2024 Annual Meeting and Alumni Reunion Online Program

2024 Annual Meeting and Alumni Reunion

June 13-14, 2024 I The Starr Center, Boston, MA

Joan W. Miller, MD

MEETING CO-CHAIRS

David Glendenning Cogan Professor of Ophthalmology and Chair, Department of Ophthalmology, Harvard Medical School; Chair of Ophthalmology, Mass Eye and Ear and Mass General Hospital; Ophthalmologist-in-Chief, Brigham and Women’s Hospital

Joseph B. Ciolino, MD

Associate Professor of Ophthalmology, Harvard Medical School; Associate Director of Harvard Ophthalmology Alumni; Henry Freeman Allen Cornea Scholar, Mass Eye and Ear

Eric Gaier, MD, PhD

Assistant Professor of Ophthalmology, Harvard Medical School; Site Director of the Harvard Ophthalmology Residency Program, Boston Children’s Hospital

Rachel Huckfeldt, MD, PhD

Assistant Professor of Ophthalmology, Harvard Medical School; Director, Inherited Retinal Degenerations Fellowship, Mass Eye and Ear

Joseph F. Rizzo III, MD

Simmons Lessell Professor of Ophthalmology, Harvard Medical School; Director of Harvard Ophthalmology Alumni, Co-director, Harvard Ophthalmology Mobility Enhancement and Vision Rehabilitation Center of Excellence; Director, Neuro-Ophthalmology Service, Mass Eye and Ear

ANNUAL MEETING PROGRAM - Thursday, June 13, 2024

The Starr Center - Second Floor, 185 Cambridge Street, Boston, MA

11:30-12:15 pm

12:15–

Registration & Lunch

Co-chair Welcome & Annual Meeting Overview

Rachel Huckfeldt, MD, PhD (2013, 2016) and Eric D. Gaier, MD, PhD (2017, 2019)

Introduction of the 2024 Alumni Grand Rounds Speaker

Rachel Huckfeldt, MD, PhD (2013, 2016) - Assistant Professor of Ophthalmology, Harvard Medical School; Director, Inherited Retinal Degenerations Fellowship, Mass Eye and Ear

1:32–1:44 pm

1:44–1:56 pm

1:56–2:08 pm

2:08–2:20 pm

2:20–2:30 pm

2:30–2:35 pm

2:35–2:40 pm

The 2024 Alumni Grand Rounds Lecture

Advancing Eye Health Equity by Leveraging Implementation Science and Telemedicine

Yao Liu, MD, MS (2012) - Assistant Professor, Glaucoma Service Chief, Fellowship Director, UW Department of Ophthalmology & Visual Sciences; Director, UW Teleophthalmology Program, University of Wisconsin

Boston Keratoprosthesis: Current Options and Future Directions

Thomas Dohlman, MD (2014) - Assistant Professor of Ophthalmology, Harvard Medical School Medical Director, Boston Keratoprosthesis Program, Mass Eye and Ear

Access to Vision Screening and Pediatric Eye Care in the US

Isdin Oke, MD, MPH (2021) - Assistant Professor of Ophthalmology, Harvard Medical School

Use of Advanced Driver Assistance Systems by Drivers With Vision Impairment

Alexandra R. Bowers, PhD - Associate Professor of Ophthalmology, Harvard Medical School; Associate Scientist, Schepens Eye Research Institute of Mass Eye and Ear

Rethinking Diagnostic Approaches to Orbital Inflammation

Michael K. Yoon, MD - Associate Professor of Ophthalmology, Harvard Medical School; Associate Director, Ophthalmic Plastic Surgery Service, Ophthalmology Fellowship Programs Leader, and Fellowship Director, ASOPRS Ophthalmic Plastic Surgery Fellowship, Mass Eye and Ear

Role of the Endothelial Glycocalyx in Endothelial Cell Biology

Patricia A. D'Amore, MD, MBA - Charles L. Schepens Professor of Ophthalmology, Harvard Medical School; Vice Chair, Basic and Translational Research and Co-Director, AMD Center of Excellence, Harvard Ophthalmology; Director, Howe Laboratory and Associate Chief of Basic and Translational Research, Mass Eye and Ear

Harvard Ophthalmology Research Scholars Program Overview and Introduction of the Research Scholars Class of 2024

Silas L. Wang, MD - Instructor in Ophthalmology, Harvard Medical School

The Harvard Ophthalmology Research Scholars Experience

Brionna Bennett (2023) - Medical School Candidate, University of South Carolina School of Medicine

2024 Harvard Ophthalmology Excellence in Mentoring Award

David G. Hunter, MD, PhD (1991) - Professor and Vice Chair for Promotions and Reappointments, Department of Ophthalmology, Harvard Medical School; Ophthalmologist-in-Chief, Boston Children’s Hospital

Break 2:40-3:10 pm

3:10–3:17 pm

The Paradigm Shift in the Approach to Retinal Disease: 25 Years After PDT, VEGF, and OCT

Joan W. Miller, MD (1989, 1991) - David Glendenning Cogan Professor of Ophthalmology and Chair, Department of Ophthalmology, Harvard Medical School; Chair of Ophthalmology, Mass Eye and Ear and Mass General Hospital; Ophthalmologist-in-Chief, Brigham and Women’s Hospital

3:17–3:29 pm

3:29–3:41 pm

3:41–3:53 pm

3:53–4:05 pm

4:05–4:17 pm

4:20–4:25 pm

4:25–4:30 pm

4:30–5:00 pm

5:00–5:05 pm

Methotrexate for Proliferative Vitreoretinopathy

Dean Eliott, MD - Stelios Evangelos Gragoudas Professor of Ophthalmology, Harvard Medical School; Co-director, Diabetic Eye Disease Center of Excellence, Harvard Ophthalmology; Director, Emeritus, Retina Service and Fellowship Director, Vitreoretinal Surgery Fellowship, Mass Eye and Ear

Glaucoma and Ocular Hypertension After Other Ocular Surgery

Michael M. Lin, MD (2018) - Assistant Professor of Ophthalmology, Harvard Medical School Associate Director, Glaucoma Service, Mass Eye and Ear

Integrating Genetic Associations and Single-cell Genomics Uncovers Causal Genes and Cell Types for Glaucoma

Ayellet V. Segrè, PhD, MSc - Assistant Professor of Ophthalmology, Harvard Medical School; Genetic Biostatistician and Assistant Scientist, Schepens Eye Research Institute of Mass Eye and Ear

A Dedicated Chalazion Clinic: Impact on Patient Care and Early Residency Training

Prashant Yadav, MD (2013) - Instructor in Ophthalmology, Harvard Medical School; Medical Director of the Ophthalmology Consult Service, Mass Eye and Ear

Visual Morbidity From Optic Pathway Gliomas: Results from a Multicenter, Prospective Study

Gena Heidary, MD, PhD (2008, 2010) - Associate Professor of Ophthalmology, Harvard Medical School; Director, Pediatric Neuro-Ophthalmology Service and Director of Ophthalmology Fellowship Training, Boston Children’s Hospital

Perspective on Mariana Dieste Mead

Joseph F. Rizzo III, MD (1986) - Simmons Lessell Professor of Ophthalmology, Harvard Medical School; Co-director, Harvard Ophthalmology Mobility Enhancement and Vision Rehabilitation Center of Excellence; Director, Neuro-Ophthalmology Service, Mass Eye and Ear

Introduction of the 2024 Mariana Dieste Mead Lecturer

Joseph B. Ciolino, MD (2009) - Associate Professor of Ophthalmology, Harvard Medical School; Henry Freeman Allen Cornea Scholar, Mass Eye and Ear

2024 Mariana Dieste Mead Lecture

Scleral Lenses: A Promise Fulfilled and a Platform for the Future

Deborah S. Jacobs, MD, MS (1991, 1992) - Associate Professor of Ophthalmology, Part-time, Harvard Medical School; Director, Ocular Surface Imaging Center, Mass Eye and Ear

Annual Meeting Closing Remarks

Rachel Huckfeldt, MD, PhD (2013, 2016) and Eric D. Gaier, MD, PhD (2017, 2019)

Mass Eye and Ear - Seventh Floor Dining Room, 243 Charles Street, Boston, MA

Evangelos S. Gragoudas, MD Reception 5:15-7:00 pm

ACCREDITATION STATEMENT

In support of improving patient care, Boston Children’s Hospital is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team. Fees associated with AMA PRA Category 1 Credits™ have been provided by the HMS Department of Ophthalmology. Fees associated with COPE credit hours have been provided by the HMS Department of Ophthalmology. For complete CME information, visit: https://eye.hms.harvard.edu/annualmeeting.

OPHTHALMOLOGISTS: Physician Boston Children’s Hospital designates this live activity for a maximum of 10 AMA PRA Category 1 Credits™. Physicians should claim only credit commensurate with the extent of their participation in this activity.

OPTOMETRISTS: Optometric CE Boston Children’s Hospital designates this live activity for a maximum of 10 COPE Credit Hours. Optometrists should claim only the credit commensurate with the extent of their participation in the activity. The course number is 240624-JA.

TEXT-IN-ATTENDANCE FEATURE

Send 4649 to 617-648-7950 during the session to record your attendance.

ALUMNI REUNION PROGRAM - Friday,

The Starr Center - Second Floor, 185 Cambridge Street, Boston, MA

7:30-8:00 am

8:00–8:05 am

8:05–8:12 am

June 14, 2024

Registration & Lunch

Co-chair Welcome & Alumni Reunion Overview

Joseph F. Rizzo III, MD (1986) and Joseph B. Ciolino, MD (2009)

8:12–8:28 am

8:28–8:44 am

8:44–9:00 am

9:00–9:16 am

Glaucoma Service Founding and Innovation

Janey L. Wiggs, MD, PhD (1990, 1991, 1992) - Paul Austin Chandler Professor of Ophthalmology, Harvard Medical School; Co-Director, Harvard Ophthalmology Glaucoma Center of Excellence; Associate Director, Howe Laboratory, and Associate Chief, Ophthalmology Clinical Research, Mass Eye and Ear

Creating Your Own Path: Exploring Career Opportunities

J. Daniel Diaz, MD (2019) - Vitreoretinal Surgeon, Retinal Consultants of Miami

A Novel Intravitreal Anti–IL-6 Monoclonal Antibody for Uveitic Macular Edema (UME)

Eduardo Uchiyama, MD (2014) - Vitreoretinal Surgeon and Uveitis Specialist, Retina Group of Florida; Clinical Affiliate Assistant Professor, Department of Surgery, Schmidt College of Medicine, Florida Atlantic University

The Power of Peer and Near-Peer Mentoring

Erin M. Salcone, MD (2009) - Assistant Professor of Surgery and Assistant Professor of Pediatrics, Geisel School of Medicine, Dartmouth

Developing Values-Based Physician Leaders

Fina C. Barouch, MD (2004) - Assistant Clinical Professor of Ophthalmology, Tufts University School of Medicine; Attending Physician, Lahey Hospital & Medical Center

Break 9:20-10:00 am

10:00–10:07 am

BGL to the OGI: A Brief History of Inherited Retinal Degeneration Research at Mass Eye and Ear

Eric A. Pierce, MD, PhD (1994, 1996) - William F. Chatlos Professor of Ophthalmology, Harvard Medical School; Director, Ocular Genomics Institute and Director, Berman-Gund Laboratory for the Study of Retinal Degenerations, Mass Eye and Ear

10:07–10:12 am Development Announcement

10:12–10:33 am

10:33–10:54 am

10:55–11:00 am

11:00–11:30 am

Endoscopic Vitrectomy: Seeing is Believing

Thomas C. Lee, MD (1999) - Associate Professor of Clinical Ophthalmology, Keck School of Medicine, University of Southern California; Chief, Division of Ophthalmology, Director, Vision Center, and Associate Chair in Ophthalmology, Children’s Hospital Los Angeles

Building Healthcare Capacity Globally-Cases and Lessons From The Road

Mehul C. Mehta, MBBS (1994) - Instructor in Ophthalmology, Harvard Medical School; Senior Medical Advisor, Albright Stonebridge Group

Introduction of Distinguished Research Achievement Awardee

Ula V. Jurkunas, MD (2006) - Associate Professor of Ophthalmology, Harvard Medical School; Co-director, Harvard Ophthalmology Cornea Center of Excellence; Associate Director, Cornea Service, Mass Eye and Ear

11:30-1:00 pm

2024 Distinguished Research Achievement Award Lecture

The Capricious Nature of Innovation

Reza Dana, MD, MSc, MPH (1995) - Claes H. Dohlman Professor of Ophthalmology, Harvard Medical School; Vice Chair for Academic Programs, Harvard Ophthalmology; Co-director, Harvard Ophthalmology Cornea Center of Excellence; Director, Cornea and Refractive Surgery Service, Mass Eye and Ear

Group Photo & Lunch

1:00–1:10 pm

1:10–1:30 pm

1:30–1:51 pm

1:51–2:12 pm

2:15–2:20 pm

2:20–2:50 pm

The Development of Modern Corneal Science and the 50-Year Jubilee of the Boston KPro at Mass Eye and Ear

Reza Dana, MD, MSc, MPH (1995) - Claes H. Dohlman Professor of Ophthalmology, Harvard Medical School

Eleftherios Paschalis Ilios, PhD (2013) - Assistant Professor of Ophthalmology, Harvard Medical School

Department Update

Joan W. Miller, MD (1989, 1991) - David Glendenning Cogan Professor of Ophthalmology and Chair, Department of Ophthalmology, Harvard Medical School; Chair of Ophthalmology, Mass Eye and Ear and Mass General Hospital; Ophthalmologist-in-Chief, Brigham and Women’s Hospital

From Academia to Private Practice: Opportunities for Patient Care

Dale C. Oates, MD, PhD (1989) - Glaucoma Surgeon, Cape Cod Eye Surgery & Laser Center

Associate Staff, Tufts Medical Center

Glaucoma at the Center of the Earth

Donald L. Budenz, MD, MPH (1984) - Kittner Family Distinguished Professor and Chair, University of North Carolina School of Medicine

Introduction of Distinguished Clinical Achievement Awardee

Lucia Sobrin, MD, MPH (2005) - Charles Edward Whitten Professor of Ophthalmology, Harvard Medical School

Associate Director, Retina Service; Associate Chief of Clinical Data Science; Director, Morse Laser Center; Co-Fellowship Director, and Ocular Immunology and Uveitis Fellowship, Mass Eye and Ear

2024 Distinguished Clinical Achievement Award Lecture

Unequal Vision

Julia A. Haller, MD (1980) - Ophthalmologist-in-Chief and William Tasman, MD Endowed Chair, Wills Eye Hospital; Professor and Chair of Ophthalmology, Sidney Kimmel Medical College at Thomas Jefferson University

Break 2:50-3:30 pm

3:30–3:37 pm

History of the Retina Service and Proton Therapy at Mass Eye and Ear

Demetrios G. Vavvas, MD, PhD (2003, 2007) - Solman and Libe Friedman Professor of Ophthalmology, Harvard Medical School; Director, Retina Service, Mass Eye and Ear

Ivana K. Kim, MD (2001, 2003) - Associate Professor of Ophthalmology, Harvard Medical School

3:37–3:42 pm Development Announcement

3:42–4:03 pm

4:03–4:24 pm

4:30–5:00 pm 4:25–4:30 pm

5:00–5:05 pm

Empathy to Discovery

Peter Reed Pavan, MD (1979) - Professor Emeritus, University of South Florida

Reflections of a Resident from 1974

Donald W. Putnoi, MD (1974) - Retired, Founder, Putnoi Eye Care

Introduction of the Distinguished Innovator Awardee

Joan W. Miller, MD (1989, 1991) - David Glendenning Cogan Professor of Ophthalmology and Chair, Department of Ophthalmology, Harvard Medical School; Chair of Ophthalmology, Mass Eye and Ear and Mass General Hospital; Ophthalmologist-inChief, Brigham and Women’s Hospital

2024 Distinguished Innovator Award Lecture

The History of Pharmacological Therapy for Retinal Diseases

David R. Guyer, MD (1992) - Co-Founder, President, and CEO, Eyebiotech Limited; Former Professor and Chairman of the Department of Ophthalmology, NYU Grossman School of Medicine

Closing Remarks & 2025 Save the Date

Joseph F. Rizzo III, MD (1986) and Joseph B. Ciolino, MD (2009)

The Four Seasons Hotel - Second Floor, 200 Boylston Street, Boston, MA

6:00-9:30 pm

Trainee Poster Contest, Reception, and Gala Dinner

TRAINEE POSTER CONTEST -

Friday, June 14, 2024

Trainee Poster Contest Submissions

Ela Arnon Katz - Natural History of a Patient With MYO7A Usher Syndrome

Helia Ashourizadeh - Impact of Time to First Anti-Vascular Endothelial Growth Factor Injection on Visual Acuity in Treatment-naïve Patients With Neovascular Age-Related Macular Degeneration

Grace Baldwin - After Retinal Detachment Repair, Optical Coherence Tomography Angiography Metrics Demonstrate a Larger Effect Size on Contrast Sensitivity Compared to Visual Acuity

Romy Bejjani - Long-term Visual Outcomes of Photodynamic Therapy in Patients With Central Serous Chorioretinopathy in a Tertiary Care Center and in the IRIS® Registry

Xinyi Ding - Assessment of Intraretinal Microvascular Abnormalities and Their Clinical Significance in Eyes With Non-Proliferative Diabetic Retinopathy Using Swept-Source Optical Coherence Tomography Angiography

Samet Gulkas - Regional Retinal Vessel Diameter and Progression Risk of Diabetic Retinopathy on Ultrawide Field Images

Sierra Ha - Structure-function Associations Between Quantitative Contrast Sensitivity Function and Peripapillary Optical Coherence Tomography Angiography in Diabetic Retinopathy

Ayush Parikh - Etiologies, Clinical Characteristics, and Management of Pediatric Macular Holes: A Retrospective Review A08

The Four Seasons Hotel, Second Floor, 200 Boylston Street, Boston, MA

Trainee Poster Contest Submissions (Continued)

Ioanna Ploumi - Impact of Predominant Peripheral Lesions on Retinal Microvasculature and Risk of Vitreous Hemorrhage in Proliferative Diabetic Retinopathy

Francesco Romano - Associations Between Contrast Sensitivity Function, Optical Coherence Tomography Features and Progression From Intermediate to Late age-related Macular Degeneration

Priya Shah - Analysis of Choroidal Thickness Differences Between Sexes in Central Serous Retinopathy, Pattern Dystrophy, Age-Related Macular Degeneration and Healthy Controls

