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September 2012 Those watching the use of the treatment evolve said there are few disadvantages with it. However, "you could damage the endothelium if the cornea is very thin, but if you have a severe, complicated keratitis, you have little alternative," Dr. Mortensen said. Looking at the research Research into collagen crosslinking for infectious keratitis is ongoing around the world, although it is not yet an approved treatment in the U.S. "The first clinical study was a pilot study," said Dr. Mortensen, who has completed studies in this area along with Karim Makdoumi, M.D. "In this study, 16 patients received collagen crosslinking as pri- mary therapy for suspected bacterial keratitis. No antibiotics were allowed prior to the treatment." The investi- gators found that all eyes had improvement in symptoms, and only two eyes required antibiotics to fully heal. One patient needed amniotic membrane patching for epithelialization due to corneal edema. That study was published earlier this year in Graefe's Archives for Clinical and Experimental Ophthalmology. There has been other emerging research related to collagen crosslinking for infectious keratitis. "Everything sounds exciting and promising, but there have only been a handful of cases reported," Dr. Hersh said. Additionally, there has yet to be a U.S.-based clinical trial. Dr. Price, along with Stephen Trokel, M.D., and Amilia Schrier, M.D., New York, are involved with an investigational new drug study through the U.S. FDA to use the procedure. They have preliminary results that they are presenting at meetings, and there is a related man- uscript under review, Dr. Price said. They have treated 40 eyes so far. Although Dr. Price said they would need 200 eyes to make sound conclusions about dosing duration, given the heterogeneous nature of infectious keratitis, collagen crosslinking seems to work better in bacterial infections and in infections that are in the anterior part of the cornea. "Infections that are deeper don't get treated, and that is a con- cern. Posterior infections are harder to eradicate," he said. Their study in- volves the use of antibiotics as well. The stronger results in eradicat- ing bacteria from Dr. Price and colleagues seem to support what an in vitro study from 2008 reported. That study, published in Investigative Ophthalmology & Visual Science, found that riboflavin/UV treatment was more successful in wiping out bacteria but not as effective with fungal infections. A randomized study that compares collagen crosslinking, antibiotic use, and no treatment is needed, Dr. Price said. Further research avenues Clinicians are excited about the treatment possibilities of crosslink- ing for keratitis, but they also acknowledge that a good deal of research still needs to take place. "Research needs to show safety and efficacy, since little has been published in this area," Dr. Stulting said. In addition to the need for a clinical trial to compare crosslinking to antibiotic use, the most effective dosing—and the time devoted to treatment—should receive further exploration, said Dr. Hersh. "Research needs to look into proper dosing, how long is that dosing, and the power of the UV administra- tion," he said. Some companies are examining the use of higher-powered lights that will speed up treatment time, Dr. Mortensen said. There also needs to be more in- formation on what kinds of organ- isms collagen crosslinking can and cannot eradicate, Dr. Price said. EW Editors' note: The doctors mentioned have no financial interests related to this article. Contact information Hersh: 201-883-0505, phersh@vision-institute.com Mah: 858-554-7996, mah.francis@scrippshealth.org Mortensen: jes.mortensen@comhem.se Price: 800-317-3937, fprice@pricevisiongroup.net Stulting: 770-255-3330, dstulting@woolfsoneye.com