Goetz, MS, National Eye Institute; Erika Nelson, BS, National Eye Institute

CVI is a leading cause of pediatric visual impairment in the United States. Despite the disease burden, children with CVI are often misdiagnosed or their condition is not recognized until later in life due to a gap in clinician awareness and a lack of consensus definition. A working definition developed at a Trans-NIH Workshop in November 2023 defines CVI as a spectrum of visual impairment caused by an underlying structural and/or functional brain abnormality, which impacts development of visual function and processing. The visual dysfunction in CVI is greater than expected by any co-morbid ocular conditions. The visual abnormalities in CVI may manifest as lower- or higher-order afferent visual deficits, with or without efferent (oculomotor) disturbances, which adversely affect functional vision. While CVI may be co-morbid with other neurodevelopmental disorders, CVI is not primarily a disorder of language, learning, or social communication. Although the neurologic insult resulting in CVI occurs in the developing brain, individuals with a diagnosis of CVI may require long-term support extending into adulthood. In this SIG, expert panelists will share proposed definitions of CVI and research opportunities. Attendees will benefit by understanding ongoing initiatives and will have an opportunity to engage with experts in active discussion to help inform and be involved in future efforts.

Panelists

Cerebral/Cortical Visual Impairment: The National Eye Institute perspective
Michael F. Chiang, MD, FARVO, National Eye Institute, NIH
Updates on CVI definition and diagnostic criteria
Melinda Y. Chang, MD, Assistant Professor, University of Southern California, Children’s Hospital Los Angeles
Neuroplasticity in cerebral visual impairment
Lotfi B. Merabet, OD, PhD, MPH, Massachusetts Eye and Ear; Harvard Medical School
Visual dysfunction and eye tracking in CVI
Glen T. Prusky, PhD, Burke Neurological Institute, Weill Cornell Medicine
Neuroimaging in CVI
Corinna M. Bauer, PhD, Harvard Medical School, Massachusetts General Hospital

Ocular toxicity due to immunotherapies
June 20 | 6 - 7:30pm EDT

Organizers: Meghan Berkenstock, MD, Wilmer Eye Institute; Jasmine H. Francis, MD, Memorial Sloan Kettering Cancer Center; Lauren A. Dalvin, MD, Mayo Clinic

Treatment of systemic malignancies has evolved in the last 12 years with the FDA approval of immunotherapies. As new receptors and molecular targets within pathways are identified, new agents are developed and studied in clinical trials. Unfortunately, the same ligands targeted by the immunotherapy agents may also be located in the eye or adnexa. Similarly, off-target delivery of cytotoxic payloads may negatively impact ocular structures. Several meetings would occur, where each focused on one drug class per session. This SIG will also provide a forum to allow ARVO members to ask questions to ophthalmologists specializing in ocular toxicity management about the basic science behind or treatment of adverse events associated with these medications. Finally, this SIG would serve as a platform for discussion on how to create a resource for practitioners on ocular toxicities. Special attention would be paid to developing a system that is accessible and comprehensive , remains current and up to date and, legally complaint. Likewise, a dialog on developing systems for seamless communication between ophthalmologists and medical oncology care teams would be included in each meeting.

Panelists

Meghan Berkenstock, MD, Wilmer Eye Institute
Jasmine H. Francis, MD, Memorial Sloan Kettering Cancer Center
Lauren A. Dalvin, MD, Mayo Clinic

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OCT biomarkers of intraocular inflammation
June 25 | 9 - 10:30am EDT

Organizer: Edmund Tsui, MD, MS, UCLA Stein Eye Institute

Uveitis is a vision threatening disease where accurate evaluation and treatment of inflammation is crucial to prevent the development of ocular complications and vision loss. Optical coherence tomography (OCT) of the anterior and posterior segment have recently been used in research settings to objectively quantify intraocular inflammation, such as anterior chamber cell, vitreous cell, vitreous haze, and structural biomarkers. Current research has sought to quantify the number of hyperreflective foci, which represent cells in the aqueous or vitreous, as well as the signal intensity, which has correlated with vitreous haze. Evaluation of the retinal and choroidal vasculature with OCT has also provided additional insight into disease monitoring. However, more research surrounding standardization of image acquisition and image analysis, still needs to be performed. Our SIG seeks to review the current landscape of OCT biomarkers of intraocular inflammation and discuss strategies in image acquisition and processing and formulate studies for further collaboration. This SIG will be an interactive discussion that also seek to discuss ideas and challenges in implementation of OCT as an objective measure of intraocular inflammation.