Assel Talaspayeva - Comparison of the Portable Retinal Thickness Analyzer and Spectral Domain Optical Coherence Tomography Retinal Thickness Measurements in Diabetic Eyes

Fatma Ali - Exogenous Methicillin-Resistant Staphylococcus Aureus Endophthalmitis is Caused by MultidrugResistant Lineages That are Associated With Poor Outcomes

Buravej Assavapongpaiboon - In-transit Metastases in Conjunctival Melanoma: A Potentially Underrecognized Phenomenon That Likely Portends an Unfavorable Prognosis

Yeganeh Farsi - Incidence of Ocular Graft-versus-host Disease During Tapering of Immunomodulatory Therapy Following Allogeneic Hematopoietic Stem

Asahi Fujita - Treatment Patterns and Outcomes of Childhood Glaucoma in the United States: Analysis of the IRIS® Registry

Ma Carmela Guevarra - A Novel

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and Quantitative Volumetric Analysis of Orbital Muscle and Fat for Diagnosis of Thyroid Eye Disease and Associated Optic Neuropathy

Anagha Lokhande - Geographic Disparities in Glaucoma Surgical Care: An IRIS® Registry (Intelligent Research in Sight) Analysis

Shah

Melissa Yuan - Clinical Characteristics, Outcomes, and Complications Associated with Delayed Diagnosis of Intraocular Foreign Body

Asmaa Zidan - Vision Outcome of Nerve Growth Factor Treatment for Neurotrophic Keratopathy: An IRIS® Registry Study

Roshni Bhat - Exogenous Metabolites Associated With Age-Related Macular Degeneration (AMD): A CrossSectional Study

Haemin Kang - Association of Plasma Metabolites With Treatment Response After Intravitreal Anti-vascular Endothelial Growth Factor Injections in Neovascular Age-related Macular Degeneration

Drenushe Krasniqi - Navigating the Vascular Terrain of the Human Optic Nerve in 3D

Renee Liu - Proliferative Diabetic Retinopathy and Center-Involving Diabetic Macular Edema Display Strong Genetic Associations With Common Variants in Asian Populations

Yan Luo - Understanding Equity in Vision-Language Learning for Glaucoma Diagnosis With Deep Learning

Jean Moon - Role of Endomucin in Angiogenesis and Cytoskeletal Organization

Min Shi - Personalizing Circumpapillary Retinal Nerve Fiber Layer Thickness Norms With Individual Retinal Anatomy in Glaucoma

Trainee Poster Contest Submissions (Continued)

Krupa Sourirajan - Urine Metabolites Associated With Microperimetric Retinal Sensitivity in Age-Related Macular Degeneration

Wai Lydia Tai - Transcriptomic Shift in Retinal Ganglion Cell During DNA Methyltransferase-mediated Axon Regeneration

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Shuai Wang - Immunosubunit β5i Knockout Suppresses Neovascularization and Restores Autophagy in Retinal Neovascularization by Targeting ATG5 for Degradation

Lei Xi - Mast Cell Inhibition Attenuates Tissue Damage and Neovascularization in an Experimental Laser-Induced Choroidal Injury

Maryam Zekavat - Connecting Ocular and Systemic Health: Phenome- and Genome- wide Analyses of Retinal Layer Thicknesses From Optical Coherence Tomography Imaging Across 44,823 UK Biobank Participants

Yadav Adhikari - Polyploidy Leads to

Folorunso - Corneal Epithelial Cells Predominantly Secrete TIMP-2, Which has Anti-Inflammatory and Pro-Wound

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Changrim Lee - Biocompatible

Mohit Parekh - Cell Cycle From G2/M to G0/G1 Promotes Senescence and Fibrosis Leading to the Development of Fuchs Endothelial Corneal Dystrophy

Vinay Kumar Pulimamidi - Specific Targeting of Mast Cells via ST-2 Receptor in Ocular Diseases

Janiece Rosado - Do Drivers With Vision Impairments Engage in Distracting Secondary Tasks While Driving?

Maryam Shayan - Characterization of an Inducible, Conditional HIF-1α Knockout Mouse Strain and Induction of Experimental Chronic Autoimmune Uveitis in the Strain

Rohan Singh - Early Infiltrating Regulatory T-cells (Tregs) Differentially Impact Graft Site Antigen Presenting Cells (APCs) and Graft Survival

Pier Luigi Surico - NK-1R Antagonism Suppresses the Expression of Pain-Associated Neuronal Activity Markers Following Corneal Mechanical Injury

Yi Ni Toh - Driving With hemianopia: Do Peripheral Prism Glasses Improve Hazard Detection at Intersections? D14

For a full program including the complete Trainee Poster abstracts, scan the QR code or visit: https://rb.gy/2quo7b

Candidate:

Ella Arnon Katz

Poster #: A01

Natural History of a Patient With MYO7A Usher Syndrome

Ella Arnon Katz, Anne Fulton

Purpose: Study the natural progression of retinal disease in a single patient diagnosed with Usher syndrome and Cystic Macular Edema (CME) over a span of more than a decade, utilizing multiple biomarkers and clinical tools.

Methods: We followed the natural history of a male patient with Usher syndrome and CME, between the years 2011 (age 9) to 2023 (age 21). We used the following tools to characterize the right eye: VA,GVF,OCT(EZ area and CRT).

Results: (a) The Ellipsoid Zone maintained its elliptical structure with a measured eccentricity of 0.61±0.04 over the years. However, its area decreased by nearly 50% during the study period, at an average rate of 0.44±0.04 mm2/yr. (b) The Visual Field decreased by about 80% over the same timeframe, with an average rate of 8±2% per year. (c) Central Retinal Thickness increased over time, with a temporary decrease correlated with the onset of medical treatment. After stopping the Diamox, the central retinal thickness decreased (d) Visual Acuity remained good and remained nearly unchanged over the years, bounded between 20/25 to 20/50.

Conclusions: Despite the loss of peripheral photoreceptors and the development of significant CME at the center, visual acuity remained stable throughout the years. The central retinal thickness, as measured by OCT, decreased at the onset of dorzolamide drops and Diamox tablet. However, it then increased despite continued medication usage. Interestingly, despite the large CME developed during 2015-2019, no significant indication of changes in the Ellipsoid Zone area or the Goldman Visual Field was observed during these years. In our patient's late teens, there was a considerable decline in the ellipsoid zone area. Goldman visual field, exhibited a significant decline during our patient's early teens.

Candidate: Helia Ashourizadeh

Poster #: A02

Impact of Time to First Anti-Vascular Endothelial Growth Factor

Injection on Visual Acuity in Treatment-naïve Patients With Neovascular Age-Related Macular Degeneration

Helia Ashourizadeh, Nicole Grinspan, Elizabeth J. Rossin, Nimesh Patel, John B. Miller,Deeba Husain, Justin Keener, David M. Wu, Demetrios Vavvas, Joan W. Miller, Saghar Bagheri, Grayson W. Armstrong

Purpose: Prior studies have examined the frequency and intervals of anti-vascular endothelial growth factor (VEGF) injections in neovascular Age-related Macular Degeneration (nAMD), but few have assessed the impact of time from symptom onset to treatment initiation on visual outcomes, which is the subject of this retrospective chart review.

Methods: Using International Classification of Diseases codes and manual chart review, treatment-naïve nAMD patients presenting to Massachusetts Eye & Ear Emergency Department (MEE ED) from 2009 to October 2023 were identified. Patient demographics, medical history, date of symptom onset and first antiVEGF injection, anti-VEGF agent, number of injections, and best-corrected visual acuity (BCVA) measurement monthly for the first year, then at 18, 24, and 36 months were collected. Exclusion criteria were cataract surgery during treatment, missing timing of symptom onset, history of other retinal disorders, or prior antiVEGF therapy. A linear mixed-effects model using R (Ver. 4.3.2) assessed impact of time from symptom onset to first anti-VEGF injection on visual acuity at 6 months, 1, 2, and 3 years.

Results: A total of 42 eyes of 42 patients with treatment-naïve nAMD presenting to MEE ED were reviewed, with a mean 9.88 ± 3.23 (range: 4-17) follow up visits over 3 years. Mean age was 77.50 ± 8.51 years, with 64.3% women. Time from symptom onset to first anti-VEGF injection ranged from 0 to 215 days (mean: 40.21 ± 60.99 days) (Table 1). After adjusting for confounders (age, sex, baseline BCVA, number of injections, medication), interval between symptom onset and initial injection correlated with BCVA outcomes at 1, 2, and 3-year follow-up. Specifically, each additional day in the interval corresponded to a 0.01 increase in logMAR BCVA at 1-year follow-up (p-value <0.001). Time from ED visit to injection, which was on average 7.7 days (range 0-42), was not significantly associated with BCVA outcomes (Table 2).

Conclusions: Despite our small sample size to date, our results suggest that treatment-naive nAMD patients with longer intervals between initial symptom onset and first anti-VEGF injection may have worse long-term visual outcomes, supporting the importance of prompt diagnosis, referral, and treatment.

Candidate: Grace Baldwin

Poster #: A03

After Retinal Detachment Repair, Optical Coherence Tomography

Angiography Metrics Demonstrate a Larger Effect Size on Contrast

Sensitivity Compared to Visual Acuity

Grace Baldwin, Jocelyn Rodriguez, Rachel Tandias, Itika Garg, Filippos Vingopolouos, Jack Tracy, Hanna Choi, Hannah Wescott, Ines Lains, Jade Y. Moon, Rebecca Zeng, Ying Cui, Raviv Katz, Rongrong Le, Edward S. Lu, Diane N. Sayah, Zakariyya Hassan, Demetrios Vavvas, Deeba Husain, Joan W. Miller, Leo Kim, John B. Miller

Purpose: To evaluate the relationship between the contrast sensitivity (CS) and wide-field swept-source optical coherence tomography angiography (WF SS-OCTA) metrics in eyes after retinal detachment (RD) repair.

Methods: This cross-sectional observational study included 62 eyes that underwent RD repair at least six months prior, including 35 macula-off and 27 macula-on, without another ophthalmic pathology. Visual function was assessed with visual acuity (VA) and CS using the Quantitative CS function (qCSF) Test. The qCSF metrics included area under the Log of the CS curve (AULCSF), contrast acuity (CA), and contrast sensitivity (CS) thresholds at 1 to 18 cycles per degree (cpd). Imaging was performed on the same day with WF SSOCTA (PLEX® Elite 9000, Carl Zeiss Meditec), 3x3, 6x6, and 12x12 mm images. OCTA metrics included vessel density (VD) and vessel skeletonized density (VSD) in the superficial (SCP) and deep capillary plexus (DCP), and whole retina (WR). Mixed effects multivariable regression analyses controlling for age, lens status, and macula on/off status were performed. Standardized beta coefficients were calculated by refitting the standardized data.

Results: VA did not show any significant associations with VD or VSD on any OCTA image size. On the other hand, increased VD and VSD was significantly associated with improved CS among all the OCTA image sizes. On 3x3 mm OCTA images, all the CS metrics (AULCSF, CA, and CS at 1-18 cpd) showed significant associations with VD and VSD, with the largest effect size between CS at 12 cpd and VD in the DCP (β = 0.42, p = 0.001). On 6x6 mm images, AULCSF and CS at 12 cpd, showed significant associations with VD and VSD, with the largest effect size between VSD in the SCP and CS at 12 cpd (β = 0.37, p = 0.004). On 12x12 mm images, all the CS metrics, except CS at 18 cpd, showed significant associations with VD and VSD, with the largest effect size between VD and VSD in the DCP and CS at 12 cpd (β = 0.41, p = 0.003).

Conclusions: Among eyes that underwent RD repair, increased VSD and VD was significantly associated with improved CS, but not VA. Vascular metrics consistently demonstrated the largest effect size on CS at 12 cpd. These results suggest that CS, compared to VA, may better reflect the microvascular changes that occur after RD repair both near the macula and peripherally. Thus, monitoring CS among eyes before and after RD repair may aid in clinical management and could serve as a helpful prognostic tool.

Candidate: Romy Bejjani

Poster #: A04

Long-term Visual Outcomes of Photodynamic Therapy in Patients With Central Serous Chorioretinopathy in a Tertiary Care Center and in the IRIS® Registry

Romy Bejjani, Eric Goldberg, Connor Ross, Elizabeth Rossin, Demetrios G. Vavvas, Tobias Elze, Alice C. Lorch, Joan W. Miller

Purpose: To compare long-term (≥5 years) visual outcomes in central serous chorioretinopathy (CSCR) eyes treated with photodynamic therapy (PDT) to untreated eyes in a tertiary care center and the IRIS® Registry (Intelligent Research in Sight).

Methods: We reviewed CSCR patients followed for ≥5 years at Massachusetts Eye and Ear (MEE) from 20072024 and in the IRIS® registry (2000-2017), excluding eyes with choroidal neovascular membrane, focal laser, severe retinopathy, or anti-VEGF injections before PDT. We estimated and plotted best visual acuity (VA) trends in PDT-treated and untreated eyes using mixed linear and linear splines regression models.

Results: There were 26 CSCR eyes treated with PDT and 37 untreated eyes from the MEE database. Median (IQR) baseline VA was 0.3(0.16-0.47) and 0.1(0-0.18) in eyes with PDT and untreated eyes, respectively. Corresponding final VAs were 0 (0, 0.3) and 0 (0, 0.1). Mixed linear and linear splines models showed a flat VA trend overall, with no significant difference among subgroups. In the IRIS® Registry, there were 167 eyes treated with PDT and 4445 without treatment. Baseline VA was 0.25(0.1, 0.4) and 0.1(0, 0.22) respectively and improved after 5-6 years to 0.1 (0, 0.29) and 0.08 (0, 0.18), respectively. Regression models of a matched subset (163 patients) showed a small significant trend of long-term VA improvement but no intergroup difference.

Conclusions: Findings from both the MEE sample and IRIS® Registry show that despite worse vision at baseline, PDT is associated with a long-term trend of VA stabilization or improvement similarly seen in untreated eyes.

Candidate: Xinyi Ding

Poster #: A05

Assessment of Intraretinal Microvascular Abnormalities and Their

Clinical Significance in Eyes With Non-Proliferative Diabetic Retinopathy Using Swept-Source Optical Coherence Tomography Angiography

Xinyi Ding, Jeannie Xu, Francesco Romano, Cade Bennett, Itika Garg, Mauricio D. Garcia, Katherine Overbey, Filippos Vingopoulos, Ioanna Ploumi, Matthew J. Finn, Peyman Razavi, Leo A. Kim, David M. Wu, Deeba Husain, Demetrios G. Vavvas, John B. Miller

Purpose: To assess the severity and clinical significance of intraretinal microvascular abnormalities (IRMAs) using swept-source OCT Angiography (SS-OCTA) in eyes with non-proliferative diabetic retinopathy (NPDR).

Methods: Cross-sectional study. SS-OCTA was performed on 139 eyes from 101 subjects with NPDR. The montage of 12x12-mm angiography centered on the macula and optic nerve was evaluated by two masked graders for 1) the presence of IRMAs in each 6x6-mm quadrant, including center, supertemporal (ST), inferotemporal (IT), supernasal (SN), and inferonasal (SN) to the macula, and SN and IN to the optic nerve; 2) subtypes of IRMAs (dilated trunk, net shape, loop, sea fan and tufted IRMAs). Non-perfusion areas (NPA) were quantified using FIJI. After adjusting for age, diabetes duration, and prior anti-VEGF treatments, logistic and linear regression models were employed to evaluate the relationships between IRMA features and DR severity or NPA.

Results: IRMAs were present in 58.3% of all NPDR eyes, more prevalent in severe (96.9%) than mild (28.8%) to moderate (70.6%) NPDR. Significant predictors of severe NPDR included the presence of IRMAs in the 6x6 mm macular quadrant (OR: 8.7, p < 0.01), more extensive IRMAs (OR: 2.2, p < 0.01), a greater variety of IRMAs(OR: 4.2, p < 0.01), and the presence of specific forms like net shape (OR: 16.1, p=0.02), sea fan (OR: 26.0, p < 0.01), and tufted IRMAs (OR: 13.4, p=0.03). NPA was found to be significantly associated with the presence of IRMAs (beta=11.2, p<0.001). Specifically, in eyes with IRMAs, NPA showed a unique correlation with IRMAs within the 6x6 mm macular quadrant (beta=6.1, p=0.04) and IRMAs with loops (beta=7.3, p=0.04).

Conclusions: IRMA is detectable across all NPDR severities utilizing SS-OCTA. In addition to more central location and the extent of IRMAs, the diversity of subtypes as well as the presence of net shape, sea fan, and tufted IRMAs also indicate a more severe disease. Notably, the occurrence of IRMAs, particularly when involving the central region, is significantly correlated with NPA.

Candidate: Samet Gulkas

Poster #: A06

Regional Retinal Vessel Diameter and Progression Risk of Diabetic Retinopathy on Ultrawide Field Images

Samet Gulkas, Mohamed Ashraf, Assel Talaspaveya, Ward Fickweiler, Jennifer K. Sun, Paolo S. Silva, Lloyd P. Aiello

Purpose: To describe the relationship between regional retinal vessel diameters (RVD) on ultrawide field images (UWFI) and the 3-year risk of progression of diabetic retinopathy (DR) among eyes with early DR.

Methods: Retinal images from eyes with mild and moderate nonproliferative DR (NPDR) were graded at a centralized reading center ≥ 1-step DR progression from baseline to 3-year follow-up based on the clinical Early Treatment Diabetic Retinopathy Study (ETDRS) severity scale. A customized semi-automated tool (AVRTool) measured RVD at 1 DD (inner) and 3.5 DD (outer) from the optic nerve. Mean arteriole and venule diameter (µm) in the inner and outer zones (IA/IV, OA/OV) were assessed. Demographic, refraction, and systemic factors were retrieved from the electronic records.

Results: A total of 757 unique UWFI were evaluated [387 (51.1%) with mild NPDR, 370 (48.9%) with moderate NPDR at baseline, and 43.8% of the entire cohort with progression]. The mean time to DR progression was 34.8±3.9 months. Increasing DR severity was associated with decreasing arteriolar and increasing venular diameter in inner zone, and increasing venular diameter in outer zone (nonprogressors/progressors/p-value: OA-104.03/103.1.6/0.23, OV-117.4/120.4/<0.001, IA-105.7/103.2/0.004, IV 125.7/127.5/0.02). After correcting for baseline differences in age, gender, diabetes duration, HbA1c, hypertension, 1-Step progression was associated with only increasing outer venular diameters in cases with mild DR (B/p-value: OV 0.043/0.002), and both decreasing inner and outer arteriolar diameters in cases with moderate NPDR (B/p-value: IA -0.029/0.014; OA -0.044/0.003). 2-Step or more progression was associated with only decreased inner arteriolar diameter in both cases with mild or moderate NPDR (Mild; B/p-value: IA0.044/0.006, Mod; B/p-value: IA 0.031/0.014).

