The eye is a recognised source of biomarkers for cardiovascular and neurodegenerative disease risk. Here, we characterise the breadth of these associations and identify biological axes that may mediate them. Using UK Biobank data, we developed a multi-omic analysis pipeline integrating physiological, radiomic, metabolomic, and genomic information. We trained adversarial autoencoders (Ret-AAE) to represent optical coherence tomography (OCT) images and colour fundus photographs as 256-dimensional embeddings. Ret-AAE derived embeddings were associated with a range of cardiovascular and neurodegenerative diseases, including ischaemic heart disease, cerebrovascular disease, Parkinson’s disease, and dementia. Examining associations across diverse omics datasets, we provide evidence linking ophthalmic imaging features to neurological and cardiovascular anatomy and function, lipid metabolism, and gene sets associated with neurodegenerative pathology. Collectively, our findings demonstrate that ophthalmic features reflect complex, multisystem biological processes, and reinforce the role of the eye as a composite indicator of systemic health.

P.A.K is a cofounder of Cascader Ltd. and has acted as a consultant for insitro, Retina Consultants of America, Roche, Boehringer-Ingleheim, and Bitfount and is an equity owner in Big Picture Medical. He has received speaker fees from Zeiss, Thea, Apellis, and Roche, and grant funding from Roche. He has received travel support from Bayer and Roche. He has attended advisory boards for Topcon, Bayer, Boehringer-Ingleheim, and Roche. A.F.F is cofounder and NED of OculomeX Health Ltd and adsilico Ltd and has acted as a consultant for these companies. The remaining authors have no disclosures.

All funding acknowledgements are provided in the manuscript. No payment was received with respect to this study. No third party services were utilised.

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The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

The UK Biobank study was (UKB) conducted with the approval of the North-West Research Ethics Committee (ref 06/MRE08/65), in accordance with the principles of the Declaration of Helsinki, all participants gave written informed consent and were free to withdraw at any time.

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