Panelists

Ameenat “Lola” Solebo, PhD, FRCOphth, Great Ormond Street Hospital for Children NHS Trust
Rupesh Vijay Agrawal, MD, FRCS, MMed, Tan Tock Seng Hospital
Francesco Pichi, MD, Cleveland Clinic, Abu Dhabi
Alessandro Invernizzi, MD, University of Milan

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Get outer here: Should we consider the inner retina in AMD?
June 25 | 6 - 7:30pm EDT

Organizer: Lisa Nivison-Smith, B.Sc (Hons), PhD, School of Optometry and Vision Science, University of New South Wales, SYDNEY

Advances in retinal imaging have resulted in a wealth of evidence showing that the inner retina undergoes anatomical and physiological changes alongside the outer retina in age-related macular degeneration (AMD). However, there is a critical gap in understanding how this knowledge translates to improving outcomes for patients with AMD. Considering that the retina functions as a sum of its parts, measuring the compromise of the inner retina may be essential to determine the full extent of AMD pathophysiology and optimizing AMD diagnostics and interventions. This session will discuss: • What inner retina changes exist in AMD? • What are the origins of inner retinal changes in AMD? • What are the considerations of inner retinal changes in clinical assessment? Attendees will be encouraged to exchange ideas on how we can best harness current understanding of retinal imaging, biomarkers, and anatomy, to develop ideas for clinical translation of inner retinal assessments in AMD as well as furthering our understanding of the pathophysiology of AMD.

Presentations

Inner retinal changes in the early stages of AMD
Matt Trinh, PhD, School of Optometry and Vision Science, University of New South Wales, SYDNEY

This presentation will provide an overview of the neuronal and vascular changes which have been recently observed in the inner retina in the early stages of AMD using a range of clinical retinal imaging techniques. The diagnostic and prognostic applications of these changes will also be discussed.
Central retinal artery and retinal VD/FAZ in AMD
Glenn Yiu, MD, PhD, Department of Ophthalmology, UC Davis

This presentation will provide an overview of the retina vascular changes noted in AMD including those concerning the central retinal artery calibre and vessel density and foveal avascular zone geometry.
Imaging to detect inner retinal changes in neovascular AMD
Enrico Borrelli, MD, PHD, University of Turin

This presentation will emphasise the inner retinal changes in the late, neovascular stage of AMD and this implications of the changes in clinical management

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Photoreceptor loss as an endpoint in clinical trials
June 25 | 9 - 10:30pm EDT

Organizers: Jayashree Sahni, MD, PhD, FRCOphth, Novartis Pharma AG & University of Liverpool; Nadia K. Waheed, MD, MPH, Tufts University School of Medicine, New England Eye Center @ Tufts Medical Center

With the identification of novel targets, the number of interventional clinical trials in ophthalmology has increased. The measurement of photoreceptor (PR) integrity using artificial intelligence/machine learning (AI/ML) algorithms on OCT is gaining traction in geographic atrophy, with reports suggesting better prediction of disease progression and potential to show greater benefit of novel therapies. However several steps including (a) standardization of image acquisition protocols (b) definition & terminology of PR alteration (normal vs attenuated vs loss) (c) AI algorithms developed using these definitions (d) well-powered natural history studies data on what PR change is clinically significant (e) validation and regulatory approval of algorithms, including suitability and performance of the algorithm when confounded by other retinal structural changes (f) conclusive structure/function correlation are needed. This SIG will bring together a panel of experts from industry and academia to a) Illustrate the potential for the broad application of PR loss as an endpoint for multiple retinal diseases. b) Discuss similarities and differences in parameters used to define PR loss in AI algorithms from recent literature and need for harmonization c) Discuss path forward with academic, industry and health authority collaboration to address gaps in order to leverage this novel endpoint for clinical trial and the real world