Conclusions: Our study found that the average inner retinal arteriolar diameter, as measured by the AVRTool on UWFI, was linked to a significant progression of DR, specifically a 2 step or greater increase in severity. In contrast, neither venular diameter nor measurements taken from the peripheral retina showed a correlation with DR progression. These findings suggest a possible stronger relationship between inner arteriolar changes and DR worsening. However, further research with larger sample sizes is essential to ascertain whether these measurements can predictively indicate progression in prospective datasets.

Candidate: Sierra Ha

Poster #: A07

Structure-function Associations Between Quantitative Contrast

Sensitivity Function and Peripapillary Optical Coherence Tomography Angiography in Diabetic Retinopathy

Sierra Ha, Xinyi Ding, Francesco Romano, Katherine Overbey, Filippos Vingopoulos, Itika Garg, Cade Bennett, Isabella Stettler, Ioanna Ploumi, Grace Baldwin, Matthew Finn, Peyman Razavi, Demetrios Vavvas, Deeba Husain, Nimesh Patel, Leo Kim, John B. Miller

Purpose: Diabetic retinopathy (DR) has been associated with changes in the peripapillary retinal nerve fiber layer (pRNFL) and microvasculature. However, it remains unclear how these structural changes may affect visual function. Recent findings suggest that contrast sensitivity (CS) demonstrates greater sensitivity than visual acuity (VA) in discerning presence and severity of DR, despite VA being the traditional functional outcome measure in DR studies. Thus, this study aims to investigate the association between various swept-source OCT angiography (OCTA) metrics centered on the optic disc and function alterations, as assessed by VA and CS, in DR.

Methods: This cross-sectional study included 114 eyes of 80 patients (22 control, 27 diabetic without DR, 14 mild non-proliferative DR (NPDR), 24 moderate/severe NPDR, and 27 proliferative DR eyes) that underwent quantitative contrast sensitivity function (qCSF) testing (Adaptive Sensory Technology) and same-day imaging with 6x6 mm OCTA centered on the optic disc (Plex® Elite 9000) between June 2019 and January 2024. The Peripapillary Nerve Fiber Layer Microvasculature Density algorithm v0.9 available on the ARI Network was used to calculate capillary perfusion density (CPD), capillary flux index (CFI), and retina nerve fiber layer (RNFL) thickness in the temporal, superior, nasal, and inferior sectors surrounding the optic disc. CPD was defined as the total area of perfused microvasculature per unit area in a region of measurement, while CFI was defined as the total weighted area of perfused microvasculature per unit area in a region of measurement. Mixed-effects multivariable regression models controlling for age, lens status, and presence of diabetic macular edema were used to evaluate associations between OCTA metrics and both VA and qCSF metrics. All models accounted for nesting of eyes within patients. Associations were reported as standardized beta coefficients by refitting the standardized data.

Results: Mean CFI and CPD were decreased in later stages of DR across all sectors (standardized β range: -1.22 to -0.18; p<0.05). RNFL thickness in the superior and inferior regions were negatively associated with the severity of DR (standardized β range: -0.75 to -0.21; p<0.05). Mean CFI and CFI across all sectors were associated with AULCSF, CA, and CS at 6 and 18 cpd, (standardized β range: 0.19 to 0.32; p<0.05), but not with VA. CPD was not associated with qCSF metrics or VA (all p>0.05). Higher mean RNFL/CFI ratio and the ratio in multiple sectors were associated with decreased AULCSF, CA, and CS at 1-12 cpd, (standardized β range: -0.33 to -0.19; p<0.05), but not with VA.

Conclusions: Peripapillary microvasculature changes in DR, as detected by OCTA, correlate better with changes in contrast sensitivity than VA. Additionally, microvascular changes may be more sensitive than retinal neurodegenerative changes in the progression of DR, as indicated by the strong association of CFI across all sectors with CS as well as the significant relationship between the RNFL/CFI ratio and decreased CS. This study highlights the potential of peripapillary flow metrics in predicting functional changes in CS and further supports the use of qCSF as a functional endpoint in DR trials.

Candidate: Ayush Parikh

Poster #: A08

Etiologies, Clinical Characteristics, and Management of Pediatric Macular Holes: A Retrospective Review

Ayush A. Parikh, Sandra Hoyek, Bertan Cakir, Shizuo Mukai, Nimesh A. Patel

Purpose: To report on the etiologies and outcomes of pediatric macular holes (MH).

Methods: Case series of pediatric patients with macular holes from 2005 to 2023 at a tertiary eye care center (Mass Eye and Ear).

Results: Forty-six eyes of 46 patients were included. Patients were predominantly male and Caucasian, and mean age was 13 years. Blunt trauma was the most common MH etiology (84.8%), and presentation occurred at an average of 34.9 days after injury. Of 46 eyes, 37 were observed, of which 27 (73%) MH closed within an average of 91.2 days. Visual acuity improved from 1.17 logMAR (20/300) to 0.56 logMAR (20/75). Seventeen patients underwent surgery with pars plana vitrectomy, posterior vitreous detachment, membrane peel, and fluid-gas exchange. Hole closure was achieved in 12 (71%) eyes, and visual acuity improved from 1.07 logMAR (20/225) to 0.61 logMAR (20/80) by postoperative year 1.

Conclusions: Pediatric patients with a history of blunt eye trauma warrant close retinal exam to evaluate for macular holes, which may have a delayed presentation. The present findings suggest that both observation and surgical intervention may achieve high rates of hole closure and vision improvement

Candidate: Ioanna Ploumi

Poster #: A09

Impact of Predominant Peripheral Lesions on Retinal Microvasculature and Risk of Vitreous Hemorrhage in Proliferative Diabetic Retinopathy

Ioanna Ploumi, Jenny Gan, Xinyi Ding, Francesco Romano, Katherine Overbey, Mauricio Garcia, Itika Garg, Filippos Vingopoulos, Matthew Finn, Peyman Razavi, Jocelyn Rodriguez, Cade Bennett, Nimesh Patel, Deeba Husain, Demetrios Vavvas, John Miller

Purpose: To investigate the association of predominant peripheral lesions (PPLs) with retinal microvasculature on WF SS-OCTA and the risk of VH in eyes with PDR.

Methods: The cross-sectional part of this study included 111 PDR eyes of 84 patients with same-day UWF-FP (California; Optos plc., Dunfermline, UK) and WF SS-OCTA (PLEX® Elite 9000; Carl Zeiss Meditec, Dublin, CA). A subset of 101 eyes from 75 patients followed for at least 3 months were included in the prospective part of this study, where the history of complications and treatments was reviewed. UWF-FP were graded by 2 independent graders for the presence of and the number of fields with PPLs – defined as more than 50% of diabetic lesions subjectively residing in the extended field compared to the respective ETDRS field. Only 1 field with PPLs was required for the eye to be graded as having PPLs. Ischemic index (ISI) and common SS-OCTA vascular metrics were calculated on FIJI and ARI network, respectively. 6×6- and 12×12-mm retinal microvasculature alterations were compared between eyes with and without PPLs utilizing the Mann-Whitney U test. The association between the presence and extent of PPLs and the development of VH was evaluated using generalized estimating equations and multilevel Cox mixed-effects regressions.

Results: PPLs were present in 36 out of 111 eyes (32.4%). OCTA parameters, including ISI, vessel density and vessel skeletonized density did not show significant differences in groups with or without PPLs. Over a period of 18.1 10.2 months, 34 VH events occurred in 23 eyes – 14 having a history of VH (recurrent VH) and 9 having no VH history (new VH). There was an association between the presence of PPLs and the development of new VH (p=0.04), but not for recurrent VH. The number of peripheral fields with PPLs was a significant predictor for the new development of VH, after adjusting for age, DM duration and prior anti-VEGF as well as PRP (HR= 1.92, p=0.03).

Conclusions: While 6x6- and 12x12-mm OCTA metrics in eyes with or without PPLs are comparable, the presence and extent of PPLs are associated with the new development of VH. Given the advancement of UWF imaging technologies, the development of a new DR grading scheme to account for PPLs may enhance our ability to predict the risk of VH in patients with PDR.

Candidate: Francesco Romano

Poster #: A10

Associations Between Contrast Sensitivity Function, Optical Coherence Tomography Features and Progression From Intermediate to Late age-related Macular Degeneration

Francesco Romano, Cade Bennett, Filippos Vingopoulos, Xinyi Ding, Ioanna Ploumi, Mauricio Garcia, Augustine Bannerman, Isabella Stettler, Katherine Overbey, Inês Laìns, Demetrios Vavvas, Deeba Husain, Leo A. Kim, Joan W. Miller, John B. Miller

Purpose: Establishing detailed associations between structure, function, and clinical outcomes in intermediate agerelated macular degeneration (iAMD) remains an unmet need. Our study aims to (1) cross-sectionally investigate the relationships between established optical coherence tomography (OCT) biomarkers and quantitative contrast sensitivity function (qCSF)-measured contrast sensitivity (CS), and (2) longitudinally assess their relationship with the progression from iAMD to late stages of the disease.

Methods: This cross-sectional and longitudinal observational study was conducted at the Retina Service of Massachusetts Eye and Ear (Boston, MA, USA) between April 1, 2017, and July 31, 2021. We included eyes with (1) baseline diagnosis of iAMD per the Beckman classification, (2) same-day OCT and qCSF test, (3) visual acuity (VA) ≥20/200 Snellen, and (4) 24+ months of follow-up. qCSF was tested monocularly, and the analyzed metrics included the area under the logCSF curve (AULCSF), contrast acuity (CA), and CS thresholds at 1-to-18 cycles per degree (cpd).

Two independent graders reviewed macular OCT scans for cuticular drusen, subretinal drusenoid deposits (SDD), hyporeflective drusen cores (hDC), refractile drusen, and the number of hyperreflective foci (HRF). Outer nuclear layer (ONL) thickness and retinal pigment epithelium (RPE) volume were semi-automatically collected for the central subfield (1 mm) and inner ring (1-3 mm) of the ETDRS grid.

Data on progression to wet AMD or geographic atrophy (GA) was obtained from clinical charts and confirmed using available imaging studies.

Generalized linear mixed-effects models assessed the associations between qCSF and OCT biomarkers. Cox regression models evaluated the impact of qCSF and OCT on progression to late AMD. All models were subject to nesting and adjusted for age and lens opacity following LOCS III classification.

Results: We included 205 iAMD eyes from 134 patients (age: 73 [69-78] years; females: 63%). Multivariable regression revealed that higher RPE volume in the central subfield and a greater number of HRF were associated with reduced AULCSF, CA and CS at 6-12 cpd (p<0.05). ONL thinning in the inner ring and a greater number of HRF were associated with reduced CS at 1 and 3 cpd (p<0.05). During follow-up, 35 eyes developed wet AMD (17%) and 53 progressed to GA (26%). Cox regression revealed that SDD, ONL thinning in the inner ring and reduced CS at 1.5 cpd were associated with wet AMD development (p<0.05). Further, higher RPE volume in the inner ring, hDC, SDD, a higher number of HRF and reduced CS at 1 cpd were associated with progression to GA (all p<0.05).

Conclusions: Our study reveals the structure-function relationships between established OCT biomarkers and qCSF-measured CS in iAMD. Notably, eyes with increased RPE volume in the central 1 mm, thinning of the parafoveal ONL and a higher number of HRF were significantly associated with a reduction in most qCSF metrics. These findings have significant implications for understanding the impact of AMD alterations on CS function. Furthermore, different OCT alterations (e.g., SDD) and reduced CS at low spatial frequencies were variably associated with progression to late AMD, offering valuable insights for the stratification and prognostication of patients with iAMD in research and clinical settings.

Candidate: Priya Shah

Poster #: A11

Analysis of Choroidal Thickness Differences Between Sexes in Central Serous Retinopathy,

Pattern Dystrophy, Age-Related Macular Degeneration and Healthy Controls

Priya Shah, Panisa Singhanetr, Isaac Bleicher, Demetrios Vavvas, Elizabeth J. Rossin

Purpose: Our goal is to assess the influence of sex on choroidal thickness in patients from Massachusetts Eye and Ear (MEE) with central serous chorioretinopathy (CSCR), pattern dystrophy, and healthy control patients while controlling for age and spherical equivalent (SE). Previous research reports in healthy populations, males have a thicker choroid than females. There have also been several studies that identify characteristics of different macular diagnoses to be related to the choroidal changes in their pathophysiology, and one study has found that male patients with CSCR have a thicker choroid than females with CSCR. Another study found that patients with adult-onset foveomacular vitelliform dystrophy, a type of pattern dystrophy, and control patients have similar choroidal measurements.

Methods: A retrospective analysis was conducted of 523 CSCR patients, 222 pattern dystrophy patients, and 663 healthy patients who presented to Massachusetts Eye and Ear. The choroidal thickness was measured using enhanced depth imaging optical coherence tomography (EDI-OCT) if available, or optical coherence tomography (OCT) images on the Heidelberg software. Patients who received 2+ anti-VEGF injections, PDT prior to initial presentation, or had CNVM at any point of the diagnosis were excluded from the study since these treatment options cause thinning of the choroid. We then compared the SFCT (subfoveal choroidal thickness) means between males and females using an unpaired two-sided t-test and then modeled the effect of sex on SFCT (and peak of irregularity (POI) for CSCR) using a linear regression while controlling for age and spherical equivalent (SE). Only OD was used for bilateral disease patients.

Results: A multivariable linear regression indicated that choroidal thickness in all CSCR patients was significantly associated with sex (males n = 374, mean age = 49.2; females n = 149, mean age = 53.2; P=0.035) when controlling for age. When controlling for age and spherical equivalent, the choroidal thickness was also significantly associated with sex (P=0.088). In pattern dystrophy patients, there was no significant association between choroidal thickness and sex when controlling for age and spherical equivalent (males n = 114, mean age = 67.8; females n = 108, mean age = 70.8; P = 0.483). In the control group, the choroidal thickness was significantly associated with sex (males n = 353, mean age = 67.0; females n = 310, mean age = 68.6; P=0.0095) when controlling for age and spherical equivalent.

Conclusions: There is a statistically significant effect of sex on SFCT for patients with CSCR and healthy controls. The results also indicated that there is no statistically significant difference effect of sex on SFCT for patients with pattern dystrophy. When analyzing CSCR based on its subgroups, sex has a significant effect on choroidal thickness only for acute CSCR patients, but no significant effect was seen when analyzing the other CSCR subgroups. Because the overall understanding of CSCR and pattern dystrophy is uncertain, appreciating contributing factors will help better understand both diagnoses' etiology.

Candidate: Assel Talaspayeva

Poster #: A12

Comparison

of

the Portable Retinal Thickness Analyzer

and Spectral Domain Optical Coherence Tomography Retinal Thickness Measurements in Diabetic Eyes

Assel Talaspayeva, Samantha Hersh, Doan Duy, Samet Gulkas, Ward Fickweiler, Mohamed Ashraf, Ryo Kubota, Jennifer K. Sun, Lloyd Paul Aiello, Paolo S. Silva

Purpose: The portable Retinal Thickness Module (RTM, Kubota Vision) is a novel home-based patientadministered optical coherence tomography (OCT) device to measure retinal thickness and identify macular edema. This prospective instrument validation study evaluated the accuracy of patient self-administered imaging using the RTM device in comparison to spectral domain (SD-OCT) device for measuring retinal thickness in diabetic eyes.

Methods: Patients underwent nonmydriatic imaging with the RTM device followed by SD-OCT scans (Macular cube, Spectralis, Heidelberg) during a single office visit. The retinal thickness was quantified using cloud-based AI algorithms provided by the manufacturer. The primary outcome measure was central subfield retinal thickness (CST) on the RTM compared with that derived from Spectralis.

Results: A total of 66 eyes from 33 diabetic patients [15.2% no DR, 18.2% mild nonproliferative DR, 16.7% moderate, 9.1% severe and 34.8% proliferative DR; 33.3% with diabetic macular edema] were enrolled. Mean age was 53.7±16.5 (24-81) and diabetes duration 25.2±12.7 (6-63) years, 57.6% type 2 diabetes, 51.5% females, 74.2% phakic Mean BCVA was 20/32. RTM ungradable rate was 24.2% (ungradable rate for the first 20 eyes was 55% and next 46 eyes was 10.8%). Mean CST was 326±105.7 μm (Spectralis) and 299.1±71.9 μm (RTM). Mean difference in CST was 27.7±85.6 μm with moderate correlation (r=0.59, <0.0001) between RTM and Spectralis measures. RTM sensitivity/specificity for detecting CST ≥310 on Spectralis was 1.00/0.82 and positive/negative predictive value 0.63/1.00. For CST≥ 400, these values were 0.67/0.91 and 0.33/0.97.

Conclusions: This study demonstrates that the portable RTM device may become a feasible home-based tool for OCT-based imaging for measuring retinal thickness and detecting macular edema in diabetic eyes. There was high sensitivity (1.00) and moderate specificity (0.82) in identifying eyes with CST ≥ 310, suggesting potential utility in DR screening. Without mydriasis, gradable images were obtained in slightly over 75% of the cohort with ungradable images reduced to 10% after the initial 10 patients. Further refinement of the device will be essential to optimize its agreement with SD-OCT measurements, reduce the ungradable rate and validate its effectiveness in larger cohorts for remote home DR monitoring.

Candidate: Fatma Ali

Poster #: B01

Exogenous Methicillin-Resistant Staphylococcus Aureus

Endophthalmitis is Caused by Multidrug-Resistant Lineages That are Associated With Poor Outcomes

Fatma Zaki Alkhidr Ali, Camille Andre, Jie Sun, Lucia Sobrin, Paulo Bispo

Purpose: Correlating molecular epidemiology and genomic traits of methicillin-resistant Staphylococcus aureus (MRSA) endophthalmitis with clinical features and outcomes.

Methods: Demographics, clinical picture, management outcomes were extracted from medical records of the patients from 2014-2022. Antibiotic resistance profiles and genotypes were characterized using phenotypic tests and genomic sequencing.

