Riboflavin/UVA for infectious keratitis holds promise for the future

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Encouraging results have been achieved using topical riboflavin and ultraviolet A irradiation to treat infectious keratitis.

By Cheryl Guttman Krader; Reviewed by Ashley Behrens, MD

The combination of topical riboflavin and ultraviolet A (UVA) light irradiation holds exciting potential as a treatment for infectious keratitis.

Further research is needed, however, before this novel photochemical therapy might be considered for routine use in the management of corneal infections, according to Ashley Behrens, MD.

“In vitro studies and some clinical reports show encouraging results using riboflavin/UVA as a treatment for microbial keratitis,” said Dr. Behrens, KKESHWEI Professor in International Ophthalmology, Wilmer Eye Institute, Johns Hopkins School of Medicine, Baltimore, and executive medical director, The King Khaled Eye Specialist Hospital, Riyadh, Saudi Arabia. “However, some authors report lower success rates, and there is also evidence from patients undergoing corneal crosslinking for ectatic disease developing infectious keratitis after the treatment.”

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Therefore, riboflavin/UVA for treatment of infectious keratitis should be considered a work in progress, Dr. Behrens noted.

“We recommend further research to better characterize its efficacy, and that for now, its off-label use should be undertaken cautiously and only as an adjuvant treatment in select cases,” he said.

What research has shown so far

Dr. Behrens has done pioneering research in the use of riboflavin/UVA as a treatment for infectious keratitis. He said that the mechanism of action is likely explained by the generation of free radicals and other cytotoxic riboflavin byproducts (e.g., lumichrome) generated when riboflavin is irradiated by UVA.

Results of a laboratory study conducted by Dr. Behrens and colleagues several years ago (Invest Ophthalmol Vis Sci. 2008;49:3402-3408) demonstrated the antimicrobial efficacy of riboflavin/UVA against a number of important ocular pathogens, including drug-resistant species.

In another in vitro investigation, they found that the combination of riboflavin/UVA with propamidine (Brolene) was highly effective in destroying Acanthamoeba cysts (unpublished data). Based on that research, riboflavin/UVA was used to treat three patients with medically refractive Acanthamoeba keratitis and with a successful outcome (Ophthalmology. 2011;118:324-331).

Dr. Behrens observed that there are no controlled studies investigating the efficacy of riboflavin/UVA for the treatment of infectious keratitis, and such research would be very difficult to do.

However, a recent literature search identified 17 papers published between 2009 and 2014 reporting experience in treating 90 patients. The majority of the papers included only 1, 2, or 3 eyes, but with the data pooled, the overall response rate was 94.4%, and all eyes with Acanthamoeba keratitis improved, Dr. Behrens said.

Refining the regimen

In addition to its promising efficacy, Dr. Behrens said that riboflavin/UVA holds appeal as a treatment for infectious keratitis because of its convenience compared with current standard antimicrobial regimens. He noted that the application of riboflavin/UVA might need to be repeated a few times until clinical improvement, while the frequency of instillation of topical antibiotic drops might be reduced.

However, there is a need for further research to see if outcomes of riboflavin/UVA treatment might be improved by refining these treatment parameters, Dr. Behrens said.

“Even if we find that the results are optimized by repeating the procedure on several consecutive days, riboflavin/UVA would be a game-changer in terms of treatment for infectious keratitis considering the burden of our current intensive topical regimens,” Dr. Behrens said.

He added that riboflavin/UVA might also have application in the treatment of skin infections, although the cornea probably represents the ideal tissue target since its transparency readily allows the penetration of UVA light.

Ashley Behrens, MD

E: abehrens@jhmi.edu

This article was adapted from Dr. Behrens’ presentation during Cornea Day at the 2014 meeting of the American Society of Cataract and Refractive Surgery. Dr. Behrens holds a patent related to the technology he discussed.