Eyeworld

EW FEATURE 46 by Jena Passut EyeWorld Staff Writer Update on corneal crosslinking Procedure continues to show promise, especially when used in conjunction with others C orneal collagen crosslink- ing with riboflavin contin- ues to show great promise in treating patients with keratoconus and is widely used in Europe and other countries, while clinical trials and studies in the U.S. work to gain FDA approval. At least 20 clinical trials are ei- ther active or recruiting volunteers, according to www.clinicaltrials.gov. In the studies, crosslinking is performed by removing the corneal epithelium and applying riboflavin, also known as vitamin B2, drops to the eye until saturated. The eye is then exposed to ultraviolet (UV) light, which interacts with the ri- boflavin to produce reactive oxygen molecules that cause the stiffening of the collagen fibrils in the cornea. Keratoconus and post-refractive corneal ectasia are the two leading indicators for corneal crosslinking, according to published reports out- side of the U.S. International investigators have shown that crosslinking can halt the progression of both keratoconus and ectasia by stiffening the cornea, which in turn flattens the cornea and improves a patient's vision. Pa- tients in European studies have been followed for up to 8 years after re- ceiving the treatment, and the ef- fects have been shown to be long term. The first major study patients were treated in the United States in 2008 by R. Doyle Stulting, M.D., then at Emory University, as part of a physician-sponsored investiga- tional drug study. Dr. Stulting is the past president of ASCRS and is now at Woolfson Eye Institute, Atlanta. "The history is that there was a clinical trial being performed by Peschke Meditrade GmbH (Hunenberg, Switzerland), and I was the medical monitor. It was partially done, and they stopped funding the trial and sold the data to Avedro (Waltham, Mass.)." Avedro took over the trial in Phase III and continues to work to- ward closing that follow-up stage. Dr. Stulting is now involved in a sec- ond clinical trial run by TopCon Corp. (Tokyo). "We are using a light and ri- boflavin preparation made by Sooft (Montegiorgio, Italy), and we are in the middle of recruitment with some early data from that," he said. "We will see what we wind up with as the data roll in and we get approvals or no approvals." Dr. Stulting said he has high hopes for the routine use of the pro- cedure in the United States, espe- cially with so much back-up data from Europe and other continents. "In the IND [Investigational New Drug] procedure, we treated about 80 patients, and if you look at the data that have been published since 2003, they're very consistent," he said. "We essentially reproduced them with our physician-sponsored IND and with the Peschke Meditrade study. With the TopCon study, it is looking like the data is going to be the same. The numbers are very con- sistent and, in my assessment, it works and will become the standard of treatment for keratoconus and other ectatic diseases as soon as the diagnosis is made. I feel pretty strongly that it does what everyone says it does." When to use with refractive surgery Before corneal crosslinking, kerato- conus patients' only options for vi- sion correction included spectacles, rigid gas permeable contact lenses, and intracorneal ring segments. While the results from years of data from overseas support the use of crosslinking to stiffen the cornea, the procedure can't correct vision alone. Sometimes refractive inter- vention is indicated as well. Crosslinking is used either in combination with refractive surgery for keratoconus patients or as a pro- phylaxis to reduce any risk of the patient developing corneal ectasia post-op. Ramon Naranjo-Tackman, M.D., Association to Prevent Blind- ness in Mexico, Mexico City, said that in a normal cornea he prefers doing the refractive surgery and then applying the crosslinking im- mediately after. "If you have a cornea that is weakened by ectasia, then you should do a photorefractive keratec- tomy, a surface ablation, and apply the crosslinking at the same time," he said, adding that patients should be carefully counseled about what will occur after the procedure. "If you want to get a stable result and a non-variable refractive state of the cornea, then you should apply both, but tell patients that it's going to take at least a couple of weeks for them to get a stable visual effect." Dr. Naranjo-Tackman said that he worries about the long-term ef- fects of the crosslinking. "Crosslinking hasn't been stud- ied enough," he said. "I do believe that one has to take care of the lim- bal area since we are overexposing limbal cells to UV radiation and we don't know the long-term effects." To mitigate the possible effects on the limbal cells, there is a novel approach to protect the area from harmful rays. The surgeon pene- trates a 14-mm hole in the center of a bandage contact lens with a 9-mm trephine ordinarily used in penetrat- ing keratopathy. "Then I stain that lens with some dark ink and I use this as extra protection for the limbal area during the half hour the procedure takes," Dr. Naranjo-Tackman said. Efekan Coskunseven, M.D., di- rector of the refractive surgery de- partment, Dunya Eye Hospital, Istanbul, Turkey, has a different opinion on timing crosslinking and a refractive procedure. "What we see after crosslinking is improvements in K levels and re- fraction up to 1.5 or 2 D," he said. "That is why we think it is proper to first do the crosslinking and then wait more than 6 months to see the improvements in K levels and refrac- tions before topo-guided refractive treatment. Otherwise, we think that if you do [the procedures] at the same time, there may be a hyperopic shift." Dr. Coskunseven said it is im- perative to remove the epithelium February 2011 CORNEA May 2011 AT A GLANCE • Many crosslinking clinical trials are underway in the U.S. • Losing limbal cells is a concern for at least one surgeon • Removing epithelium is key to the procedure working correctly Figure 1 Source: Efekan Coskunseven, M.D. Figure 2 Source: Efekan Coskunseven, M.D. Figure 3 Source: Efekan Coskunseven, M.D.

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