Results: 25% (N=9) of SA endophthalmitis cases were MRSA. Clonal complex 5, SCCmec type II, multidrug resistant strains (USA100 like) dominated the population (100%). 56% of patients were male with median age 82.7 years. Causes were ocular surgery (67%) and intravitreal injection (IVI,33%). 100% showed BCVA ≤ HM. 100% underwent IVI of antibiotics and 67% pars plana vitrectomy (PPV). BCVA improved in 56%, 33%, and 22% at 1, 3, and 6 months/one year respectively. 2 cases advanced to evisceration and phthisis. PPV within 48 hours had better clinical outcomes.

Conclusions: USA100 strain causes severe exogenous MRSA endophthalmitis. Urgent IVI of antibiotics and PPV may save the eye.

Candidate: Buravej Assavapongpaiboon

Poster #: B02

In-transit

Metastases

in

Conjunctival

Melanoma: A Potentially Underrecognized Phenomenon That Likely Portends an Unfavorable Prognosis

Buravej Assavapongpaiboon, Thomas Dohlman, Nahyoung G. Lee, Nandini Venkateswaran, Anna M. Stagner

Purpose: The phenomenon of in-transit metastasis has been well described in cutaneous melanoma, where it is associated with higher stage disease as well as eventual lymph node and distant metastases, and increased mortality. Loco-regional metastases (outside of lymph nodes) in conjunctival melanomas have not been well described. The authors hypothesize that like some skin melanomas, conjunctival melanomas display the phenomenon of in-transit metastasis, which likely results in a more aggressive clinical course and may be underrecognized by ophthalmic pathologists and ocular oncologists.

Methods: A retrospective observational study identified and characterized three patients with in-transit metastasis in the setting of conjunctival melanoma, either at the time of initial diagnosis or subsequently. Review of clinical data including imaging studies and slit lamp photography, as well as re-review of hematoxylin and eosin and immunohistochemical stained sections was undertaken.

Results: Three patients aged 39, 41 and 95 years were diagnosed with conjunctival melanoma. In one patient, a subepithelial nodule of melanoma without an intraepithelial component arose from the superior tarsal conjunctiva one year after complete excision of a recurrent melanoma of the inferior bulbar conjunctiva. In another other two patients, in-transit metastases presented as large discrete nodules mimicking pyogenic granuloma which were entirely separate from a synchronous primary melanoma/melanoma in situ. In addition to no overlying in-situ component, metastatic foci were also cytomorphologically distinct, with marked epithelioid cell atypia and loss of expression of some normal melanocytic markers. All patients were treated with immune checkpoint inhibition after excision. Two patients had local recurrences and one ultimately underwent exenteration. Multimodality imaging showed no lymph node or distant metastases at the time of this report.

Conclusions: In-transit metastases of conjunctival melanomas occur as they do in the skin. Histopathologically, the metastatic foci may show a more aggressive morphology than the primary tumor, and by definition, do not display an overlying intraepithelial component. Caution must be taken to avoid misdiagnosis as recurrence and/or second foci of invasive disease.

Candidate: Yeganeh Farsi

Poster #: B03

Incidence

of Ocular

Graft-versus-host

Disease During Tapering of Immunomodulatory Therapy Following Allogeneic Hematopoietic Stem Cell Transplantation

Yeganeh Farsi, Rohan B. Singh, Pier Luigi Surico, Erdem Yuksel, Reza Dana

Purpose: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an effective therapeutic intervention in patients with hematologic malignancy. Ocular graft versus host disease (oGVHD) is a common and potentially severe complication of allo-HSCT. In this study, we assessed the incidence of oGVHD upon tapering of immunomodulatory (IM) drugs in patients following allo-HSCT.

Methods: We performed a retrospective study including patients who underwent allo-HSCT and developed oGVHD during the IM dose tapering. We assessed the incidence, oGVHD event rate and ocular surface disease parameters including corneal fluorescein staining, tear break-up time (TBUT), and Schirmer’s test results. All calculations were performed with 95% confidence (95% CI) and p-value <0.05 was considered statistically significant.

Results: A total of 77 patients (62% male) with oGVHD for whom we had comprehensive information on the timing of their IM therapy were included in the analysis. The mean time to develop oGVHD was 17.2± 15.16 months (range: 1- 126 months) post- transplantation. The event rate of oGVHD increased overtime on tapering all IM drugs except Methotrexate (p<0.05). The risk of oGVHD was significantly higher after the fourth tapering of IM drugs; patients receiving Sirolimus were at the highest risk of oGVHD (odds ratio: 6.42, P<0.0001), followed by Cyclosporine (odds ratio: 5.00, P<0.0001), Tacrolimus (odds ratio: 4.05, P<0.0001), and Mycophenolate (odds ratio: 2.44, P=0.03). Schirmer scores were significantly decreased after the fourth tapering of Tacrolimus and Cyclosporine [odds ratio: 3.72 (p=0.002) and 3.65 (p=0.032)] compared to the values reported at previous tapering timepoints. Similarly, TBUT was significantly reduced in patients receiving Tacrolimus. (odds ratio: 3.41, P<0.0001). The CFS scores were moderately increased following each tapering of the IM drugs.

Conclusions: IM tapering following allo-HSCT increases the risk of developing oGVHD, especially following the fourth tapering. Close observation and adequate patient education about the early signs of oGVHD for these patients should be kept in mind to prevent severe complications of oGVHD.

Candidate: Asahi Fujita

Poster #: B04

Treatment

Patterns and Outcomes of Childhood Glaucoma in the United States: Analysis of the IRIS Registry

Asahi Fujita, Daniel M. Vu, David S. Friedman, Elizabeth C. Ciociola, Kanza Aziz, Kasem Seresirikachorn, Alice Lorch, Joan Miller, Tobias Elze*, Nazlee Zebardast*

* co-senior

authors

Purpose: Childhood glaucoma is a rare disease with potentially devastating visual outcomes. Because of the rarity of the disease, literature on the treatment patterns and surgical outcomes of childhood glaucoma is limited to small numbers of patients. In addition, most of the previous studies were conducted in South Asia, where most patients were lost to follow-up due to limited access to care. The treatment patterns and outcomes of childhood glaucoma in North America remain unknown.

Methods: This retrospective cohort study uses the IRIS® Registry (Intelligent Research in Sight), a large electronic health record database encompassing ophthalmic information from across the United States. We included patients with childhood glaucoma by the International Classification of Disease (ICD) codes for glaucoma (ICD-9: 365.1-365.9, ICD-10: H40.1-H40.9, H42, H44.51, Q15.0), age ≤ 18 at first diagnosis between 2013 and 2020, and with ≥ 2 years of follow-up. We identified glaucoma-related surgeries using CPT codes for angle surgery (65850, 65820, 66174, 66175), filtration surgery (66170, 66172, 66183, 0449T), tube surgery (66179, 66180), cyclodestruction (66710, 66711), and laser trabeculoplasty (65855). We calculated the percentage of patients who received IOP lowering medications and that of patients who underwent glaucomarelated procedures. We analyzed changes in IOPs and visual acuities after surgery for up to 5 years and reoperation rates.

Results: 9277 eyes of 5676 patients (mean age 11 years) were included. 569 eyes (6%) were coded as primary congenital glaucoma, 1830 eyes (20%) were juvenile open-angle glaucoma, and 4260 (46%) eyes were glaucoma suspects. Out of 5017 glaucoma eyes, 808 eyes (16%) underwent surgeries, and 4698 eyes (94%) received medication. Tube surgery was the most common choice of procedure (32%) followed by laser trabeculoplasty (24%). Laser trabeculoplasty was mainly performed for juvenile open-angle glaucoma. Mean IOP of tube surgery was 29.4 (SD: 10.6) mmHg preoperatively and 16.7 (6.0) mmHg at year 5. Angle, tube, and filtration surgeries were associated with good control of IOP over the five years following surgery. Tube surgery had the lowest re-operation rate (14%) followed by laser trabeculoplasty (29%).

Conclusions: We investigated treatment patterns and outcomes of childhood glaucoma using a large nationwide registry. 16% of the eyes with childhood glaucoma underwent surgery, and 94% received medications. Tube surgery was the most common choice of surgery. Treatment patterns in our study were different from previous reports from academic hospitals in South Asia, probably because our data represented mostly community hospitals in the U.S. Angle, tube, and filtration surgeries were associated with good control of IOP over the five years following surgery.

Candidate: Ma Carmela Guevarra

Poster #: B05

A Novel 13q32.1 Deletion in a Filipino Congenital Microcoria (MCOR) Family

Ma. Carmela Guevarra, Edward Ryan Collantes, Michael Sibulo, Divine Joe Grace Marcelino, Nilo Vincent FlorCruz, Janey Wiggs

Purpose: Congenital Microcoria (MCOR) is a rare ocular disease characterized by abnormally small pupils due to absence of the dilator pupillae muscle. MCOR has been associated with early onset glaucoma in some cases. The disease is inherited as a dominant trait and large-scale chromosomal rearrangements (mainly deletions) involving 13q32.1 have been identified. In this study, we identify a novel 13q32.1 deletion in a Filipino MCOR family involving TGDS and GPR180 genes as well as a putative SOX21 regulatory region providing additional insight into the genetic etiology of this condition.

Methods: 4 members from a 4 generation Filipino family with 32 individuals were recruited for the study. Subjects underwent comprehensive ophthalmologic examination and DNA extraction. Whole genome sequencing was performed, SNP and indel variant calling workflows were followed using GATK Best Practices, and structural variants were mapped using the GATK-SV pipeline. SNPs and indels were analyzed using seqr and SVs with Integrated Genomics Viewer. Single cell RNA sequence data was accessed from the Broad single cell portal.

Results: Abnormally small pupils (<2mm) were observed in 3 of the 4 family members. Intraocular pressures were normal except for the 16 year old proband who was also diagnosed with glaucoma. Screening for mutations causing early onset glaucoma and other potential variants was inconclusive. Analyses of copy number variants (CNVs) revealed a 37-kilobase deletion on chromosome 13q32.1 in 3 affected members and not in the unaffected member. The deletion extended from 13:94,590,353 to 94,637,698 encompassing GPR180 and TGDS genes and a regulatory region containing enhancers for SOX21. Single cell RNA data suggests expression in iris and ciliary body for both GPR180 and TGDS but with GPR180 having higher expression at 78% and 54% respectively.

Conclusions: Large scale 13q32.1 deletions involving GPR180 and TGDS segregate with disease in this Filipino family and together with other deletions previously described support a locus for MCOR in this chromosome region. In addition, a region regulating expression of SOX21, another gene involved in eye development, is also included in the deleted critical region. Further work is needed to define the MCOR causal gene or genes located in 13q32.1.

Candidate: Dhruva Gupta

Poster #: B06

Visual Field Improvement in Glaucoma: A Large Single Center Study

Dhruva Gupta, Saber Kazeminasab Hashemabad, Hannah Rana, Mohammad Eslami, Nazlee Zebardast, Mengyu Wang, Eric D. Gaier, Tobias Elze

Purpose: Glaucoma is defined by damage to the optic nerve that results in progressive visual field (VF) loss. There is open debate whether VF loss in glaucoma is reversible. Neuroplasticity, which allows the brain to adapt in response to disease, is a proposed mechanism by which VF improvement may occur in glaucoma. A prevailing challenge, however, is distinguishing true improvement from test retest variation of VF measurements. In this study, we set out to identify eyes exhibiting true improvement and address other confounders that may explain improvement.

Methods: We modified a well-established statistical method, permutation of pointwise linear regression (PoPLR), to distinguish VF improvement from random variation. From the Massachusetts Eye and Ear Glaucoma Service dataset, we filtered for eyes with 8-16 VF measurements over 8-12 years with a fixation loss (FL) less than 20% and false positive rate (FPR) less than 15%. We applied PoPLR to classify eyes in one of the following VF outcomes: improvement, deterioration, or stability. Targeting potential confounders that may yield apparent VF improvement, we examined the association of cataract extraction, intraocular pressure (IOP), and recovery of other neurologic/ophthalmic diseases. Among VF outcomes, we compared rates of cataract extraction and YAG capsulotomy using chi-square analysis, and IOP variability using ANOVA analysis with Tukey’s HSD post-hoc test. Glaucoma-specific archetypal analysis was applied to decompose VFs into their constituent archetypes. Logistic regression was used to determine which archetypes were associated with an increased likelihood of VF improvement. A p-value less than 0.05 was considered significant.

Results: We isolated 1,219 eyes and found that VF deterioration, improvement, and stability occurred in 23.6%, 17.9%, and 58.4% of eyes, respectively. All rates significantly exceeded the 5% threshold for random fluctuation. Between eyes with VF improvement and stability, rates of cataract extraction were similar χ2 (2, N=107) = 0.826, p = 0.64. Significant differences in IOP variation existed across VF outcomes (p < 0.001), but VF improvement and stability were similar (2.07±1.00mmHg vs. 2.06±1.14mmHg, p = 1.00). While archetypes representing other neurologic/ophthalmic conditions had a higher likelihood of improvement, so did the glaucomatous VF pattern of inferior altitudinal loss.

Conclusions: Our findings support that VF improvement in glaucoma is a true phenomenon. Because eyes with VF improvement and stability had similar rates of cataract extraction and trends in IOP variability, these factors cannot fully account for VF improvement. Inferior altitudinal loss was a glaucomatous defect that had a greater chance of improvement. Next steps are not only to rule out other possible confounders, but also characterize how glaucomatous regions of the VF may undergo improvement over time.

Candidate: Lisa Lin

Poster #: B07

Deep-Learning Based Automated Segmentation and Quantitative Volumetric Analysis of Orbital

Muscle and Fat for Diagnosis of Thyroid Eye Disease and Associated Optic Neuropathy

Lisa Y. Lin, Adham M. Alkhadrawi, Saul Langarica, Kyungsu Kim, Sierra K. Ha, Nahyoung Grace Lee, Synho Do

Purpose: Thyroid eye disease (TED) is characterized by proliferation of orbital tissues and complicated by compressive optic neuropathy (CON). This study aims to utilize deep-learning (DL)-based automated segmentation model to segment orbital muscle and fat volumes on computed tomography (CT) images and provide quantitative volumetric data. Additionally, this study aims to develop a machine learning (ML)- based classification model to distinguish patient with TED and TED with CON.

Methods: Subjects with TED who underwent clinical evaluation and orbital CT imaging were included. Patients with clinical features of CON were classified as severe TED, and those without were mild TED. Normal patients were used for controls. A U-Net DL- model was used for automatic segmentation of orbital muscle and fat volumes from orbital CTs and volumetric analysis of muscle and fat were performed. ML-based classification models utilizing volumetric data and patient metadata were performed to distinguish normal, mild TED, and severe TED.

Results: Two-hundred and eight one subjects were included. Automatic segmentation of orbital tissues was performed and muscle volumes between normal, mild, and severe TED were found to be statistically different. A classification model utilizing volume data and limited patient data had an accuracy of 0.838 and an AUC of 0.929 in predicting normal, mild TED, and severe TED.

Conclusions: DL-based automated segmentation of orbital images for TED patients was found to be accurate and efficient. A ML-based classification model using volumetrics and metadata led to high diagnostic accuracy in distinguishing TED and TED with CON. By enabling rapid and precise volumetric assessment, this may be a useful tool in future clinical studies.

Candidate: Anagha Lokhande

Poster #: B08

Geographic Disparities in Glaucoma Surgical Care: An IRIS® Registry (Intelligent

Research in Sight) Analysis

Anagha Lokhande, Kanza Aziz, Louis R. Pasquale, Lucy Q. Shen, David S. Friedman, Michael V. Boland, Alice C. Lorch, Joan W Miller, Mengyu Wang, Nazlee Zebardast, Tobias Elze

Purpose: To quantify differences in glaucoma surgeries based on geography and practice/provider characteristics.

Methods: IRIS Registry data from 2013 – 2020 were included. Cases of micro-invasive glaucoma surgery (MIGS, i.e., iStent microstent, endocyclophotocoagulation, XEN Gel Stent, goniotomy or ab interno trabeculotomy or Trabectome, and canaloplasty) and filtering glaucoma surgery (glaucoma drainage device [GDD] and trabeculectomy) associated with glaucoma diagnosis (with severity stratified by the International Classification of Diseases, Ninth and Tenth Revisions) were selected based on Current Procedure Terminology codes. Urbanization of practice zip codes was classified using Rural-Urban Commuting Area Codes from the United States (US) Department of Agriculture. Associations between procedure counts and practice, provider, and geographic characteristics were assessed using chi-square tests and multivariate logistic regression adjusted for patient demographics (age, gender, and race), glaucoma severity, the interaction between glaucoma severity and urban location, and, as provided by the US Census, zip code population density.

Statistical significance was set at p < 0.05.

Results: Most glaucoma surgeries were performed in ophthalmology group practices (55.2%) and urban locations (90.8%). Glaucoma subspecialists performed 72.9% of GDD surgeries, 63.4% of XEN Gel stent surgeries, and 69.0% of trabeculectomies (Table 1). Figure 1 shows the geographic distribution of glaucoma procedures in the mainland US. Urban practice location was associated with a lower likelihood of receiving an iStent (odds ratio [OR] = 0.43, p < 0.0001) and higher odds of receiving endocyclophotocoagulation (OR = ARVO 2024 1, 2 3 4 3 3 3 3 3 1 3 1 2.23), goniotomy or canaloplasty (OR = 1.57), GDD (OR = 1.85), and trabeculectomy (OR = 1.59) (p <0.0001). No significant association was found between urban practice location and the likelihood of XEN Gel stent.

Conclusions: Ophthalmology group practices and practices in urban areas account for most glaucoma surgeries. Glaucoma subspecialists performed most filtering glaucoma surgeries. Urban practice location is a significant predictor of receiving most types of MIGS and filtering glaucoma surgery, which may represent barriers to accessing complex surgical glaucoma care for patients outside urban areas.

Candidate: Madhura Shah

Poster #: B09

Sequential NAION: Associated Risks and Temporal Distribution of Events

Madhura P. Shah, Drenushe Krasniqi, Tatiana Hathaway, Tais Estrela, Joseph F. Rizzo

Purpose: Non-arteritic anterior ischemic optic neuropathy (NAION) is the most common acute optic neuropathy in patients over age 50, and there is a 15-25% risk of a sequential (sNAION) event in the fellow eye. The Ischemic Optic Nerve Decompression Trial reported 326 patients with NAION (mean follow-up: 5.1 years) with a 14.7% incidence of sNAION; median time between study enrollment and sNAION was 1.2 years.

Methods: Retrospective query of the electronic health record (EHR) at a specialty eye hospital for encounters with ICD-10 code for “ischemic optic neuropathy” (right, left, bilateral, or unspecified), text phrase “NAION”, or “ischemic optic neuropathy”. With manual chart review, 451 patients with other diagnoses were excluded (search methodology evaluated in companion abstract) and date of vision loss, rather than ICD-10 code association, was recorded.

