Thursday, June 11, 2026 - The Starr Center - Second Floor, 185 Cambridge Street, Boston, MA
12:00-12:30 pm
Registration & Lunch
Physician, Surgeon, and Investigator, Mass Eye and Ear 12:30–
1:29–1:41 pm
1:41–1:53 pm
1:53–2:05 pm
2:05–2:15 pm
2:15–2:20 pm
2:20–2:25 pm
2:25–2:30 pm
Welcome & Overview - Rachel Huckfeldt, MD, PhD (2013, 2016) and Eric D. Gaier, MD, PhD (2017, 2019) Annual Meeting Co-Chairs
Special Resident Grand Rounds
Dennis Akrobetu, MD - PGY4 Ophthalmology Resident, Harvard Medical School, Mass Eye and Ear
Janice Ong, MD - PGY3 Ophthalmology Resident, Harvard Medical School, Mass Eye and Ear
Maryam Zekavat, MD, PhD - PGY4 Ophthalmology Resident, Harvard Medical School, Mass Eye and Ear
Henry W. Zhou, MD, MS - PGY4 Ophthalmology Resident, Harvard Medical School, Mass Eye and Ear
Immune Engineering: The Key to Next-Generation Cell Therapy - Sunil K. Chauhan, DVM, PhD
Associate Professor of Ophthalmology, Harvard Medical School
Associate Scientist, Schepens Eye Research Institute of Mass Eye and Ear
Rational Laboratory Testing in Uveitis: A Bayesian Approach - K. Matthew McKay, MD (2019)
Instructor in Ophthalmology, Harvard Medical School
Cellular Hypoxia in Retinal Inflammation and Fibrosis - Yihe Chen, MD (2017)
Assistant Professor of Ophthalmology, Harvard Medical School
Assistant Scientist, Mass Eye and Ear
Leveraging the All of Us Research Program to Advance Ocular Knowledge
Inas F. Aboobakar, MD (2021)
Instructor in Ophthalmology, Harvard Medical School
Physician, Surgeon, and Investigator, Mass Eye and Ear
Glymphatic Transit in Idiopathic Intracranial Hypertension - Marc A. Bouffard, MD (2017)
Instructor in Ophthalmology and Assistant Professor of Neurology, Harvard Medical School
Physician and Surgeon, Mass Eye and Ear
Harvard Ophthalmology Research Scholars Program and Introduction of the Class of 2026
Silas L. Wang, MD and Alex R. Bowers, PhD
Co-Directors, Harvard Ophthalmology Research Scholars Program, Mass Eye and Ear
The Harvard Ophthalmology Research Scholar Experience - Kevin Lopez, MS (2024)
Medical School Candidate, Charles R. Drew University of Medicine and Science
2026 Harvard Ophthalmology Excellence in Mentoring Awards - David G. Hunter, MD, PhD (1991)
Professor of Ophthalmology and Vice Chair for Promotions and Reappointments, Ophthalmology, Harvard Medical School
Ophthalmologist-in-Chief and Richard M. Robb Chair in Ophthalmology, Boston Children’s Hospital
Celebrating the Career and Legacy of Evangelos S. Gragoudas, MD - Dean Eliott, MD
Stelios Evangelos Gragoudas Professor of Ophthalmology, Harvard Medical School Director, Vitreoretinal Surgery Fellowship, and Senior Scientist, Mass Eye and Ear
Break 2:30-3:10 pm
3:10–3:22 pm
Beyond the Lens: Managing Cataract Surgery in Patients With Developmental Delays
Deborah K. VanderVeen, MD
Professor of Ophthalmology, Harvard Medical School Director, Pediatric Cataract Service, and Director, Retinopathy of Prematurity Service, Boston Children's Hospital
3:22–3:34 pm
3:34–3:46 pm
3:46–3:58 pm
3:58–4:10 pm
4:10–4:15 pm
Gene-agnostic Therapy for Retinitis Pigmentosa - Ryoji Amamoto, PhD
Assistant Professor of Ophthalmology, Harvard Medical School
Assistant Scientist, Mass Eye and Ear
Role of Omics in Age-related Macular Degeneration - Deeba Husain, MD (2001, 2003)
Professor of Ophthalmology, Harvard Medical School
Director, Medical Retina Fellowship, and Associate Scientist, Mass Eye and Ear
Randomized Controlled Trial of a Spike Timing-Dependent Synaptic Plasticity-Driven Amblyopia Treatment - Eric D. Gaier, MD, PhD (2017, 2019)
Assistant Professor of Ophthalmology, Harvard Medical School
Site Director, Harvard Ophthalmology Residency, and Neuro-Ophthalmologist,Boston Children’s Hospital
Trauma on the Slopes: Oculofacial Injuries Associated With Skiing and Snowboarding
Daniel R. Lefebvre, MD (2012)
Assistant Professor of Ophthalmology, Harvard Medical School
Physician, Surgeon, and Assistant Scientist, Mass Eye and Ear
Perspective on Mariana Dieste Mead & Introduction of the Mariana Dieste Mead Awardee
Joseph F. Rizzo III, MD (1986)
Simmons Lessell Professor of Ophthalmology and Director of Alumni, Ophthalmology, Harvard Medical School
Director, Neuro-Ophthalmology Service,and Senior Scientist, Mass Eye and Ear
4:15–4:55 pm
4:55–5:00 pm
2026 Marianna Dieste Mead Humanistic Leadership in Medicine Award
Taking the Road Less Traveled in Academic Ophthalmology
John H. Kempen, MD, MPH, PhD, MHS
Professor of Ophthalmology, Part-time, Harvard Medical School
Director of Epidemiology, Ophthalmology, and Senior Scientist, Mass Eye and Ear
Closing Remarks - Rachel Huckfeldt, MD, PhD (2013, 2016) and Eric D. Gaier, MD, PhD (2017, 2019
Annual Meeting Co-Chairs
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. The activity number is 132945. For complete CME information, visit: www.eventleaf. com/e/AMAR2026
OPHTHALMOLOGISTS: Physician Boston Children’s Hospital designates this live activity for a maximum of 12.0 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 12.0 COPE Credit Hours. Optometrists should claim only the credit commensurate with the extent of their participation in the activity. The course number is 104604-GO
TEXT-IN-ATTENDANCE: Send 892781 to 844-998-2674 during the session to record your attendance.
Mass Eye and Ear, 7th Floor Lank Dining Room - 243 Charles Street, Boston, MA
2026 Annual Meeting and Alumni Reunion
ALUMNI REUNION
Friday, June 12, 2026 - The Starr Center - Second Floor, 185 Cambridge Street, Boston, MA
8:00-8:30 am
8:30–8:41 am
Registration & Breakfast
Welcome Alumni - Joseph F. Rizzo III, MD (1986) and Joseph B. Ciolino, MD (2009) Alumni Reunion Co-Chairs
8:41 am 2021 Class Speaker Introduction - Edward S. Lu, MD - PGY4 Resident, Harvard Medical School
8:42–8:57 am
8:57 am
8:58–9:13 am
9:13
9:14–9:29 am
Mass Eye and Ear Emergency Department: Through the Years - Clifford Kim, MD (2021) Instructor in Ophthalmology and Associate Director, Ophthalmology Residency, Harvard Medical School
Physician and Surgeon, Mass Eye and Ear
Class Speaker Introduction - Henry W. Zhou, MD - PGY4 Resident, Harvard Medical School
9:29 am
How Open Globes Opened Doors: A Reflection on the Mass Eye and Ear Trauma
Experience - Yewlin E. Chee, MD (2013, 2016)
Associate Professor of Ophthalmology, University of Washington School of Medicine Ophthalmologist, Eye Institute at Harborview Medical Center
Embracing the Unexpected: Commitment to Excellence and Enjoying the Ride Kristen M. Hawthorne, MD (2011) Ophthalmologist, Howerton Eye Clinic
Class Speaker Introduction - David X. Zhao, MD - PGY2 Resident, Harvard Medical School
Co-founder, Cartesian Therapeutics
General Partner, Thirsty Brook Investments
10:30 am 2001 Class Speaker Introduction - Janice X. Ong, MD - PGY3 Resident, Harvard Medical School
Retinal Arterial Embolism - Ron Adelman, MD, MPH, MBA (2001)
Professor Emeritus of Ophthalmology and Director, Retina and Macula Service, Yale School of
10:51 am 1996 Class Speaker Introduction - Darren A. Chen, MD - PGY4 Resident, Harvard Medical School
10:52–11:12 am
11:12–11:17 am
11:17–11:50 am
The Vision Benefit: Origins & Opportunities - Glenville A. March Jr, MD (1996)
Co-founder, March Vision Care Co-principal, Strategem Investments
Introduction of the Distinguished Research Achievement Awardee
Demetrios G. Vavvas, MD, PhD (2003, 2007)
Solman and Libe Friedman Professor of Ophthalmology, Harvard Medical School Director, Retina Service, Mass Eye and Ear
2026 Distinguished Innovation Award Lecture
Translational Studies in Vision Restoration - José-Alain Sahel, MD (1987)
Distinguished Professor and Chairman, Department of Ophthalmology, University of Pittsburgh Director, University of Pittsburgh Medical Center Vision Institute
Executive Vice President and Chief, UPMC Health Technology Advancement Program, UPMC Enterprises
1:10–1:30 pm
Department Update - Rishi P. Singh, MD (2005)
Chair, Department of Ophthalmology, Harvard Medical School
Chair of Ophthalmology, Mass Eye and Ear, Mass General Brigham
1:30 pm 1991 Class Speaker Introduction - Ayush Parikh, MD - PGY3 Resident, Harvard Medical School
1:31–1:51 pm
From Fellow to Teacher: Extending the Reach of Mentorship in Ophthalmology
Helen K. Wu, MD (1991, 1992)
Cornea and Refractive Surgeon, Newton Wellesley Eye Associates
1:51 pm 1986 Class Speaker Introduction - Andrew R. Griswold, MD, PhD - PGY3 Resident, Harvard Medical School
1:52–2:12 pm
2:12–2:17 pm
2:17–2:50 pm
New Treatments: Why Function, Treatment Burden, and Cost Should Take Precedence Over Anatomy - Susan B. Bressler, MD (1986)
Julia G. Levy, PhD Professor of Ophthalmology, Johns Hopkins School of Medicine, Wilmer Eye Institute
Introduction of the Distinguished Clinical Achievement Awardee
Janey L. Wiggs, MD, PhD (1990, 1991, 1992)
Paul Austin Chandler Professor of Ophthalmology and Vice Chair, Ophthalmology Clinical Reearch, Harvard Medical School
Associate Director, Howe Laboratory, and Associate Chief, Ophthalmology Clinical Research, Mass Eye and Ear
2:50-3:35 pm
2026 Distinguished Clinical Achievement Award Lecture
OCT for Glaucoma - Joel S. Schuman, MD (1990)
Professor of Ophthalmology and Kenneth L. Roper, MD Endowed Chair, Thomas Jefferson University
Vice Chair, Research Innovation, and Co-Director, Glaucoma Service, Wills Eye Hospital Professor, Biomedical Engineering, Drexel University School of Biomedical Engineering, Science and Health
Break
3:35 pm 1981 Class Speaker Introduction - Hursuong Vongsachang, MD, MPH - PGY4 Resident, Harvard Medical School
3:36–3:56 pm
Eyes on 1981 - Claudia U. Richter, MD (1981, 1982)
Clinical Assistant Professor, Ophthalmology, Tufts University School of Medicine
3:56 pm 1976 Class Speaker Introduction - Dennis Y. Akrobetu, MD - PGY4 Resident, Harvard Medical School
3:57–4:17 pm
4:17–4:22 pm
The ATP Enigma - Jack V. Greiner, OD, DO, PhD (1976, 1978)
Associate Professor of Ophthalmology, Part-time, Harvard Medical School
Associate Clinical Professor, Ophthalmology, Tufts University School of Medicine
Introduction of the Distinguished Research Awardee - David G. Hunter, MD, PhD (1991) Professor of Ophthalmology and Vice Chair for Promotions and Reappointments, Ophthalmology, Harvard Medical School
Ophthalmologist-in-Chief and Richard M. Robb Chair in Ophthalmology, Boston Children’s Hospital
4:22–4:55 pm
4:55–5:00 pm
2026 Distinguished Research Achievement Award Lecture
Regulating Angiogenic Signaling to Promote Beneficial Angiogenesis and Prevent Retinopathy of Prematurity - Mary Elizabeth Hartnett, MD (1990)
Michael F. Marmor, MD Professor in Retinal Science and Diseases, Professor of Ophthalmology, and Director, Pediatric Retina, Stanford University School of Medicine
Closing Remarks
Joseph F. Rizzo III, MD (1986) and Joseph B. Ciolino, MD (2004, 2009) - Meeting Co-Chairs
Mandarin Oriental Hotel, 776 Boylston Street, Boston, MA
6:00-7:30 pm
Trainee Poster Contest & Reception
Gala Dinner 7:30-10:00 pm
TRAINEE POSTER CONTEST
Candidate: Lu Huang
Poster #: 1
Re-Establishing Retinal Homeostasis and Preserving Retinal Structure and Function by IGFBPL1 in Experimental Dry Age-Related Macular Degeneration
Lu Huang, Kin-Sang Cho, Anton Lennikov, Karen Chang, Wai Tai, Lydia Wai, Ajay Ashok, Menglu Yang, Yuancheng Ryan Lu, Farris ElZarid, Ethan Yao, Bruce R. Ksander, Dongfeng Chen
Purpose: Oxidative stress and chronic inflammation disrupt retinal homeostasis, accelerating degeneration. We previously identified Insulin-like growth factor-binding protein-like 1 (IGFBPL1) as an endogenous guardian of retinal immunostasis, here we want to investigate its role in retinal degeneration.
Methods: Sodium iodate (SI) administration in C57BL/6J mice mimics late-stage dry age-related macular degeneration (dAMD), which affects 170 million people worldwide over age 40 and is marked by retinal pigment epithelium (RPE) and photoreceptor degeneration. Single intravitreal injection of IGFBPL1 in our dAMD mice significantly improved retinal degeneration within one week.
