Corneal cross-linking shows promise in treating infectious keratitis

Early scientific research shows that riboflavin and ultraviolet A light generate reactive oxygen species that eliminate multiple pathogens.

Issue: July 10, 2012

CHICAGO — Corneal cross-linking with riboflavin may be a viable alternative treatment option for infectious keratitis, a speaker said here.

“Cross-linking is a promising therapy for infectious keratitis for multiple different pathogens that we’ve identified thus far,” J. Bradley Randleman, MD, said during Cornea Subspecialty Day preceding the American Society of Cataract and Refractive Surgery annual meeting.

Riboflavin treatment of bacterial infections is not a new concept in medicine, having been used to purify infected platelets and plasma used in blood transfusions. Pathogen reduction technology uses riboflavin excitation to eliminate pathogens from platelets and plasma, Dr. Randleman said.

Cross-linking generates reactive oxygen species that are effective against various pathogens. It also increases corneal resistance to collagen enzymatic degradation.

“It can not only kill off organisms but protect the cornea in so doing,” Dr. Randleman said.

Both riboflavin and ultraviolet A light are required for efficacy. The ultraviolet light induces a dose-response relationship; the efficacy of riboflavin does not increase at concentrations higher than 0.01%, Dr. Randleman said.

“Some studies have shown that it is actually less efficacious at higher concentrations,” he said.

While cross-linking was found to be less effective against Acanthamoeba in vitro, it has proved to be effective in vivo, Dr. Randleman said.

Jes Mortensen, MD, and other clinicians have published clinical data on cross-linking in the treatment of infectious keratitis, Dr. Randleman noted.

In an initial case, a contact lens wearer had a nonresponsive ulcer that tested negative for bacterial cultures. After unsuccessful treatment with topical antibacterial, antifungal and antiprotozoal agents, a single cross-linking treatment resulted in 20/20 vision.

Dr. Randleman also cited a study in which cross-linking with riboflavin eliminated infectious keratitis with multiple organisms in five eyes. Another study showed that cross-linking treated three therapy-resistant Acanthamoeba cases. A third study reported seven eyes with bacterial keratitis were treated. A fourth study showed lower efficacy, with cross-linking proving successful in six of 14 multifactorial cases.

A primary therapy pilot study included 16 eyes of 16 patients with clinical diagnoses of bacterial keratitis. Thirteen eyes tested culture-positive. Results showed that after cross-linking, two eyes required subsequent antibiotics to resolve symptoms of keratitis.

Clinicians need to address questions about potential cross-linking protocols and methods in the treatment of infectious keratitis, Dr. Randleman said.

“Is cross-linking potentially a primary treatment or a secondary treatment?” he said. “Should this be the first thing we do for infectious keratitis in the future, or should it be added after someone has failed antibiotic therapy for a specified length of time? Could it, in fact, even be a solo treatment? Can cross-linking be the only single treatment that you will need, or is it something that, again, should have an antibiotic before or after?” – by Matt Hasson

References:

Ehlers E, Hjortdal J, Nielsen K, Søndergaard A. Riboflavin-UVA treatment in the management of edema and nonhealing ulcers of the cornea. J Refract Surg. 2009;25(9):803-806.
Iseli HP, Thiel MA, Hafezi F, Kampmeier J, Seiler T. Ultraviolet A/riboflavin corneal cross-linking for treating infectious keratitis. Cornea. 2008;27(5):590-594.
Makdoumi K, Mortensen J, Crafoord S. Infectious keratitis treated with corneal crosslinking. Cornea. 2010;29(12):1353-1358.
Makdoumi K, Mortensen J, Crafoord S. Response to: evaluation of combined riboflavin and ultraviolet A as an alternative treatment for keratitis [published online ahead of print February 17, 2012]. Graefes Arch Clin Exp Ophthalmol. doi:10.1007/s00417-012-1951-6.
Martins SAR, Combs JC, Noguera G, et al. Antimicrobial efficacy of riboflavin/UVA combination in vitro for bacterial and fungal isolates: A potential new treatment for infectious keratitis. Invest Ophthalmol Vis Sci. 2008;49(8):3402-3408.
Moren H, Malmsjö M, Mortensen J, Ohrström A. Riboflavin and ultraviolet A collagen crosslinking of the cornea for the treatment of keratitis. Cornea. 2010;29(1):102-104.
Sauer A, Letscher-Bru V, Speeg-Schatz C, et al. In vitro efficacy of antifungal treatment using riboflavin/UV-A combination and amphotericin B. Invest Ophthalmol Vis Sci. 2010;51(8):3950-3953.
Schnitzler E, Spörl E, Seiler T. Irradiation of cornea with ultraviolet light and riboflavin administration as a new treatment for erosive corneal processes, preliminary results in four patients. Klin Monbl Augenheilkd. 2000;217(3):190-193.
Schrier A, Greebel G, Attia H, Trokel S, Smith EF. In vitro antimicrobial efficacy of riboflavin and ultraviolet light on staphylococcus aureus, methicillin-resistant staphylococcus aureus pseudomonas Aeruginosa. J Refract Surg. 2009;25(9):S799-802.
Wollensack G, Spoerl E, Seiler T. Riboflavin/ultraviolet-a-induced collagen crosslinking for the treatment of keratoconus. Am J Ophthalmol. 2003;135(5):620-627.

For more information:

J. Bradley Randleman, MD, can be reached at Emory Vision, 875 Johnson Ferry Road, Suite 100, Atlanta, GA 30342; email: jrandle@emory.edu.
Disclosure: Dr. Randleman has no relevant financial disclosures.