Macular Choriocapillaris and Retinal Microvascular Alterations Across the Prediabetes–Early Type 2 Diabetes Continuum

Abstract

Purpose To characterize macular microvascular alterations across the dysglycemia spectrum, from prediabetes (pre-DM) to early type 2 diabetes (T2DM), before clinically detectable diabetic retinopathy develops. Methods In this cross-sectional study, participants with pre-DM, recent-onset T2DM, and age-matched healthy controls underwent swept-source optical coherence tomography angiography. Quantified metrics included vessel density (VD), perfusion density (PD), foveal avascular zone acircularity, and choriocapillaris flow-deficit (FD) density and size. One eye per participant was analyzed. Feature importance was assessed using a random forest model with SHAP values. Results Analysis of 309 eyes (79 controls, 85 pre-DM, 75 T2DM <3 years, and 70 T2DM 3–7 years) showed that microvascular impairment is evident from the prediabetic stage. Compared with controls, participants with prediabetes had lower VD and PD in both superficial and deep capillary plexuses, together with higher choriocapillaris FD density (all P < 0.05). Retinal capillary metrics were similar between pre-DM and early T2DM (all P > 0.05), whereas choriocapillaris impairment progressed across dysglycemia stages, with large-size FD density increasing from pre-DM to T2DM <3 years and T2DM 3–7 years (9.3 ± 0.9 vs. 9.7 ± 1.1 and 9.8 ± 1.0, P < 0.05). Among OCTA metrics, choriocapillaris FD density showed the strongest discriminatory ability and was the most influential feature in SHAP analysis. Conclusions Macular microvascular impairment begins in prediabetes. Retinal capillary changes plateau early, whereas choriocapillaris impairment progresses with worsening dysglycemia, suggesting greater sensitivity of choriocapillaris metrics for monitoring early metabolic disease.