Corneal endothelial changes in type 2 diabetes mellitus: a systematic review and meta-analysis with subgroup comparisons by diabetic retinopathy status and disease duration

Background Type 2 diabetes mellitus (T2DM) affects multiple ocular structures, yet the extent of corneal endothelial alterations across different stages of diabetic retinopathy (DR) and disease duration remains unclear. This meta-analysis quantified corneal endothelial changes in T2DM across subgroups defined by DR status and diabetes duration. Methods This systematic review adhered to PRISMA and MOOSE guidelines (PROSPERO: CRD420261473313). Five databases were searched from inception through July 15, 2026. Cross-sectional studies comparing endothelial cell density (ECD), coefficient of variation (CV), and percentage of hexagonal cells (HEX) in T2DM patients versus controls or between T2DM subgroups were included. Study quality was assessed using the AHRQ checklist. Effect sizes were calculated as Cohen’s d using fixed-effect or random-effects models based on heterogeneity. Sensitivity analyses used the leave-one-out method; publication bias was assessed with funnel plots, Egger’s test, and trim-and-fill analysis. Results Twenty-two studies (5,878 eyes) were included. T2DM patients showed significantly lower ECD (d = −0.35, P < 0.001), higher CV (d = 0.25, P < 0.001), and lower HEX (d = −0.28, P < 0.001) versus controls. Eyes with DR had lower ECD (d = −0.22, P = 0.002), higher CV (d = 0.26, P = 0.005), and lower HEX (d = −0.23, P = 0.02) versus eyes without DR. No significant differences emerged between PDR and NPDR. Longer disease duration (≥10 years) was associated with lower ECD (d = −0.39, P = 0.04) and lower HEX (d = −0.18, P = 0.003). Sensitivity analyses showed that HEX (T2DM vs. controls), CV (PDR vs. NPDR), and CV (duration comparison) were not robust; trim-and-fill reversed the CV duration result. Conclusions T2DM is associated with impaired corneal endothelial morphology, with greater changes in the presence of DR and longer duration. Several estimates were sensitive to individual studies or publication bias, warranting cautious interpretation. Preoperative endothelial assessment may be beneficial in diabetic patients, particularly those with DR or long disease duration. Systematic review registration https://www.crd.york.ac.uk/PROSPERO/view/CRD420261473313 , identifier CRD420261473313.