Results: Enhancement of visual functions was shown by improved optomotor and electroretinogram responses. Restoring retinal structure was shown by: 1) optical coherence topography assessment of outer nuclear layer (ONL) thickness; 2) increased cone numbers and elongated outer segments by Peanut Agglutinin staining; 3) improved RPE morphology and tight-junction integrity demonstrated by RPE65 and Zonula Occludens-1 immunolabeling. In vitro, IGFBPL1 promoted the survival and reduced oxidative stress in human fetal RPE cultures challenged by SI. Expression of IGFBPL1 and its interacting receptor insulin-like growth factor 1 receptor (IGF1R) in normal mouse RPE tissue were verified by qPCR and immunolabeling. While IGFBPL1 reduced inflammation and oxidative stress and increased RPE or photoreceptor gene expression at different time points in vivo, IGF1R inhibitor diminished the protective effects of IGFBPL1.
Conclusions: Here, we show single IGFBPL1 administration preserves vision and photoreceptor/RPE integrity in SI-induced retinal degeneration in an IGF1R-dependent manner, highlighting IGFBPL1 as a promising therapeutic strategy that restores retinal homeostasis to halt or slow progressive retinal degeneration.
Candidate: Jyoti Sharma
Poster #: 2
Eltacimig: A Bispecific Antibody Targeting TNF-α and VEGF for the Treatment of Neovascular Age-Related Macular Degeneration
Jyoti Sharma, Bin Yan, Victor S.M.C. Correa, Musa Salam, Shewa Osmani, Demetrios Vavvas, Eleftherios I. Paschalis
Purpose: Age-related macular degeneration (AMD) remains a leading cause of irreversible central vision loss, affecting ~196 million people globally. Despite frequent intravitreal anti-VEGF injections as standard of care for neovascular AMD (nAMD), a substantial proportion of patients still progress to neuroretinal atrophy because persistent neuroinflammation remains untreated. This highlights an urgent unmet need for therapies targeting both the angiogenic and inflammatory arms of AMD pathogenesis. This study describes the development and preclinical characterization of Eltacimig, a first-in-class bispecific antibody simultaneously targeting TNF-α and VEGF.
Methods: Using structural prediction models, eight Fc-containing bispecific antibodies were engineered in two clinically established formats: CrossMab (n=4) and Fab/scFv-Fc (n=4). FcRn-binding capacity was preserved to support intraocular durability, while LALA-PG mutations were introduced to silence Fc-mediated effector functions, including ADCC and CDC. Two lead candidates were expressed in CHO cells and characterized by SDS-PAGE, SEC-HPLC, and LC-MS. In vitro activity was assessed using a TNF-α-mediated FADD cell-death assay (rTNF-α, 0.578 nM; Eltacimig, 4.6 nM; adalimumab comparator, 4.6 nM) and a VEGF165-induced HUVEC proliferation assay (rVEGF165, 2.275 nM; Eltacimig, 13.65 nM; bevacizumab or aflibercept comparator, 13.65 nM). In vivo efficacy was evaluated in a rabbit rVEGF-induced retinal vascular leakage model using fluorescein angiography on Days 2 and 5, with intravitreal Eltacimig administered on Day 2. Efficacy and tolerability were further assessed in an African green monkey DLAAA model of persistent vascular leakage, with one eye treated with intravitreal Eltacimig (2.4mg) and the fellow eye treated with aflibercept (1.2mg), followed weekly by fluorescein angiography, fundus examination, and slit-lamp biomicroscopy.
Results: Lead scFv-Fc and CrossMab Eltacimig candidates were produced at high yield and purity: scFv-Fc, 275.65 mg/L, 99.90% by SEC-HPLC, endotoxin <0.0093 EU/mg; and CrossMab, 398.90 mg/L, 99.91% by SEC-HPLC, endotoxin <0.0092 EU/mg. Both formats neutralized TNF-α-mediated FADD cell death and inhibited VEGF165-induced HUVEC proliferation, with activity comparable to adalimumab, bevacizumab, and aflibercept (p<0.0001). In rabbits, scFv-Fc Eltacimig significantly suppressed rVEGF-induced retinal vascular leakage (p=0.0017). In the African green monkey DLAAA model, CrossMab Eltacimig showed greater leakage reduction than aflibercept at all timepoints, with relative improvements of 63%, 59%, 50%, and 20% at Weeks 1, 2, 3, and 4, respectively. Eltacimig was not associated with intraocular inflammation, whereas the aflibercept-treated eye developed grade 2+ inflammation requiring steroid rescue therapy.
Conclusions: Eltacimig is a dual-target bispecific antibody designed to inhibit both VEGF-driven angiogenesis and TNF-α–mediated inflammation, an axis not addressed by current nAMD therapies, including VEGF/Ang-2 blockade with faricimab. In pilot rabbit and nonhuman primate studies, Eltacimig reduced retinal vascular leakage and showed favorable ocular tolerability. These findings support further IND-enabling development, particularly for nAMD patients with persistent leakage, inflammatory activity, or fibrotic progression despite standard therapy.
Candidate: Maria Anna Bantounou
Poster #: 3
Familial Hypercholesterolemia, Cumulative Low-Density Lipoprotein Cholesterol Exposure, and Risk of Age-Related Macular Degeneration
Maria Anna Bantounou, Maria Emfietzoglou, Tiarnán D. L. Keenan, Gustavo Sakuno, Konstantinos G Baroutis, Joan W. Miller, Demetrios G. Vavvas
Purpose: Lipid dysregulation has been implicated in age-related macular degeneration (AMD) pathogenesis. AMD is a leading cause of vision loss among adults over 60. Familial hypercholesterolemia (FH), characterized by lifelong elevation of low-density lipoprotein cholesterol (LDL-C), provides a unique human model to examine the effects of sustained cumulative LDL-C exposure. We investigated the risk of incident AMD among individuals with FH vs matched controls.
Methods: We conducted a retrospective cohort study using the Complete Patient Data Science Repository. Individuals with familial hypercholesterolemia (FH) and non-FH controls were eligible if they had at least 1 lipid measurement after age 50 years. FH participants were matched 2:1 to controls on demographic characteristics, cardiometabolic comorbidities, comorbidity burden, and healthcare utilization variables. The primary outcome was incident clinically documented age-related macular degeneration (AMD), analyzed using subdistribution hazard ratios (sHRs) with death treated as a competing event. Additional analyses included exclusion of controls with lipoprotein disorders, AMD subtype analyses, an active-comparator analysis comparing FH with other lipoprotein disorders, and a negative-control outcome analysis using macular hole. The association between lifetime cumulative LDL-C exposure, measured as LDL-C years, and AMD risk was also modeled.
Results: We included 6,974 participants with FH and 13,948 matched controls. Over 9.5±6.6 years, AMD occurred in 141 FH participants (2.0%) vs 172 controls (1.2%) (sHR=1.50, 1.20–1.87; P=0.0004). Results were stronger after excluding controls with lipoprotein disorders (sHR=1.89, 1.49–2.42; P<0.0001) and consistent for exudative AMD (sHR=1.78, 1.21–2.62; P=0.0034), nonexudative AMD (sHR=1.37, 1.08–1.74; P=0.010), active-comparator analysis (FH vs lipoprotein disorders; sHR=1.49, 1.19–1.85; P=0.0004). No association was observed for macular hole (sHR=1.02; P=0.90). Cumulative LDL-C was strongly associated with AMD (P<0.0001), FH remained independently associated after LDL-C years adjustment (P=0.027).
Conclusions: FH was associated with an approximately 50% higher risk of clinically documented AMD compared with matched controls, with stronger associations when FH was compared with individuals without lipoprotein disorders. The graded pattern across comparator groups, together with the strong association between cumulative LDL-C burden and AMD, supports the hypothesis that chronic LDL-C exposure may contribute to AMD risk. Prospective studies incorporating longitudinal lipid measurements, multimodal retinal imaging, and genetic data are needed to confirm these observations and clarify the underlying biological mechanisms.
Candidate: Lilly Krupp
Poster #: 4
Association of Human Plasma Metabolomics With Contrast Sensitivity in Age-Related Macular Degeneration
Lilly Krupp, Caroline Awh, Kevin Mendez, Francesco Romano, Haemin Kang, Ioanna Ploumi, Augustine Bannerman, Grace Baldwin, Filippos Vingopoulos, Roshni Bhat, Krupa Sourirajan, Ying Zhu, Ines Lains, Joan W. Miller, Demetrios G. Vavvas, Jessica Lasky-Su, Deeba Husain, John B. Miller
Purpose: Quantitative contrast sensitivity function (qCSF) testing has shown associations with age-related macular degeneration (AMD) stages, OCT biomarkers, and progression to late AMD, even in the absence of associations with visual acuity. Thus, qCSF is emerging as a reliable way of assessing visual function for both early diagnosis and progression in AMD. Metabolomics, the study of molecules <1KD in our body, has provided insight into the pathophysiology of AMD. We evaluated the associations between circulating plasma metabolite levels and qCSF metrics in patients with AMD.
Methods: This cross-sectional study included patients with AMD (all stages) and age-matched controls over 50 years of age. Fasting blood samples were collected and metabolomic profiling with ultra-performance liquid chromatography-mass spectrometry (LC-MS) was done at Metabolon Inc. as previously published by our group. Most patients underwent same day qCSF and metabolite testing, and all were tested within 3 months of metabolite testing. qCSF metrics included contrast sensitivity (CS) thresholds at 6 spatial frequencies (1-18 cpd), low contrast visual acuity (LCVA), and area under the logarithm of contrast sensitivity function (AULCSF). Associations between qCSF and metabolite levels were tested using multilevel mixed-effects linear modelling, adjusting for multiple covariates and inter-eye correlation. The statistical significance threshold (p<0.0007) was calculated using the effective number of independent tests (ENT95%) to adjust for multiple comparisons.
Results: 123 eyes of 63 patients with AMD and 80 control eyes of 43 patients were included. In patients with AMD, 2 metabolites, trans-2-hexenoylglycine (a lipid involved in fatty acid metabolism) and N2-acetyl,N6methyllysine (an amino acid involved in lysine metabolism) were significantly associated (negatively) with both LCVA and AULCSF (p<0.0007) compared to controls. These 2 metabolites were also significantly associated (negatively) with CS thresholds at 6 cpd (p<0.0007) in the AMD group but not the control group.
Conclusions: Higher plasma levels of specific fatty acid-related lipids and amino acids were significantly associated with decreased qCSF metrics in AMD patients. The link between CS and the disruption of lipid and amino acid metabolism in AMD supports further investigation into metabolomic biomarkers for disease progression.
Candidate: Bianca Arraiza Carlo
Poster #: 5
In Vitro 3-D Hydrogel Model for the Type 1 Boston Keratoprosthesis
Bianca Arraiza Carlo, Antonio Esquivel Herrera, Mark Krauthammer, Michael Bednar, Eleftherios I. Paschalis, Thomas H. Dohlman
Purpose: The Boston Keratoprosthesis Type I (B-KPro) is an artificial cornea implanted in patients with severe corneal disease. Historically, B-KPro research has relied on animal models and in vitro experiments studying specific features of the device. Despite these advances, to our knowledge, no 3D in vitro studies currently exist that model the complex microenvironment surrounding the implanted device. In this study, we construct an in vitro model consisting of a collagen-rich microgel with murine corneal fibroblasts and the B-KPro device to mimic aspects of the in vivo microenvironment, and evaluate fibroblast cytotoxicity and proliferation.
Methods: Five sample groups (n = 2 wells each) were established: cells only, gel only, cell-laden gel, cellladen gel with KPro, and medium only, the latter serving as a negative control for background absorbance. Cell-laden microgels were prepared using Rat-tail Collagen I, Corning Matrigel, 1 N NaOH, and murine corneal fibroblasts. Acellular gels were prepared identically, with PBS substituted for the cell suspension to maintain equivalent volume. For KPro-containing samples, the backplate was placed within the gel base and encapsulated with an additional gel layer, leaving the optic exposed. All gels were incubated until solidified, then flooded with culture medium, which was replaced daily throughout the experiment. Cytotoxicity was assessed on days 2, 5, 7, and 14; cell proliferation was assessed on days 5, 7, and 14, both per the manufacturer's protocol. Statistical comparisons were performed using Welch's t-test or two-way ANOVA followed by Tukey's multiple-comparison test using GraphPad Prism 11.
Results: Cell proliferation was comparable between the KPro-containing gel and cell-laden gel alone on days 5 and 14 (p = 0.9637; p = 0.9698), with a non-significant increase in the KPro group on day 7 (p = 0.3689). Estimated cell counts in the KPro group increased significantly between days 5 and 14 (88,800 ± 56,309 vs. 990,675 ± 236,291; ***p < 0.001). On day 2, the KPro group exhibited significantly lower cytotoxicity than the cell-laden gel alone (p = 0.0170). Cytotoxicity was comparable between groups on days 5 and 7 (p = 0.1619; p = 0.9698). *p < 0.05; ns, not significant (p ≥ 0.05). Acellular gels showed no proliferation or LDH activity, confirming absence of background absorbance.
Conclusions: The B-KPro was successfully incorporated into the murine corneal fibroblast 3D hydrogel model without gel retraction or structural failure. No significant increase in cytotoxicity was observed in KProcontaining gels relative to cell-laden gels alone across all timepoints, suggesting the device is well-tolerated by corneal fibroblasts. Proliferation kinetics confirmed consistent cell growth, with substantial growth achieved by day 14. These results support the use of this collagen-Matrigel microgel platform as a viable in vitro model for B-KPro Type I biocompatibility assessments and lay a foundation for future 3D hydrogel models designed to evaluate KPro-corneal tissue interactions.
