Artificial intelligence-based analysis of retinal vascular changes in the preclinical and early stages of diabetic retinopathy using ultra-widefield fundus imaging: an observational cross-sectional study.

BACKGROUND

Subclinical retinal microvascular remodeling may occur before clinically detectable diabetic retinopathy (DR). This study investigated artificial intelligence (AI)-derived ultra-widefield retinal vascular metrics in patients with type 2 diabetes mellitus (T2DM) with and without non-proliferative DR (NPDR), and evaluated their potential for early vascular phenotyping and diagnostic discrimination.

METHODS

In this observational cross-sectional single-center study, 237 participants were included: 63 healthy controls (103 eyes), 101 patients with T2DM without DR (No-DR; 201 eyes), and 73 patients with NPDR (132 eyes). Non-mydriatic 200-degree ultra-widefield fundus images were analyzed using an AI-based vascular segmentation and quantification system. AI-exported values coded as -1 were treated as missing, and sparse parameters were excluded from primary inference. Intergroup comparisons of retained vascular parameters were performed using age- and sex-adjusted mixed-effects models with participant as a random intercept, followed by Benjamini-Hochberg false discovery rate (FDR) correction. Multiparameter logistic models were evaluated using 5-fold subject-level cross-validation.

RESULTS

After quality control, covariate adjustment, and FDR correction, 38 vascular-parameter rows remained significant. Whole-field vessel density was highest in the No-DR group, intermediate in NPDR, and lowest in controls [control, 0.017 (0.008-0.023); No-DR, 0.026 (0.020-0.032); NPDR, 0.021 (0.015-0.026); FDR P < 0.001]. Fractal-dimension metrics showed similar early alterations, with arterial fractal dimension increased in No-DR and intermediate in NPDR [control, 1.287 (1.164-1.359); No-DR, 1.380 (1.328-1.420); NPDR, 1.329 (1.271-1.374); FDR P < 0.001]. Whole-field mean vessel diameter was lower in No-DR than in controls, whereas total vessel length decreased across controls, No-DR, and NPDR (FDR P < 0.001 for both). Regional heatmaps showed that significant density and fractal-dimension signals clustered mainly in the superotemporal, superonasal, and inferotemporal regions. Cross-validated models showed good discrimination for No-DR versus control (AUC, 0.853; 95% CI, 0.807-0.893), NPDR versus control (AUC, 0.785; 95% CI, 0.720-0.841), and No-DR/NPDR versus control (AUC, 0.830; 95% CI, 0.788-0.873), but more modest discrimination between NPDR and No-DR (AUC, 0.658; 95% CI, 0.596-0.720).

CONCLUSION

AI-derived ultra-widefield retinal vascular metrics demonstrate early, spatially heterogeneous microvascular remodeling in T2DM before clinically apparent DR. Vessel density, fractal dimension, vessel diameter, and vessel length provide complementary information, and multiparameter vascular modeling may support early detection and risk stratification. External validation and longitudinal studies are required before clinical implementation.