Retinal fundus imaging as biomarker for ADHD using machine learning for screening and visual attention stratification.

Attention-deficit/hyperactivity disorder (ADHD), characterized by diagnostic complexity and symptom heterogeneity, is a prevalent neurodevelopmental disorder. Here, we explored the machine learning (ML) analysis of retinal fundus photographs as a noninvasive biomarker for ADHD screening and stratification of executive function (EF) deficits. From April to October 2022, 323 children and adolescents with ADHD were recruited from two tertiary South Korean hospitals, and the age- and sex-matched individuals with typical development were retrospectively collected. We used the AutoMorph pipeline to extract retinal features and used four types of ML models for ADHD screening and EF subdomain prediction, and we adopted the Shapely additive explanation method. ADHD screening models achieved 95.5%-96.9% AUROC. For EF function stratification, the visual and auditory subdomains showed strong (AUROC > 85%) and poor performances, respectively. Our analysis of retinal fundus photographs demonstrated potential as a noninvasive biomarker for ADHD screening and EF deficit stratification in the visual attention domain.