Development and validation of an artificial intelligence-based tool to detect subclinical atheroesclerosis using non-mydriatic retinal funduscopic images: the Aitheroscope project.

AIMS: Current cardiovascular risk scores may underestimate the risk of future cardiovascular events, particularly in younger individuals with prolonged exposure to risk factors. In contrast, imaging-based detection of subclinical atherosclerosis provides a more accurate assessment of cardiovascular risk by identifying established vascular disease. We aimed to develop and prospectively validate an artificial intelligence-based tool using retinal fundus images to detect ultrasound-confirmed subclinical atherosclerosis. METHODS AND RESULTS: In this prospective observational study, 931 participants (mean age 52.6 years; 70.2% women) without prior cardiovascular disease underwent standardized clinical evaluation, non-mydriatic retinal imaging, and carotid and femoral ultrasound to detect subclinical atherosclerosis. A multimodal AI model integrating deep learning from retinal images with radiomic and clinical data was developed in a derivation cohort (n = 781) and evaluated in a held-out prospective test set (n = 150).Subclinical atherosclerosis was present in 50.8% of participants. In the prospective test set, the AI model demonstrated good discrimination. In image-only mode, the model achieved an area under the curve (AUC) of 0.80 (95% CI 0.73-0.87), with sensitivity of 88.2%. In the enhanced mode incorporating clinical variables, performance improved to an AUC of 0.86 (95% CI 0.80-0.92), with sensitivity of 93.4% and a negative predictive value of 90.6%. Discrimination was higher in younger individuals and those at low-to-intermediate cardiovascular risk. CONCLUSION: AI-based retinal image analysis enables non-invasive detection of systemic subclinical atherosclerosis. This scalable approach may enhance early identification of high cardiovascular-risk patients, particularly in populations in whom risk is underestimated.