Deep learning-derived retinal biomarker associated with diabetes-related amputation in type 2 diabetes

Diabetic foot (DF)-related amputation remains a major cause of morbidity in patients with type 2 diabetes, yet biomarkers associated with amputation risk remain limited. We aimed to assess the independent association between a deep learning (DL)-derived retinal biomarker using coronary artery calcification (Dr. Noon CVD) and DF-related amputation in patients with type 2 diabetes. This retrospective observational study conducted in a university hospital in South Korea included 392 individuals with type 2 diabetes receiving ophthalmic care (79 with DF-related amputation and 313 without). Participants were randomly split into training (70%) and validation (30%) sets. Model performance in relation to DF-related amputation was assessed using area under the receiver operating characteristic curve (AUC), continuous net reclassification index (cNRI), and integrated discrimination improvement (IDI). Prespecified rule-out (sensitivity ≥0.85) and rule-in (specificity ≥0.90) thresholds were also applied. Adding the retinal biomarker to a basic clinical model showed incremental association with DF-related amputation in the validation set (AUC 0.146, 95% CI: 0.046-0.249; cNRI 0.629, 95% CI: 0.184-1.027; IDI 0.062, 95% CI: 0.012-0.110). The full model achieved an AUC of 0.791, and the association remained consistent across sensitivity analyses using DF risk score derived from the external dataset. Under a 27% amputation prevalence (based on the reported prevalence of amputation among patients with diabetic foot), sensitivity was 87.5% with a negative predictive value of 92.6% at the rule-out cutoff; specificity was 90.4% with a positive predictive value of 56.3% at the rule-in cutoff. A DL-derived retinal biomarker shows meaningful association with DF-related amputation beyond conventional diabetes variables.