Answering Your Patients’Questions About Cross-Linking

Many centers worldwide are now offering cross-linking as a first-line treatment for conditions such as keratoconus, corneal ectasia, and pellucid marginal degeneration.

By Roy S. Rubinfeld, MD; William B. Trattler, MD; Neil F. Martin, MD; Marwa A. Adi, MD; and The CXL-USA Study Group

Interest in corneal collagen cross-linking is increasing rapidly in the United States. Corneal cross-linking was first used to treat keratoconic patients in the 1990s soon after animal studies demonstrated promising results. According to one estimate, roughly 400 centers across the globe now offer cross-linking as a first-line treatment for keratoconus, corneal ectasia, and pellucid marginal degeneration (Ray Stein, MD, personal communication, 2009). International experience that includes some long-term studies has been very positive.1-6 Due to the current regulatory environment and other factors, the United States is perhaps the only developed country that does not have cross-linking available as a routine, noninvestigational procedure at this time.

Keratoconus is not an uncommon disease: its prevalence ranges between one in 500 to one in 10,000.7 Most corneal specialists believe that the condition actually occurs more often than these estimates, because technology is now able to detect this disease at earlier stages and in more subtle forms. One such device is the Pentacam Comprehensive Eye Scanner (Oculus, Inc., Lynnwood, WA), which can measure the back surface of the cornea.8

Cross-linking is relatively straightforward. The surgeon instills riboflavin (vitamin B2) eye drops after epithelial removal, as in preparation for PRK. These drops are instilled for 30 minutes, and anesthetic eye drops are used to enhance the patient’s comfort during the procedure. After the riboflavin has saturated the cornea, the surgeon applies the UV light source—calibrated to provide a steady irradiance of light—for 30 minutes to each eye. For patients who have corneas between 300 and 400 µm thick, a hypotonic riboflavin solution can be used to swell the cornea to greater than 400 µm before treatment. This process protects the endothelium, lens, and other intraocular structures by ensuring that only safe levels of UV light penetrate to the deeper corneal layers. A bandage contact lens is sometimes placed on the eye immediately after surgery, and antibiotic and nonsteroidal eye drops are then instilled. The surgeon observes the patient postoperatively until the epithelium is intact (generally 2-5 days), and then he or she follows the patient with serial refractions , topography, and other measurements over the ensuing months and years.

As with many conditions, the earlier the patient is treated, the better the results are. In some countries, cross-linking is used for patients as young as 10 years who are found to have forme fruste (preclinical) or frank (clinical) keratoconus. This first-line treatment makes it much less likely that these patients will develop severe irregular astigmatism and ultimately require corneal transplantation.3 If cross-linking is performed early, it may be possible to prevent the development of keratoconus in some eyes with preclinical signs of keratoconus. Patients who have keratoconus can also benefit from cross-linking treatment. Roughly 60% to 70% of patients experience a significant improvement in their BSCVA after treatment.2 In our experience, patients usually move one “step” up what we refer to as the vision-correction spectrum. In other words, if they are intolerant of their rigid contact lenses and are headed toward a corneal transplant, we can often avoid transplantation and restore their comfort with contact lenses. If they are doing well in rigid lenses, we can sometimes get them into soft lenses. If they are wearing soft lenses well, we are often able to provide better vision with glasses.

The CXL-USA Study Group is actively enrolling patients in a multicenter investigational study to gather data on the safety, efficacy, and optimal techniques for crosslinking. Current diagnostic criteria for enrollment include keratoconus (both clinical and preclinical forms), pellucid marginal degeneration, and post-LASIK ectasia. Some post- RK patients are being enrolled as well. Patients must be 18 years of age or older, and their thinnest corneal measurement must be 300 µm. We look forward to expanding our indications for cross-linking to bullous keratopathy and corneal ulcers8 in the near future.

Because more and more patients with corneal conditions are now seeking information about cross-linking and becoming interested in pursuing this option, the CXL-USA Study Group has developed a list of frequently asked questions (see CXL-USA Study Group: Patients’ Frequently Asked Questions). We encourage clinicians to make this information available to patients who desire to learn more about their medical conditions and the best available treatment options.

Marwa A. Adi, MD; Neil F. Martin, MD; and Roy S. Rubinfeld, MD, are on staff at The Washington Hospital Center in Washington, DC, and in private practice with Washington Eye Physicians & Surgeons in Chevy Chase, Maryland. Dr. Adi may be reached at Dr. Martin may be reached at Dr. Rubinfeld is also a clinical associate professor at Georgetown University Medical Center. He may be reached at (301) 654-5290;

William B. Trattler, MD, is the director of cornea at the Center for Excellence in Eye Care in Miami, and he is onon the voluntary faculty of Bascom Palmer Eye Institute and The Florida International University School of Medicine. He is also co-chief medical editor of Advanced Ocular Care. Drs. Rubinfeld and Trattler have a financial interest in CXL USA, LLC. Dr. Trattler may be reached at (305) 598-2020;