Panelists

Jayashree Sahni, MD, PhD, FRCOphth, Novartis Pharma AG
Nadia K. Waheed, MD, MPH, Tufts University School of Medicine, New England Eye Center @ Tufts Medical Center
SriniVas R. Sadda, MD, FARVO, Doheny Eye Institute/ University of California - Los Angeles
Philip J. Rosenfeld, MD, PhD, FARVO, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine
Ursula Schmidt-Erfurth, MD, PhD, FARVO, Medical University of Vienna

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Intraocular pressure-independent models of glaucoma
July 11| 9 - 10:30am EDT

Organizers: Kevin C. Chan, PhD, FARVO, New York University Grossman School of Medicine; Henry Tseng, MD, PhD, Duke Eye Center

Glaucoma patients often continue to lose vision despite successful treatment with current intraocular pressure (IOP) lowering therapies, partly because IOP is only a major clinical risk factor for glaucoma, and a majority of primary open-angle glaucoma (POAG) patients have low or normal intraocular pressure. There is no neuroprotective therapy that minimizes retinal ganglion cell (RGC) loss in glaucoma, as the mechanism of RGC degeneration remains largely unclear. A major challenge in glaucoma research is the limited experimental model systems to study RGC degeneration independent of IOP. Unveiling the processes underlying age-dependent, progressive, and non-IOP-dependent features of RGC neurodegeneration in glaucoma will be crucial for basic and clinical applications. In this SIG, speakers will discuss exciting progress made in studying non-IOP-dependent RGC loss. We will discuss the challenges and opportunities of how novel retinoid, rodent, and non-human primate models can help uncover neurodegenerative mechanisms in glaucoma and identify potential drug compounds for pre-clinical pharmaceutical trials.

Presentations

Retinoids and iPSC-based glaucoma model systems
Jason S. Meyer, PhD, Department of Medical and Molecular Genetics, Indiana University School of Medicine

One way to study glaucomatous neurodegeneration independent of intraocular pressure (IOP) is to utilize human retinal ganglion cells (RGC) derived from induced pluripotent stem cells. These cells can be studied in culture and induced to form a retinoid which allows multiple layers of the retina and RGC connections to be modeled. This talk will discuss current approaches and new developments.
Rodent models of normal tension glaucoma
Richard T. Libby, PhD, FARVO, University of Rochester School of Medicine

This talk with give an overview of recent developments in rodent glaucoma models that do not involve inducing elevated intraocular pressure.
Non-human primate models of glaucoma
Anita Chan, MBBS, MMed, FRCS, FRCPath, Singapore National Eye Center, Singapore Eye Research Institute

While few non-human primate (NHP) models of glaucoma exist, this talk will address the challenges involved in creating an NHP model of glaucoma independent of IOP.

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Ocular Surface Innervation Consortium: Progress and future directions
July 11 | Noon - 1:30pm EDT

Organizers: Anthony St. Leger, PhD, Assistant Professor, University of Pittsburgh School of Medicine; Stephen C. Pflugfelder, MD, FARVO, Baylor College of Medicine

The NEI funded Ocular Surface Innervation Consortium was initiated to gain a deeper understanding of ocular surface innervation in health and disease. Eight teams are studying various aspects, including animal models, multiomic methods, nerve labeling and in vivo confocal imaging. The purpose of the SIG is to present preliminary discoveries made by consortium members, new models and methods, and challenges encountered. Discussion topics will include: animal models, cornea and cornea projecting nerve labeling, functional assays, -omics data sets and analysis, imaging, and predictive interaction networks by machine learning/artificial intelligence.

Panelists

Daniel R. Saban, PhD, Department of Ophthalmology, Department of Integrative Immunobiology, Duke University School of Medicine
Anthony St. Leger, PhD, Assistant Professor, University of Pittsburgh School of Medicine
Stephen C. Pflugfelder, MD, FARVO, Baylor College of Medicine
Pedram Hamrah, MD, FARVO, Tufts Medical Center

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Bioactive lipids in corneal and ocular surface disease
July 11 | 6 - 7:30pm EDT

Organizers: Nawajes Mandal, PhD, University of Tennessee Health Science Center, Memphis, TN, USA; Shizuya Saika, MD, PhD Department of Ophthalmology, Wakayama Medical University School of Medicine, Japan.