Results: A total of 672 patients were identified with at least unilateral involvement. Kaplan–Meier survival analysis (12 month censure) revealed that 31% of patients had sNAION with mean follow up of 8 years. Mean age at first NAION episode was 59.5 ±12.7 ydisears. Median time between sNAION episodes was 19.5 months. The probability of remaining event-free at 12 months was 57% (95% CI: 50%-65%), with a cumulative incidence of the sequential NAION of 43% at 12 months. Age at first NAION episode (p<0.0001), hyperlipidemia (p=0.0076), systemic hypertension(p=0.0013), and cardiovascular risk (p=0.021) were each associated with shorter time between NAION episodes.

Conclusions: This study assessed risks of sNAION derived from the largest cohort of patients with sNAION ever reported. The risk of sNAION is higher than previously reported. And, this study is the first to document that specific systemic factors influenced the timing between events.

Candidate: Melissa Yuan

Poster #: B10

Clinical Characteristics, Outcomes, and Complications Associated with Delayed Diagnosis of Intraocular Foreign Body

Melissa Yuan, Lindsay K. Kozek, Sandra Hoyek, Jose Davila, Leo Kim, Filippos Vingopoulos, Dan Gong, Lucy Young, Frances Wu, Grayson Armstrong MPH, Dean Eliott, Lucia Sobrin, John B Miller, Nimesh A. Patel

Purpose: Intraocular foreign bodies (IOFB) are present in 14 to 42% of open globe injuries in adults in the US and are typically diagnosed promptly in the initial trauma evaluation. However, rarely, the diagnosis of IOFB can be missed or delayed, causing ocular morbidity. While there have been various previous case reports of delayed or missed IOFBs, we aim to characterize delayed presentation of IOFBs in a multicenter retrospective study, with a focus on factors leading to the missed IOFBs as well as complications following IOFB.

Methods: This non-consecutive case series of adult patients was a retrospective, multicenter study of adult patients with delayed diagnosis of IOFB. Patients were included if they had initially presented elsewhere and were found to have a missed diagnosis, or if they presented with a delay to seek care.

Results: 18 eyes of 18 patients were included. Average±SD presenting logMAR VA was 0.45±0.70 (Snellen equivalent 20/56). The most common presenting symptom was subjectively decreased vision in 11 patients (61%); 1 patient (6%) was asymptomatic. The general emergency department accounted for most initial evaluations (11 patients; 61%), but 6 patients (33%) were seen by an optometrist, ophthalmologist, or both, and 1 patient (6%) by their PCP. The most common anatomic locations of the IOFB were in the iris/anterior chamber (4, 22%) or phakic lens (4, 22%), followed by pars plana/ciliary body (3; 17%), vitreous (3; 17%), or retina (3; 17%). Complications at presentation included endophthalmitis in 1 patient (6%), retinal detachment in 1 patient (6%), and retinal tears in 4 patients (22%). Siderosis was seen in 5 patients (28%). During follow-up, 1 patient (6%) developed a retinal detachment and 1 patient (6%) developed a giant retinal tear. The average±SD final logMAR visual acuity (VA) was 0.13±0.32 (Snellen equivalent 20/26). At last follow-up, 15 eyes (83%) had VA 20/30 or better. Median length of follow-up was 139 days (IQR 86-557).

Conclusions: Delayed IOFBs often present with good vision and self-sealing wounds, and thus can be difficult to detect in the emergency and outpatient specialty settings. Missed IOFBs can be associated with siderosis, retinal detachment, and endophthalmitis. Visual outcomes can be salvaged with prompt treatment in the majority of cases.

Candidate: Asmaa Zidan

Poster #: B11

Vision Outcome of Nerve Growth Factor Treatment for Neurotrophic Keratopathy: An IRIS® Registry Study

Asmaa A. Zidan, Joshua B. Gilbert, Eric Goldberg, Connor Ross, Tobias Elze, Alice C. Lorch, Joan W. Miller, Reza Dana, Jia Yin*

*on behalf of the IRIS® Registry Analytic Center Consortium

Purpose: Neurotrophic keratopathy (NK) is a rare corneal disease with impaired innervation, healing, and resulting vision impairment. Herein, we aim to assess the impact of nerve growth factor (NGF) treatment on the visual outcomes in NK patients.

Methods: Retrospective analysis of NK patients diagnosed from 2016-2023 using the American Academy of Ophthalmology Intelligent Research in Sight Registry (IRIS). An interrupted time series statistical model was employed to assess the best-corrected distance visual acuity (VA) changes after NGF treatment.

Results: The study included 31,316 NK patients, with 1,476 receiving NGF. At diagnosis, NGF-treated patients had worse VA than non-treated (mean [IQR]); 0.70 [0.40, 1.30] logMAR vs. 0.30 [0.10, 0.60] logMAR, p<0.001) and a higher frequency of corneal ulcer and melting (44.99%, 4.88% vs. 34.27%, 1.89%) (p<0.0001, p=0.04).

NGF treatment improved VA by 0.13±0.01 logMAR units after 8 weeks of treatment and changed the rate of VA decline from 0.17±0.03 to -0.06±0.0 logMAR units per year (p<0.001).

Conclusions: Despite initial disease severity, NGF treatment was associated with a significant improvement in visual acuity and a halt in the progression of visual decline.

Candidate: Roshni Bhat

Poster #: C01

Exogenous Metabolites Associated With Age-Related Macular Degeneration (AMD): A Cross-Sectional Study

Roshni Bhat, Ines Lains, Kevin Mendez, Krupa Sourirajan, Haemin Kang, Joao Gil, Rufino Silva, John Miller, Ivana Kim, Demetrios Vavvas, Jessica Lasky-Su, Joan Miller, Deeba Husain

Purpose: The pathophysiology of multifactorial diseases such as age-related macular degeneration (AMD) is not fully understood. Metabolomics, study of small molecules (<1KD) in our body fluids and tissue, provides insight into molecular mechanisms underlying such multifactorial diseases. Previous metabolomics and AMD work focused primarily on associations with endogenous metabolites. Our work aims to further investigate associations of AMD with exogenous plasma and urinary metabolites.

Methods: A cross-sectional study consisting of AMD patients and a control group (>50 years) from Boston, US and Coimbra, Portugal (PT) was conducted. Color fundus photographs (CFP) for both eyes of all participants were used for AREDS grading of AMD. Fasting plasma and urine samples were collected and used for metabolomic profiling using Ultrahigh Performance Liquid Chromatography – Mass Spectrometry (Metabolon, Inc). We utilized multivariate logistic (outcome AMD vs. no AMD) and ordinal logistic (outcome stages of AMD) mixed-effect regression models accounting for both eyes and adjusted for age, gender, and BMI. Statistical significance (p<0.0021) was adjusted using ENT80, which accounts for 80% of variance across multiple independent tests.

Results: We included 391 eyes (286 AMD, 105 control) from 196 patients in the US and 580 eyes (443 AMD, 137 control) from 290 patients in PT. In the US cohort, plasma analysis revealed significant positive associations of tartronate with both presence and staging of AMD, and a negative association of 1,2,3benzenetriol sulfate levels with AMD staging. Among urinary metabolites, o-cresol sulfate from the benzoate metabolic pathway, along with other chemical pathway metabolites, were negatively associated with AMD staging. In the PT cohort plasma, significant negative associations were found between AMD outcome and two metabolites: pyruvate from a food component/plant sub-pathway and a benzoate metabolite. Urinary metabolite profiling highlighted several chemical pathway metabolites, including benzoate derivatives, that were negatively associated with AMD staging.

Conclusions: To the best of our knowledge, this is the first study to reveal significant associations between exogenous metabolites, their metabolic pathways, and the prevalence and staging of AMD. These findings are crucial for identifying target metabolites for future AMD risk assessment and progression strategies.

Candidate: Haemin Kang

Poster #: C02

Association of Plasma Metabolites With Treatment Response After

Intravitreal Anti-vascular Endothelial Growth Factor Injections in Neovascular Age-related Macular Degeneration

Haemin Kang, Ines Lains, Kevin Mendez, Archana Nigalye, Raviv Katz, Georgiy Kozak, Hanna Choi, Augustine Bannerman, Rodrigo A Alvarez, David Wu, Ivana K. Kim, John B. Miller, Demetrios G. Vavvas, Joan W. Miller, Deeba Husain

Purpose: To assess associations between plasma metabolomic profiles and treatment response to three loading intravitreal anti-vascular endothelial growth factor (VEGF) injections in patients with neovascular agerelated macular degeneration (nAMD).

Methods: From the prospective, longitudinal study, we included patients with treatment-naïve neovascular AMD undergoing three loading intravitreal anti-VEGF injections. All patients were imaged with the same optical coherence tomography (OCT; Heidelberg) protocol. Images were assessed by two independent graders at baseline and 4-to 6-weeks after the third injection. Treatment response was defined as no evidence of suband intra-retinal fluid on OCT one month after the third injection. Fasting blood samples were collected at the time of study enrollment, and metabolomic profiling was conducted using ultra-performance liquid chromatography-mass spectrometry (UPLC-MS). Multilevel mixed-effects linear modeling accounting for the inclusion of two eyes of the same patients were used to assess associations between plasma metabolites and treatment response. Covariates included age, sex, body mass index (kg/m2), smoking history, presence of choroidal vascularization at the time of metabolomic analysis, time gap between metabolomic analysis and the first anti-VEGF injection, and anti-VEGF agents.

Results: We included 131 eyes of 101 patients, most were female (69 patients, 68.3%) with a mean age of 77.7±8.5 years. 51 eyes (38.9%) were treatment responders after 3-loading anti-VEGF therapy. After adjusting covariates, multilevel mixed-effects linear analysis identified 5 plasma metabolites associated with treatment response in our study population. These included 4 lipid metabolites and one amino acid metabolite. Three lipid metabolites were involved in bile acid metabolism, including taurodeoxcholate (β=2.04, P=0.002), taurochenodeoxycholate (β=1.76, P=0.008), and glycodeoxycholate (β=1.802, P=0.008).

Conclusions: Our results suggest that plasma bile acids seems to be associated with good treatment response after 3-loading anti-VEGF injections. Previous work has shown that bile acids are protective against AMD, and may also be associated with better treatment response in nAMD. These data thus can contribute to a better understanding of the pathophysiology of diverse responses seen in daily clinical practice. Plasma metabolites can be used as biomarkers to predict responses to initial anti-VEGF therapy in nAMD patients, providing more individualized treatment plan.

Candidate: Drenushe Krasniqi

Poster #: C03

Navigating the Vascular Terrain of the Human Optic Nerve in 3D

Drenushe Krasniqi, Tatjana Jakobs, Joseph F. Rizzo III

Purpose: Non-arteritic anterior ischemic optic neuropathy (NAION) is the second most common optic neuropathy in adults. Despite extensive research, the etiology of NAION remains uncertain, although there is general consensus that reduced perfusion through the paraoptic short posterior ciliary arteries (sPCAs) and their branches causes ischemia. However, a 3D visualization of these vessels has never been performed.

Methods: Multiple methods of analysis are being performed. First, both orbits were harvested from a patient with clinically-presumed NAION. The orbits were fixed and 10-micron serial sections stained (mostly) with Hematoxylin and Eosin (H&E) were made throughout both orbits (2500 slides on the involved side). These slides are being scanned and digitized using a Zeiss Axio Scan, Z1 microscope at a 20x magnification level. We are employing Zeiss (Zen) software to create a 3D reconstruction of the blood vessel, and Zeiss's advanced image segmentation tool [Intellesis: an artificial intelligence ("Al") system] to distinguish veins and arteries. Second, we also have sectioned two additional fresh human orbits and stained them with the Verhoeff-Van Gieson stain to visualize the vasculature and connective tissue structure. We plan on sectioning at least four more orbits. Third, we are performing a quantitative 3D imaging of other human orbits with “tissue clearing” using light-sheet fluorescence microscopy to hopefully demonstrate the vascular tree of the paraoptic vessels in real time.

Results: Our study demonstrates substantial progress in visualizing ocular vasculature through method refinement and innovative techniques. Initially facing challenges with peri-neural vessel stretching and limited visualization, our persistent optimization efforts yielded significant advancements. Prolonged bleaching enhanced clarity, enabling identification of key ocular vasculature components like the ophthalmic artery and posterior ciliary arteries. Serial sectioning facilitated construction of a central retinal artery model for flow dynamics simulations. The Verhoeff-Van Gieson staining is providing detailed vessel visualization. These findings highlight the efficacy of our evolving methodologies in unraveling ocular vascular intricacies, contributing to our understanding of ocular physiology and pathology.

Conclusions: This multi-faceted approach marks a significant step forward in exploring the vascular terrain of the human optic nerve. The comprehensive analysis of vascular structures, coupled with advancements in technology and artificial intelligence, sets the stage for more nuanced investigations into optic nerve biomechanics. The results not only enhance our understanding of NAION but also other vascular-related optic neuropathies.

Candidate: Renee Liu

Poster #: C04

Proliferative Diabetic Retinopathy

and Center-Involving Diabetic Macular Edema Display Strong Genetic Associations With Common Variants in Asian Populations

Renee Liu, Penny Bencheck, A Rizza, Ricky E. Chan, Rehana Khan, Ashley Li, Gayatri Susarla, Hengtong Li, Charumathi S. Sabanayagam, Ching-Yu Cheng, Kim Brustoski, Rajiv Raman, Lucia Sobrin, Sinnakaruppan Mathavan, Sudha K. Iyengar

Purpose: To identify common genetic variants associated with diabetic retinopathy (DR) and center-involving diabetic macular edema (ciDME) assessed by optical coherence tomography (OCT) in South Indian patients with type 2 diabetes (T2D).

Methods: Patients with T2D were recruited at Sankara Nethralaya in Chennai, South India. Both eyes of each patient were imaged with color fundus photographs, which were graded for degree of DR, and a subset of patients were imaged with structural OCT. Demographic and clinical data were recorded. Blood was drawn for lipids, hemoglobin A1c (HbA1c), and DNA extraction for genetic analysis. DNA was genotyped on the Expanded Multi-Ethnic Genotyping Array (MEGAEX) array, and imputation to 1000 Genomes was performed. Genome-wide association analyses were performed using generalized linear mixed models (GLMM) in R using the GENESIS package. For the analyses, we compared patients with and without DR, with and without proliferative DR (PDR), and with and without ciDME. All analyses were adjusted for HbA1c and duration of diabetes. Replication for the DR and PDR outcomes was performed in an independent cohort from Singapore with fixed effects meta-analysis.

Results: 2261 patients were included in the DR vs. no DR analysis, and there were no genome-wide significant associations with adjustment for HbA1c and duration of diabetes. For the PDR outcome, we compared cases with PDR to controls without DR. Variant rs11199996 in an intergenic region on chromosome 10 was associated with presence of PDR at a genome-wide significant level (OR=4.1, P=2.88 X 10-8). In the replication cohort from Singapore, the effect estimate was in the same direction (OR=2.0, P=0.08) and metaanalysis yielded a final OR of 3.4 (P=1.88 X 10-8). This same variant also achieved genome-wide significance when we compared cases with PDR to controls without PDR (e.g., participants with nonproliferative DR or no DR), achieving an OR of 3.0 in meta-analysis of the discovery cohort with the Singapore replication cohort (P=4.39 X 10-8). 385 participants had OCT scans that were gradable for ciDME. Variant rs10169007 in SGPP2 was associated with ciDME at a genome-wide significant level (OR = 0.02, P = 1.47 X 10-8). Replication for the ciDME outcome was not available as the Singapore cohort did not have OCT data. SGPP2 codes for a protein that degrades the bioactive signaling molecule sphingosine 1-phosphate and plays a role in pro-inflammatory signaling.

Conclusions: A genetic variant on chromosome 10 was significantly associated with PDR in a meta-analysis including both South and East Asian participants. In addition, a genetic variant in SGPP2 was associated with a novel endophenotype of ciDME.

Candidate: Yan Luo

Poster #: C05

Understanding Equity in Vision-Language Learning for Glaucoma Diagnosis With Deep Learning

Yan Luo, Min Shi, Yu Tian, Mohammad Eslami, Saber Kazeminasab, Tobias Elze, Lucy Q. Shen, Louis R. Pasquale, Nazlee Zebardast, Michael V. Boland, David S. Friedman, Mengyu Wang

Purpose: This study investigated equity issues in vision-language artificial intelligence (AI) models for glaucoma detection.

Methods: We randomly selected 10,000 pairs of SLO fundus and visual field (VF) with accompanying clinical notes within the timeframe of 30 days from 10,000 patients tested between 2015 and 2022 from Mass Eye and Ear. We chose the last test for each eye and included one eye per patient randomly. The patients were categorized into non-glaucoma (VF mean deviation >= -1 dB and normal VF glaucoma hemifield test and pattern standard deviation (PSD) results) and glaucoma categories (VF mean deviation < -3 dB and abnormal VF glaucoma hemifield test and PSD results). 7,000, 1,000, and 2,000 samples were used for training, validation, and testing, respectively. The average age is 60.9 \pm 16.2 years. The patients were from three racial groups: Asian (8%), Black (15%), and White (77%). Females constituted 56% of subjects. We designed and developed fair contrastive language-image pre-training (FairCLIP) to enhance equity in glaucoma detection. T-test with bootstrapping sampling was used to compare the performance of different models measured by the area under the receiver operating characteristic curve (AUC).

Results: Within the setting of learning with both notes and diagnostic labels, FairCLIP consistently outperforms CLIP in terms of AUC across all racial groups, with Asian (0.85 vs. 0.82 with p < 0.001), Black (0.79 vs. 0.76 with p < 0.001), and White (0.82 vs. 0.81 with p < 0.001) populations, indicating improved equity across demographic groups. Similarly, FairCLIP enhanced equity in glaucoma detection, with higher AUC values compared to CLIP for both non-Hispanic (0.82 vs. 0.80 with p < 0.001) and Hispanic (0.79 vs. 0.75 with p < 0.001) ethnicities. Additionally, FairCLIP achieved slightly higher AUC values for females compared to CLIP (0.66 vs. 0.64 with p < 0.001) and consistently outperformed CLIP across various language preferences, emphasizing its superior fairness in diagnosing glaucoma across diverse language groups. Within the setting of learning with only clinical notes, FairCLIP also improved performance from 0.71 to 0.73 (p < 0.001) for the Black group.

Conclusions: Our experiments revealed significant demographic disparities in glaucoma detection using SLO fundus photos and clinical notes. FairCLIP, our proposed approach, significantly enhanced both accuracy and equity.

