Can the effect of transepithelial corneal collagen cross-linking be improved by increasing the duration of topical riboflavin application? An in vivo confocal microscopy study.

Objective: To evaluate the effect of transepithelial corneal collagen cross-linking (CXL) with prolonged riboflavin application by in vivo confocal microscopy and to compare this effect with that of standard CXL with complete epithelial debridement.

Methods: In eyes with progressive keratoconus, CXL procedure was performed with standard technique and transepithelial technique after prolonged riboflavin drop application for 2 hr. Patients were evaluated with in vivo confocal microscopic examination preoperatively and at postoperative months 1 and 6.

Results: The depth of CXL effect was similar in both groups (i.e., 380.86 ± 103.23 μm in standard CXL group and 342.2 ± 68.6 μm in transepithelial CXL group) (P=0.4). The endothelial cell counts and morphological parameters (i.e., pleomorphism and polymegathism) were not significantly affected in both groups (P>0.05 for all). In the standard CXL group, in vivo confocal microscopy revealed anterior stromal acellular hyperreflective honeycomb edema with posteriorly gradually decreasing reflectivity and increasing number of keratocytes and some sheets of longitudinally aligned filamentary deposits. The keratocytes were seen to repopulate in the posterior-to-anterior direction. In transepithelial CXL group, although the depth of CXL effect was similar, less pronounced keratocyte damage, extracellular matrix hyperreflectivity, and sheets of filamentary deposits at the posterior stroma was observed.

Conclusions: Transepithelial CXL with prolonged peroperative riboflavin application can achieve similar depth of effect in the stroma with less pronounced confocal microscopic changes as compared with the standard CXL with complete epithelial debridement.