NOV 2013

EyeWorld is the official news magazine of the American Society of Cataract & Refractive Surgery.

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Page 48 of 122

46 EW FEATURE Corneal crosslinking November 2013 Crosslinking shows promise by Michelle Dalton EyeWorld Contributing Writer AT A GLANCE • Corneal crosslinking is under investigation in the U.S. • Physicians can join clinical trials or join a physician-led IRB to offer the technique. • Riboflavin is delivered externally, eliminating most safety issues associated with compounding. CXL is relatively easy to set up and implement, study investigators say C orneal collagen crosslinking (CXL) was developed almost 15 years ago, and has proven to be a viable first-line treatment for people with keratoconus, pellucid marginal degeneration, and postLASIK ectasia. The technique involves strengthening the cornea by applying riboflavin and exposing the riboflavin to an ultraviolet A light treatment. While the procedure is approved in Europe, it is still under investigation in the United States. If approved, clinicians will be able to use CXL primarily to reduce or stop the progression of keratoconus in its earliest stages, experts say. There are several commercial units available outside of the United States "such as Avedro [Waltham, Mass.], Topcon [Oakland, N.J.], and Peschke [Hunenberg, Switzerland], and they all work very well," said Eric D. Donnenfeld, MD, partner at Ophthalmic Consultants of Long Island, Rockville Centre, N.Y., and clinical professor of ophthalmology, NYU Medical School, New York. In the U.S., several groups are investigating the technique. Two basic types of corneal crosslinking procedures are under investigation in the U.S.—epithelium off, which is similar to PRK where the epithelium is removed before the riboflavin is administered and the loading time is shorter; and epithelium on, where the corneal epithelial surface is left intact (also called transepithelial corneal crosslinking), but the latter requires a longer riboflavin loading time. Debate continues about the ability of the riboflavin molecule to penetrate the cornea as effectively with the epithelium on as with it off. For epithelial-off CXL, the risks are "essentially the same as PRK, and we offer the patient the alternatives of no treatment, contact lenses, Intacs [Addition Technology, Des Plaines, Ill.], and a penetrating keratoplasty or deep anterior lamellar keratoplasty," Dr. Donnenfeld said. Because there are no FDA approved crosslinking devices in the U.S., the only legal way to provide corneal crosslinking for patients is to participate in a clinical trial, said William Trattler, MD, cornea specialist, Center for Excellence in Eye Care, Miami. Dr. Trattler noted that there is no way to legally import a non-approved medical device into the U.S. and use it to treat patients, unless the device is used as part of a clinical trial. Otherwise, there would be nothing stopping clinicians from purchasing and importing many exciting technologies available in Europe, such as new multifocal intraocular lenses or even advanced excimer lasers. Setting up a CXL clinical trial site For clinicians interested in becoming involved in a CXL program, there are ways to do so, Dr. Donnenfeld said. Physicians can join or refer to an existing commercial study, but most are closed to new sites. They also can start or join a physician-led IRB, and "there are many that currently exist," Dr. Donnenfeld said. (See sidebar for some examples of studies currently recruiting patients in the U.S.) Currently, there are more than 100 sites participating in clinical trials for crosslinking in the U.S. Avedro is the only company with an ongoing study to get a UV light source and riboflavin formulation through the FDA approval process. Avedro also partnered with the American-European Congress of Ophthalmic Surgery to run a 100site study on crosslinking. Other studies are being conducted to better understand the results and patient selection for crosslinking. continued on page 48 CXL studies at a glance Here, a glance at some of the various studies underway in the U.S. (all information from ClinicalTrials.gov): A Multi-Center, Randomized, Controlled Evaluation of the Safety and Efficacy of the KXL System With VibeX (Riboflavin Ophthalmic Solution) for Corneal Collagen Cross-Linking in Eyes With Keratoconus or Corneal Ectasia After Refractive Surgery; NCT01459679 This phase 3 study is evaluating three wavelengths: the KXL System 15 mW/cm2, 30 mW/cm2, and 45 mW/cm2. The objectives of this study are to evaluate and compare the safety and efficacy of three treatment regimens for corneal collagen crosslinking performed with VibeX (riboflavin ophthalmic solution) and the KXL System in impeding the progression of and/or reducing maximum corneal curvature. The study, sponsored by Avedro, began recruiting in July 2012, and the estimated completion date is December 2014. Collagen Crosslinking With Ultraviolet-A in Asymmetric Corneas; NCT01024322 This phase 4 study is evaluating the efficacy of ultraviolet A (UVA)-induced crosslinking of corneal collagen as a method to increase the biomechanical and biochemical stability of the cornea by inducing additional crosslinks within or between collagen fibers using UVA light and the photomediator riboflavin. In keratoconus, the interventions are ciprofloxacin or moxifloxacin or other; in ectasia the interventions are nonsteroidals, and in degeneration, the interventions are steroids. The study, initiated by the CXLUSA group, started in October 2009, and primary completion date is estimated for December 2014. Combined Collagen Crosslinking/Ultraviolet-A and PRK or LASIK in Forme Fruste Keratoconus or Eyes With Potentially Elevated Risk of Ectasia; NCT01726283 This study is being performed to evaluate the efficacy of ultraviolet A (UVA)-induced CXL in strengthening and optimizing the biomechanical and biochemical stability of the cornea in patients with forme fruste keratoconus (FFKC), corneas that are suspicious for FFKC and corneas thought to be at higher risk of developing ectasia that will be undergoing laser vision correction. This study is also sponsored by CXLUSA, and is expected to be complete by December 2014. Microwave Treatment and Corneal Collagen Crosslinking for Keratoconus; NCT01672814 This phase 3 study compares the outcomes of the Vedera KXS procedure (a microwave-based procedure, also known as Keraflex) combined with corneal collagen crosslinking to CXL alone for the treatment of keratoconus. The goal is to improve corneal shape in patients with keratoconus. Patients were randomized into one of two treatment groups: Vedera KXS combined with corneal collagen crosslinking or collagen crosslinking alone. The Vedera KXS procedure performs a controlled application of microwave energy in an annular configuration. This study, sponsored by the Cornea and Laser Eye Institute (Teaneck, N.J.), had a primary completion date of August 2013, with an estimated study completion date of August 2014. Collagen Cross-Linking for Keratoconus/Ectasia With and Without Intacs; NCT01081561 This phase 2/phase 3 study will determine the efficacy of collagen crosslinking for progressive keratoconus and ectasia after LASIK. It will try and determine which is a more effective treatment: collagen crosslinking alone or collagen crosslinking combined with Intacs, a treatment that has already been proven to be effective in decreasing corneal curvature in patients with keratoconus. The study, sponsored by the Cornea Genetic Eye Institute, has an estimated primary completion date of June 2014.

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