Endothelial Safety Of Corneal Cross-Linking In Thin Corneas: Cct 400-450 µm Versus >450 µm Subgroup Analysis

To compare the endothelial safety profile of standard corneal collagen cross-linking (CXL) between keratoconus eyes with central corneal thickness (CCT) 400-450 µm (thin cornea subgroup) and CCT >450 µm (standard subgroup) using serial specular microscopy.

Department of Ophthalmology, Recep Tayyip Erdogan University Training and Research Hospital, Rize, Turkey. Prospective subgroup analysis.

From a cohort of 60 keratoconus eyes undergoing standard epithelium-off CXL, eyes were stratified by preoperative CCT after epithelial removal: Group A (thin cornea, CCT 400-450 µm) and Group B (standard, CCT >450 µm). Specular microscopy (Tomey EM-4000) was performed preoperatively and at 1, 3, and 6 months post-CXL. Endothelial cell density (ECD), coefficient of variation (CV), hexagonal cell percentage (HEX), and CCT were compared between groups at each time point. Primary outcome was ECD change at 6 months. An ECD loss >10% was considered clinically significant. Statistical analysis included independent t-test, Mann-Whitney U test, and repeated measures ANOVA with group interaction (SPSS 23.0; p<0.05).

Group A included 22 eyes (CCT 428±14 µm) and Group B 38 eyes (CCT 482±21 µm). Baseline ECD was similar (2819±308 vs 2863±318 cells/mm²; p=0.598). At 1 month, ECD loss was greater in Group A (3.1% vs 1.4%; p=0.038) with higher CV (36.8±6.2% vs 34.1±5.1%; p=0.042). By 6 months, recovery was comparable: 0.7% vs 0.4% loss (p>0.5). No eye showed >10% ECD loss. Group×time interaction was not significant for ECD, CV, or HEX (p>0.18). Topographic stabilization was similar (90.9% vs 92.1%; p=0.872).

CXL in thin corneas (CCT 400-450 µm) causes slightly greater but still transient endothelial perturbation at 1 month compared with standard-thickness corneas, with complete recovery by 6 months. No clinically significant endothelial cell loss was observed in either group. These findings confirm the endothelial safety of standard CXL down to the 400 µm threshold and may reassure clinicians managing keratoconus patients with borderline corneal thickness.