UVA-light and riboflavin-mediated corneal collagen cross-linking.

Keratoconus and other corneal conditions associated with progressive stromal thinning including keratectasia after laser-assisted in situ keratomileusis (LASIK) and pellucid marginal degeneration represent therapeutic challenges. Until recently, available therapies including contact lenses, epikeratoplasty, intrastromal corneal rings, and corneal transplantation targeted, in principle, the abnormal shape of the cornea by mechanical means. The underlying molecular pathogenic mechanisms of corneal ectasia were not addressed with any of these therapies until the introduction of corneal collagen cross-linking to clinical practice in 1999.1 This breakthrough clinical application was the result of multiple laboratory observations and discoveries made over preceding decades. Early experiments of Cannon and Foster2 showed that degraded normal collagen or synthesis of abnormal collagen might play a role in the pathogenesis of keratoconus. This concept was later confirmed by subsequent clinical and experimental studies. Keratoconus was characterized by progressive stromal thinning and ectasia3 as a result of increased expression of lysosomal and proteolytic enzymes4–7 and decreased concentration of protease inhibitors,5,8 which result in corneal thinning and altered configuration of corneal collagen lamellae.9,10