The biology of corneal cross-linking derived from ultraviolet light and riboflavin

Over the past 20 years, corneal crosslinking (CXL) has been used by surgeons to halt progression in eyes with keratoconus. We reviewed the literature regarding the mechanism of action of CXL, the role of each of its components the strong biologic reaction, and their effects on cell interaction, proteins involved, wound healing, and cytotoxic reaction. CXL surgery involves a photochemical response in which ultraviolet light at a given wavelength and riboflavin participate. The combination of irradiation with UVA light and riboflavin leads to an intense process of apoptosis of keratocytes in the anterior stroma. Differences in light irradiation, as well as the importance of riboflavin and its vehicle, were also detailed. The surgery creates additional chemical bonds between the amino terminals of the collagen side chains and the proteoglycans of the extracellular matrix. A photosensitization reaction catalyzed by riboflavin classically involves the production of singlet oxygen. Microstructure studies show changes in the size of the fibril and potentially in the interfibrillar space, that the most significant changes related to the stiffening effect of CXL occur in the anterior third of the cornea and that short irradiation times, especially below 5 min, may not have the same biological effect. Changes in the riboflavin vehicle, with the incorporation of Hydroxypropyl methylcellulose as a carrier, can lead to faster diffusion and a more intense photochemical reaction. These are findings that can impact the optimal adjustment of irradiation time according to the riboflavin (and its carrier) used. Many studies have suggested that CXL is safe and effective in the standard and accelerated protocols that have been used by surgeons. After the initial depletion of anterior keratocytes, keratocyte density seems to return to average 6–12 months after surgery when corneas are examined with the confocal microscope.