Oculomics meets exposomics: a roadmap for applying multi-modal ocular biomarkers in precision environmental health...

Precision environmental health (PEH) is an emerging field that seeks to understand how diverse environmental exposures interact with individual biological and genetic factors to influence health outcomes. While recent advances in exposomics have enabled systematic characterization of the exposome, the integrated compilation of all physical, chemical, biological, and psychosocial influences that affect biology and health, identifying and developing sensitive biomarkers remains a critical challenge. The human eye offers unique potential for non-invasive biomarker discovery. Ocular biomarkers can be utilized not only for diagnostics and therapeutic responses of ocular diseases, but also for monitoring environmental exposures and predicting systemic health outcomes. Retinal imaging modalities such as color fundus photography, optical coherence tomography, and optical coherence tomography angiography capture biomarkers linked to environmental exposures and systemic conditions like cardiovascular and neurodegenerative diseases, a field known as oculomics. Similarly, ocular fluids, such as tears, aqueous humor and vitreous humor, may also reflect pollution-induced oxidative stress and inflammation and systemic health conditions. This paper summarizes current evidence on how ocular biomarkers can bridge environmental exposures and systemic health outcomes, and proposes future research directions using state of the art methodologies such as exposome-wide association studies, high dimensional mediation analysis, and multi-modal foundation models. Despite encouraging progress, significant challenges remain, including the need for large and standardized datasets, rigorous validation, and ethical safeguards to ensure equitable application. Advances in artificial intelligence, including federated learning, alongside global consortium efforts, will be essential to overcome these barriers. Addressing these gaps will unlock the full potential of oculomics and exposomics, advancing the goals of precision environmental health.