Effect Of Corneal Collagen Cross-Linking On Corneal Endothelial Cell Morphology In Keratoconus: A Prospective Controlled Study With Specular Microscopy

To evaluate the effect of corneal collagen cross-linking (CXL) on corneal endothelial cell density (ECD), morphology, and central corneal thickness (CCT) in keratoconus patients compared with age-matched healthy controls using specular microscopy.

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

Sixty eyes of 60 keratoconus patients (aged 14-35) who underwent standard Dresden protocol CXL (epithelium-off, riboflavin 0.1%, UVA 370 nm, 3 mW/cm², 30 min) and 60 age/sex-matched controls were enrolled. Patients with CCT <400 µm post-debridement, prior surgery, recent contact lens use, guttata, or connective tissue disorders were excluded. Specular microscopy (Tomey EM-4000) was performed preoperatively and at 1, 3, and 6 months. Parameters: ECD, mean cell area, CV, hexagonality (HEX), and CCT. Statistics: repeated measures ANOVA, paired and independent t-tests (SPSS 23.0; p<0.05).

Preoperative ECD was comparable between groups (2847±312 vs 2921±287; p=0.178). At 1 month, ECD decreased 2.0% (p=0.034), CV increased (p=0.012), and HEX decreased (p=0.008). By 6 months, all parameters returned to near-baseline with no significant differences versus controls (all p>0.05). CCT decreased at 1 month (p=0.003) but recovered by 6 months (p=0.267). Keratometry stabilized or improved in 91.7%.

Standard CXL causes transient, reversible changes in corneal endothelial cell density and morphology. Statistically significant but clinically modest reductions in ECD and hexagonality at 1 month fully recover by 6 months, confirming the endothelial safety of the Dresden protocol in keratoconus patients with adequate stromal thickness. These findings support the protective threshold of 400 µm recommended to prevent UV-induced endothelial damage during CXL.