PURPOSE: To provide a background regarding the biochemical rationale for corneal collagen cross-linking (CXL) and outline its current use, critically evaluate the current literature for the use of CXL in nonectatic disorders, highlight limitations and areas for further research, and address additional novel applications of CXL. METHODS: A literature search was performed using the EMBASE and MEDLINE database from 1970 to November 2011. Keywords included "corneal collagen cross linking," "crosslinking," "cross-linking," "ultraviolet," "riboflavin," "corneal edema," and "keratitis" in various combinations. A search through the references of retrieved articles was also performed. RESULTS: Cross-linking for corneal edema showed a temporary improvement in objective measures of central corneal thickness, corrected distance visual acuity, and corneal clarity along with subjective measures such as pain and irritation. Cross-linking was also tolerated as an adjunctive therapy for infectious keratitis without complications. In all studies, the progression of corneal melting was halted after treatment, avoiding the need for emergency keratoplasty. CONCLUSIONS: Cross-linking with riboflavin and ultraviolet A light is a promising, minimally invasive treatment for corneal ectasia. A growing number of studies suggest additional application in corneal edema and infectious keratitis may be beneficial. However, further studies are needed to address long-term outcomes and safety concerns.
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