Deep-learning prediction of cardiovascular outcomes from routine retinal images in individuals with type 2 diabetes.

Background: Prior studies have demonstrated an association between retinal vascular features and cardiovascular disease (CVD), however most studies have only evaluated a few simple parameters at a time. Our aim was to determine whether a deep-learning artificial intelligence (AI) model could be used to predict CVD outcomes from routinely obtained diabetic retinal screening photographs and to compare its performance to a traditional clinical CVD risk score.

Methods: We included 6127 individuals with type 2 diabetes without myocardial infarction or stroke prior to study entry. The cohort was divided into training (70%), validation (10%) and testing (20%) cohorts. Clinical 10-year CVD risk was calculated using the pooled cohort equation (PCE) risk score. A polygenic risk score (PRS) for coronary heart disease was also obtained. Retinal images were analysed using an EfficientNet-B2 network to predict 10-year CVD risk. The primary outcome was time to first major adverse CV event (MACE) including CV death, myocardial infarction or stroke.

Results: 1241 individuals were included in the test cohort (mean PCE 10-year CVD risk 35%). There was a strong correlation between retinal predicted CVD risk and the PCE risk score (r = 0.66) but not the polygenic risk score (r = 0.05). There were 288 MACE events. Higher retina-predicted risk was significantly associated with increased 10-year risk of MACE (HR 1.05 per 1% increase; 95% CI 1.04-1.06, p < 0.001) and remained so after adjustment for the PCE and polygenic risk score (HR 1.03; 95% CI 1.02-1.04, p < 0.001). The retinal risk score had similar performance to the PCE (both AUC 0.697) and when combined with the PCE and polygenic risk score had significantly improved performance compared to the PCE alone (AUC 0.728). An increase in retinal-predicted risk within 3 years was associated with subsequent increased MACE likelihood.

Conclusions: A deep-learning AI model could accurately predict MACE from routine retinal screening photographs with a comparable performance to traditional clinical risk assessment in a diabetic cohort. Combining the AI-derived retinal risk prediction with a coronary heart disease polygenic risk score improved risk prediction. AI retinal assessment might allow a one-stop CVD risk assessment at routine retinal screening.