Lipids are essential components of every cell, but lipids as signaling molecules (bioactive lipids) for cellular physiology and metabolism is a recent discovery. Consequently, lipid metabolism and signaling are increasingly associated with many human diseases. Lipid signaling and lipid pathways are therefore being actively investigated to determine their role in the pathophysiology of the disease, find novel targets for therapeutic development, and be recognized as disease biomarkers. Bioactive lipids in corneal and ocular surface diseases are underexplored areas. Bringing together a group of clinical experts and ocular lipid biologists, this SIG will discuss the current standings of our understanding of lipid signaling in the cornea and ocular surface diseases and identify the gaps where future research should focus.

Presentations

Role of ceramide and sphingosine 1-phosphate in corneal diseases
Nawajes Mandal, PhD, Department of Ophthalmology, University of Tennessee Health Science Center, Memphis, TN, USA
Role of S1P Receptor 3 in corneal inflammation and neovascularization
Shizuya Saika, MD, PhD, Department of Ophthalmology, Wakayama Medical University School of Medicine, Japan.
Meibum and tear sphingolipids and dry eye
Anat Galor, MD, MPH, University of Miami/Miami VA Medical Center
PUFA and dry eye
Penny A. Asbell, MD, MBA, FARVO, University of Memphis

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Oral medications for management of retinal diseases
July 11 | 6 - 7:30pm EDT

Organizers: Rajat N. Agrawal, MD, MS, Retina Global; Charles DeBoer, MD, PhD, Byers Eye Institute at Stanford

Anti-VEGF injections are the current standard of care for management of retinal diseases and help preserve vision in a significant number of patients. But a substantial number of patients do not tend to do well with these injections. Also, the treatment burden associated with receiving multiple intravitreal injections over time leads to lack of compliance in a number of patients, affecting outcomes. There is a a strong push for developing a drug with a different mechanism of action and a different formulation to address the unmet need. Oral medications are currently in development for retinal diseases, which bring a unique set of challenges and perspectives. Being oral, they affect both eyes equally, while as systemic drugs, they may affect other systems in the body. This SIG will cover all relevant aspects of the process for getting these new types of drugs in retina to the patient, including clinical development, regulatory pathway and post-approval process, along with input from companies as well as perspectives on venture fund support for these initiatives.

Panelists

Arshad M. Khanani, MD, MA, Managing Partner, Director of Clinical Research and Director of Fellowship at Sierra Eye Associated and Clinical Associate Professor at University of Nevada, Reno.
Maryam Mokhtarzadeh, MD, Senior Director, Regulatory Strategy, Regenxbio, Inc
George Magrath, III, MD, MBA, Ocuphire Pharma
Ram Palanki, BS, PharmD, Regenexbio Inc
Firas M Rahhal, MD, Partner, Retina Vitreous Associates Medical Group & ExSight Ventures

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Methodological considerations for real world data studies in ophthalmology
July 11 | 9 - 10:30pm EDT

Organizer: Durga S. Borkar, MD, MMCi, Duke University Eye Center

Real world data (RWD) are any data collected in routine clinical practice, including administrative claims, electronic medical record (EMR), imaging analyses, and patient-reported outcomes. Leveraged appropriately, RWD in ophthalmology can generate meaningful real world evidence to describe patient outcomes and inform care delivery. There are numerous methodological considerations in leveraging RWD that differ from clinical trials. Maximizing the potential of RWD in ophthalmology requires a deep understanding of data collection methods, data standards and interoperability, and the inherent strengths and limitations of each data source. This SIG will convene a panel of experts from across a variety of backgrounds to discuss methodological considerations in RWD uses in ophthalmology research, from visual acuity data derived from EMRs, approaches for capturing and interpreting output from optical coherence tomography imaging, and leveraging RWD for economic analyses. The panel will discuss important methodological considerations required to appropriately leverage each of RWD sources in the most meaningful way and engage in a conversation with the broader audience on the biggest areas for development in real world evidence generation and research.

