Eyeworld Daily News

EW SHOW DAILY 52 Monday, May 9, 2016 Meeting Reporter by Chiles Aedam R. Samaniego EyeWorld Asia-Pacific Senior Staff Writer F ollowing the long-await- ed U.S. Food and Drug Administration approval of Avedro's crosslinking system—including the ribo- flavin formulations Photrexa Viscous and Photrexa and the KXL System (Waltham, Massachusetts)—experts laid out the FDA indications, the science, and the evidence on which approval was based in an EyeWorld event held Saturday night at Mardi Gras World. The crosslinking system was approved for the treatment of pro- gressive keratoconus on April 15, 2016. Avedro's products are the first and currently only FDA-approved therapeutic treatment indicated for progressive keratoconus. The FDA label includes no contraindications, though it warns of the potential for ulcerative keratitis, recommending monitoring for resolution of epithe- lial defects, and lists known adverse reactions as being corneal opacity (haze), punctate keratitis, corneal striae, corneal epithelium defect, eye pain, reduced visual acuity, and blurred vision—reactions, said Rajesh Rajpal, MD, McLean, Virgin- ia, that are primarily related to the healing process. The Avedro protocol follows epithelial debridement with the instillation of 1 drop of Photrexa Viscous on the eye every 2 minutes for 30 minutes, with an additional drop every 2 minutes for an ad- ditional 2 to 3 drops as necessary irradiation used in corneal crosslink- ing is safe. "This is a structure that we can have profound effects on in your clinic by using crosslinking," Prof. Marshall said. The evidence FDA approval was based on 2 randomized, controlled, 12-month clinical trials, with the primary efficacy criteria chosen being mean change in Kmax on topography of 1 D or more between the treatment and control. "We used Kmax as a proxy for either advancement of the keratoconus, stability of the kerato- conus, or improvement," said Peter Hersh, MD, Teaneck, New Jersey. Both studies showed the treat- ment effective—"about 1.4 D of actual improvement in keratometry in one study, and 1.7 D of improve- ment in cone height in the other study," Dr. Hersh said. "This as com- pared to the sham treatment group where keratoconus, as expected in this progressive disease, continued. "Clearly we can see that over the first year, crosslinking is effi- cacious in improving maximum keratometry in these patients." Safety was assessed in 512 eyes undergoing crosslinking. Corneal haze was the most common adverse reaction, with other reactions hav- ing primarily to do with epithelial removal and healing. "Corneal haze is an expected concomitance of crosslinking—if you do crosslinking, you're going to see haze," Dr. Hersh said. The haze typically presents as generalized early on after treatment, evolving over time to a demarcation line typically 250 to 300 microns deep in the cornea, which likely suggests the depth of the actual crosslink. "I think that you're going to find crosslinking to be a very useful adjunct to your practice—it certainly is the biggest breakthrough in the treatment of keratoconus in many years," Dr. Hersh said. "It offers hope to these patients for a much improved prognosis." EW Editors' note: This EyeWorld Corporate Education symposium was sponsored by Avedro. New horizons in 2016: Corneal crosslinking Avedro celebrates the approval of its crosslinking system amid the festively ostentatious floats of Mardi Gras World. until a yellow flare is detected in the anterior chamber. Once a yellow flare is observed, ultrasound pachymetry is per- formed. If the corneal thickness is less than 400 microns, 2 drops of Photrexa are instilled every 5 to 10 seconds until the corneal thickness increases to at least 400 microns. Irradiation should not be performed unless this 400-micron threshold is met and the yellow flare is seen. The eye is irradiated for 30 continuous minutes at 3 mW/cm 2 at a wavelength of 365 nm, entered over the cornea, using the KXL sys- tem; throughout irradiation, topical instillation of Photrexa Viscous continues every 2 minutes. The science "This treatment has been based on science and intensively inves- tigated," said John Marshall, PhD, London. "I want to give you some confidence that we understand what we are doing. "Crosslinking is a natural process," Prof. Marshall said. He and his colleagues have observed this natural crosslinking with the fluorescein technique, using which they were able to watch the "trans- gression of the highly flexible S-H bonds to highly inflexible sulfur to sulfur bonds." "We also studied that process in the cornea, and the cornea grows stiffer, naturally, as we all age," he said. The concept for crosslinking to treat progressive keratoconus was to recreate this stiffening process artificially, by soaking the cornea in riboflavin and applying ultraviolet radiation as per the crosslinking protocol previously described. Experimentally, corneas went from soft to stiff. But just how rigid were the corneas after crosslinking? Measuring the corneas with inter- ferometry, researchers were able to show—"quite conclusively," Prof. Marshall said—that this technique increased corneal rigidity 3 to 5 times. Meanwhile, the parameters set for irradiation were drawn from previous studies with lasers that elucidated the limits to which the cornea could be exposed to radiation without damaging the endothe- lium—so, Prof. Marshall said, the Himani Goyal, MD Todd Hovis, MD Congratulations to the winners of EyeWorld's iPad giveaway Friday Saturday

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