Cross-linking of collagen refers to the ability of collagen fibrils to form strong chemical bonds with adjacent fibrils. In the cornea, collagen cross-linking occurs naturally with aging due to an oxidative deamination reaction that takes place within the end chains of the collagen. It has been hypothesized that this natural cross-linkage of collagen explains why keratoectasia (corneal ectasia) often progresses most rapidly in adolescence or early adulthood but tends to stabilize in patients after middle-age.
In addition to the cross-linking that occurs commonly with corneal maturation, there are several other pathways that can lead to crosslinkage. Glycation refers to a reaction seen predominantly in diabetics that can lead to the formation of additional bonds between collagen. In the pathway most relevant to this topic, oxidation has been shown to be able to trigger corneal crosslinkage through the release of oxygen free radicals.
The bases for the currently employed corneal collagen cross-linking techniques were developed in Europe by researchers at the University of Dresden in the late 1990’s. UV light was used to induce collagen cross-linking in riboflavin soaked porcine and rabbit corneas via the oxidation pathway. The resultant corneas were shown to be stiffer and more resistant to enzymatic digestion. Investigation also proved that the treated corneas contained higher molecular weight polymers of collagen due to fibril crosslinking. Safety studies showed that the endothelium was not damaged by the treatment if proper UV irradiance was maintained and if the corneal thickness exceeded 400 microns.
Published data shows that CXL not only halts the progression of the keratoconus, but in some cases reverses some of the steepness of the cornea. The primary purpose of crosslinking is to halt the progression of ectasia. Likewise, the best candidate for this therapy is an individual with keratoconus or ectasia after LASIK|post-refractive surgery ectasia who has documented progression of the disease. There currently are no definitive criteria for progression, but parameters to consider are change in refraction (including astigmatism), uncorrected visual acuity, best corrected visual acuity, and corneal shape (topography and tomography).
Corneal collagen cross-linking is NOW fully FDA approved in the United States.