Getting Double Crossed.

Keratoconus is a non-inflammatory corneal dystrophy in which the cornea deforms due to thinning and protrusion. The biomechanical strength of the cornea depends on the lamellar organization of the collagen fibers that comprise the corneal stroma, regulated by an interconnecting network of proteoglycans. Although the pathogenesis of keratoconus remains unclear, it appears that a primary event leads to the loss and/or slippage of collagen fibrils and changes to the extracellular matrix in the corneal stroma. Recently, the corneal collagen cross-linking procedure (CXL) has been developed. CXL is accomplished by instilling riboflavin drops onto the cornea and then irradiating the cornea with ultraviolet-A (365-nm) light (Figure 1). CXL aims to halt the keratoconus disease process by stabilizing the collagen lamellae, mimicking the age-related cross-linking that occurs in the cornea due to the accumulation of non-enzymatic glycation end products over time. The treatment results in mechanical stiffening of the cornea, with the clinical goal being a consequent decrease in progression of the disease process. In vitro studies show that stress measurement increases immediately after CXL in human corneas by more than 300%. When activated with ultraviolet-A light in the presence of oxygen, riboflavin is converted into excited singlet and triplet states, which then undergo a series of chemical reactions resulting in the formation of reactive species that interact with corneal proteins and lead to the formation of chemical bonds. Several different pathways lead to the formation of cross-link bonds, driven by the relative availabilities of oxygen, riboflavin, and ultraviolet light. Under aerobic conditions, singlet oxygen and hydroxyl radicals are the reactive oxygen species produced that react with the collagen to form these bonds. Under anaerobic conditions, radical riboflavin may also lead to the production of cross-link bonds. Balancing the competing aspects of the reaction by controlling the rate of oxygen consumption allows for control of the distribution of cross-link bonds formed in the cornea. Several changes have been reported in both in vitro and clinical studies of the cornea after CXL. These include increased collagen fiber diameter, Getting Double Crossed