The Biomarker Landscape of Ocular Ageing: Emerging Insights and Applications

ABSTRACT Ageing is a complex, multifactorial biological process characterised by progressive molecular, cellular, and functional decline across organ systems, ultimately increasing susceptibility to chronic diseases and mortality. The eye, with its transparent and easily accessible structures, offers a unique and non-invasive platform for studying systemic ageing and detecting early biological alterations. Recent advances in retinal imaging, optical coherence tomography (OCT), and artificial intelligence (AI) have heightened interest in ocular biomarkers as indicators of biological age and predictors of age-related disease risk. This systematic review synthesises evidence on molecular, imaging-based, OCT-derived, and lens-related biomarkers of ocular ageing, highlighting their associations with systemic ageing, morbidity, and mortality. Key biomarkers include the retinal age gap, retinal microvascular alterations, OCT-derived structural parameters and the Lens age index. Collectively, these markers capture both localised manifestations of ocular ageing and broader systemic health trajectories, making them valuable candidates for early disease detection and biological risk assessment. Beyond diagnostic applications, these biomarkers may enhance personalised risk stratification, support preventive interventions, and facilitate integration with systemic ageing clocks. However, their clinical adoption faces challenges, including variability in measurement techniques, lack of standardised protocols, and limited validation across diverse populations. Addressing these barriers through harmonised methodologies, longitudinal studies, and multi-omics integration will be critical to establishing ocular biomarkers as robust and clinically reliable measures of ageing. Ultimately, their implementation could advance precision medicine, enabling earlier intervention and improved healthspan outcomes. Keywords: Ocular ageing, Biomarkers, Retinal age gap, OCT, Lens age, Systemic ageing, Morbidity, Artificial intelligence, Preventive interventions, Precision medicine.