Sequential in vivo confocal microscopy study of corneal wound healing after cross-linking in patients with keratoconus

Abstract

PURPOSE: To evaluate the short- and long-term sequential histological changes of the cornea in vivo after corneal collagen cross-linking (CXL) in patients with keratoconus. METHODS: Eighteen patients with keratoconus (Amsler-Krumeich classification: stages I, II, and III) underwent CXL with riboflavin/ultraviolet A (UVA) in one eye. The corneas were examined preoperatively and within 5 hours, 7 and 14 days, and 1, 3, 6, 9, 12, 18, 24, and 36 months after the procedure using in vivo confocal microscopy. RESULTS: Early changes included edema, superficial nerve loss, cellular modifications, and isolated endothelial damage. At intermediate time points, there was nerve fiber regeneration, increased reflectivity of the extracellular matrix, enlarged keratocytes and extracellular deposits, and remodeling of the endothelial layer (two eyes). At later time points, loss of keratocytes and remodeling of the extracellular deposits were noted. CONCLUSIONS: Although the cornea has no significant tissue modifications clinically after CXL, this study has shown that corneal wounding by riboflavin/UVA collagen CXL induces cellular wound-healing mechanisms and alters the normal structure and cellularity of the cornea for up to 36 months.