Panelists

Considerations in using real world images for Artificial Intelligence algorithm generation
Zhongdi Chu, PhD, Verana Health
Web-based software tracking of prospectively defined, minimum treatment outcome sets
Mark C. Gillies, MBBS, PhD, University of Sydney
Understanding visual acuity in real world data and electronic health records
Michael Mbagwu, MD, Verana Health, Stanford University
Methodological considerations in leveraging electronic health record data for glaucoma research, SOURCE data repository
Joshua D. Stein, MS, MD, University of Michigan
Leveraging real world evidence for economic analyses
David Tabano, PhD, Genentech

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The Role of Corticoids and Their Receptors in Glaucomatous Eyes: Potential New Drug Targets in Glaucoma?
July 23 | 9 - 10:30am EDT

Organizers: Mariana Botrel Cunha, MD, Centre de Recherche des Cordeliers, From Physiopathology of Ocular Diseases to Clinical Development, Sorbonne University, Université de Paris Cité, Inserm, Paris, France; Francine F. Behar-Cohen, MD, PhD, FARVO, Centre de Recherche des Cordeliers, From Physiopathology of Ocular Diseases to Clinical Development, Sorbonne University, Université de Paris Cité, Inserm, Paris, France; Assistance Publique Hôpitaux de Paris, Ophtalmopole, Cochin Hospital, Université de Paris Cité, Paris, France; Department of Ophthalmology, Hôpital Foch, France; Abbot F. Clark, PhD, FARVO, FAAO, Department of Pharmacology & Neuroscience, North Texas Eye Research Institute, University of North Texas Health Science Center, Fort Worth, TX

Glaucoma, a leading cause of global irreversible blindness, is characterized by the progressive loss of retinal ganglion cells (RGCs) and optic nerve (ON) atrophy. While current treatments aim at reducing intraocular pressure (IOP), RGC loss and ON axon degeneration may occur independently of normal IOP. Consequently, recent progress has been made in developing potential new drug targets and neuroprotective therapies to restore visual function. Prolonged use of glucocorticoids (GCs) can lead to iatrogenic secondary ocular hypertension (OHT) and GC-induced glaucoma (GIG), mimicking primary open-angle glaucoma (POAG) clinically and pathologically. In light of this, the present session explores the role of corticoids and their receptors in glaucomatous eyes, emphasizing the molecular mechanisms behind GC-induced OHT, GIG, and POAG. Additionally, the discussion addresses potential new drug targets in glaucoma, focusing on neuroprotective strategies and corticoid receptor manipulation. Attendees are invited to contribute by sharing research findings, clinical experiences, and insights. Proposing new research questions and innovative treatment opportunities for glaucoma is also encouraged.

Panelists

Corticoids and their receptors in ocular physiology and glaucoma
Francine F. Behar-Cohen, MD, PhD, FARVO, Centre de Recherche des Cordeliers, From Physiopathology of Ocular Diseases to Clinical Development, Sorbonne University, Université de Paris Cité, Inserm, Paris, France; Assistance Publique Hôpitaux de Paris, Ophtalmopole, Cochin Hospital, Université de Paris Cité, Paris, France
Effects of intravitreal steroid injections on intraocular pressure and the associated risks of ocular hypertension and steroid-induced glaucoma
Baruch D. Kuppermann, MD, PhD, Gavin Herbert Eye Institute, University of California, Irvine, Irvine, California.
Steroid responders, Glucocorticoid-induced ocular hypertension, and glucocorticoid-induced glaucoma - Underlying molecular mechanisms and animal models
Wai Kit Chu, DPhil, Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong, Hong Kong
Glucocorticoid receptors and potential new drug targets in glaucoma
Abbot F. Clark, PhD, FARVO, FAAO, Department of Pharmacology & Neuroscience, North Texas Eye Research Institute, University of North Texas Health Science Center, Fort Worth, TX
Aldosterone as a potential contributor to glaucoma and novel treatment opportunities
Tomomi Higashide, MD, PhD, Department of Ophthalmology, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan.

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Advancements in defining and understanding the human ocular surface microbiome
July 23 | Noon - 1:30pm EDT

Organizers: Anat Galor, MD, MPH, University of Miami/Miami VA Medical Center; Anthony St. Leger, PhD, University of Pittsburgh School of Medicine

Recently, a great amount of effort, both financial and personnel-related, has been devoted towards defining and understanding the human ocular surface microbiome. The National Eye Institute has selected five teams to participate in a funded consortium to develop and optimize protocols towards collecting and analyzing the microbiome signatures from healthy human subjects. In addition to this, the consortium aims to establish causal relationships between specific microbes and physiological responses from host epithelial and immune cells. The purpose of this SiG is to present data from the consortium to include the definition of the microbiome signature using genomic approaches, isolating, and identifying live bacteria using culturomics, and establishing causal relationships using cell culture and in vivo animal models.

