Abstract
To evaluate the feasibility of integrating genetic, imaging, and demographic data for predictive modelling of treatment outcomes in neovascular age-related macular degeneration (nAMD). Proof-of-concept retrospective cohort study with prospective DNA collection. Patients with unilateral nAMD receiving anti-vascular endothelial growth factor (anti-VEGF) therapy on a treat-and-extend regimen at a single tertiary centre were recruited. Polygenic risk scores (PRS) for AMD were derived from genotyping data (NIHR Bioresource). Optical coherence tomography (OCT) biomarkers-intraretinal fluid (IRF), subretinal fluid (SRF), pigment epithelial detachment (PED), and subretinal hyperreflective material (SHRM)-were automatically quantified using a deep learning segmentation model. Predictors of treatment outcomes included PRS, age at first injection, and OCT feature volumes at baseline. XGBoost was used for binary outcomes and linear regression for continuous outcomes, employing five-fold cross-validation. (1) macular dryness (no IRF/SRF) at 24 months, (2) average treatment interval in year 2, and (3) age at first injection. 106 participants were included. The multimodal model integrating age, imaging, and PRS predicted macular dryness at 24 months with AUC = 0.903, outperforming imaging alone (AUC = 0.701). PRS was associated with younger age at first injection (β = –4.69, 95% CI [–8.93, –0.44], P = 0.031) but not with treatment burden (β = –6.39, P = 0.13). Integrating PRS with OCT-derived imaging biomarkers and patient age is technically feasible and improves predictive performance of modelling for anatomical treatment outcomes in nAMD. PRS reflects genetic susceptibility to nAMD and contextualizes the predictive value of imaging biomarkers for treatment response.
Data availability
The full list of variants and effect sizes used for PRS computation is available in the EBI PGS catalogue (PGS001834). Data and code are available upon reasonable request to the corresponding author.
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Funding
Supported by a Moorfields Eye Charity Springboard Award (R190001A). The funders had no role in study design, data collection, analysis, or interpretation.
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Conception and design: KB Funding acquisition: KB Data collection: IM, NP, TS, GZ, TL, PB, YWC, VC, KB Analysis and interpretation: IM, NP, TL, AS, TS, ASS, GZ, GN, PB, YWC, VC, KB Manuscript drafting and critical revision: IM, NP, AS, TL, TS, ASS, SKW, GZ, GN, PB, YWC, VC, PAK, SS, ARW, KB All authors approved the final manuscript.
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KB has received speaker fees from Novartis, Bayer, Roche; meeting or travel fees from Novartis and Bayer; consulting fees from Novartis, Roche, Bayer and Boehringer-Ingleheim; research support from Apellis, Novartis, and Bayer; employment AAvantgarde Bio. PAK received grants or contracts by a UK Research & Innovation Future Leaders Fellowship (MR/R019050/1) and The Rubin Foundation Charitable Trust; consulting fees from Retina Consultants of America, Topcon, Roche and Boehringer-Ingleheim; payment or honoraria from Zeiss, Topcon, Novartis, Boehringer-Ingleheim, Apellis, Roche and AbbVie; support for attending meetings and/or travel from Bayer, Topcon and Roche; Active patents: Generalizable medical image analysis using segmentation and classification neural networks https://patents.google.com/patent/US10198832B2/en and Pending Patents: Predicting disease progression from tissue images and tissue segmentation maps https://patents.google.com/patent/US20220301152A1/en; participation on a Data Safety Monitoring Board or Advisory Board for Topcon, Bayer, Boehringer-Ingleheim, RetinAI and Novartis; Bitfount (stock options) and Big Picture Medical (stock). SS received grants (paid to her institution) from Bayer and Boehringer Ingelheim; consulting fees for participation on advisory boards from AbbVie, Amgen, Apellis, Bayer, Biogen, Boehringer Ingelheim, Novartis, Eyebiotech, Eyepoint Phamaceuticals, Janssen Pharmaceuticals, Nova Nordisk, Optos, Ocular Therapeutix, Kriya Therapeutics, OcuTerra, Roche, Stealth Biotherapeutics, and Sanofi; honoraria for lectures from Bayer, and Roche, for presentations from Bayer, Roche, Astellas, and Abbvie, and for manuscript writing and educational events from Bayer, Roche, and Boehringer Ingleheim; support for attending meetings and/or travel from Boehringer Ingelheim, Roche, and Bayer; participation in Data Safety Monitoring Boards for Bayer and Novo Nordisk; is a Trustee of the Macular Society and Chair of the Royal College of Ophthalmologists’ Scientific Committee; and has stock options in Eyebiotech. All other authors declare no competing interests.
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Moghul, I., Pontikos, N., Sharma, A. et al. Integrating genetics, age and imaging to predict treatment outcomes in neovascular age-related macular degeneration: a proof-of-concept study. Sci Rep (2026). https://doi.org/10.1038/s41598-026-41931-3
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DOI: https://doi.org/10.1038/s41598-026-41931-3