Candidate: Jean Moon

Poster #: C06

Role of Endomucin in Angiogenesis and Cytoskeletal Organization

Jean Moon, Zhengping Hu, John Fornagiel, Patricia A. D’Amore

Purpose: The endothelial glycocalyx, lining the apical surface of the endothelium, is involved in a host of vascular processes. The layer contains a network of membrane-bound proteoglycans and glycoproteins. One such glycoprotein is endomucin (EMCN), which our lab has revealed is a modulator of VEGFR2 function. Intravitreal injection of siEMCN into the eyes of P5 mice impairs vascular development. In vitro silencing of EMCN suppresses VEGF-induced proliferation and migration. Signaling pathways that drive cell migration converge on cytoskeletal remodeling. By coupling co-immunoprecipitation with liquid chromatography/mass spectrometry, we identified interactions between EMCN and proteins associated with actin cytoskeleton organization. The aim of the study is to investigate the influence of EMCN on cytoskeleton dynamics in angiogenesis.

Methods: The effects of EMCN were evaluated ex vivo using a choroidal explant sprouting assay and in vitro by phalloidin staining in human retinal endothelial cells (HRECs). Following AAV-mediated Cre deletion in choroidal punches isolated from EMCN-floxed mice, explants were maintained for six days. Angiogenesis was quantified by measuring the vascular sprouting area. To knockdown EMCN, HRECs were transfected with siRNA directed against human EMCN or non-targeting siRNA. Post-transfection, serum starved HRECs were stimulated with VEGF. To overexpress EMCN, cells were infected with adenovirus expressing myc-tagged EMCN. Actin was stained with phalloidin conjugated to Alexa Fluor 594. Analyses of sprouting area and mean fluorescence intensity were performed in ImageJ.

Results: The sprouting area was significantly reduced in choroidal explants with EMCN knockdown exposed to AAV-Cre (2.6 0.4 mm2) compared to tissue treated with AAV-GFP control (1.1 0.2 mm2). Western blot verified EMCN knockdown in HRECs. In the absence of VEGF, there were significantly lower absolute levels of F-actin. A comparable reduction in actin filaments was observed in siEMCN transfected cells stimulated with VEGF. Notably, overexpression of EMCN induced cell surface projections that coincided with an increased concentration of F-actin.

Conclusions: Loss of EMCN inhibited mouse choroidal sprouting, and EMCN expression correlated with formation of F-actin containing stress fibers. Our findings support further study of EMCN’s role in endothelial cell rearrangement and cell shape changes during angiogenesis.

Candidate: Min Shi

Poster #: C07

Personalizing Circumpapillary Retinal Nerve Fiber Layer Thickness Norms With Individual Retinal Anatomy in Glaucoma

Min Shi, Yan Luo, Yu Tian, Mohammad Eslami, Saber Kazeminasab, Hannah Rana, Tobias Elze, Lucy Q. Shen, Louis R. Pasquale, Nazlee Zebardast, Michael V. Boland, David S. Friedman, Mengyu Wang

Purpose: To generate individualized RNFL norms based on optic nerve anatomy from OCT-derived fundus images using deep learning and subsequently generate RNFL deviation maps to predict VF MD.

Methods: Reliable pairs of Cirrus OCT scans and 24-2 visual fields (VFs) tested within 30 days from Massachusetts Eye and Ear were included in this study. First, we trained a deep learning model to use OCT fundus image to predict corresponding RNFLTs (Figure 1a) in eyes with normal VFs (mean deviation (MD) ≥1 dB and normal glaucoma hemifield test [GHT] and pattern standard deviation [PSD] results). The R-squared (R2) was used to measure the accuracy of RNFLT map prediction. Second, we used our deep learning model to predict corresponding RNFLT maps from OCT fundus images of eyes with normal and abnormal VFs. The RNFLT deviation map was computed by subtracting the predicted normal RNFLT maps from the actual RNFLT maps. To validate the utility of our personalized RNFLT norm prediction, we compared if the average RNFLT deviation is better correlated with MD compared with average actual RNFLTs.

Results: We included 18,000 reliable pairs of OCT scans and VFs from 17,835 eyes of 13,821 patients with an age of 57.2 ± 16.1 years. The average MD of VFs was -1.4 ± 3.67 dB. 10,000 OCT scans with normal VFs (MD: 0.06 ± 0.72 dB) were used to train the deep learning model, and the remaining 8,000 OCT scans with a mean MD of -3.3 ± 4.9 dB (including 2,419 OCT scans with normal VFs, MD: 0.04 ± 0.73 dB) were used for evaluating the prediction performance. The average R2 of RNFLT map prediction on 2,419 OCT scans of individuals with normal VFs was 0.81 ± 0.13 (Figure 1b). The correction coefficient (R) of average RNFLT deviations with VF MDs was 0.42, almost doubling the correlation score (R = 0.19) the average actual RNFLT maps achieved. The two examples (Figure 2) show how the deep learning model reasonably predicts the RNFLT map from the corresponding OCT image, even though the actual RNFLT maps showed substantial RNFLT thinning.

Conclusions: The OCT fundus image encoding retinal anatomical information can be used to predict personalized RNFLT norms, which significantly improved the structure-function correlation with VFs. The deep learning predicted norms may improve the diagnostic accuracy of OCT for glaucoma patients.

Candidate: Krupa Sourirajan

Poster #: C08

Urine Metabolites Associated With Microperimetric Retinal Sensitivity in Age-Related Macular Degeneration

Krupa Sourirajan, Kevin Mendez, Georgiy Kozak, Gregory Tsougranis, Ines Lains, Haemin Kang, Augustine Bannerman, Roshni Bhat, Hanna Choi, Archana Nigalye, Ivana K. Kim, Demetrios G. Vavvas, David M. Wu, John B. Miller, Joan W. Miller, Deeba Husain

Purpose: Best-corrected visual acuity (BCVA) has known limitations in patients with age-related macular degeneration (AMD). Microperimetry can represent an alternative reliable measure. Metabolomics, the comprehensive study of metabolites, has revealed significant insights into the pathogenesis of AMD and can contribute to better understand microperimetry changes in this disease. This study aimed to analyze associations between urine metabolites and microperimetry in AMD patients.

Methods: Prospectively recruited cross-sectional study including patients with AMD and a control group (>50 years). All patients were imaged with color fundus photos for AMD classification. Microperimetry was performed using the MAIA microperimetry system (Centervue, Italy), employing a 37-point full-threshold protocol. Fasting urine samples were used for metabolomic profiling (Metabolon Inc). Multilevel mixed-effects linear models were used to assess associations between urine metabolites and retinal sensitivity. Statistical significance was determined by considering the number of independent tests that accounted for 80% of the variance (ENT80).

Results: We included 151 eyes (42 Control, 18 Early AMD, 73 Intermediate AMD, 18 Advanced AMD). Accounting for multiple comparisons, 8 urine metabolites were significantly associated with mean retinal sensitivity (p< 0.0017). These include 3 lysine metabolites (2-oxoadipate, N6-acetyllysine and 5hydroxylysine), 1 purine metabolite (urate), 1 leucine, isoleucine, and valine metabolite (ethylmalonate), 1 tryptophan metabolite (3-hydroxyanthranilate), 1 progestin steroid (5alpha-pregnan-3beta,20alpha-diol disulfate), and 1 aminosugar metabolite (erythronate). Two of these metabolites were also found in our previous analysis of plasma metabolites.

Conclusions: To our knowledge, we present the first assessment of associations between urinary metabolites and retinal microperimetry sensitivity in AMD, lending credence to our group’s prior research which highlighted the significance of these pathways in AMD's pathophysiology. The most significant urine metabolites were found in Lysine and Tryptophan pathways. Notably the overlap of our prior findings using plasma and urine metabolites suggest that they might play a role in visual impairment and AMD.

Candidate: Wai Lydia Tai

Poster #: C09

Transcriptomic Shift in Retinal Ganglion Cell During DNA Methyltransferase-mediated Axon Regeneration

Wai Lydia Tai, Kin-Sang Cho, Emil Kriukov, Ajay Ashok, Xuejian Wang, Aboozar Monavarfeshani, Wenjun Yan, Yingqian Li, Timothy Guan, Joshua R.

Sanes, Petr Baranov, Dong Feng Chen

Purpose: Damage to the central nervous system (CNS) is irreversible owing to its lack of regenerative capacity. Using the eye as a model, our pilot finding demonstrated that suppression of a single epigenetic factor, DNA methyltransferase 3a (Dnmt3a), specifically in retinal ganglion cells (RGCs), enabled robust axonal regrowth following optic nerve crush (ONC) injury. This study aims to identify the RGC transcriptomic changes underlying Dnmt3a deficiency-enabled axon regrowth after ONC.

Methods: ONC was performed in mice with conditional knockout of Dnmt3a (CKO) specifically in RGCs driven under the Vglut2 promoter and littermate control. RGCs from adult control and CKO mice were collected at 2 days after ONC and underwent RNA extraction for bulk RNA-sequencing (RNA-seq) or nucleus isolation for single nuclei RNA-seq (snRNA-seq) using the 10X platform. We generated our R- and Python-dependent pipeline for the deep downstream analysis of the sequencing data. Expressions of differentially expressed genes (DEGs) related to neuronal growth and injury were quantified by qPCR.

Results: Profiling the RGC transcriptome with snRNA-seq showed no apparent alteration in RGC type distribution between control and CKO mice. However, genes enriched in growth-related pathways (e.g., optic nerve morphogenesis, axon development) were significantly upregulated while the ones associated with neuron death, axon injury response, and neuroinflammation were downregulated in CKO RGCs compared to control upon the pathway-ssGSEA-to-pattern analysis. Bulk RNA-seq reflected the snRNA-seq data which showed transcriptomic shifts toward a pro-regenerative state in the CKO RGCs, and qPCR verified DEG changes detected in RNA-seq.

Conclusions: Collectively, these data highlight Dnmt3a as a key regulatory switch of RGC axon regeneration. Strategic inhibition of Dnmt3a may open a potential therapeutic paradigm for neuronal degenerative diseases and utilizing epigenomic modification as a mean of neurogenesis modulation.

Candidate: Yu Tian

Poster #: C10

External Eye Photos for Diabetic Retinopathy Detection with Deep Learning

Yu Tian, Min Shi, Yan Luo, Mohammad Eslami, Saber Kazeminasab, Hannah Rana, Leo A. Kim, Louis R. Pasquale, Meenakashi Gupta, Tobias Elze, Lucia Sobrin, Mengyu Wang

Purpose: To develop a deep learning model to automatically detect vision-threatening diabetic retinopathy using external eye photos.

Methods: Since external eye photos can be taken by mobile devices without requiring the patients to visit a clinical or pharmacy site hosting fundus cameras or OCT devices, we aim to build a deep learning model for diabetic retinopathy (DR) detection using external eye images, which has immense potential to enhance largescale DR screening. In this study, we used 7,845 samples from 6,451 patients (age: 58.5 ± 20.3 years) from Massachusetts Eye and Ear with external eye photos with corresponding demographic information and DR diagnostic information from electronic medical records. We developed an EfficientNet model to predict the vision-threatening DR (moderate + severe non-proliferative diabetic retinopathy [NPDR] + PDR) vs. the rest (normal + mild NPDR) (Figure 1 [a]). Our models were trained using 4,570 samples from 3,951 patients and tested with 3,275 samples from 2,500 patients. The area under the receiver operating characteristic curve was used to evaluate the overall performance and that between different demographic groups, and Grad-CAM was used to evaluate the model’s Interpretability.

Results: The self-reported patient demographic information is as follows: Gender: female: 53.8% and male: 46.2%; Race: White: 87.6%, Black: 7.3%, Asian: 5.1%; Ethnicity: Hispanic: 6.7%, non-Hispanic: 87.4%. Furthermore, 4.2% of the patients are vision-threatening DR. The performance disparities across races and ethnicities were substantial (White: 0.85, Black: 0.81, Asian: 0.77; Hispanic: 0.86, Non-Hispanic: 0.91). There was also a small disparity of 0.02 between males and females. The p-value between different races was p < 0.001, indicating that the disparity between racial groups is significant. Those results indicate that the development of equitable learning algorithms to improve the accuracy of minority groups is crucial. We have also shown the Grad-CAM images to indicate the important regions for predicting the DR diagnosis.

Conclusions: Our deep learning model can accurately predict vision-threatening DR using only the external eye photos.

Candidate: Shuai Wang

Poster #: C11

Immunosubunit β5i Knockout Suppresses Neovascularization and Restores Autophagy in Retinal Neovascularization by Targeting ATG5 for Degradation

Liyang Ji, Li Li, Ying Zhao, Shengqiang Liu, Jingmin Li, Jinsong Zhang, Qi Zhao, Shuai Wang

Purpose: To investigate the functional role of immunoproteasome subunit β5i in pathologic retinal neovascularization (RNV) and its ability to link the immunoproteasome and autophagy.

Methods: Oxygen-induced retinopathy (OIR) was induced in wild-type (WT) and β5i knockout (KO) mouse pups on a C57BL/6J background. Proteasome catalytic subunit expression and proteasome activity were evaluated by quantitative real-time PCR (qPCR) and proteasome activity. Retinal vascular anatomy and neovascularization were characterized and quantified by retinal vascular flat-mount staining, fluorescence angiography, platelet endothelial cell adhesion molecule (PECAM) immunostaining, and hematoxylin and eosin staining. Correlation factors, including VEGF and ICAM-1, were detected by qPCR. Autophagy was examined by transmission electron microscopy (TEM). Autophagy biomarkers, including LC3, P62, ATG5, and ATG7, were measured by immunostaining and immunoblotting. The protein interaction between β5i and ATG5 was detected by immunoprecipitation.

Results: We observed that β5i had the greatest effect in WT OIR mice. Fundus fluorescence angiography, retinal flat-mount staining, and PECAM staining revealed that pathologic RNV decreased in β5i KO OIR mice compared with WT OIR mice. Concurrently,TEM, immunostaining, and immunoblotting showed that autophagy was induced in β5i KO OIR mice compared to WT OIR mice through increases in autophagosome and LC3 expression and a decrease in P62. Mechanistically, β5i interacted with ATG5 and promoted its degradation, leading to autophagy inhibition and pathogenic RNV.

Conclusions: We observed that β5i had the greatest effect in WT OIR mice. Fundus fluorescence angiography, retinal flat-mount staining, and PECAM staining revealed that pathologic RNV decreased in β5i KO OIR mice compared with WT OIR mice. Concurrently,TEM, immunostaining, and immunoblotting showed that autophagy was induced in β5i KO OIR mice compared to WT OIR mice through increases in autophagosome and LC3 expression and a decrease in P62. Mechanistically, β5i interacted with ATG5 and promoted its degradation, leading to autophagy inhibition and pathogenic RNV.

Candidate: Lei Xi

Poster #: C12

Mast Cell Inhibition Attenuates Tissue Damage and Neovascularization in an

Experimental Laser-Induced Choroidal Injury

Lei Xi, Vinay K Pulimamidi, Olufemi S. Folorunso, Nishant R. Sinha, Rahul K. Verma, Sunil K. Chauhan

Purpose: Choroidal neovascularization (CNV) is a major cause of vision loss in age-related macular degeneration. Previously, we demonstrated that mast cell activation promotes ocular surface tissue damage and angiogenesis. However, the pathogenic role of mast cells in choroidal injury is not well understood. In this study, we investigated the contribution of mast cells in laser-induced choroidal injury.

Methods: Choroidal injury was induced with an argon laser (532nm) in 8–12-week-old male C57BL/6 mice (N=8-10 in each group). A single laser injury spot was targeted around the optic nerve in the right eye of each mouse using the Micro III image guide system. Cromolyn (50mg/kg), a mast cell inhibitor or saline (control treatment) was administered intraperitoneally (IP) twice a day for 14 days. Choroidal injury was monitored in vivo through optical coherence tomography (OCT), color fundus photography, and fundus fluorescence angiography (FFA) in cromolyn-treated and saline-treated mice on day 3, day 7, day 14 and day 30. Retinal pigment epithelia (RPE) & choroidal tissue flat mounts were immunostained for neovascularization (NV) and mast cells with isolectin B4 (IB4) and Avidin, respectively on day 3, day 7, day 14 and day 30. Area of injury, fluorescence angiography (FA), and IF staining were quantified with Image J software. On day 7, mast cell tryptase activity was quantified colorimetrically using tissue from the choroidal injury area (2mm diameter).

Results: Cromolyn suppresses mast cell activation in laser-induced choroidal injury. Mast cell inhibition reduces the area of tissue damage in laser-induced choroidal injury in mice. Mast cell inhibition reduces the area of laser-induced choroidal neovascularization. Mast cell inhibition reduces inflammation in laser-induced choroidal injury.

Conclusions: Injury-induced activation of mast cells contribute to choroidal tissue damage and neovascularization. Blocking mast cell function could be a potential therapeutic approach to mitigate the extent of choroidal injury and neovascularization.

Candidate: Maryam Zekavat

Poster #: C13

Connecting Ocular and Systemic Health: Phenome- and Genome- wide Analyses of Retinal Layer Thicknesses From Optical Coherence Tomography Imaging Across 44,823 UK Biobank Participants

Seyedeh Maryam Zekavat, Saman Doroodgar Jorshery, Sayuri Sekimitsu, Tobias Elze, Ayellet V. Segre, Janey L. Wiggs, Jay C. Wang, Pradeep Natarajan, Nazlee Zebardast

Purpose: The human retina is a multi-layered tissue which offers a unique window into systemic health. Largescale analyses of retinal imaging with phenotypic and genomic data offer the potential to identify novel retinal imaging biomarkers of health and biological pathways for retinal physiology.

Methods: We conducted phenome- and genome- wide analyses of 9 retinal layer thicknesses (GCC, RNFL, GCL, IPL, INL, OPL+ONL, PS, RPE+BM, CSI) using segmented Topcon OCT images across 44,823 UK Biobank participants. Phenome-wide analyses associated layer thickness with 1,866 incident ICD-based conditions (over 10-year follow-up) and 88 quantitative traits, after adjusting for age, sex, smoking, height, weight, and spherical equivalent. Genome-wide analyses were performed to identify genetic loci linked to retinal layer thicknesses.