Candidate: Grace Coyne
Poster #: 6
A Path to Biomarkers: Extracellular Vesicle DNA in Sjögren’s Disease
Grace M. Coyne, Yi Li, Fei Liu, Menglu Yang
Purpose: Sjögren’s disease (SJD) is an autoimmune disease involving glandular dysfunction of the lacrimal and salvatory glands and multiple other systems. Diagnoses of SJD are challenging due to the variety of clinical presentations, creating an average delay of 6 months from onset to diagnosis. DNA is associated with the pathogenesis of SJD, and DNA encapsulated in extracellular vesicles (EV-DNA) provides direct entry of DNAs into the glandular cells. In the current study, we investigated the EV-DNA profile from human tear fluid, aiming to understand the pathological roles of EV-DNAs in SJD, and identify potential biomarkers.
Methods: Human tear samples of Sjögren’s Disease and non Sjögren’s patients collected by Schirmer strips were subject to EV isolation using an automatic acoustic fractionation method. NOD.B10.H2b mouse was used as a model of SJD. EVs were isolated from the tear fluid and serum. Size distribution was analyzed by NTA, and DNA fragment length was analyzed by Bioanalyzer.
Results: EVs were successfully isolated from human tear fluid, with an average amount of 5x10^8 EV/ml. More EV-DNA was found in tear samples from SJD patients compared to controls, with a 1000-2000 bp fragment length. Due to the low volume of mice tear fluid, eye wash collected from 10 mice was pooled as one, ensuring at minimal 10^8 EVs/ml harvested. The total eye wash volume was used as a reference. The size distribution of serum EV between NOD.B2.H2b and wildtype control is significantly different. Due to the small volume of tear fluid EV, the DNA enrichment analysis was conducted in serum. From NOD.B10.H2b mice, 10^12 EV/ml was isolated, 20% of which are positive for Hoechst staining, indicating the presence of DNA. EVDNA was also extracted from mouse serum. exoDNA from NOD tear fluid carries short fragments which are absent in BalbC (~174bp); EVs from NOD mice also carries more long fragments (>1000bp) than wildtype.
Conclusions: Tear fluid derived EV and EV-DNA shows distinct characteristics between SJD and nondiseased controls, underscoring its potential relevance to pathogenesis and biomarker development.
Candidate: Antonio Esquivel Herrera
Poster #: 7
Corneal Myofibroblast-Mediated T Cell Immunomodulation: A Potential Role for Galectin-3
Antonio Esquivel Herrera, Mark Krauthammer, Seokjoo Lee, Michael Bednar, Sunil Chauhan, Reza Dana, Thomas H. Dohlman
Purpose: To investigate whether galectin-3 (gal-3), a β-galactoside-binding lectin with known immunomodulatory functions, mediates corneal myofibroblast-induced suppression of T cell immunity in vitro.
Methods: MK/T-1 corneal fibroblasts were stimulated with TGF-β1 to induce differentiation into myofibroblasts. Gal-3 expression in myofibroblasts was quantified by qPCR and ELISA, while expression of gal-3 counterreceptors (CD71, CD43, CD45) by T cells was analyzed by flow cytometry. CD4⁺CD25 effector T cells (Teff) were isolated from the cervical lymph nodes of BALB/c mice 2 weeks following penetrating keratoplasty (PK) by magnetic sorting and cultured (5 × 10⁵ cells/well) with CD3/CD28 stimulation, either alone or with corneal myofibroblasts at ~70% confluence. After 24 h, Teff activation was assessed by CD69 and CD40L expression via flow cytometry. To assess the functional relevance of gal-3, Teff cells were cultured with recombinant galectin-3 (10 µg/mL) for 24 h, and activation (CD69, CD40L), apoptosis (Annexin V/PI), and IFN-γ secretion (ELISpot) were evaluated. Bovine serum albumin (BSA) served as the control.
Results: Corneal myofibroblasts express high galectin-3 levels, with 74,522 ± 7,657 copies/10⁶ GAPDH by qPCR and 3,223 ± 78.6 pg/mL by ELISA. Compared with isotype controls, Teff cells derived from the draining lymph nodes of mice undergoing PK express galectin-3 counterreceptors CD43, CD45, and CD71, with corresponding mean fluorescence intensity (MFI) values shown in the panels. MFI was quantified following gating on CD4⁺ CD25 Teff cells. CD43 MFI: 612.3 ± 66.5 vs isotype: 54 ± 4, CD45 MFI: 759.3 ± 76 vs isotype: 45.6 ± 4, CD71 MFI: 59.8 ± 1.8 vs isotype: 53.8 ± 4. Recombinant galectin-3 (10 µg/mL) significantly reduced Teff cell activation compared to untreated Teff, lowering CD69⁺ frequencies from 41.2 ± 0.3% to 30.5 ± 1.6% and CD40L⁺ from 27.2 ± 0.8 % to 19.6 ± 1.0%. Compared to Teff cells only, galectin-3 (10 µg/mL) significantly increased Teff cell apoptosis, as shown by Annexin V⁺/PI⁺ frequencies of 60.0 ± 1.1% versus 41.7 ± 0.6%. IFN-γ ELISpot analysis of Teff cells showed a trend toward fewer spot-forming units with gal-3 (10 µg/mL) treatment (217.3 ± 14.5 [Gal-3] vs. 244.7 ± 22.8 [Stimulated Teff cells]).
Conclusions: Gal-3 and its receptors are expressed by corneal myofibroblasts and Teff cells, respectively, and recombinant gal-3 has an immunosuppressive effect on T cells, regulating effector T cell activation, function, and survival in vitro. These results suggest a potential role for gal-3 in mediating myofibroblast regulation of T cell immunity.
Candidate: Olufemi Folorunso
Poster #: 8
Upregulation of Fibroblast-Expressed MMP15 Amplifies Collagenolysis and Matrix Disorganization in Corneal Stroma
Olufemi Folorunso, Ekaterina Ivleva, Lei Xi, Emil Kriukov, Vinay Pulimamidi, Nishant Sinha, Meghanashree Malavvar Shreenivas, Kanika Arora, Petr Baranov, Sunil Chauhan
Purpose: Corneal stroma is a connective tissue that consists of collagen fibers, which determine its shape, tensility, and optical clarity. Progressive stromal pathology (like keratoconus) results in matrix degeneration and vision loss. Soluble MMPs are implicated in several pathological conditions; however, the biological functions of MMP15, a membrane-type II matrix metalloproteinase (MT2-MMP), have not been elucidated in corneal pathophysiology. This study investigated MMP15 expression in corneal pathology that targets stromal collagen. Additionally, we employed cell-mediated collagenolysis and an experimental model of stromal injury to gain insight into the biological function of MMP15.
Methods: We analyzed three RNA-seq datasets from the NCBI GEO2R databases on keratoconus studies to establish the differential expression of MMP15 in corneal pathology. The in-silico finding was evaluated using an in vitro collagenolysis assay. We utilized a mouse model of corneal stromal injury to investigate the role of MMP15 in tissue matrix disorganization and to confirm the specific function of MMP15 using histological, molecular, and ultrastructural analyses.
Results: The RNA-seq data revealed a significantly upregulated MMP15 in the stroma of keratoconus compared to normal corneas (p<0.0001). This upregulation was mainly due to stromal fibroblasts expressing MMP15 but not epithelia (p<0.05). Moreover, inflammation-driven upregulation of MMP15 in corneal fibroblasts was associated with increased collagenolysis. The preclinical assessment showed that injury-induced corneal opacity was mitigated by topical neutralization of MMP15 (p<0.0001). Histological and ultrastructural analysis of the injured cornea showed that upregulated MMP15 was associated with increased stromal matrix disorganization and infiltration of inflammatory cells. However, neutralizing MMP15 significantly restored the structural arrangement of collagen fibrils and reduced inflammation. Mechanistically, neutralizing MMP15 significantly reduced the gene expression of ECM-degrading proteins (MMP2, MMP9, MMP10, and MMP13; p<0.0001), as well as inflammatory (TNFα and IL6; p<0.0001) and profibrotic (TGFβ; p<0.001) cytokines.
Conclusions: These findings demonstrate that cell surface-expressed MMP15 plays a crucial role in promoting the pathological degradation of the corneal extracellular matrix and the associated inflammatory response.
Candidate: Mark Krauthammer
Poster #: 9
Natural Killer Cells May Promote Corneal Transplant Failure Through Direct Corneal Fibroblast Killing in a Murine Model of Pediatric Penetrating Keratoplasty
Mark Krauthammer, Antonio Esquivel Herrera, Michael Bednar, Sunil Chauhan, Reza Dana, Thomas H. Dohlman
Purpose: Penetrating keratoplasty survival is significantly decreased in the pediatric population, and heightened innate immunity has been implicated as a factor in decreased graft survival. Here, we evaluate the specific mechanisms by which Natural Killer (NK) cells contribute to graft failure in a murine model of pediatric penetrating keratoplasty.
Methods: Donor corneal grafts from 10-week-old C57BL/6 male mice were transplanted into young (3.5-weekold) or adult (10-week-old) BALB/c male mice. Graft survival was followed for 8 weeks post transplantation. A subset of transplant recipients was euthanized at day 14 and the population of graft-infiltrating NK cells was evaluated by flow cytometry. Quantities of all NK cells (CD45+CD3-CD49+) and activated NK cells (CD45+CD3-CD49+IFNγ+) were assessed. In vitro co-cultures consisting of NK cells and corneal fibroblasts were performed and fibroblast cell viability was assessed after 24 hours using the CellTiter 96TM Aqueous (MTS) assay. A subset of NK cells was activated with IL-12 (10ng/ml).
Results: Eight-week graft survival was 20% in young mice and 45% in adult mice. On flow cytometric analysis, there were significantly higher frequences of graft-infiltrating NK cells in young compared to adult recipients (12.95±4.8 vs 4.55±1.5 percent out of corneal WBC, for young and adult mice, respectively, p<0.01), with similar frequencies of activated NK cells (1.83±0.9 vs 2.09±1.1 percent out of corneal WBC, for young and adult mice, respectively, p=0.35). Significantly lower viability of corneal fibroblasts was seen upon co-culture with activated NK cells versus non-activated NK cells (81.5±0.1 vs 94.36±6.4, p=0.03).
Conclusions: In a murine model of penetrating keratoplasty, young recipients had lower corneal graft survival and greater NK cell graft infiltration The increased presence of NK cells, along with decreased corneal fibroblast viability upon co-culture with NK cells in vitro, suggest that NK cell-mediated killing of corneal fibroblasts may contribute to the decreased graft survival seen in young mice.
Candidate: Kofi Asiedu
Poster #: 10
Impact of Keratoconus and Cross-Linking on Corneal Immune Cells and Nerves
Kofi Asiedu, Helen He, Nicholas J. Whitcomb, Hyunjoo J. Lee
Purpose: To characterize differences in immune cells and nerves in corneas with keratoconus (KCN), with and without corneal cross-linking (CXL).
Methods: In vivo corneal confocal microscopy (IVCM) was performed on both eyes of KCN patients and the left eyes of age-matched non-KCN controls, excluding eyes with scarring or prior surgery other than CXL. Comparisons were made between (1) KCN and control eyes, excluding contact lens wearers and post-CXL eyes (n = 23 and 16), and (2) KCN eyes with and without CXL (n = 27 and 14). Central corneal nerve parameters and immune cell densities were evaluated using eight IVCM images per eye processed with ACCMetrics and ImageJ. Data normality was confirmed, and group differences were assessed using independent-samples t-tests.
Results: Central T-cell density (62.09 ± 88.58 vs. 15.81 ± 13.01 cells/mm2, p = 0.021) and total immune cell density (76.74 ± 110.78 vs. 24.31 ± 18.47 cells/mm2, p = 0.036) were significantly higher in the KCN group compared to controls. Central dendritic cell density in the KCN group did not differ significantly from controls (14.65 ± 25.36 vs. 8.50 ± 8.48 cells/mm2, p = 0.289). KCN eyes showed significantly lower corneal nerve fiber density (15.99 ± 6.93 vs. 21.34 ± 5.51 mm/mm2, p = 0.012), nerve fiber length (11.22 ± 3.89 vs. 13.99 ± 2.58 mm/mm2, p = 0.011), branch density (18.99 ± 10.74 vs. 31.49 ± 20.11 no./mm2, p = 0.034), and fractal dimension (1.4497 ± 0.0519 vs. 1.4847 ± 0.0328, p = 0.008) compared to controls. KCN eyes s/p CXL exhibited lower T-cell density (8.93 ± 7.58 vs. 59.93 ± 82.66 cells/mm2, p = 0.004) and lower total immune cell density (15.64 ± 16.77 vs. 74.15 ± 103.19 cells/mm2, p = 0.008) compared to untreated KCN eyes. There was no significant difference in dendritic cell density between the KCN eyes s/p CXL and the untreated KCN eyes (14.22 ± 23.54 vs. 6.71 ± 9.66 cells/mm2, p = 0.16). No significant differences were found in corneal nerve parameters between the untreated KCN and KCN s/p CXL eyes (all p > 0.05).
Conclusions: Keratoconus was associated with increased T-cell infiltration and reduced corneal nerve density, suggesting a neuroimmune imbalance in disease progression. While CXL did not further change nerve architecture, it significantly reduced corneal T-cell density, indicating modulation of corneal immune activity after treatment.
Candidate: Michael Bednar
Poster #: 11
Infectious Keratitis After Type I Boston Keratoprosthesis: Microbiology, Clinical Outcomes, and Prophylaxis
Michael Bednar, Ines Fenniri, Mark Krauthammer, Antonio Esquivel Herrera, Kathryn Colby, Joseph Ciolino, Samir Melki, Hajirah N. Saeed, Ula Jurkunas, James Chodosh, Eleftherios I. Paschalis, Camille Andre, Thomas H. Dohlman
Purpose: To evaluate clinical outcomes and prophylactic regimens of infectious keratitis (IK) in Type I Boston keratoprosthesis (BKPro).
Methods: A retrospective review of 266 eyes with a BKPro at Massachusetts Eye and Ear between 2006 and 2025 was performed. BKPro eyes diagnosed with IK were identified, and microbiologic data, outcomes, and prophylactic regimens were analyzed.
