Collagen Cross-linking for Microbial Keratitis

Collagen cross-linking is gaining popularity not only for arresting the progression of keratoconus but also other indications including management of corneal infections. In this review article, we analyzed the published literature to understand the level of evidence for its use in corneal ulcer. Photoactivated riboflavin and ultraviolet A light are known to possess antimicrobial properties. The treatment also induces formation of inter- and intra-fibrillar bonds, thereby making the corneal collagen resistant to the action of proteases arresting stromal melt. Both properties are well documented in in vitro experiments. The antimicrobial action is seen against bacteria, fungi, and parasites. The animal experiments have documented its efficacy against bacterial and fungal keratitis models. The literature on its application in human corneal infection is highly variable and comprises case reports, case series, and comparative nonrandomized and randomized trials. The treatment has been used as primary treatment, adjunctive treatment along with antibiotics, as the first line of treatment as well as for failed medical treatment cases. Even the cases included are of variable severity caused by a variety of microorganisms including culture-negative cases. Furthermore, the treatment protocols are also variable. While most reports show beneficial effects for bacterial corneal ulcer cases, especially those with superficial infiltrate, the effect has been mixed for fungal and parasitic keratitis. In view of these characteristics, we infer that the level of evidence for its use in corneal ulcer is at most weak. We need well-characterized, high-quality, clinical trials of sufficient power to assess its true value.