Retinal Vascular Features and Risk of Colorectal Cancer Incidence and Mortality: A Population-Based Cohort Study

INTRODUCTION: Colorectal cancer (CRC) screening remains limited by invasiveness and suboptimal sensitivity of current methods. Retinal microvasculature, a noninvasive window into systemic vascular health, may reflect CRC-associated angiogenesis and inflammation. We investigated whether artificial intelligence (AI)-derived retinal vascular features (RVFs) are associated with CRC risk and prognosis. METHODS: This analysis included UK Biobank participants with baseline fundus imaging. Multidimensional RVFs, including tortuosity, branching angle, caliber, density, and complexity, were quantified using the Retina-based Microvascular Health Assessment System (RMHAS). Associations of RVFs with incident CRC and mortality among patients with CRC were evaluated using univariable and multivariable Cox regression models. RESULTS: Among 55,798 participants (mean age 55.47 ± 8.09 years; 55.07% female), over a median follow-up of 11.32 years, 652 incident CRC cases (including 488 colon cancers and 260 rectal cancers) and 171 post-CRC deaths were documented. After full adjustment, four RVFs showed significant associations with CRC risk: increased arterial tortuosity (hazard ratio [HR] 1.03, 95% confidence interval [CI] 1.01-1.06), wider venular minimum branching angle (HR 1.09, 95% CI 1.02-1.17), smaller arterial maximum branching coefficient (HR 0.90, 95% CI 0.82-0.99), and reduced venular angular asymmetry (HR 0.89, 95% CI 0.82-0.96). For mortality, higher venular tortuosity (HR 1.14, 95% CI 1.00-1.31) and increased arterial maximum length diameter ratio (HR 1.16, 95% CI 1.01-1.32) were associated with elevated risk, whereas venular caliber (HR 0.81, 95% CI 0.67-0.98) and venular length diameter ratio (HR 0.82-0.84) were inversely associated with mortality. Distinct RVF patterns were observed between colon and rectal cancers. CONCLUSION: Specific AI-derived RVFs were independently associated with CRC risk, its subtypes, and mortality. These findings suggest that retinal microvascular changes may reflect systemic processes related to carcinogenesis and point to the potential of retinal imaging as a noninvasive tool for CRC risk stratification.