Results: Thirty-six eyes developed IK, with a 5-year probability of 14% and an incidence rate of 2.3 cases per 100 eye years. Explantation was required in 69% (n=25) and 31% (n=11) resolved without surgery. Of 35 cultured eyes, 23 grew organisms: 43% (n=10) bacterial (80% gram positive, 10% gram negative, 10% acid fast) and 57% (n=13) fungal. Five eyes with cultures growing coagulase-negative staphylococci were excluded as possible contaminants. All fungal cases were on topical steroids, antibiotics, and no antifungal prophylaxis.
Conclusions: IK is a potentially severe complication following BKPro implantation, frequently necessitating device explantation. The absence of antifungal prophylaxis in all fungal cases suggests a potential role for modifying preventive regimens.
Candidate: Ines Fenniri
Poster #: 12
Clinical and Genomic Correlates of Bacterial Keratitis
Inès Fenniri, Andrew Van Camp, Thomas H. Dohlman, Michael S. Gilmore, Camille André
Purpose: To relate clinical features and outcomes of bacterial keratitis to pathogen and WGS defined lineages.
Methods: Retrospective review of clinically diagnosed bacterial keratitis with corneal scraping at a tertiary eye hospital. Data on risk factors, ulcer features, treatment and vision were collected. A composite poor outcome was perforation at presentation, therapeutic penetrating keratoplasty (TPK), final best corrected visual acuity (BCVA) ≥1.0 logMAR or complete re epithelialisation >21 days. Culture positive isolates underwent whole genome sequencing (WGS) for species, multilocus sequence type, clonal complex and, for pneumococci, inferred vaccine serotype. Analyses focused on Staphylococcus spp., Streptococcus spp. and Pseudomonas aeruginosa. WGS provided MLST/clonal complex (CC), and pneumococcal MLSTs were linked to vaccine serotypes using published associations.
Results: A total of 185 isolates were analysed: S. aureus 75, S. epidermidis 18, S. pneumoniae 20, and P. aeruginosa 72. Median age was 62 years (IQR 45–68); 58 % were female (65/113); 3 % were paediatric (< 18 years). Ocular surface disease was present in 78 % of eyes, pre-existing corneal graft in 28 %, recent ocular surgery (< 30 days) in 33 % , prior topical corticosteroid use in 34 %, and contact lens wear in 15 %. Median ulcer area was 7.0 mm² (IQR 2.7–18.2, n = 54); central 3-mm involvement 44 %; hypopyon 25 %. Median topical antibiotic duration was 39 days (IQR 26–118, n = 43). By organism, staphylococcal keratitis showed smaller ulcers (S. aureus median 3.5 mm²) and shorter topical therapy (median 37 days). Pneumococcal keratitis presented with larger ulcers (median 7.7 mm², n = 11), prolonged topical therapy (median 56 days, n = 10). WGS revealed organism-specific lineage architecture. S. aureus (n = 75) was distributed across recurrent clonal complexes — CC5 (n = 24), CC8 (n = 11), CC30 (n = 11), CC15 (n = 10), CC45 (n = 9) — accounting for 87 % of isolates. S. epidermidis (n = 18) was strongly monoclonal, with 16/18 isolates (89 %) belonging to CC2 (CC2-II 12, CC2-I 4). S. pneumoniae keratitis (n = 20) was genetically diverse, comprising 16 distinct CCs with no dominant lineage; pneumococcal MLSTs were inferred non-PCV13, with only partial predicted PCV20 coverage. P. aeruginosa (n = 72) showed broad ST diversity with low-frequency recurrent STs (ST253 n = 7; ST309, ST390 n = 4 each) and 15 singletons. The S. aureus resistome included blaZ in 67 %, fosB in 71 %, ermA in 24 %, and mecA (MRSA) in 16 %.
Conclusions: Bacterial keratitis at this tertiary cornea referral center was substrate-driven, with most affected eyes having pre-existing ocular surface disease and one quarter a previous corneal graft. Staphylococci predominated numerically and were associated with smaller ulcers and shorter treatment than pneumococcal or pseudomonal keratitis, which clustered with worse outcomes. WGS revealed a restricted set of staphylococcal lineages (notably S. epidermidis CC2 and recurrent S. aureus CCs) versus genetically diverse, predominantly non-PCV13 pneumococcal lineages, supporting integration of genomic surveillance into risk stratification and vaccine planning.
Candidate: J. Tatiana Hathaway
Poster #: 13
Conjunctival
WNT-Activated Melanocytoma: A Potential Clinicopathologic Mimicker of Melanoma With a Broad Histomorphologic Spectrum
J. Tatiana Hathaway, Anna Stagner
Purpose: Combined nevi of the conjunctiva (two distinct populations of melanocytes) are common. Nevi with a “deep penetrating” second melanocytic population are now classified as Wnt-activated melanocytoma (WAM ) given an understanding of the specific molecular genetic alterations seen. WAM is increasingly recognized in conjunctiva. Accurate diagnosis is essential for risk stratification and to avoid misdiagnosis of melanoma. The authors report a large series of conjunctival WAM emphasizing histomorphology, immunophenotype, and clinical features.
Methods: Conjunctival melanocytic lesions diagnosed as combined nevus with “deep penetrating” component or WAM were identified from 2018-2025. Hematoxylin and eosin and immunohistochemical-stained sections were critically re-reviewed. Available clinical history was collected, and slit lamp photography was reviewed. Molecular genetic testing was also performed.
Results: Sixteen patients (age 9-65 years, median 31) were identified (10 female, 6 male). The most frequent anatomic sites were plica/caruncle 6/16 (37.5), bulbar conjunctiva 5/16 (31.3%), eyelid margin 3/16 (18.8%), and limbus 2/16 (12.5%). All tumors were composed of conventional nevomelanocytic melanocytes and a second population of spindled to epithelioid melanocytes with amphophilic, pigmented cytoplasm, accompanied by numerous melanophages. The latter melanocytic population showed evidence of Wnt pathway activation in all cases where immuonstains were performed (14/14, nuclear staining for β-catenin and/ or LEF1 and/or Cyclin D1). PRAME was negative in WAM when investigated. Ki-67 proliferative indices were low (≤1–2%), with focal labeling limited to the Wnt-activated component. When clinical history was available (13 cases), 8/13 (61.5%) had a provided history of significant darkening +/- enlargement of a previously noted lesion. In 3/13 cases (23.1%), there was strong clinical suspicion for melanoma. Four cases were diagnostic dilemmas where slides were sent as consultative material. Molecular analysis revealed BRAF mutations in 10 cases, with additional CTNNB1 mutations in 5 cases. No TERT promoter mutations were detected, and all evaluable tumors demonstrated low tumor mutational burden.
Conclusions: Conjunctival WAM shows a predilection for plica/caruncle, is composed of two distinct populations of melanocytes, and may clinically and histopathologically raise concern for melanoma. β-catenin, LEF1 and Cyclin D1 are useful surrogate markers of Wnt pathway activation. A clinical history of significant darkening, and/or enlargement of a prior nevus is common. Molecular genetic studies support the diagnosis by identifying alterations in genes associated with Wnt pathway activation. Malignant transformation appears uncommon but may occur.
Candidate: Helia Ashourizadeh
Poster #: 14
Association of Deep-Learning-Based Reticular Pseudodrusen Burden and Dark Adaptation in Age-Related Macular Degeneration
Helia Ashourizadeh, Ariel Yuhan Ong, , Robbert R Struvyen, David A. Merle, Kevin Mendez, Souvick Mukherjee, Afonso Lima Cabrita, Demetrios G Vavvas, Ivana K. Kim, Joan W. Miller, Zhichao Wu, John B. Miller, Pearse A. Keane, Deeba Husain, Ines Lains
Purpose: Dark adaptation (DA) is a promising functional assessment for age-related macular degeneration (AMD). Reticular pseudodrusen (RPD) (also known as subretinal drusenoid deposits) have been linked to worse DA, but prior work has focused mainly on RPD presence rather than quantification, or was limited to cross-sectional designs. Deep learning (DL) algorithms can provide scalable and reproducible quantification of RPD on optical coherence tomography (OCT). The objective of this study is to evaluate cross-sectional and longitudinal associations between presence and extent RPD quantified using a deep learning (DL) algorithm and dark adaptation (DA).
Methods: Prospective longitudinal study of patients with non-advanced AMD and a control group (>50 years old). All participants had baseline imaging with Spectralis (Heidelberg Engineering) OCT and were tested with a 20-minutes dark adaptation protocol (MacuLogix). Rod intercept time (RIT) and area under the dark adaptation curve (AUDAC) were calculated. For eyes with RIT >20 minutes, a value of 20 was assigned for analyses. A validated DL algorithm was used to quantify the total RPD area and volume (square root– and cube root–transformed, respectively). Additionally, the DA testing locus in the superior macula (5° eccentricity) was projected onto the en face OCT plane, and RPD extent within this area was assessed both as a binary variable and by quantifying area density (%). For longitudinal analyses, only AUDAC was considered as an outcome, and only eyes with at least two annual visits with OCT and DA were included. Linear multivariable mixed effect models accounting for age, sex, smoking, AMD stage, presence of RPD, and inter-eye correlation were computed.
Results: At baseline, we included 545 eyes (52 early AMD, 285 intermediate AMD, 208 controls) from 310 patients (mean age 69.6±7.4 years). A total of 128 (23.49%) eyes were found to have RPD. In addition to presence of RPD (p=6.1x10-7), both greater RPD area and volume were associated with worse RIT (β=1.2 and β=7.6, p≤4.4x10-4, respectively) and AUDAC (β=0.03 and β=0.2, p≤ 8.3x10-5, respectively). Global RPD density, rather than local density at the DA testing site, was independently associated with delayed RIT (β 0.223, p<1.89x10-2) and higher AUDAC (β 0.007, p<0.001). In longitudinal analysis (204 eyes; 67 controls, 137 AMD; follow-up 2.8±1.8 years) also accounting for presence of RPD, a higher baseline RPD area and volume were also associated with more pronounced changes in AUDAC (β=3.6x10-2 and β=1.8x10-1, p<8.3x10-3). Greater RPD area and volume at any available visit were associated with increased ΔAUDAC/year (β=3.6x10-2 and β=1.8x10-1, p<8.3x10-3, respectively) and with worse AUDAC in the subsequent visit(β=4.6x10-2 and β=2.03x10-1, p<5.8x10-3, respectively).
Conclusions: To our knowledge, this is the largest study to date assessing RPD quantification and its associations with DA. Our findings suggest that, independent of RPD presence, greater baseline RPD extent is associated with worse rod-mediated DA and longitudinal decline over time, highlighting their potential as functional-structural biomarkers.
Candidate: Afonso Vieira Lima Cabrita
Poster #: 15
Age-Related Macular Degeneration Stage Is Associated With Increased Choroidal Thinning: A Longitudinal Deep Learning Study
Afonso Lima-Cabrita, Robbert Struyven, Souvick Mukherjee, Ariel Ong, David Merle, Justin Engelmann, Eric Goldberg, Helia Ashourizadeh, Jooyoung Chang, Ally Wang, Lilly Krupp, Katrina Schneider, Ivana Kim, Demetrios Vavvas, Joan Miller, Tobias Elze, Pearse Keane, Deeba Husain, John Miller, Ines Lains
Purpose: To assess how age-related macular degeneration (AMD) stage relates to deep learning (DL)-derived volumetric choroidal changes over time.
Methods: Prospective longitudinal study including eyes with all AMD stages and controls. A validated DL model was used to derive 3D choroidal thickness (CT), vessel thickness (CVT) and vessel density (CVD) from OCT volumes. Multivariable mixed-effects models with time interaction and accounting for confounders were used to estimate rates of choroidal change by AMD stage versus controls.
Results: We included 703 eyes (2,690 visits), mean aged 71.6±8.3 years and median follow-up 4.1 years (IQR 2.6-5.9). Eyes with intermediate AMD (n=322), geographic atrophy (n=55) and choroidal neovascularization (n=98) had faster annual global CT, CVT and CVD loss than controls (n=188) (CT -3.3, -3.9, and -3.7 vs -1.9 µm/year; all p≤0.007; CVT -1.8, -2.4, and -2.3 vs -0.9 µm/year; all p<0.0001; CVD -0.41, -0.60 and -0.74 %/year vs -0.16%, all p<0.0001).
Conclusions: AMD stage was associated with greater choroidal vascular thinning, supporting a link between vasculopathy and AMD severity and suggesting that DL metrics may serve as biomarkers of progression and treatment response.
Candidate: Maryam Zekavat
Poster #: 16
Photoreceptor Outer Segment
Thinning and Polygenic Risk Interact to Predict Incident AMD Risk: Evidence From the UK Biobank
Seyedeh Maryam Zekavat, Sayuri Sekimitsu, Zhi Yu, Ines M. Lains, Deeba Husain, Demetrios G Vavvas, Elizabeth J. Rossin, Rishi Singh, Nazlee Zebardast, Jay C Wang, Pradeep Natarajan
Purpose: Optical coherence tomography (OCT) and genomic data are widely available but not well integrated for risk stratification in age-related macular degeneration (AMD). Prior work has identified photoreceptor segment thinning as the retinal layer most predictive of future AMD. Here, we integrate OCT, electronic health record, and genomic data from 50,149 UK Biobank participants to evaluate the interaction between photoreceptor outer segment (OS) thickness and AMD-linked genomic variants in predicting incident AMD.
Methods: Retinal imaging, genomic, and electronic health record data across 50,149 UK Biobank individuals were used (enrollment ages 40-70y, 54% female, 818 developed AMD over a median 13.6-year follow-up). Enrollment OCT images were segmented using the Topcon algorithm to quantify OS thickness. An AMD polygenic risk score (PRS) was constructed using summary statistics from >12 million variants. Associations between OS thickness, AMD PRS, and incident AMD (ICD H35.3) were assessed using a Cox proportional hazards model, including an interaction term between the two. The results were verified using 444 manuallygraded prevalent AMD OCT and fundus images. Next, we associated AMD-associated genetic alleles individually with OS thicknesses and evaluated their interaction with OS thickness on future AMD risk. Analyses were adjusted for age, age², sex, smoking status, and genetic ancestry.
