Phenotypic screening and genetic insights for predicting major vascular-related diseases using retinal imaging

Retinal photography is a valuable non-invasive tool for assessing vascular health, but genetic evidence linking retinal microcirculation to major vascular-related diseases (e.g., myocardial infarction [MI], stroke, and chronic kidney disease [CKD]) remains scarce. This study investigates their relationships from both phenotypic and genetic perspectives. Phenotypically, we developed a retinal imaging-based screening model to evaluate 10-year risk of these conditions, incorporating quantitative analyses to pinpoint specific vascular abnormalities. Genetically, we analyzed retinal image-derived traits to explore their genetic and causal relationships with vascular-related diseases. Internal validation with 25,840 UK Biobank participants and external temporal validation with 4558 participants confirmed the model's superiority over traditional risk models. Mendelian randomization suggested causal relationships between retinal traits and stroke and MI, as well as the impact of CKD on retinal microcirculation. These findings reinforce the connection between retinal microcirculation and major vascular-related events, highlighting the potential of retinal imaging for early detection in clinical settings.