Comprehensive review of collagen cross-linking

Researchers used the Medline database, textbooks, and industry literature to put together a comprehensive review of the history, techniques, important studies, and areas of needed future research for collagen cross-linking.

Since 2003 there has been a handful of studies on the efficacy and safety of cross-linking in humans. While the methodologies of these studies differed in terms of inclusion and exclusion criteria, treatment parameters, outcome measures, and analysis, they all reported varying degrees of improvement in visual acuity and reduction in keratometry, with a progressive trend in improvement for the duration of follow-up, which in some cases was more than three years. No major complications were noted, although some studies have since retreated their non-responders.

The primary challenge in identifying a treatment for keratoconus is understanding the pathophysiology of the disease. Cross-linking is a scientifically sound approach to reducing the risk of ectasia and has the potential to revolutionize the way the disease is managed in the future, but concerns remain regarding the safety and long-term efficacy of the treatment. More research needs to be done on the treatment's long-term affect on tissue and IOP before standard protocols for such things as indications for retreatment and minimum corneal thickness can be developed. There is also plenty of room for research into eliciting the natural or pathological cross-linkage mechanisms through enzymatic or non-enzymatic glycosylation.

The authors conclude that while this is an area of exciting potential, questions remain regarding long-term effects, and as such it is incumbent upon surgeons to make it clear that the procedure is irreversible and provide patients with appropriate information on cross-linking's efficacy and risks.