Results: Both lower OS thickness (HR=1.23 per SD decrease; P=2.5×10-⁹) and higher PRS (HR=1.31 per SD increase; P=1.2×10-¹²) were independently associated with incident AMD, with a significant interaction between them (P=2.9×10-⁵). Individuals in the highest PRS quartile and lowest OS thickness quartile had a 4.4-fold increased risk of AMD (P=3.2×10-¹³), while those with intermediate PRS (25th-75th percentile) and OS thickness >25th percentile had a 1.6-fold increased risk (P=9.4×10-³), compared to the lowest-risk group in the bottom quartile of PRS and top quartile of OS thickness. In manually-graded images, decreased OS thickness was observed across AMD severity grades with a significant PRS interaction (P=0.019). The AMD risk loci associated with OS thinning with strongest interaction with OS thickness on AMD risk included CFH (rs570618, rs10922109, rs61818925) and C3 (rs147859257).
Conclusions: OS thickness and polygenic risk interact to predict incident AMD, with complement-linked genes driving the interaction with OS thickness on AMD risk. These findings support integrating OCT-derived OS thickness with genomics to improve AMD risk stratification.
Candidate: Mousa Moradi
Poster #: 17
VF-Guided Self-Supervised RNFL Phenotyping Enables Enhanced Clustering and Genetic Discovery in Glaucoma
Mousa Moradi, Mohammad Eslami, Mengyu Wang, Tobias Elze, Nazlee Zebardast
Purpose: This study introduces a VF-guided self-supervised framework that strengthens RNFL phenotyping by integrating structural OCT with functional VF signals. While RNFL-only features are common, adding VF cues produces richer representations, improves clustering, and yields more informative imaging traits for genetic discovery.
Methods: We introduced a multiview phenotyping framework combining RNFL OCT and VF images using a momentum contrastive learning (MoCo) architecture and a variational autoencoder (VAE). Two encoders (RNFL and VF) were trained with cross-modal alignment to force RNFL embeddings to encode VF-relevant functional information, while inference uses RNFL-only embeddings. From the original set of 10,864 patients with 26,562 VFs and 46,963 OCT scans, we matched 5,534 images for 1,845 patients within ±6-month intervals (VF ≥ 3 with FPR < 30%, OCT signal ≥ 7, and < 5% missingness). After training on 5,372 artifactcorrected MEE images, RNFL embeddings (32-128D) were evaluated, and 64D features were projected to a 15-dimensional (D) VAE latent space. Grid searches tested VAE dimensions (5-30D) and clustering methods (FCM and GMM) for 4-15 clusters, assessed using latent-space indices (Silhouette, Calinski, Davies) and pixel-level normalized cross correlation (NCC). Optimal latent vectors were then applied to UK Biobank OCT/genomic data, where the same artifact-correction pipeline yielded 74,075 scans. GWAS was performed on aggregated 15-D latent traits from both eyes using a mixed-model association framework, and both Manhattan and QQ plots were used to assess association signals and calibration.
Results: VF-guided training improved latent-space cluster separation, with Silhouette, Calinski, and Davies scores of 71.4%,100%, and 95.4%, respectively (for both FCM and GMM). At the pixel level, GMM outperformed FCM, yielding a higher normalized cross-correlation (NCC = 36 vs. 34%). In the UK Biobank, GWAS performed on the aggregated 15-D latent traits identified 59 loci, with Manhattan and QQ plots demonstrating clear and well-calibrated association signals.
Conclusions: VF-guided contrastive learning produces richer RNFL representations, improves clustering, and substantially increases GWAS discovery. Latent vectors provide meaningful genetic signal enrichment, supporting multimodal self-supervision as a powerful phenotyping strategy for glaucoma research.
Candidate: Niloufar Bineshfar
Poster #: 18
Genome-Wide Association Study Identifies Novel Loci for Visual Field Decline in Glaucoma
Niloufar Bineshfar, Yan Zhao, Liyin Chen, Kanza Aziz, Puja A. Mehta, Felipe A. Medeiros, Michael Kass, Louis R. Pasquale, Ayellet V. Segrè, Janey L. Wiggs, Nazlee Zebardast
Purpose: Glaucoma is a leading cause of irreversible blindness worldwide. While over 300 loci have been associated with glaucoma susceptibility, the genetic contribution to disease progression is largely unknown. The aim of this study is to identify genetic variants associated with the rate of visual field decline.
Methods: We conducted a genome-wide association study (GWAS) of glaucoma progression, defined as the slope of visual field mean deviation (MD) over ≥1 year, in two longitudinal cohorts: the Ocular Hypertension Treatment Study (OHTS; n=1,012) and the Mass General Brigham (MGB) Biobank (n=633). Analyses were stratified by ancestry and adjusted for baseline age, sex, and top genetic principal components; OHTS analyses were additionally adjusted for treatment randomization arm and MGB analyses for genotype batch. Sensitivity analyses further adjusted for mean intraocular pressure (IOP). Results were combined using random-effects meta-analysis.
Results: Across cohorts, 1,645 participants (1,317 European ancestry; 328 African ancestry) with ≥3 reliable visual fields over ≥1 year of follow-up were included (on average 12.8 years in OHTS and 8.4 years in MGB). In European ancestry, meta-analysis identified 17 LD-independent genome-wide significant loci, including loci near FMNL2, LRRC16A, PDE4B, NLGN1, and GRIK2, with effect sizes ranging from β = −0.26 to −0.14 dB/year. In African ancestry, 22 LD-independent loci reached genome-wide significance, including near LRP1B, CNTN3, CD109, CAMK1D, and RGS6. Most European meta-analysis loci remained genome-wide significant after adjustment for mean IOP, suggesting effects beyond pressure-mediated mechanisms. Colocalization analyses implicated candidate genes with regulatory effects including ASCC3, LOXL4, FAT3, NT5E, SLC35A1, and SNX14 as putative causal mechanisms for VF decline loci.
Conclusions: This multi-cohort GWAS of glaucoma progression identified both shared and novel loci influencing the rate of VF decline. These findings suggest that the genetic architecture of glaucoma progression is partly distinct from disease susceptibility and highlight new pathways that may inform risk stratification and therapeutic development.
Candidate: Sepehr Fekrazad
Poster #: 19
Surgical AI for Personalized Glaucoma Procedure Selection
(Traditional vs Micro-Invasive Glaucoma Surgery): A Multi-Arm Random Forest Framework
Sepehr Fekrazad, Michael V. Boland, David S. Friedman, Tobias Elze, Nazlee Zebardast, Mohammad Eslami
Purpose: Selecting between traditional glaucoma surgery and micro-invasive glaucoma surgery (MIGS) is challenging because outcomes vary substantially across patient risk profiles, and current decision-making relies largely on population-level evidence and surgeon experience rather than individualized estimates. We hypothesized that a supervised machine learning framework could generate patient-specific success probabilities for each procedure class and identify procedure choices associated with higher expected outcomes than observed practice. We conducted a retrospective analysis to evaluate model performance, key predictors, and potential clinical utility for assisting surgical decision-making.
Methods: We analyzed electronic health record data from 3,410 eyes undergoing first-time glaucoma surgery at Massachusetts Eye and Ear. Procedures were grouped as traditional (trabeculectomy, tube shunts; n=1,796) or MIGS (iStent, CyPass, XEN, canaloplasty, ECP, goniotomy; n=1,614). One hundred preoperative features were derived from OCT metrics (RNFL, GCIPL thickness), visual field indices (mean deviation, pattern standard deviation, VFI), tonometry, central corneal thickness, cup-to-disc ratio, medication burden, ocular history, and demographics. Missing values were handled with multiple imputation and continuous predictors standardized. The cohort was split into training and held-out test sets, with hyperparameters tuned by crossvalidation. Random Forest classifiers predicted surgical success, defined as ≥20% IOP reduction from baseline without reoperation within 180 days after a 4-week postoperative grace period. To estimate the effect of modelrecommended choices versus observed practice, propensity scores for each procedure class were estimated with multinomial logistic regression, and recommendations were evaluated using inverse propensity scoring (IPS) and doubly robust (DR) estimators, which combine outcome modeling with propensity weighting to reduce confounding by indication.
Results: Model performance was moderate, with AUROC 0.75 for MIGS and 0.67 for traditional surgery, indicating better separation of successes from failures within the MIGS cohort. The observed test-set success rate was 58%, while model-recommended choices yielded higher expected success rates under both estimators (IPS 0.71 ± 0.12; DR 0.63 ± 0.06), corresponding to an absolute gain of 5–13 percentage points over observed practice. Top predictors included preoperative IOP, age, central corneal thickness, cup-to-disc ratio, and baseline visual field mean deviation and pattern standard deviation.
Conclusions: The higher AUROC for MIGS suggests these outcomes may be more predictable than filtering procedures, potentially reflecting fewer postoperative wound-healing challenges and more deterministic outflow mechanics. Retrospective causal evaluation indicated that model-informed choices could yield higher expected success than observed patterns, highlighting an opportunity to complement surgeon judgment with individualized risk estimates rather than population-level assumptions. Limitations include the single-center retrospective design and residual confounding from unmeasured variables; prospective external validation is needed before clinical deployment.
Candidate: Asahi Fujita
Poster #: 20
Development of Perimetric Glaucoma and Outcomes of Interventions in Pseudoexfoliation Syndrome With and Without Ocular Hypertension
Asahi Fujita, Mousa Moradi, Rishi Shah, Tobias Elze, Nazlee Zebardast, David S. Friedman
Purpose: To investigate the incidence of perimetric glaucoma and the effectiveness of interventions in eyes with pseudoexfoliation syndrome (PXF) with and without ocular hypertension (OHTN).
Methods: We assembled a longitudinal cohort of patients with at least one Humphrey Visual Field (HVF) test recorded at Mass Eye and Ear between 2010 and 2023. From this cohort, we identified patients with PXG or PXF using two domain-specific natural language models and confirmed the PXF status of the eye of interest through chart review. Glaucoma incidence was defined by consecutive glaucoma-positive HVFs identified by PyGlaucoMetrics, which employs validated algorithms to estimate glaucoma probability from reproducible HVF data. We estimated the cumulative incidence of perimetric glaucoma using the Kaplan–Meier method and applied a multivariable Cox regression model to identify associated factors. Primary outcomes included the incidence rates of perimetric glaucoma. Secondary outcomes included hazard ratios (HR) for demographic and clinical factors, as well as the IOP reduction observed following each procedure type.
Results: A total of 485 eyes from 369 patients were included. The 4-year cumulative incidence rates of perimetric glaucoma were 26.5% (95% confidence interval (CI): 20.7–32.0%) in eyes without OHTN and 37.5% (95% CI: 24.3–48.4%) in those with OHTN (log-rank test, P = 0.005). Factors associated with incident glaucoma were older age (HR: 1.39 [95% CI: 1.19–1.62], per 5 years), OHTN (2.18 [1.39–3.42]), higher cup-todisc ratio (CDR, 1.17 [1.04–1.31], per 0.1 higher CDR), and phakia (1.94 [1.13–3.34]). During follow-up, incident OHTN was observed in 14.6% of eyes with PXF without baseline OHTN. However, 87.3% of eyes that developed glaucoma had no documented OHTN, based on measured IOP at any office visit. Standalone lens extraction reduced the mean IOP from 15.8 ± 2.5 mmHg with 0.40 ± 0.78 medications preoperatively to 12.9 ± 2.7 mmHg with 0.28 ± 0.57 medications at 1 year postoperatively.
Conclusions: More than one-fourth of eyes with documented PXF without OHTN and more than one-third of those with OHTN developed perimetric glaucoma within 4 years. Older age, OHTN, higher CDR, and phakia were associated with incident glaucoma. Nearly 90% of eyes with normal baseline IOP that later developed glaucoma had no documented OHTN at any office visit. Standalone lens extraction reduced IOP by 3 mmHg at 1 year postoperatively.
Candidate: Yi Ni Toh
Poster #: 21
Peripheral Prism Glasses Improve Blind-Side Hazard Detection in Drivers with Hemianopia
Yi Ni Toh, Patrick Baker, Eli Peli, Alex Bowers
Purpose: Drivers with homonymous hemianopia can compensate for their hemifield loss by blind-side scanning. Hazards from larger bearing angles require large scans with head movement and are more difficult to detect than hazards from smaller angles. If scanning is insufficient, hazards may be missed, but peripheral prism glasses may help. In this pilot study we compared the effects of new 100∆ multi-periscopic prisms (MPPs; 42° expansion), and commercial 65∆ Fresnel prisms (FPPs; 30° expansion), on detection of blind-side hazards approaching from small and large angles.
Methods: Ten participants with homonymous hemianopia each wore both prism types in counterbalanced order. Visit 1 was baseline (no prisms), and Visits 2–3 tested MPPs or FPPs after ≥4 weeks of at-home use when walking or as a passenger in a car. Participants drove urban routes with intersections in a high-fidelity simulator (220° field of view). Hazards included near- and mid-eccentricity pedestrians (~4° and ~14°, respectively) at mid-block locations and far-peripheral motorcycle hazards (~55°) at intersections. Detection was signaled by horn press, and scanning was recorded with a six-camera tracking system.
Results: Participants missed 75% of far-peripheral blind-side motorcycle hazards without prisms. Missed detections reduced to 59% with FPPs (p = .32) and 48% with MPPs (p = .01). For pedestrians, missed detections were similar across prism conditions for far eccentricity (49%, 42%, 39%; all p > .49) and remained rare for near eccentricity (12–18%; all p > .91). Seeing-side misses were near floor (0–1%) for all hazards. Most blind-side motorcycle misses without prisms stemmed from inadequate scanning: 51% insufficiently large scans and 19% no scan. FPPs reduced scanning-related misses to 46% (no-scan 4%), and MPPs further reduced them to 33% (no-scan 5%). Blind-side head-scan frequency increased from 1.1 scans per intersection (no prisms) to 1.9 with FPPs (p = .07) and 2.3 with MPPs (p = .01). Seeing-side scans rose modestly (no prisms: 0.8; FPPs: 1.1; MPPs: 1.3; all p > .72).