Panelists

Anthony St. Leger, PhD, Assistant Professor, University of Pittsburgh School of Medicine
Cintia S. De Paiva, MD, PhD, FARVO, Associate Professor, Baylor College of Medicine
Seesandra V. Rajagopala, PhD, Research Assistant Professor of Medicine, Vanderbilt University
Laura Ensign-Hodges, PhD, Professor of Ophthalmology, Johns Hopkins School of Medicine

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Exploring cellular and organoid platforms for advancing disease understanding and therapeutic development in retinal disorders
July 23 | 6 - 7:30pm EDT

Organizers: Hugo Quiroz-Mercado, MD, Association to Prevent Blindness (APEC); Luis Alfonso Hernández Piñamora, MD, Association to Prevent Blindness

The main purpose of this session is to present and discuss the current state of research related to retinal cell therapy and organoids for disease modeling and therapeutic interventions. We aim to address the following key points: 1. The future direction of advancements in retinal cell platforms and organoids. 2. The present state of research and developments in this field. 3. The challenges and obstacles we face in progressing towards the desired direction in the field of cellular therapies and organoids. The session aims to provide a comprehensive overview of current research in this field and to foster innovative research protocols that propel the field forward.

Panelists

Gemma Marfany Nadal, PhD, Universidad de Barcelona
Alex Garanto, PhD, Associate Professor & Research Group Leader (RGL) at Dept. Pediatrics and Dept. Human Genetics, Radboudumc
Andres Lisker Cervantes, MD, Research Associate at CellSight Ocular Stem Cell and Regeneration Program, Department of Ophthalmology, Sue Anschutz- Rodgers Eye Center, University of Colorado, School of Medicine, Aurora, CO, USA
Thomas Vincent Johnson III, MD, PhD, Shelley and Allan Holt Rising Professor of Ophthalmology. Assistant Professor of Ophthalmology at Wilmer Eye Institute, Johns Hopkins Medicine.

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Evaluating biomarkers of Angiopoietin-2 inhibition in retinal vascular diseases
July 23 | 9 - 10:30pm EDT

Organizer: SriniVas R. Sadda, MD, FARVO, Doheny Eye Institute/ University of California - Los Angeles

Anti-VEGF therapies have improved outcomes in diabetic macular edema (DME), neovascular age-related macular degeneration (nAMD), and retinal vein occlusion (RVO), however they do not address the multifactorial nature of the diseases. In the phase 3 YOSEMITE/RHINE (DME) and TENAYA/LUCERNE (nAMD) studies, dual inhibition of Ang-2/VEGF-A with faricimab demonstrated improved anatomical outcomes with extended durability vs aflibercept Q8W. Determining the additional benefits of Ang-2 inhibition on disease biomarkers is an opportunity to explore how the biology may translate into improved clinical outcomes for patients. To assess the impact of dual Ang-2/VEGF-A inhibition on biomarkers in retinal vascular diseases, a panel of experts will discuss the scientific knowledge in the field of vascular biology as well as clinical findings from the phase 3 trials of faricimab on emerging Ang-2 biomarkers and their correlation with clinical outcomes.

Panelists

Mechanisms of ang2 action and secretion
Susan E. Quaggin, MD, Department of Medicine Northwestern Medicine & Feinberg School of Medicine.
The role of Ang2 inhibition in the context of MNV and DME
Karl G. Csaky, MD, PhD, FARVO, Retina Foundation of the Southwest
Novel target identification in AMD
Rajendra S. Apte, MD, PhD, FARVO, Departments of Ophthalmology, Developmental Biology and Medicine Washington University in St. Louis School of Medicine
Real world analysis of retinal fluid biomarkers in patients switched to faricimab
Charles Clifton Wykoff, MD, PhD, Retina Consultants of Houston
The role of inflammation in exudative retinal diseases
Daniel R. Saban, PhD, Department of Ophthalmology Department of Integrative Immunobiology Duke University School of Medicine

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