Results: Mean age was 56 (SD 8 years), 55% were female, and 56% were never-smokers. Significant associations (P<3x10-5) were detected between each standard deviation of retinal layer thinning and hazard ratio for development of future ocular (RNFL-glaucoma 1.77; PS-AMD 1.39), neuropsychiatric (GCL-multiple sclerosis 2.87, epilepsy 1.55; PS-schizophrenia 1.90), cardiac (PS-myocardial infarction 1.17, hypertension 1.09; CSI-hypertrophic cardiomyopathy 2.05), metabolic (PS-Type 2 diabetes 1.28, diabetic polyneuropathy 1.67), and pulmonary disease (PS-COPD 1.31, chronic bronchitis 1.52), as well as end-organ failure (PSrespiratory failure 1.46, heart failure 1.21, NASH 1.53), and mortality (PS-1.16; GCC-1.12). Genome-wide association identified 259 loci associated with retinal layer thicknesses acting through diverse biological pathways. Consistent genetic and epidemiologic analyses suggested a putative link between thinner RNFL and glaucoma, PS and AMD, as well as poor cardiometabolic and pulmonary traits (elevated BMI, body fat, creatinine, heart rate, lower cardiac ejection fraction, poor pulmonary function tests) with thinner PS, elevated blood pressure with thinner RNFL and CSI, and elevated HDL cholesterol with thinner RPE+BM.

Conclusions: In conclusion, we identified multiple inherited genetic loci and acquired systemic cardiometabolic-pulmonary conditions associated with thinner retinal layers, and identify retinal layers wherein thinning is predictive of future ocular and systemic conditions.

Candidate: Yadav Adhikari

Poster #: D01

Polyploidy Leads to Senescence in an UVA-based Mouse Model of FECD

Yadav Adhikari, Mohit Parekh, Vicki P. Losick, Ula V. Jurkunas

Purpose: Fuchs endothelial corneal dystrophy (FECD) is characterized by corneal endothelial (CE) cell loss along with the development of extracellular matrix deposits known as guttae, resulting in loss of corneal function and edema. The gradual loss of CE cells that are post-mitotic state and exhibit limited proliferative capacity in vivo, is accompanied by neighboring cell enlargement to maintain the intact monolayer. However, the mechanism of cell loss in FECD has not been studied. Here, we investigate whether replacement of lost cells occurs via polyploidy, where adjacent cells by enlarging their cell size and nuclear content cause abnormal tissue repair response and lead to pathologic findings seen in FECD.

Methods: 8 weeks old female C57 mice were irradiated on the right eye with 500 J/cm of ultraviolet-A (UVA) light while the unexposed left eye served as control. Nuclear ploidy of CE cells was analyzed by measuring DAPI intensity within each nuclear boundary normalized to an internal control, corneal epithelium, known to be diploid. Changes in cell size and development of multinucleated cells was evaluated using ZO-1 immunostaining. The development of senescence and fibrosis was analyzed by immunostaining against H3K9me3 and FN-1, respectively. One-Way ANOVA with Tukey’s HSD was used for statistics.

Results: After day-2 post UVA, CE cells underwent endocycling, engaging in multiple rounds of DNA synthesis without nuclear division resulting in the formation of giant polyploid nuclei. This resulted in increased nuclear ploidy at day-3 (10.9±0.4C) compared to control (5.4±0.0C) (p<0.0001). Subsequently, post day-7, the large endocycled nuclei divided into multiple nuclei, giving rise to multinucleated polyploid cells. ZO-1 staining revealed a progressive increase in the percentage of multinucleated cells, reaching its maximum at day-14 (21±3%vs 0±0% in control) (p<0.001). Additionally, the percentage of senescent cells (35±11% vs 0±0% in control) (p<0.0001), and FN-1 immunointensity (254±41 vs 65 7 in control) (p<0.01) increased at day-14, parallel to the evolution of multinucleated polyploid cells.

Conclusions: We demonstrate that UVA-induced oxidative stress triggers polyploidy in CE cells resulting in the formation of multinucleated polyploid cells which corelates with development of cellular senescence and fibrosis in FECD.

Candidate: Jonathan Doyon

Poster #: D02

Spatio-temporal Collision Envelope in Virtual Reality Walking With Colliding Pedestrians

Jonathan K. Doyon, Sujin Kim, Alex D. Hwang, Jae-Hyun Jung

Purpose: Safe locomotion depends on maintaining a collision envelope (i.e., safety margin) that flexibly adapts to dynamic situations. We previously characterized dynamic collision envelopes spatially as the minimum egocentric radial distance maintained while walking with other colliding pedestrians. Spatial collision envelope sizes depended on relative walking speeds between the subject and the colliding pedestrian. From this finding, we hypothesized that collision envelopes may be driven by temporal distances (time-to-collision, TTC) rather than spatial distances.

Methods: To this end, we used virtual reality (VR) walking scenarios for Meta Quest 2 head-mounted display (HMD). Normal vision (NV, n=10) and homonymous hemianopia (HH, n=7) subjects physically walked with free gaze in a VR shopping mall presented in the HMD. Subjects naturally avoided (speed/path changes) a colliding pedestrian among 10 non-colliders. Head-on (farther distance, faster relative speed) or rear-end (closer distance, slower relative speed) colliders approached from initial bearing angles of 20°, 40°, and 60°. Collisions had an initial 6-second TTC, which linearly decreased to 0 if the subject failed to avoid.

Results: We computed instantaneous TTC (which fluctuates with gait, body volumes, and path changes) in the egocentric domain as the spatial distance between subject and collider divided by the projection of the instantaneous velocity toward the walking direction of the subject. We considered the minimum TTC across relative bearing angles to be the subject’s spatio-temporal collision envelope as reaction to the collision. We computed instantaneous TTC (which fluctuates with gait, body volumes, and path changes) in the egocentric domain as the spatial distance between subject and collider divided by the projection of the instantaneous velocity toward the walking direction of the subject. We considered the minimum TTC across relative bearing angles to be the subject’s spatio-temporal collision envelope as reaction to the collision. The radius (faster=0.77 seconds ±0.27, slower=0.79s ±0.54, p=0.84) and area (faster=3.26s2 ±1.20, slower=3.87s2 ±1.79, p=0.26) of spatio-temporal collision envelopes were consistent regardless of distance and relative walking speeds. HH had more conservative spatio-temporal collision envelopes (0.86s ±0.48) than NV (0.63s ±0.23, p<0.01) during avoidance.

Conclusions: This finding may suggest that collision avoidance may be driven by the spatio-temporal collision envelope based on the minimum TTC that allows enough time (rather than distance) to react.

Candidate: Olufemi Folorunso

Poster #: D03

Corneal Epithelial Cells Predominantly Secrete TIMP-2, Which has Anti-Inflammatory and Pro-Wound Healing Functions

Olufemi Folorunso, Nishant Sinha, Vinay Pulimamidi, Lei Xi, Rahul Verma, Sunil Chauhan

Purpose: Tissue inhibitors of metallopeptidase (TIMPs) regulate the extracellular matrix (ECM), impacting homeostasis, cell migration, and proliferation. Altered TIMPs expression under pathological conditions worsens disease progression. Yet, TIMP functions in corneal wound healing remain unclear. Here, we investigated the expression of TIMPs in human corneal epithelial cells (HCLE) and examined their biological functions in the context of corneal epithelial injury.

Methods: We profiled TIMP-1, 2, 3, and 4 expression and secretion in immortalized HCLE under IL-1β stimulation (inflammatory milieu) and scratch-wound conditions. The highest expressed TIMP was selected for further analysis. HCLE at >90% confluence was scratch-wounded and treated with 2.0 μg/mL recombinant (r) TIMP. At three times daily, rTIMP at 0.1 mg/mL was used to treat corneal epithelial injury in mice (C57BL/6, 68 weeks, male, n = 5/group). Cells and cornea were harvested for quantitative and qualitative analyses. Quantitative RT-PCR was used to quantify injury-induced MMPs and inflammatory cytokines. Microscopically, we assessed the rate of wound closure, cell proliferation, corneal re-epithelization, transparency, and healing. A 2-way ANOVA analysis with a significant mean difference at p<0.05 was performed, and data were presented as mean±SEM.

Results: HCLE demonstrated upregulated mRNA expression and protein secretion of TIMP1 and TIMP2 under inflammatory and scratch-wound conditions. However, TIMP2 expression was significantly 3.4-fold higher at the mRNA level (p<0.0001) and 2.6-fold higher at the protein level (p<0.0001) compared to TIMP1. In the scratch wound assay, the addition of 2.0 μg/mL rTIMP2 significantly (3-fold) promoted wound closure compared to both untreated (p<0.0001) and TIMP2-neutralizing antibody-treated cells (p<0.001). Furthermore, rTIMP2 significantly suppressed inflammatory cytokines (IL-1β, IL-6, IL-8, and TNFα; p<0.05) and MMPs (MMP3, 9, and 13; p<0.05). Finally, topical treatment with 0.1 mg/mL rTIMP2, in comparison to protein controltreated injuries, significantly enhanced corneal re-epithelialization within 48 hours (30% vs 60%, p<0.01) and suppressed the expression of IL-1β, IL-8, MMP2, MMP3, MMP9, and MMP13 (p<0.05).

Conclusions: Corneal epithelial cells predominantly secrete elevated levels of TIMP2. Topical treatment with recombinant TIMP2 promotes corneal epithelial wound healing and mitigates inflammation, suggesting a potential therapeutic application in corneal inflammatory diseases.

Candidate: Mark Krauthammer

Poster #: D04

Clinical and Molecular Characterization of Corneal Neovascularization in Young vs Adult Mice

Mark Krauthammer, Antonio Esquivel Herrera, Akitomo Narimatsu, Seokjoo Lee, Sunil Chauhan, Reza Dana, Thomas H. Dohlman

Purpose: To evaluate hemangiogenesis and VEGF ligand and receptor expression in young versus adult mice using a suture model of corneal neovascularization (NV).

Methods: Three interrupted figure-of-eight intrastromal corneal sutures were placed in young (3.5 week old) and adult (8 week old) male BALB/c mice. Corneal NV was evaluated by slit-lamp microscopy at days 1,3,7 and 14 after suture implantation. mRNA levels of VEGFA, VEGFC, VEGFR1 and VEGFR2 were additionally evaluated on days 3, 7 and 14. The change in mRNA level in sutured corneas was compared to naive (unsutured) control corneas by calculating the following ratio: (Young-Naïve)/ (Adult-Naïve) and then evaluating the expression of each ligand relative to its corresponding receptor (VEGFA/VEGFR1 and VEGFCVEGFR2). Whole mount corneal immunohistochemistry (IHC) was performed on day 14. Corneal blood vessels were stained with anti-CD31 antibody.

Results: Both young and adult mice demonstrated a significant induction of clinically apparent NV through day 14. At day 14, mRNA levels of VEGFA were significantly higher in young (3937 537 copies/106 GAPDH) versus adult mice (2167 292 copies/106 GAPDH, p=0.011) and mRNA levels of VEGFR1 were also significantly higher in young (2703 389 copies/106 GAPDH) versus adult mice (1541 331 copies/106 GAPDH, p=0.039). There was a trend towards significance for VEGFC (1417 323 copies/106 GAPDH vs. 532 271 copies/106 GAPDH, p=0.05) and there was no difference in level of VEGFR2 (2029 486 vs 2021 549, respectively, p=0.99). In evaluating change in mRNA expression relative to naïve controls, we found a 1.48-fold increase in VEGFA compared to VEGFR1 and a 1.7-fold increase in VEGFC compared to VEGFR2. IHC revealed a difference in the pattern of NV between groups. Young mice demonstrated small caliber vessels reaching centrally with 10-12 clock hours of involvement whereas adult mice more commonly exhibited larger caliber vessels reaching the central cornea with fewer clock hours of involvement. The extent of corneal NV in mean number of clock hours was 11±0.84 in young vs. 6.6±4.28 in adult mice (p=0.046).

Conclusions: In a suture-induced model of corneal NV we observed significantly greater mRNA expression of VEGFA and VEGFR1 in young versus adult mice and a greater increase in VEGFA and VEGFC in young versus adult mice relative to unsutured control when normalized to their respective receptors, as well as differences in pattern of NV on IHC, with a significantly greater circumferential extent of corneal NV in young mice. These results suggest distinct hemangiogenic responses in young versus adult mice with potentially more robust responses to injury in young mice, a finding that correlates anecdotally with clinical observations in the pediatric population.

Candidate: Changrim Lee

Poster #: D05

Biocompatible Metal-Organic Hybrid Films Named Titaminates Preserve

the Growth and Function of Conjunctival Epithelial Cells

Changrim Lee, Srinath Murali, Veronica Anne-Line Kathrine Killi, Ola Nilsen, Darlene A. Dartt

Purpose: Infections, autoimmune diseases, or chemical/thermal burns can scar the conjunctiva, requiring transplantation. The purpose of this study is to explore the biological potential of metal-organic hybrid films in developing a functional conjunctival equivalent for transplantation.

Methods: Using a molecular layer deposition (MLD) technique, 7 hybrid films - 4 titanium-based hybrid films (TiO2, Ti-glycine, Ti-aspartic aid, and Ti-glycine-aspartic acid) and 3 zinc-based hybrid films (ZnO, Zn-glycine, Zn-cysteine) - were prepared on a plain glass coverslip. A total of 8 films, including unmodified glass coverslip (NT), were tested for their biocompatibility on the growth and function of human primary conjunctival epithelial cells (HCjECs). The degree of outgrowth was measured by brightfield tile-imaging, proliferation capacity by colorimetric redox indicator resazurin, secretion of MUC5AC by ELISA, and reconstruction of the native state of conjunctival epithelium by immunofluorescence.

Results: Two types of Ti-based films (titaminates) - TiO2 and TiG – outperformed NT in HCjEC outgrowth. The outgrowth on the other two titaminates - TiD and TiGD - was similar to NT. None of the Zn-based films supported the HCjECs growth. Proliferative capacity and degree of MUC5AC secretion of HCjECs per mm2 cell area were similar across the films. TiO2 and TiG were the best to reproduce the native state of the conjunctiva. HCjECs outgrown from forniceal conjunctival tissue explants on these two films showed a similar percentage of goblet, stratified squamous, and undifferentiated cells to the native epithelial cell composition in the forniceal conjunctiva.

Conclusions: Outperformance of TiO2 and TiG indicates that titanium alone or in combination with glycine has high utility in reproducing the native state of functional conjunctival epithelium. The use of titanium in combination with glycine should be considered when developing a substrate for conjunctival transplantation.

Candidate: Wei Hau Lew

Poster #: D06

Field Expansion for Acquired Monocular Vision: Simplified Fitting With Clinical Confrontation Test

WeiHau Lew, Sandhya Shekar, Jaehyun Jung

Purpose: Acquired monocular vision (AMV) reduces the visual field to ~150° (55° nasal and 95° temporal), posing a higher risk of collision on the side of the affected eye. Previously, we prototyped a 3D-printed multiplexing prism (MxP) attached to a frame as an assisted device for field expansion achieved by overlapping the shifted view from the blindside to the nasal field of the seeing eye. The custom fitting (based on calculation) requires accurate measurement of various parameters (back vertex distance, pupillary distance, and prescription) with multiple iterations (time and labor), which is impossible in clinical settings. While that method aimed to maximize the field, the farthest field expansion was highly compressed and perceptually impractical. Moreover, the prism was not easy to remove when the patients did not need it.

Methods: We simplified the fitting based on the patient's perception with the modified confrontation test. To provide a balanced image quality for various ocular features, an MxP kit of assorted sizes (3 base × 3 apex size) was designed. For better cosmetics, we developed a magnetic clip-on MxP that can be attached or detached effortlessly. A tiny wedge of different heights was positioned at the top to provide the tilt needed for field expansion. We piloted 8 normal vision subjects by patching one of their eyes. Subjects moved their arms outside-in to estimate the visual field with and without MxP. They compared finger size between the two arms while the tilt was adjusted so that the nasal image was about 80% in size. The apex size, which governs diplopia, was determined by reference to the hands extended anteriorly. For validation, Goldmann perimetry was performed to measure the nasal field with and without MxP and the amount of diplopia. The image quality (transmission and magnification) at the prism's base was calculated.

Results: With this method, MxP expanded the nasal field from 56°±4.7 to 80°±3, (average field expansion of 23°) on perimetry with minimal diplopia (7°±4). At the nasal edge of the prism (base), the field expansion had a highly perceivable image with good quality. The average transmission was 42.3% and a magnification factor of 0.57.

Conclusions: This simplified fitting method fetched good field expansion and balanced image quality in a shorter chair time. A clinical trial including patients with AMV has commenced to test these fitting methods.

Candidate: Edward (Ned) Lu

Poster #: D07

Assessing the Impact of the Resident Research Showcase

Edward Lu, Julie Irish, Alice C. Lorch, Lori Newman, Ankoor S .Shah, Eric Gaier

Purpose: To assess resident and faculty views of the Ophthalmology Resident Research Showcase (RRS) and its impact on resident research productivity.

Methods: The RRS, held annually from 2020 to 2023, featured a 2-hour virtual or hybrid event during which Ophthalmology faculty delivered short project “pitches” to residents who were encouraged to contact faculty afterwards to begin a research project. Surveys were distributed to residents and faculty after the 2023 RRS. ACGME surveys from 2017-2024 were analyzed.

Results: All residents (8/8) indicated the RRS effectively exposes them to mentors and projects, and 75% (6/8) indicated the RRS effectively connects residents with faculty. 18/24 (75%) faculty perceived the RRS effectively exposes residents to mentors and research projects. For the 2020-2022 RRS, 42% (5/12 residents) reported contacting mentors, 25% (3/12) presenting at a meeting as primary author, and 17% (2/12) completing at least one project. For the 2023 RRS, 75% (6/8 residents) contacted mentors and 38% (3/8) started projects. The total number of conference presentations increased after the first RRS in 2020 (27 in 2020, 69 in 2021, 54 in 2022).

Conclusions: Residents and faculty indicated the RRS is useful to expose residents to research projects. The RRS may increase the number of conference presentations.

Candidate: Mohit Parekh

Poster #: D08

Cell Cycle From G2/M to G0/G1 Promotes Senescence and Fibrosis Leading to the Development of Fuchs Endothelial Corneal Dystrophy

Mohit Parekh, Yadav Adhikari, Raymond Wong, Neha Deshpande, Ula V. Jurkunas

Purpose: Fuchs endothelial corneal dystrophy (FECD) is a female predominant, age-related disorder, characterized by corneal endothelial cell (CEnC) loss. Ultraviolet-A (UVA) light has been shown to recapitulate the changes seen in FECD in females due to oxidative metabolism of estrogen. Previously, we have shown that acute exposure to UVA causes CEnC re-entry into G2/M phase and activation of p21, indicative of early senescent phenotype. However, the effects of chronic stress (CS), as seen in degenerative aging process, have not been explored. In this study, we investigate if prolonged exposure to oxidized estrogen (4-OHE2) and UVA, leads to a shift in cell cycle regulators and a pro-fibrotic phenotype seen in guttae formation in FECD.