Conclusions: The results suggest that both FPPs and MPPs increased head scanning at intersections which reduced blind-side scanning-related misses. Consistent with the MPPs’ wider field expansion and better image quality, effects were greater for MPPs than FPPs, but detection performance was still worse than on the seeing side.
Candidate: Seonggyu Choe
Poster #: 22
Preserved Time-To-Contact Estimation in Central Vision Loss Despite Less
Stable Gaze
Seonggyu Choe, Yi Ni Toh, Viviana Fernandez, Calliope Galatis, Elisabeth Wögerbauer, Heiko Hecht, Alex R Bowers
Purpose: The ability to judge the time-to-contact (TTC) of approaching objects is important for safe mobility, but little is known about whether compromised foveal vision and altered ocular motor control in central vision loss (CVL) negatively affect TTC estimation. We examined TTC-judgments and associated eye movements in participants with CVL and controls with normal vision (NV) and examined whether background complexity differentially affected TTC-performance in the two groups.
Methods: Sixteen CVL (median; age: 71 yrs; VA: 0.4 logMAR; CS: 1.35 logCS) and 16 NV observers (64 yrs; 0.07 logMAR; 1.65 logCS) completed a prediction-motion TTC-task. A car approached at a constant speed along an urban road and disappeared before contact (TTCs: 0.5, 1.0, 1.5, 2.0, 2.5 s), requiring estimation of its arrival time at the observer’s position. Three background conditions varied in spatial complexity (all scene elements present, schematic road/buildings outlines, and only the car with a plain background). TTC error was computed as estimated TTC minus actual TTC. Eye movements were recorded to quantify saccade frequency (> 40 º/s), gaze dispersion (area enclosing 68 % of gaze samples), and distance between gaze and target position.
Results: TTC-estimation error did not differ significantly between groups (p=.111); however, CVL participants had a trend of making longer TTC estimates (CVL: 1.29 s vs NV: 1.22 s) with greater variability (CVL: 0.32 vs NV: 0.27, p=.273). In both groups, the car-only condition produced significant underestimation of TTC relative to the other background conditions (p<.001) and underestimation errors increased at longer TTC durations (p<.001). The CVL group had more frequent saccades (p=.018), marginally larger gaze dispersion (p=.056), and greater gaze-target distance (p=.057). TTC errors correlated with saccade frequency and gaze dispersion in the NV but not the CVL group; in particular, NV participants with greater gaze dispersion had significantly larger estimation errors (underestimation) than NV with low dispersion (-0.51 s vs 0.07 s, p=.05).
Conclusions: Despite impaired foveal vision, CVL individuals achieved TTC accuracy comparable to NV. Less stable gaze behaviors may have contributed to the lack of gaze-TTC associations in the CVL compared to the NV group. The significant underestimation in the car-only condition highlights the role of background information in accurate motion prediction in NV and CVL.
Candidate: Yasaman Anvarinia
Poster #: 23
3D Imaging of Human Orbital Arteries, Veins, and Lymphatic Vessels
by Light Sheet Fluorescent Microscopy Utilizing Automated Filament Tracing to Reveal Vascular Patterns and Anomalies
Yasaman Anvarinia, Drenushe Krasniqi-Vanmeter, Marie Darche, Brendan Brinkman, Taeyong Ahn, Tatjana C. Jakobs, Douglas Richardson, Joseph F. Rizzo III
Purpose: This study explores the 3D vascular architecture of the human orbit. Improved characterization of these vessels helps to inform a mechanistic understanding of anatomical factors of the short posterior ciliary arteries (sPCA) that might predispose to non-arteritic anterior ischemic optic neuropathy (NAION) and possibly primary open angle glaucoma, two major causes of irreversible blindness.
Methods: Human orbits (N=13) were removed en bloc or with the more standard enucleation procedure, fixed, and immunolabeled (N=6) with one or more antibodies to arteries, veins, and lymphatic vessels. The orbits then were cleared with updated techniques and imaged with light sheet fluorescence microscopy (LSFM). Imaris software was used to analyze and trace individual vessels with the Filament Tracer; a customized automated algorithm expedited otherwise laborious manual tracing. Our methods generated data on the, diameter, length, spatial location and tortuosity of arteries, veins and lymphatic vessels.
Results: The 3D network of orbital vessels was revealed across multiple specimens At the optic nerve head(ONH), the smallest measurable vascular lumina were 5–10 μm in diameter. Five trunks of sPCA were traced through >10 divisions as they entered the ONH and adjacent choroid. Many vessels were markedly tortuous, especially the sPCA close to the ONH and even one central retinal artery. Endomucin labeled the venous network, and LYVE-1 demonstrated novel 3D imaging of lymphatic vessels in human orbits. Although based on our tracing method in one sample, 5,884 filaments and 14,944 vessel segments were digitally identified. In this sample, the filament length ranged from 6.1 to 35,293 μm, and segment diameters were between 3.8 and180.8 μm.
Conclusions: Our result is yielding the first high-resolution 3D maps of human orbital vasculature. Our datasets provide quantification of full vessel structure and demonstrate high spatial resolution metrics of the location, size and tortuosity of vessels that we are using to develop a blood flow model of perfusion of the ONH Our methods have also revealed a surprising degree of tortuosity and anomalies of vessels that presumably affect blood flow in less predictable ways.
Candidate: Chien-Yu Lin
Poster #: 24
Eye1k: A Multi-conditional Mouse Retina and Optic Nerve Atlas for Cross-Species Translation to Human Retinal Biology
Chien-Yu Lin, Emil Kriukov, Ekaterina Ivleva, Dong Feng Chen, Petr Baranov
Purpose: Single-cell transcriptomic atlases provide critical reference frameworks for understanding retinal cell diversity, disease mechanisms, and the translational relevance of animal models. Here we present the largest healthy mouse retina single-cell atlas to date, comprising ~1.9 million cells and nuclei, and leverage it for systematic cross-species transcriptomic comparison with the Human Retina Cell Atlas.
Methods: We integrated 1.9 million cells and nuclei from 276 publicly available datasets sourced from GEO, Genome Sequence Archive, and ArrayExpress. Data integration and batch harmonization were performed using scVI, a deep generative autoencoder model (architecture: 512/30/2 dimensions). Cell type annotation was guided by canonical markers curated from prior literature and CELLxGENE. The resulting atlas was compared against the Human Retina Cell Atlas (HRCA; Rui Chen lab, ~3.9 million cells, 2026) using dot plot visualization of shared marker genes.
Results: Our atlas resolved 10 major retinal cell types including rods, cones, bipolar cells, amacrine cells, retinal ganglion cells, horizontal cells, Müller glia, astrocytes, microglia, and RPE, consistent with established retinal taxonomy. Cross-species dot plot comparison against the HRCA revealed broadly conserved cell-typespecific expression profiles across canonical markers including Pde6a/PDE6A (rod), Arr3/ARR3 (cone), Vsx2/VSX2 (Bipolar), Rbpms/RBPMS (RGC), Onecut1/ONECUT1 (Horizontal), Gfap/GFAP (Astrocyte), Rlbp1/RLBP1 (Müller glia), and Rpe65/RPE65 (RPE). Cross-species comparison revealed broadly conserved cell-type-specific transcriptional profiles between mouse and human, with canonical markers showing concordant expression patterns and comparable fractions of expressing cells across all 10 major cell types. This conservation at the transcriptomic level supports the utility of the mouse retina as a representative model for studying human retinal biology and disease.
Conclusions: This atlas, as a part of the Eye1k ecosystem, provides a comprehensive, harmonized mouse retina reference that captures conserved and divergent transcriptional programs across species, offering a vital resource for retinal disease modeling and translational research.
Candidate: Wai Lydia Tai
Poster #: 25
Optic Nerve Regeneration and Visual Function Recovery Promoted by Poly-γ-benzyl-L-glutamate Scaffold After Optic Nerve Transection in Rat
Wai Lydia Tai, Kin-Sang Cho, Karen Chang, Hio Tong Kam, Ajay Ashok, Lu Huang, Dongfeng Chen
Purpose: The optic nerve of adult mammals is incapable of regeneration, posing a major hurdle to vision recovery in patients with eye trauma or disease. Our previous work demonstrated that a biocompatible polymer, poly-γ-benzyl-L-glutamate (PBG), promotes axon growth in mouse ONT models. Here, we extended the PBG scaffold to a rat ONT model and evaluated its effects on nerve regeneration, RGC survival, structural reinnervation, and functional visual recovery.
Methods: Unilateral ONT was performed ~1–2 mm behind the globe in 8-week-old adult Long Evans rats under isoflurane anesthesia, preserving the central ophthalmic artery and part of the nerve sheath to prevent ischemic complications and nerve retraction. A Matrigel-coated PBG scaffold sheet fabricated by electrospinning was placed directly onto the transection site in the treatment group. Controls received ONT with either no implant or a polycaprolactone (PCL) scaffold. Retina, optic nerve, and brain tissues were collected at weeks 4 and 10 post-ONT for morphometric analysis. RGC survival was assessed by beta-III tubulin immunohistology, and regenerated axons were labeled with fluorescent-conjugated cholera toxin subunit B (CTB) for imaging in optic nerve wholemounts and brain sections. RGC function was measured by photopic negative response (PhNR) electroretinogram recordings up to 8 weeks post-ONT. Visual function was assessed by optomotor response (OMR) assay to determine contrast sensitivity and visual acuity (VA).
Results: ONT resulted in significant RGC loss and visual function deficits in controls. PBG-treated rats showed improved RGC survival and robust full-length axon regeneration, with CTB-positive axons reaching the lateral geniculate nucleus, pretectum, and superior colliculus via the contralateral optic chiasm. PBG rats consistently exhibited higher PhNR amplitudes across all time points. Notably, 7/8 PBG-implanted rats achieved partial visual recovery by week 4 (VA: 0.09–0.211 cycles/degree, ~50% of contralateral eye), with 3/4 rats surviving to week 6 maintaining stable VA of 0.158–0.198 cycles/degree. No OMR was detected in any control ONT rats.
Conclusions: PBG scaffold promoted long-distance axon regeneration, reinnervation of central visual targets, and meaningful functional recovery after ONT in rats. Enhanced PhNR and early OMR reappearance suggest regenerating axons formed functional synaptic connections in the brain. As a biocompatible, degradable material, PBG represents a versatile platform for repairing neural circuits, with implications for neurodegenerative injuries and whole-eye transplantation in the future.
Candidate: Anil Upreti
Poster #: 26
Single-Cell Transcriptomic Atlas of the Demyelinating Optic Nerve Reveals Divergent Glial Responses Across Oligodendrocyte Loss, Complement Deficiency, and Microglial Depletion Models
Anil Upreti, Emil Kriukov, Everett Labrecque, Ivleva Ekaterina, Chien-Yu Lin, Petr Y. Baranov
Purpose: The optic nerve is a vulnerable CNS white-matter tract where demyelination, neuroinflammation, aging, and glial remodeling converge. Building on our broader pan-conditional mouse retina and optic nerve ecosystem initiative (EYE1K), including a harmonized single-cell/single-nucleus mouse Optic nerve atlas from 59 public datasets (~650,000 cells/nuclei), we used diseased optic nerve datasets as a practical application to define how oligodendrocyte-intrinsic loss, complement-mediated neuroinflammation, and microglial depletion in aging shape cell-type composition, microglial activation states, oligodendrocyte-lineage disease responses, and intercellular signaling.
Methods: We integrated 125,174 optic nerve cells from three published mouse models, Myrf inducible conditional knockout (iCKO; oligodendrocyte-specific, 18 weeks; GSE243788), complement C3 knockout with EAE (C3 KO; 12.5 weeks; GSE260984), and PLX5622-treated aged mice (PLX/Aged; 12 months; GSE283362), with deep generative scVI modeling (256 hidden units, 30 latent dimensions). Fourteen cell types were annotated de novo using canonical marker scoring. Microglia were subclustered in scVI latent space and scored against homeostatic, DAM, and disease signatures. Oligodendrocyte-lineage pseudobulk DESeq2, GSEA, and 46-pair ligand–receptor analysis defined disease programs.
Results: Single-cell profiling resolved 14 optic nerve cell types and revealed model-specific disease programs. C3 KO showed complement-associated neuroinflammation with a dominant IFN-γ oligodendrocyte-lineage response (NES=2.60; Iigp1, B2m) and prioritized microglial SPP1-integrin and C1Q–complement signaling. In Myrf iCKO, oligodendrocytes upregulated synaptic receptor programs (Gria1, Syt1), while 82% of microglia (n=11,171) occupied a demyelination-associated state marked by Nav2, Pcdh9, and Erbb4 that was absent from canonical DAM signatures.
Conclusions: These findings show that demyelinating optic nerve models share glial remodeling but diverge in immune activation, oligodendrocyte-lineage stress, and microglial signaling. The PCMRON framework provides a scalable deep-learning foundation for harmonizing public retina and optic nerve datasets and extracting disease-specific mechanisms. Model-specific LGALS9–TIM3 and PDGFB–PDGFRA signaling in Myrf iCKO versus complement/SPP1 signaling in C3 KO nominate divergent microglia–oligodendrocyte therapeutic nodes.
Candidate: Konstantinos Baroutis
Poster #: 27
Misfolded Protein Regulator TMED9 and Neuroprotection After Experimental Retinal Detachment
Konstantinos Baroutis, Edward Ryan A. Collantes, Juan Lorenzo Pablo, Toshio Narimatsu, Gustavo Sakuno, Maria Emfietzoglou, Irini Chatziralli, Ilias Georgalas, Panagiotis Theodossiadis, Anna Greka, Demetrios G. Vavvas
Purpose: Retinal detachment (RD) is a sight-threatening emergency in which photoreceptor (PR) degeneration begins within hours of the event and limits visual recovery despite anatomically successful surgery. TMED9, a regulator of protein quality control, has shown therapeutic potential in classic proteinopathies but has not been evaluated in acute retinal injury. Here we investigate TMED9 and its potential as a therapeutic target in experimental RD.
