Development and Validation of an AI-Based Tool to Detect Subclinical Atherosclerosis Using Non-Mydriatic Retinal Fundus Images: The AI-THEROSCOPE Project

Cardiovascular disease remains the leading cause of mortality worldwide. Current cardiovascular risk prediction models are useful for population-level risk estimation but may underestimate risk in a substantial proportion of individuals who already have subclinical atherosclerosis. Vascular ultrasound of the carotid and femoral arteries allows direct visualization of atherosclerotic plaques and improves cardiovascular risk stratification, but its widespread use is limited by the requirement for specialized equipment and trained personnel.

Retinal fundus imaging provides a non-invasive assessment of the microvasculature and has emerged as a promising tool for cardiovascular risk evaluation. Recent advances in artificial intelligence and deep learning have demonstrated the ability of retinal image analysis to identify cardiovascular risk factors and predict cardiovascular outcomes.

The AI-THEROSCOPE study is a prospective observational study designed to develop and validate an artificial intelligence model for the detection of subclinical atherosclerosis using non-mydriatic retinal fundus photographs. Adult participants without previous cardiovascular disease undergo standardized clinical evaluation, laboratory testing, carotid and femoral vascular ultrasound, and bilateral retinal fundus photography.

The presence of carotid and/or femoral atherosclerotic plaque assessed by vascular ultrasound serves as the reference standard. Deep learning techniques will be used to train and validate predictive models based on retinal images. Model performance will be evaluated using discrimination metrics including the area under the receiver operating characteristic curve (AUC), sensitivity, specificity, positive predictive value, and negative predictive value.

The ultimate objective of the project is to develop a scalable, non-invasive, and easily deployable tool that may facilitate early detection of subclinical atherosclerosis and improve cardiovascular risk stratification in clinical practice and population screening programs.