Retinal vascular signatures predict risk of depression and subsequent chronic diseases: A longitudinal study

Depression poses major global health challenges and accelerates chronic disease development, yet remains undertreated due to reliance on subjective diagnostics. The retina, as an embryological extension of the central nervous system and the organ allowing direct visualization of neurovascular structures, has been demonstrated to serve as an accessible window for systemic health assessment. This study aimed to prospectively examine associations of retinal vascular features with incident depression in healthy individuals and subsequent chronic disease development in those with depression.

This UK Biobank cohort study included 43,445 participants with acceptable-quality fundus photographs, divided into healthy (n = 40,905) and baseline depression (n = 2540) cohorts. After excluding 1033 participants with pre-existing chronic diseases, 1507 were eligible for chronic disease outcome analysis. Retinal vascular features were quantified using AutoMorph and Cox models examined associations with outcomes.

Over a median 11.3-year follow-up, wider retinal veins were associated with increased incident depression risk (central retinal vein equivalent: HR 1.25, 95% CI 1.06-1.48; vein average width: HR 1.31, 95% CI 1.12-1.54). Among those with baseline depression, lower arterial vessel density was associated with overall chronic disease risk (HR 0.71, 95% CI 0.54-0.95), while increased retinal tortuosity was associated with cardiovascular disease risk (vein tortuosity density: HR 2.24, 95% CI 1.25-4.01; artery tortuosity density: HR 1.90, 95% CI 1.17-3.07).

Retinal venous caliber and arterial tortuosity were robustly associated with incident depression and cardiovascular disease risk, respectively, supporting retinal vascular imaging as a promising biomarker candidate warranting further validation.