Methods: RD was induced in C57BL/6J mice (n=60) via ab interno subretinal injection of sodium hyaluronate (Provisc). BRD7635 (a next-generation TMED9-binding compound that promotes release of trapped proteins for lysosomal degradation) was mixed with the Provisc and co-delivered at detachment induction at low (500 μM) or high (1 mM) concentrations; controls received Provisc with vehicle alone. Eyes were harvested at Days 1, 3, and 7 post-detachment. TMED9 and ER stress markers were quantified by Western blot with total protein normalization (n=6/group, paired design). Photoreceptor apoptosis was assessed by TUNEL staining in cryosections, and positive cells were quantified per mm2 of the outer nuclear layer.
Results: We demonstrate, for the first time, that TMED9 is expressed in the murine retina and exhibits dynamic temporal regulation following RD. At Day 1, TMED9 expression decreased by 46% in detached retina compared with attached retina (p=0.002). By Day 7, this pattern reversed, with detached retinas showing 37% higher TMED9 expression (p=0.004). BRD7635 treatment significantly attenuated photoreceptor apoptosis during the critical acute phase: at Day 1, TUNEL-positive cells were reduced by 64% with low-dose (p<0.0001) and 71% with high-dose treatment (p<0.0001) compared to controls (3815±450 cells/mm2). A dose-response relationship was observed (p=0.008). Mechanistically, BRD7635 engaged TMED9 in detached retinas, decreasing TMED9 protein by 48% (p=0.0001) and the pro-apoptotic ER stress effector CHOP by 53% (p=0.007). By Day 7, apoptosis resolved to similarly low levels across all groups (~500 cells/mm2).
Conclusions: This study provides the first characterization of TMED9 in the mouse retina, reveals a biphasic expression pattern following detachment, and demonstrates that BRD7635 confers dose-dependent acute neuroprotection via in vivo TMED9 engagement and ER stress reduction. These findings identify TMED9 as a therapeutic target in acute retinal injury.
Candidate: Maria Emfietzoglou
Poster #: 28
Functional Characterization of a Novel BEST1 5′ Untranslated Region Variant in Adult-Onset Vitelliform Maculopathy
Maria Emfietzoglou, Eleftheria Valsami, Alexandra Varsamidaki, Maria Anna Bantounou, Konstantinos Baroutis, Maria Loscertales, Srinivas R. Sadda, Demetrios G. Vavvas
Purpose: To investigate whether a rare proximal BEST1 5′ untranslated region variant, c.-8G>A, has functional consequences in a patient with progressive adult-onset bilateral vitelliform maculopathy and a normal electro-oculogram.
Methods: We reviewed multimodal retinal imaging over 8 years of follow-up. Electrophysiology and genetic testing were performed as part of the diagnostic workup. Wild-type and mutant BEST1 5′UTR constructs were tested in ARPE-19 cells using luciferase reporter assays, BEST1 western blot analysis, and RT-qPCR across independent transfection experiments. In silico analyses included RNA secondary structure prediction, RNAbinding protein motif comparison, splicing prediction, and evaluation of upstream open reading frames and the Kozak consensus context.
Results: The patient progressed from large bilateral vitelliform lesions to macular atrophy, with visual acuity declining to counting fingers over 8.5 years. The c.-8G>A variant reduced luciferase reporter activity by 45.4% (P = 0.013) and reduced BEST1 protein abundance to 64% of WT (P < 0.001), whereas BEST1 mRNA showed a significant 1.49-fold increase (P = 0.019). RNA structure prediction indicated that the variant destabilizes a local stem at the variant site and induces a rearrangement that partially occludes the AUG start codon. RNA-binding protein motif, splicing, uORF, and Kozak context analyses did not identify major defects.
Conclusions: The BEST1 c.-8G>A 5′UTR variant seems to reduce protein expression through a posttranscriptional mechanism, potentially mediated by altered RNA secondary structure and affected translation initiation. These findings support classification of this phenotype as Best disease caused by a noncoding BEST1 variant, rather than genetically unexplained adult-onset vitelliform macular dystrophy, and highlight the importance of functionally interrogating noncoding variants in inherited retinal disease.
Candidate: Blake Hauser
Poster #: 29
Structure-Based Network Analysis and Genetic Associations With Retinal Conditions Combine to Identify Candidate Causative Variants for Inherited Retinal Diseases
Blake M. Hauser, Liyin Chen, Kirill Zaslavsky, Emily M. Place, Yuyang Luo, Anusha Nathan, Jason Comander, Eric A. Pierce, Kinga M. Bujakowska, Gaurav D. Gaiha, Elizabeth J. Rossin
Purpose: Although increased availability and throughput of genetic sequencing has improved variant identification, further advances are needed to understand which variants cause disease. It is particularly important to overcome this barrier when gene therapy is available as a treatment modality, as is the case for inherited retinal diseases (IRD). Our previous work has demonstrated that structure-based network analysis (SBNA) can reliably identify putative causative variants in some, but not all, patients with IRD. Using variant association analysis, we were able to elucidate a putative genetic basis for IRD in additional patients.
Methods: We applied SBNA to experimentally determined protein structures from the Protein Data Bank and artificial intelligence-generated protein structures from AlphaFold2. We used the All of Us database to identify genetic variants associated with patients with ICD-10 codes reflecting IRD diagnoses compared to controls without IRD. We compared the results for known benign and pathogenic variants from ClinVar for validation, and we subsequently applied this approach to a dataset of patients with IRD from Mass Eye and Ear (MEE) without a known genetic basis of disease.
Results: Both SBNA (AUC 0.777; 95% CI: 0.755, 0.799) and variant association strength (AUC 0.642; 95% CI: 0.617, 0.666) successfully distinguished between known benign and pathogenic variants in IRD-associated genes found within the All of Us cohort. Within a dataset of 1200 patients with clinical IRD, 544 patients did not have a known genetic basis of disease. SBNA contributed to putative genetic solutions for 55% of patients, while variant association metrics contributed for 17% of patients, 27% of which did not have a putative genetic solution identified via SBNA.
Conclusions: Both SBNA, which relies entirely on structural principles, and variant association analysis offer orthogonal approaches to identifying candidate causative variants in patients with IRD. Additionally, neither method requires training on phenotypic data, which distinguishes these approaches from other missense variant effect prediction tools and may confer broad applicability.
Candidate: Maryam Shayan
Poster #: 30
Suppression of Chronic Autoimmune Uveitis by Vitamin D Supplementation in a Preclinical Model
Maryam Shayan, Parisa Dashti, John H. Kempen, Lucia Sobrin, Yihe Chen
Purpose: Low vitamin D status has been associated with increased risk and activity of uveitis. Here, we investigated the impact of low- and high-dose vitamin D supplementation on disease severity and underlying pathogenic T cell response in a mouse model of chronic autoimmune uveitis.
Methods: C57BL/6J mice were assigned to three diets: standard chow with regular vitamin D (2.3 IU/g, control, ~ equivalent to 1400 IU daily for humans), low-dose (LD) vitamin D (7.5 IU/g, ~ equivalent to 4400 IU daily for humans) diet, or high-dose (HD) vitamin D (15 IU/g, ~ equivalent to 8800 IU daily in humans) diet. Diets started 3 weeks before CAU induction and were maintained for 12 weeks. Chronic uveitis was induced by immunization with interphotoreceptor retinoid-binding protein peptides in complete Freund’s adjuvant plus Bordetella pertussis toxin. The disease was evaluated using fundoscopy and electroretinography (ERG). At week 12, retina, draining lymph nodes (DLN), and spleen were collected for flow cytometric analysis of T cell response.
Results: Compared with the control group, the LD vitamin D group showed significantly lower fundoscopic disease scores at the very early time points post-induction (week 2 mean: 0.1 vs 0.8, p<0.05 and week 4 mean: 0.42 vs 1.0, p<0.05), but not subsequently during the 12-week follow-up; this group did not demonstrate any significant functional preservation on ERG. In contrast, the HD vitamin D group exhibited rapid, significant, and persistent disease suppression on fundoscopic evaluation, with average scores of 0 vs 1.1 (p<0.0001), 0 vs 1.5 (p<0.001), 0.1 vs 1.7 (p<0.0001), 0.5 vs 2.0 (p<0.01), 0.7 vs 2.9 (p<0.0001), and 1.1 vs 3.5 (p<0.01) at weeks 2, 4, 6, 8, 10, and 12, respectively. In addition, ERG assessment demonstrated significantly better preservation of dark-adapted (DA) b-wave amplitudes at weeks 8 (mean change from baseline: 6.7 vs -101.3 µV, p<0.05) and 12 (mean change from baseline: -22.3 vs -94.1 µV, p<0.05). Flow cytometric analysis revealed a significant decrease in retinal CD4+ T cell infiltration (0.03% vs 0.17%, p<0.05; mean absolute #: 23 vs 152, p<0.05) and significantly reduced memory Th17 cells in the DLN (mean: 0.3% vs 1.2%, p<0.05) and spleen (mean: 0.1% vs 0.6%, p<0.05) in the HD vitamin D group.
Conclusions: Oral vitamin D supplementation at 15 IU/g in mice (equivalent to 8800 IU daily for humans) is effective in suppressing the induction and progression of uveitis into chronicity, as well as decreasing the pathogenic memory CD4+ T cell response. These results support optimized vitamin D dosing as a promising, low-cost strategy to promote durable control of chronic uveitis.
Candidate: Jennifer Zhumi
Poster #: 31
IGFBPL1 Reduces Diabetes-Induced Angiofibrosis in the Human RPE/Choroidal Explants Model Ex Vivo
Jennifer P. Zhumi, Anna T. Kristensen, Noora H. Thune, Farris Elzaridi, William P. Miller, Leo A. Kim, Tor P. Utheim, Amer Sehic, Dongfeng Chen, Anton Lennikov
Purpose: Diabetic retinopathy (DR) is driven by chronic inflammation, pathological angiogenesis, and progressive fibrosis affecting millions of patients worldwide. Insulin-like growth factor binding protein-like 1 (IGFBPL1) is a newly identified anti-inflammatory protein. This study examined how diabetic conditions or high glucose exposure drive proliferative outgrowth in human RPE/choroidal explants ex vivo and compared the therapeutic effects of IGFBPL1 with aflibercept.
Methods: Human RPE/choroidal explants were isolated from healthy and diabetic human post-mortem donor eyes and embedded in Matrigel. Healthy donor explants (n=6/group) were assigned to five groups: untreated control, high-glucose media (HG; 35 mM), (mannitol, 35 mM), HG + IGFBPL1 (400 ng/ml), HG + aflibercept (1µg/ml) and cultured for 10 days. Treatments were initiated upon the onset of sprouting. Explants from diabetic donors and matched healthy controls were cultured in baseline media to assess disease associated outgrowth and the response to IGFBPL1 (400 ng/ml) or aflibercept (1 µg/ml). Explants were imaged every two days by brightfield microscopy to track sprouting. On day 10, they were stained with Calcein AM to visualize viable outgrowth, imaged, and quantified, followed by immunolabeling for Vimentin.
Results: This study establishes that diabetic proliferative disease can be effectively modeled ex vivo, and explants from DR patients retain increased proliferative capacity even in normal glucose media. IGFBPL1 treatment significantly reduced outgrowth area. Aflibercept did not produce a significant reduction in diabetesinduced proliferative activity. Vimentin immunolabeling confirmed that the expanding cellular front was composed predominantly of fibroblast-like cells.
Conclusions: IGFBPL1 robustly suppresses hyperglycemia and diabetes-driven growth and remodeling in human RPE/choroidal explants, outperforming aflibercept in limiting proliferative outgrowth. These findings identify IGFBPL1 as a promising therapeutic candidate and validate human ex vivo explants as a physiologically relevant platform for modeling diabetic proliferative disease.
Candidate: Celine Chaaya
Poster #: 32
Long-Term Systemic and Neurodevelopmental Outcomes in Neonates Treated for Retinopathy of Prematurity: Anti-VEGF vs. Laser
Darius D. Bordbar, Joseph D. Fahey, Celine Chaaya, Arthur R. Brant, Jimmy Chen, Ali O. Mukhtar, Megan E. Aurora, Rishi P. Singh, Christina Y. Weng, Nimesh A. Patel
Purpose: To evaluate whether anti-vascular endothelial growth factor (anti-VEGF) treatment (vs. laser), number of anti-VEGF treatments, and anti-VEGF agent selection is associated with 10-year mortality and systemic, developmental, and neurobehavioral outcomes among patients treated for retinopathy of prematurity (ROP).
Methods: Retrospective cohort study using TriNetX network de-identified electronic health records (20052025) with 10-year outcomes. Individuals with ROP treated at ≤1 year who received (A) anti-VEGF without laser or (B) laser without anti-VEGF were included. Anti-VEGF without laser vs. laser without anti-VEGF; ≥2 vs 1 anti-VEGF treatment; and anti-VEGF agent selection were compared. Ten-year outcomes included all-cause mortality, neurodevelopmental disorders, cerebral palsy, epilepsy, delayed milestones, asthma, and ophthalmic sequelae.
Results: After matching, cohorts A and B included 773 patients each. Compared with laser (B), anti-VEGF (A) was associated with greater mortality (HR, 1.75; 95% CI, 1.11-2.75) and lower asthma (HR, 0.80; 95% CI, 0.64-0.98), with no differences in other 10-year outcomes. These associations were not replicated in treatmentnumber subanalyses. Compared with 1 treatment (D), receipt of ≥2 treatments (C) was associated with blindness/low vision (HR, 2.59; 95% CI, 1.25-5.38), renal morbidity (HR, 2.04; 95% CI, 1.02-4.07), and delayed milestones (HR, 1.33; 95% CI, 1.07-1.66), with no differences in other outcomes. In agent-specific analyses (limited by sample size), ranibizumab (F) vs bevacizumab (E) included 113 matched pairs and was associated with greater myopia (HR, 2.17; 95% CI, 1.12-4.21).
