Riboflavin-UV crosslinking of the cornea: Wound healing and biomechanics

The corneal wound healing response to Riboflavin-ultraviolet-crosslinking (RIB-UV-CXL) depends on the specific method used in treatment. The predominance of clinical evidence supports the classical "epithelium-off" RIB-UV-CXL method being more effective in halting ectasia progression than various "epithelium-on" methods, where the corneal epithelium is maintained intact. Corneal transparency results from the precise organization of collagen fibrils and extracellular matrix, along with transparent keratocytes. The mild and transient stromal opacity seen after standard RIB-UV-CXL is linked to changes in hydration, cellularity, and matrix composition. As hydration normalizes, opacity arises from the development of corneal fibroblasts and their secretion of disordered extracellular matrix materials including collagens. Over months, as the epithelial basement membrane regenerates, transitioning stromal cells either undergo apoptosis or revert to keratocan-positive keratocytes, restoring stromal transparency. In normal healing after standard RIB-UV-CXL, the stroma is eventually repopulated predominantly by keratocytes without significant persisting fibroblasts, immune cells, or myofibroblasts. Biomechanical studies have extensively explored how CXL strengthens corneal tissue, providing insight into its therapeutic mechanisms. The purpose of this review is to evaluate the wound healing response and biomechanical changes in the cornea following RIB-UV-CXL.