EyeWorld Asia-Pacific September 2011 Issue

52 EW CORNEA September 2011 Update on corneal crosslinking by Jena Passut EyeWorld Staff Writer Procedure continues to show promise, especially when used in conjunction with others C orneal collagen crosslinking with riboflavin continues 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 US work to gain FDA approval. At least 20 clinical trials are either 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 riboflavin 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 outside of the US. 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. Patients in European studies have been followed for up to 8 years after receiving the treatment, and the effects have been shown to be long term. The first major study patients were treated in the United States in 2008 by R. Doyle Stulting, MD, then at Emory University, as part of a physician-sponsored investigational drug study. Dr. Stulting is the past president of ASCRS and is now at Woolfson Eye Institute, Atlanta, Ga., USA. “The history is that there was a clinical trial being performed by Peschke Meditrade GmbH [Hünenberg, 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., USA].” Avedro took over the trial in Phase III and continues to work toward closing that follow-up stage. Dr. Stulting is now involved in a second clinical trial run by TopCon Corp. (Tokyo, Japan). “We are using a light and riboflavin 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 procedure in the United States, especially 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 consistent 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, keratoconus patients’ only options for vision 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 intervention is indicated as well. Crosslinking is used either in combination with refractive surgery for keratoconus patients or as a prophylaxis to reduce any risk of the patient developing corneal ectasia post-op. Ramon Naranjo-Tackman, MD, Association to Prevent Blindness in Mexico, Mexico City, said that in a normal cornea he prefers doing the refractive surgery and then applying the crosslinking immediately after. “If you have a cornea that is weakened by ectasia, then you should do a photorefractive keratectomy, 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 effects of the crosslinking. “Crosslinking hasn’t been studied enough,” he said. “I do believe that one has to take care of the limbal area since we are overexposing limbal cells to UV radiation and we don’t know the long-term effects.” Source: Efekan Coskunseven, MD AT A GLANCE • Many crosslinking clinical trials are underway in the US • Losing limbal cells is a concern for at least one surgeon • Removing epithelium is key to the procedure working correctly Figure 1 Figure 2 Figure 3