Conclusions: Among matched ROP-treated patients, long-term neurodevelopmental outcomes did not differ between anti-VEGF and laser. Anti-VEGF was associated with greater mortality and lower asthma, but confidence intervals were wide and subanalyses did not replicate these associations.
Candidate: Darin Chhing
Poster #: 33
Atypical Clinical Course of Tattoo Granulomas With Uveitis: A Case Report
Darin Chhing, Eric Suhler, David Valent, Richard Bernheimer
Purpose: To describe a rare case of tattoo granulomas with uveitis that demonstrated clinical improvement after discontinuation of omalizumab in a patient with chronic spontaneous urticaria.
Methods: Case report.
Results: A 35-year-old male presented to Urgent Care with a 1-day history of bilateral eye pain and vision changes. Initial assessment suggested conjunctivitis which did not resolve with medical management. Ophthalmology referral and subsequent evaluation revealed severe bilateral iritis. Pronounced induration of multiple tattoos was concurrently present on examination. Histopathological analysis revealed well-formed noncaseating granulomas within the superficial to deep dermis, with no evidence of systemic sarcoidosis on further workup. The patient underwent treatment to reduce recurrent intraocular inflammation and ocular hypertension, with marked reduction of tattoo-associated inflammatory nodular elevation following omalizumab discontinuation.
Conclusions: This is the first case to report a possible clinical association between TAGU and omalizumab, and the first to document TAGU in a patient with chronic spontaneous urticaria. Careful inquiry regarding tattoos and examination of tattooed skin should be considered in patients with new-onset uveitis. This case highlights the importance of thorough medication review and underscores the need for additional research to determine the specific allergen(s) implicated in tattoo-associated uveitis (TAU). Further investigation is necessary to elucidate the potential relationship between TAGU and omalizumab.
Candidate: Vivian Paraskevi Douglas
Poster #: 34
Association of Age-Related Macular Degeneration and Diabetic Retinopathy in Type 1 and Type 2 Diabetes Mellitus: Clinical and Retinal Structural Insights
Vivian Paraskevi Douglas, Ward Fickweiler, Surya Jangolla, Min Ju Kang, Marc Yu, Hetal Shah, Jerry Cavallerano, Paolo S Silva, Lloyd P Aiello, Jennifer K. Sun, George L. King
Purpose: To characterize the relationship of age-related macular degeneration (AMD) with diabetic retinopathy (DR) severity and diabetic macular edema (DME) in type 1 (T1DM) and type 2 diabetes mellitus (T2DM).
Methods: Fundus photographs from the T1DM Joslin 50-Year Medalist study (N=582) were graded for DR severity and AMD status. Electronic medical records of T1DM (N=1,413) and T2DM (N=3,923) from Beetham Eye Institute (BEI) patients > 50 years were evaluated for DR severity and presence of AMD and DME. Optical coherence tomography (OCT) scans were segmented using automated layer segmentation software (Heidelberg v6.0c).
Results: In Medalists, there was an inverse relationship between DR severity and the AMD status (AMD presence: 41.1% in no-mild DR, 32.6% moderate-severe DR and 18.2% PDR, P<0.001) which remained significantly associated in multivariable models (P=0.02). Similar inverse association of DR severity with AMD was present in the BEI T1DM cohort in unadjusted (no-mild DR 14.5%, moderate-severe DR 8.2%, PDR 3.0%, P<0.001) and multivariable analyses (P<0.001) and the BEI T2DM cohort in unadjusted analysis (no-mild DR 3.1%, moderate-severe DR 2.1%, PDR 1.2%, P<0.05), but not in multivariable models (P=0.61). When DME was present, it was inversely associated with presence of AMD in both BEI T1DM (no AMD 16.7% vs AMD 7.6%, P<0.01) and BEI T2DM cohort (no AMD 23.8% vs AMD 13.9%, P<0.02). In Medalists with continuous glucose monitoring data (N=75), time below range was significantly associated with presence of AMD and absence of PDR (P=0.03). Glucagon-like peptide 1 receptor agonists and increased oral antidiabetic agent use were each inversely correlated with DR severity (P<0.01) in the BEI T2DM cohort, but not with the presence of AMD (P=0.55). Photoreceptor and outer nuclear layer thicknesses were decreased in PDR but increased in the presence of AMD in Medalists (N=545, P=0.01) and the BEI T2DM cohort (N=818, P<0.05).
Conclusions: These findings support that DR severity and other DR associated parameters are inversely associated with the presence of AMD, especially in individuals with type 1 diabetes. Detailed mechanistic and longitudinal studies are needed to elucidate why differences between DR and DM type may influence susceptibility to AMD.
Candidate: Janice Ong
Poster #: 35
Comparison of Geometric Perfusion Deficits With Standard Vessel Density
Metrics on Swept-Source OCTA and Their Association With Quantitative Contrast Sensitivity
in Diabetic Retinopathy
Janice X. Ong, Xinyi Ding, Muhammad Abidi, Jenny Gan, Ioanna Ploumi, Filippos Vingopoulos, Francesco Romano, Demetrios G. Vavvas, Deeba Husain, Leo A. Kim, Nimesh A. Patel, John B. Miller
Purpose: To compare geometric perfusion deficits (GPD), an alternative retinal nonperfusion metric, against standard metrics like vessel density (VD) on swept-source OCTA and their association with visual function measured as quantitative contrast sensitivity (CS) in diabetic retinopathy (DR).
Methods: 127 eyes of 91 patients (34 healthy eyes, 26 with diabetes (DM) without DR, 19 mild nonproliferative DR, 20 moderate-to-severe DR, and 28 proliferative DR) were included. Patients underwent quantitative CS testing and 3×3 mm SS-OCTA scans. VD was calculated using the macular density algorithm (v.0.7.3.3) on the Advanced Research and Innovation Network. GPD was calculated as percentage of nonperfusion (areas > 30 microns away from nearest vessel) using a custom FIJI macro.
Results: GPD progressively increased while VD decreased with worsening DR severity (p < 0.001). However, GPD showed greater differences between adjacent DR stages including healthy vs. DM without DR (p = 0.005) while VD only significantly differed in moderate-to-severe NPDR vs. PDR (p = 0.029). Increasing GPD and decreasing VD correlated with worse CS metrics, including area under the logarithm of the CS function (AULCSF; p < 0.003) and contrast acuity (p < 0.017) with similar effect sizes (β* = -0.381 for GPD and 0.412 for VD correlation to AULCSF).
Conclusions: Retinal ischemia measured as GPD and VD correlates with increasing DR severity and worsening CS, supporting a relationship between DR structural vascular changes and visual function. However, GPD outperforms standard VD in distinguishing incremental stages of DR severity, including identifying preclinical disease in DM before DR onset.
Candidate: Brenna Bullock
Poster #: 36
Belt Loop Versus Sutured Scleral Buckle Fixation in Combined Scleral Buckle/Pars Plana Vitrectomy for Primary Retinal Detachment Repair
Brenna L. Bullock, Demetrios G. Vavvas, Lucy H. Young, Nimesh A. Patel, Mohammad Dahrouj
Purpose: To compare operative efficiency and outcomes between encircling belt loop (scleral tunnel) versus traditional sutured scleral buckle fixation in combined scleral buckle/pars plana vitrectomy (SB/PPV) for primary retinal detachment (RD) repair.
Subjects: Eyes that underwent primary RD repair using combined SB/PPV at a single health system between April 2016-November 2025. Cohorts were defined by the buckle fixation technique used.
Main Outcome Measures: The primary efficiency outcome was operative time, and the primary efficacy outcomes were reoperation-free survival and best-corrected visual acuity (BCVA) recovery from preoperative baseline to postoperative month (POM) 3, 6, and final follow-up (POM12-18).
Methods: Operative times were compared using both linear mixed-effects and quantile (median) regression models, reoperation outcomes using Kaplan–Meier/Cox regression, and longitudinal BCVA using a mixedeffects model for repeated measures (MMRM) and a marginal model, adjusting for baseline severity covariates.
Results: 1,001 total eyes (468 belt loop, 533 sutured) were included. The sutured cohort had greater baseline case complexity overall. Unadjusted median operative time was shorter with belt loop fixation (75.5 vs 131 minutes, p<0.001). After adjustment for baseline severity and surgeon clustering, the sutured technique remained 26.7 minutes longer (95% CI 17.51–35.88, p<0.001). Reoperation rates were 12.4% and 16.1% for belt loop and sutured groups, respectively (p=0.095), with similar reoperation-free survival (log-rank p=0.280, adjusted HR 0.97, p=0.876). Second reoperations were less frequent with belt loop fixation (20.7% vs 40.7%, p=0.012). Adjusted MMRM showed no significant BCVA difference at final follow-up (+0.039 logMAR, p=0.364).
Conclusions: In combined SB/PPV for primary RD, belt loop fixation was associated with shorter operative time while achieving comparable reoperation-free survival and severity-adjusted visual recovery, supporting it as a more efficient and equally effective alternative to sutured fixation.
Candidate: Ned Lu
Poster #: 37
Outcomes of Pars Plana Vitrectomy in Inherited Retinal Degenerations
Edward S. Lu, Ahmad Al-Moujahed, Henry W. Zhou, Kirill Zaslavsky, Jason Comander
Purpose: To describe the management and outcomes of pars plana vitrectomy (PPV) for common surgical retinal conditions, including epiretinal membrane (ERM), full-thickness macular hole (FTMH), and retinal detachment, in patients with inherited retinal degenerations (IRDs).
Methods: Retrospective case series study including patients with IRDs who underwent PPV between 2007 and 2024 at Mass Eye and Ear, excluding subretinal injections. Patient demographics, clinical information, genetic testing, diagnostic testing, and surgical information were reviewed. Main outcome measures were surgical outcomes and best-corrected visual acuity (BCVA).
Results: 26 eyes from 25 patients were included. 7 patients (28%) had ERM, 10 patients (36%; 11 eyes) had FTMH, and 9 patients (36%) had other surgical indications. The mean follow-up duration was 51 months. Mean age at diagnosis of the surgical condition was 48.2 ± 21.2 years, and 16 patients (64%) were male. At postoperative month 3, BCVA (mean 1.16 ± 1.01 logMAR; P = 0.86) was similar to preoperative values. The BCVA at final follow-up (mean 1.12 ± 1.06 logMAR; P = 0.65) also did not differ significantly from baseline. In ERM eyes, mean central macular thickness improved significantly from 425 ± 158 µm preoperatively to 270 ± 79 µm at postoperative month 3 (P = 0.01). Eyes with better baseline BCVA and more intact ellipsoid zones appeared to achieve better visual outcomes. Among FTMH eyes, surgical closure was achieved in 10 eyes (91%) with 1 surgery, while 1 eye (9%) required 2 procedures.
Conclusions: These data indicate that PPV for common retinal conditions can achieve a high single-surgery anatomic success rate. However, the visual gains achieved in eyes with an IRD are generally smaller than in otherwise healthy eyes, suggesting a conservative approach to patient selection.
Candidate: Ayush Parikh
Poster #: 38
Late Retinal Detachments in Retinopathy of Prematurity
Ayush Parikh, Celine Chaaya, Ryan Meshkin, Sandra Hoyek, Francisco Altamirano-Lamarque, Shizuo Mukai, Nimesh Patel
Purpose: To investigate the clinical characteristics and outcomes of Retinopathy of Prematurity (ROP) patients with late retinal detachment (RD).
Methods: Retrospective chart review of patients with ROP who presented with a late RD, occurring at least two years after initial ROP diagnosis. Demographic information, visual outcomes and RD characteristics were obtained.
Results: A total of 38 patients with a history of ROP who presented with a late RD were included in this study (57.9% males). The median age at presentation for RD was 19 years. More than half of RDs were diagnosed incidentally on routine examination, and 52% were macula-off. Fifty percent of patients had a rhegmatogenous RD, 35.3% had tractional RD, and 14.7% had combined rhegmatogenous and tractional RD. The majority of patients (78%) underwent surgical intervention for RD repair with combined pars plana vitrectomy (PPV) and scleral buckle (46.9%), scleral buckle (34.4%), or PPV alone (18.7%), and 22% were observed due to guarded prognosis. The median logMAR vision was 1.8 (Snellen 20/1260) at presentation and 1.18 (20/300) at final follow-up. Re-detachment occurred in 23.6% of patients, of which 88.9% had additional surgery.
Conclusions: Late retinal detachments can develop in the setting of ROP and usually occur in young adulthood. Over one half were found asymptomatically on routine examination and were macula-off. The majority underwent complex surgical repair with silicone oil tamponade, and re-detachment was not uncommon. Long-term follow-up for ROP patients may be indicated to monitor for progressive traction and retinal breaks.
2026 Annual Meeting and Alumni Reunion
MEETING CO-CHAIRS
Rishi P. Singh, MD
Chair, Department of Ophthalmology, Harvard Medical School
Chair of Ophthalmology, Mass Eye and Ear, Mass General Brigham
Joseph B. Ciolino, MD
Associate Professor of Ophthalmology, Harvard Medical School
Associate Director of Alumni, Ophthalmology, Harvard Medical School
Henry Freeman Allen Cornea Scholar and Associate Scientist, Mass Eye and Ear
Eric D. Gaier, MD, PhD
Assistant Professor of Ophthalmology, Harvard Medical School
Site Director, Harvard Ophthalmology Residency, Boston Children’s Hospital
Neuro-Ophthalmologist, Ophthalmology, Boston Children’s Hospital
Rachel M. Huckfeldt, MD, PhD
Associate Professor of Ophthalmology, Harvard Medical School
Director, Inherited Retinal Degenerations Fellowship, Mass Eye and Ear
Associate Scientist and Director, Inherited Retinal Disorders Clinical Trials, Mass Eye and Ear
Joseph F. Rizzo III, MD
Simmons Lessell Professor of Ophthalmology, Harvard Medical School
Director of Alumni, Ophthalmology, Harvard Medical School
Co-Director, Mobility Enhancement and Vision Rehabilitation Center of Excellence, Harvard Medical School Director, Neuro-Ophthalmology Service, and Senior Scientist, Mass Eye and Ear