Methods: Chronic stress was induced by exposing HCEnC-21T to UVA (25J/cm2) and 4OHE2 (20 µM) on days 1 and 6. Immunostaining, cell-cycle analysis, and RT-PCR were performed on day 9. Cell sorting of G0/G1 and G2/M was conducted by fluorescence activated cell sorting (FACS). UVA-irradiated (500J/cm2) C57BL/6J female mice were treated with a senolytic cocktail of Dasatinib (1mg/kg) and Quercetin (10mg/kg).

Results: CS induced greater cell reentry to the G0/G1 (60±2%) compared to G2/M (14±2%; p<0.01) and led to accumulation of higher p16 (65±9%; p<0.001), p21 (36±6%; p<0.001) and SA-β-Gal (60±8%; p<0.001) compared to non-stressed controls. Moreover, CS induced increased expression of cyclin D1 (66±4%; p<0.05), and downregulation of cyclin dependent kinase CDK4/6 (p<0.05) and pRB (9±3%; p<0.001) compared to controls, indicating G0/G1 arrest. RT-PCR analysis of FACS-sorted cells revealed upregulation of CDKN2A (5fold; p<0.01) and ACTA2 (80-fold; p<0.001) in the G0/G1 compared to G2/M, indicating G0/G1-dependent induction of senescence and pro-fibrotic phenotype. Senolytics treatment in UVA-irradiated mice significantly reduced CDKN2A (12-fold; p<0.001), CDKN1A (8-fold; p<0.001) and ACTA2 (3-fold; p<0.001) and rescued CE cell loss (1.3-fold; p<0.001).

Conclusions: UVA and estrogen activate cell cycle re-entry into G2/M and with chronic exposure induce permanent cell cycle arrest in G0/G1 phase and irreversible senescence. This shift also leads to a pro-fibrotic phenotype as observed by upregulation of ACTA2, seen in FECD. Senolytics ameliorate senescence and fibrosis, suggesting a potential therapeutic target for preventing FECD.

Candidate: Vinay Kumar Pulimamidi

Poster #: D09

Specific Targeting of Mast Cells via ST-2 Receptor in Ocular Diseases

Vinay K. Pulimamidi, Rahul K. Verma, Nishant R. Sinha, Lei Xi, Olufemi S. Folorunso, Sunil K. Chauhan

Purpose: Mast cells play a crucial role in inflammation by releasing inflammatory mediators, which promote angiogenesis and immune cell recruitment in ocular injury. To primarily target mast cells for interventions in ocular diseases, we exploited ST-2 a cell surface receptor predominantly expressed by mast cells. In this study, we investigated the selective targeting of mast cells using a drug-loaded liposomal delivery via the ligand of ST-2 receptor.

Methods: We designed a cycloheximide loaded liposomal system which was decorated with ST2 specific ligand to selectively target mast cells. Liposomes were prepared using lipid composition composed of 48:50:2 molar ratio of phosphatidylcholine (PC), cholesterol, and Maleimide polyethylene glycol-di-stearoyl phosphorethanolamine (Mal-PEG-DSPE) by thin-film hydration and sonication method. Lipid thin layer was rehydrated with cycloheximide solution in PBS with vertexing, followed by sonication. ST-2 ligand (interleukine-33) was decorated on liposomes using NHS-Mal cross-linking chemistry. The physicochemical characteristics of these liposomes, including their shape, size, drug encapsulation efficiency, and drug release, were evaluated by TEM, Dynamic light scattering (DLS), and dialysis-bag method respectively. Further, we examined the effect of drug-loaded IL33-liposomes on the inflammatory response in human mast cells (LUVA), assessing the expression of pro-inflammatory cytokines through qRT-PCR.

Results: The drug loaded IL33-liposomes were spherical in shape with particles size of 101.7±18.3 nm with a surface charge of 1.92±0.8 mV. The conjugated liposomes showed significantly higher cellular uptake in human mast cells compared to normal liposomes without ligand. ST2-mediated activation of matured mast cells triggered a proinflammatory response, characterized by an enhanced production of proinflammatory TNFα (p<00.5) and Interleukin-1β (p<0.05)), which was significantly decreased after treatment with cycloheximide loaded liposomes in 18 h. Further, drug loaded ST2-ligand decorated liposomes induced significant apoptosis in mast cells.

Conclusions: Our data demonstrate that ST2-ligand decorated liposomes target mast cells and inhibit their inflammatory function, suggesting a potential therapeutic approach for mast cell related diseases.

Candidate: Janiece Rosado

Poster #: D10

Do Drivers With Vision Impairments Engage in Distracting Secondary Tasks While Driving?

Janiece L. Rosado, Kayla Shaw, Alex R. Bowers, Jing Xu

Purpose: Distracted driving poses a pervasive safety threat, leading to accidents and fatalities. Driver characteristics, such as being an individual with vision impairments (VI), may further increase the risk. Drivers with VI are legally permitted to drive in the US. There is very limited knowledge about whether they engage in distracting activities while driving, such as using the phone. Therefore, we conducted a questionnaire study to explore the secondary task involvement among drivers with VI and compared to drivers with normal vision (NV).

Methods: The questionnaire was administered by telephone to a group of current drivers with VI (n = 36; median age 64.5 years; 53% male) and a group of current drivers with normal vision (NV; n = 34; median age 47 years; 41% male). The survey addressed demographics, driving habits, avoidance of 11 common driving situations, involvement in 14 common secondary tasks while driving, and perceptions of situations that were distracting when driving. Causes of VI in the VI group included homonymous visual field loss (20%), glaucoma (17%), cataract (15%), age- related macular degeneration (15%), and some form of congenital or other condition such as, albinism or nystagmus (34%).

Results: The VI group reported driving with a similar frequency and mileage per week compared to the NV group (median: 5.8 days and 65 miles vs. 5 days and 95 miles). However, they avoided significantly more of the common driving situations than the NV drivers (median 4 vs. NV 1 situations, P < 0.001), especially driving at night and in bad weather. The majority of VI participants reported that they put full attention on the road when driving, and 81% of them reported limiting involvement in secondary tasks to a great extent due to their vision conditions. VI individuals reported engaging in significantly fewer types of secondary tasks while driving (4 vs. NV 7 tasks; P < 0.001). Both groups ranked hearing their phone ring and encountering roadside accident scenes as the most distracting situations when driving.

Conclusions: Drivers with VI were more likely to avoid difficult driving situations. They report engaging in common secondary tasks while driving. However, compared to those with NV, drivers with VI engage in fewer types of secondary tasks and intentionally restrict their involvement to minimize distractions due to their vision conditions. Both groups perceived the ringing of a phone and scenes of roadside accidents as highly distracting.

Candidate: Maryam Shayan

Poster #: D11

Characterization

of an Inducible, Conditional HIF-1α Knockout Mouse

Strain and Induction of Experimental Chronic Autoimmune Uveitis in the Strain

Maryam Shayan, Qiurong Zhu, Seokjoo Lee, Francesca Kahale, Yihe Chen

Purpose: Long-lived, uveitogenic memory CD4+ T cells express high levels of hypoxia-inducible factor-1α (HIF-1α). Herein, we aim to develop a tamoxifen-inducible, CD4-conditional HIF-1α knockout mouse strain to investigate the roles of HIF-1α in governing memory CD4+ T cells in experimental chronic autoimmune uveitis (CAU).

Methods: The CD4-CreERT2 mice (JAX) were crossed with Hif1afl/fl mice (JAX), and the resultant F1 B6.CD4CreERT2-Hif1afl/- strain was then backcrossed to Hif1afl/fl strain. The offspring were genotyped and examined using fundoscopy, optical coherence tomography (OCT), and electroretinogram. Mice were intraperitoneally injected with tamoxifen, and clinically followed for 4 weeks. Thereafter, lymph nodes (LN), spleen (SP) and peripheral blood (BL) were collected for flow cytometry. In addition, CAU was induced by immunization with interphotoreceptor retinoid-binding protein peptides emulsified in complete Freund’s adjuvant, with Bordetella pertussis toxin injection, and evaluated at 12 weeks.

Results: The desired B6.CD4CreERT2-Hif1afl/fl strain along with control strains, B6.CD4-Hif1afl/fl and B6.CD4-Hif1afl/- were generated. All strains exhibited normal ocular structures. Subsequent tamoxifen treatment did not induce retinal infiltrates or dysfunction in any strain. Additionally, it had no significant impact on the CD11b+ myeloid (2.1±0.2% vs 2.8±0.2% in LN, 2.4±0.3% vs 2.7±0.5% in SP, 3.5±0.2% vs 3.6±1.2% in BL) or CD3+ lymphoid pool (40±4% vs 40±2% in LN, 20±4% vs 24±3% in SP, 10±2% vs 8±3% in BL) in either the desired or control strains. Furthermore, it did not affect CD4 (47±3% vs 46±1% in LN, 49±4% vs 48±1% in SP, 45±5% vs 40±3% in BL) or CD8 (47±3% vs 48±3% in LN, 39±2% vs 44±1% in SP, 46±5% vs 49±1% in BL) subsets in any strain. At 12 weeks post-immunization, both the desired strain and littermate controls exhibited comparable retinal infiltration and structural damage as documented by fundoscopy (3.3±0.5 vs 2.8±0.5 on a scale of 0-4) and OCT (3.2±0.4 vs 3.0±0.3 on a scale of 0-4).

Conclusions: The B6.CD4CreERT2-Hif1afl/fl strain shows normal ocular development and robust CAU induction, and tamoxifen treatment does not significantly alter pools of major immune subsets, rendering this strain a novel and validated tool to study the function of HIF-1α specifically expressed by memory CD4+ T cells in chronic uveitis.

Candidate: Rohan Singh

Poster #: D12

Early

Infiltrating

Regulatory

T-cells (Tregs) Differentially Impact Graft Site Antigen Presenting Cells (APCs) and Graft Survival

Rohan Bir Singh, Tomas Blanco, Hayate Nakagawa, Akitomo Narimatsu, Seokjoo Lee, Francesca Kahale, Yihe Chen, Reza Dana

Purpose: The immune rejection is primarily attributed to T helper 1 (Th1) effector cells, whereas graft survival primarily relies on several tolerogenic mechanisms mediated by donor antigen-specific Tregs and these two mechanisms are linked by migratory APCs at the graft site. Herein, we evaluate the effect of infiltrating Tregs on the phenotype of graft site APCs following corneal transplantation.

Methods: High risk (HR) or low risk (LR) corneal transplantations were performed in BALB/c recipient mice and C57BL/6 mice were used as donors. At 3- and 7-days post-transplantation, Treg were FACS-sorted from the graft site (grafted cornea and conjunctiva) and Tregs, Th1 cells and mature APCs (CD45+CD11b+B220MHC-IIhi) were analyzed using flow cytometry. Additionally, Treg sorted at day 7 post-transplantation from the graft site of HR recipients (5x103 cells) were subconjunctivally injected into newly transplanted LR RAG1-/-or wild type (WT) recipient mice, and vice versa (n=14/group). Additionally, splenic Tregs were pre-incubated with IL-6 (100ng/ml) and injected into LR RAG-1-/- and WT recipient mice. Mice (n=8/group) were followed up for 8 weeks to evaluate graft survival. Additionally, at 2 weeks post-transplantation (n=6/group) DLNs were harvested and assessed using flow cytometry.

Results: We observed significantly lower Treg frequencies (p=0.012), FoxP3 expression (p=0.0031) and increased IL-6R expression (p=0.024) in HR recipients compared to LR recipients. Adoptive transfer of HR Tregs into LR RAG-/- mice resulted significantly higher frequencies (p=0.0039) of mature APCs compared to PBS treated controls. Conversely, LR-Treg transferred into RAG-/- mice resulted in lower frequencies (p=0.0019) of APCs compared to PBS treated controls and this effect was abolished when Treg were incubated with IL-6 prior injection. Adoptive transfer of HR Treg into LR recipient mice resulted in increased frequencies of corneal APCs (p=0.023), and enhanced Th1 infiltration (p=0.042) compared to PBS treated controls. Additionally, this led to reduced Treg (isolated from DLNs) function characterized by lower FoxP3 (p<0.0001), IL-10 (p=0.0082) and TGF- 1 expression (p=0.0034), and enhanced graft immune rejection compared to PBS treated controls (p<0.0001). Conversely, when LR Treg were injected in HR recipients, we observed significantly lower graft site APC migration (p=0.029), and Th1 infiltration (p=0.0019) in the corneal tissue. Additionally, we observed higher expression levels of FoxP3 (p=0.0015), IL-10 (p=0.038) and TGF- 1 expression (p=0.045) in Tregs isolated from DLNs, and enhanced graft survival (p<0.0001).

Conclusions: The infiltrating Tregs differentially impact graft site APC maturation depending on the graft site milieu, underlining the critical impact of graft site inflammation on frequencies and function of Tregs.

Candidate: Pier Luigi Surico

Poster #: D13

NK-1R Antagonism Suppresses

the Expression of

Pain-Associated

Neuronal Activity Markers Following Corneal Mechanical Injury

Pier Luigi Surico, Amirreza Naderi, Rohan Bir Singh, Seokjoo Lee, Francesca Kahale, Yihe Chen, Reza Dana

Purpose: Corneal injury is associated with neuronal activation causing long term pain in patients, impacting their quality of life. Ocular surface nociception is primarily mediated by a neuropeptide - Substance P (SP)which primarily activates neurokinin 1 receptor (NK-1R). The purpose of this study is to determine the effect of NK-1R antagonism on the expression levels of signature molecular markers for pain-associated neuronal activity.

Methods: Corneal mechanical injury was induced in mice with Algerbrush II. Subsequently, L-733,060 (1μg/μl), an NK1-R antagonist, or PBS was administered topically twice for 21 days. Hyperalgesia and allodynia were quantified by eye wipe test (EWT) and palpebral ratio (PR). We assessed the gene expression levels of activating transcription factor 3 (ATF3), cFos, glial fibrillary acidic protein (GFAP), transient receptor potential cation channel subfamily M Member 8 (TRPM8) and subfamily V member 1 (TRPV1) in the trigeminal ganglia (TG) of the mice before injury and on days 4 and 21 post-injury.

Results: Injured mice developed significantly worsening hyperalgesia and allodynia following injury. EWT and PR were significantly improved in L-733,060 treated group compared to controls on days 7 (p=0.008), 14 (p=0.008; p= 0.0004) and 21 (p= 0.01; p=0.05). L-733,060 treatment resulted in significantly lower expression levels of ATF3 in TG compared to PBS treated mice on day 4 (p=0.0031) and 21 (p=0.0084), comparable to non-injured mice levels. Additionally, the expression levels of Fos in TG were significantly reduced in L733,060 treated mice on days 4 (p=0.004) and 21 (p=0.001), compared to controls. Fos expression levels in L733,060 treated mice were comparable to non-injured mice at both time points. Moreover, the expression levels of GFAP in TG of L-733,060 treated mice were significantly lowered to non-injured mice expression levels on days 4 (p=0.011) and 21 (p=0.004) compared to controls. Similarly, L-733,060 treated group showed significantly lower TG expression levels of TRPV1 and TRPM8 on day 4 (p=0.009 and p=0.015, respectively) and day 21 (p=0.032 and p=0.003, respectively) compared to controls. NK1R antagonism restored TRPV1 and TRPM8 expression levels to that observed in non-injured mice at both 4 and 21 days.

Conclusions: Our data suggest that antagonism of NK-1R leads to consistent reduction of expression levels of pain-associated neuronal activity markers. Therefore, topical NK-1R inhibition represents a potential disease-modifying therapy of corneal injury-related pain.

Candidate: Yi Ni Toh

Poster #: D14

Driving With hemianopia: Do Peripheral Prism Glasses Improve Hazard Detection at Intersections?

Yi Ni Toh, Patrick Baker, Eli Peli, Alex Bowers

Purpose: At intersections, drivers with hemianopia have to make large scans with head and eye movements to detect peripheral hazards at wide angles (e.g., > 50°) on their blind side. Insufficient scanning into the blind hemifield can lead to missed detections and higher collision risk. Newly developed 100∆ oblique multiperiscopic peripheral prisms (MPPs) provide 42° field expansion and enable 15° of eye scanning into the blind hemifield. In contrast, commercially available 65∆ oblique Fresnel peripheral prisms (FPPs) offer 30° expansion, with only 5° of eye scanning possible toward the blind side before total internal reflection limits field expansion. This study investigates the effects of MPPs and FPPs on peripheral hazard detection.

Methods: Six participants with homonymous hemianopia, without neglect or cognitive decline, completed our pilot study. A crossover design was used where each participant used both types of prism glasses. They were randomly assigned to receive MPPs followed by FPPs, or vice versa. There were three driving simulator visits. The first visit served as the baseline, during which participants drove without prisms. The second and third visits evaluated driving with prisms. Before conducting driving simulator tests with each type of prism, participants were fitted with the prisms in the lab and instructed to practice using them at home for at least 4 weeks. They drove in a simulator replicating urban scenarios with many intersections, cross traffic, oncoming traffic, and pedestrians. At 10 of the intersections in each drive, a motorcycle hazard approached along the cross-street from either the left or right at an eccentricity between 50° and 60°. Motorcycles also appeared at non-intersection locations along the routes. Participants were instructed to drive normally and to press the horn button upon detecting motorcyclists. Head and eye movements were recorded with a 6-camera remote tracking system.

Results: Participants showed improved detection of blind-side hazards with prisms compared to baseline (no prism: 36%; FPPs: 55%; MPPs: 60%), with longer response times (no prism: 3.3s, FPPs: 3.7s; MPPs: 4.4s). Participants also made more blind-side and seeing-side scans per intersection with prisms compared to baseline (blind-side scans: no prism: 6; FPPs: 10; MPPs: 10; seeing-side scans: no prism: 4; FPPs: 6; MPPs: 7), with no significant difference in scan magnitudes among the different prism conditions. Interestingly, three participants had higher blind-side detection rates with FPPs, while the remaining three performed better with MPPs. However, despite the improvement with prisms, blind-side hazard detection (mean: 57%, response time: 4.1s) was still worse than seeing-side detection (mean: 83%, response time: 3.4s).

Conclusions: Hemianopic field loss leads to impaired blind-side hazard detection, posing significant mobility risks. This study provides preliminary data demonstrating the promise of peripheral prisms in improving blindside detection and scanning, potentially improving hazard detection at intersections.