Background Automated disease screening systems face challenges when applied to multi-class medical image analysis, particularly under severe class imbalance inherent in clinical datasets. Retinal fundus imaging enables non-invasive screening for multiple ocular and systemic diseases simultaneously, yet current automated systems typically assess risk for only a single pathology or a limited disease range. We developed a comprehensive AI framework for simultaneous risk stratification of 15 distinct pathological conditions from retinal fundus images and report its preliminary evaluation in a real-world clinical setting. Methods Our system combines fundus images from publicly available sources and proprietary clinical archives, addressing the significant class imbalance challenge inherent in rare condition risk assessment. We employed a hybrid deep learning architecture (CAFormer B36) with focal loss and targeted oversampling to ensure robust performance across common and rare conditions. The framework identifies retinal biomarkers associated with both primary ocular diseases (diabetic retinopathy, glaucoma, macular degeneration, cataracts, retinitis pigmentosa) and systemic conditions with retinal manifestations (hypertensive retinopathy, atherosclerotic changes, autoimmune manifestations). Dataset splitting was performed at the image level; all internal metrics should therefore be interpreted as exploratory upper-bound estimates pending patient-level replication. Results On the internal image-level test set, the system achieved ROC AUC of 0.9524–0.9971 across all 15 pathological classes, with F1 scores of 0.8968–0.9649. Notably, rare conditions with fewer than 100 training examples demonstrated robust risk stratification performance. In an exploratory single-site evaluation on 68 real-world cases, overall accuracy was 64.7% (95% CI: 52.9–76.5%). Due to the very limited number of sight-threatening cases in this small cohort (glaucoma n = 2, diabetic retinopathy n = 4), sensitivity estimates for these categories carry extremely wide confidence intervals and cannot be considered statistically reliable. These findings underscore the need for larger, prospective, multicenter studies. Conclusions This pilot proof-of-concept demonstrates the feasibility of multi-pathology risk stratification under severe class imbalance using a hybrid deep learning architecture. Internal image-level metrics show strong discriminative capability, while the preliminary single-site evaluation ( n = 68, 64.7% accuracy) reveals the challenges of real-world translation and the substantial gap that remains before clinical deployment. This work provides a methodological foundation for future prospectively validated screening systems.
Vasilev et al. (Mon,) studied this question.