Eyeworld

EW CORNEA 26 December 2011 With the treatment closer to FDA approval in the U.S., EyeWorld looks at the details of corneal crosslinking in practice C orneal collagen crosslink- ing as the standard of care treatment for progressive keratoconus and post- LASIK ectasia has been available in Canada for more than 4 years and in Europe for even longer. In the U.S., there are several clinical trials being conducted, and the one that's closest to resolution is one sponsored by Avedro Inc. (Waltham, Mass.), said Eric D. Donnenfeld, M.D., co-chairman, Cornea, Nassau University Medical Center, East Meadow, N.Y. "That data has been submitted to the FDA, and we're looking for- ward to seeing that approved," he said. An effective treatment Keratoconus is the second most common cause of corneal trans- plants in the United States, and with crosslinking, it can virtually be elim- inated, Dr. Donnenfeld said. The document of literature shows that corneal crosslinking overwhelmingly stops the progres- sion of keratoconus or ectasia and that there's a mean of approximately 1.0-2.0 D of flattening of the cornea as well, he said. While the data on post-LASIK ectasia patients is not quite as good as with keratoconic patients, it's still good, Dr. Donnenfeld said. R. Doyle Stulting, M.D., Woolfson Eye Institute, Atlanta, who is involved with clinical trials spon- sored by Topcon Medical Systems (Oakland, N.J.), also said the treat- ment is very effective, based on in- ternational data. Raymond Stein, M.D., medical director, Bochner Eye Institute, Toronto, whose practice was the first in Canada to become involved with corneal crosslinking, said, "We've been doing it for 4-and-a-half years, and we've treated approximately 2,500 eyes in that period. We haven't seen any patient who's shown pro- gression, and we've treated patients as young as 10 years of age." The majority of his patients are between 18 and 30, but he has also treated patients whose ages range from 10 all the way up to 60. "It's an extremely effective pro- cedure at preventing progression," Dr. Stein said. Who should be treated and when Dr. Donnenfeld said that any patient who has progressive disease should be treated. "Any patient who is showing worsening ectasia by keratometry often verified by refraction should be treated, and the earlier you treat patients, the better the prognosis," he explained. He added that patients who have advanced disease generally aren't as eligible for treatment be- cause these are patients who have very steep corneas, over 60 D, pa- tients with apical thinning with corneas thinner than 400 microns, and patients with apical scarring. Dr. Stulting is of the same opin- ion: "Anyone who has keratoconus or corneal ectasia should be treated at the time of diagnosis. Perhaps some of those people will not progress, but I think the risk/benefit ratio for the treatment favors a deci- sion to treat everyone once a diag- nosis is made." There's also no age limit on how young patients can be treated, Dr. Donnenfeld said. "I've treated patients as young as 14 years of age and as old as 60. The real key is whether the disease is progressing and if we can stop it from progressing safely. The same goes for refractive surgery patients," he said. In Europe, the general guideline is to wait for progression before treating, Dr. Stein said. "But our thought in Canada is that if some- one develops keratoconus at an early age, the chance [of progression] is close to 100%, and the earlier you do the treatment, the better the vi- sual prognosis because it basically locks everything in place and pre- vents deterioration of best corrected visual acuity." In Canada, patients between the ages of 10 and 28 are recommended treatment even without evidence of progressive disease, he said. However, in patients over 28, some progression is usually docu- mented, with follow-ups every 3-6 months. Topographic analysis is per- formed and if there is some further thinning or progressive steepening, crosslinking will be performed, Dr. Stein said. As for post-LASIK patients, Dr. Stein said they tend to respond or progress a little differently than the keratoconus patients. They tend to progress over time even if they're older, whereas when keratoconus pa- tients get to about 35 or 40 years of age, their corneas are usually fairly stable. So for these patients, inter- vention treatment is recommended at any age without having to have a second instrument showing progres- sion, Dr. Stein said. Crosslinking as prophylactic treatment With very little hard data to show the safety and efficacy of the pro- phylactic treatment of patients at risk of ectasia using corneal crosslinking, the jury is out right now, Dr. Donnenfeld said. "I'm convinced that if you crosslink patients who are at risk of developing ectasia, they won't de- velop ectasia. My concern is that crosslinking, which is known to flat- ten the cornea, will change the vi- sual results of LASIK or PRK, and the results will not be as good with crosslinking as they are without," he explained. A prospective trial needs to be conducted, he said. But at present, he is not crosslinking patients who have come in for LASIK because of the lack of knowledge in this area and the fact that crosslinking is not approved in the United States, he said. He added: "I think it's very rea- sonable in the United States to treat patients who have a therapeutic need for visual rehabilitation and the prevention of ectasia progres- sion, but prophylaxis is a different level of treatment and one that I'm not comfortable performing today until we have more knowledge about the outcomes." According to Dr. Stulting, pro- phylaxis for ectasia in refractive sur- gery may have a role in selected cases where there is an increased risk for ectasia. However, he would not do it across the board, he said. by Enette Ngoei EyeWorld Contributing Editor Anxiously awaiting corneal crosslinking C orneal collagen crosslinking (CCL) has been utilized for the treatment of corneal ectasia throughout the world. Studies have demonstrated the benefits of this technique as a treatment to stabilize corneas that are demonstrating progressive ectasia. CCL has been used in patients with keratoconus to prevent further thinning and steeping of the cornea, thus preventing the need for a keratoplasty. In addition, CCL has been utilized as the first-line therapy for patients with post-corneal refractive ectasia to prevent further corneal changes and in some cases achieve a slight reversal of the corneal steepening. The largest potential clinical applica- tion of CCL may be in prophylaxis rather than treatment of ectasia. Some clinicians are advocating the use of this treatment for all patients who are diagnosed with keratoconus or pellucid marginal degener- ation before the cornea has developed significant steepening and irregular astig- matism. Another prophylaxis possibility is the corneal refractive patient at a higher risk for ectasia with the CCL treatment given pre-operatively or intraoperatively. Finally, the use of CCL is being explored in patients with established keratoconus to allow for the possibility of subsequent corneal refractive surgery. Unfortunately, CCL does not have FDA approval in the U.S. at this time. Therefore U.S. patients are not receiving what ap- pears to be a safe and effective in-office procedure that in many cases will prevent the progression of ectasia and the need for a keratoplasty. I have asked Drs. Donnenfeld and Stulting, U.S. refractive surgeons who have been active in CCL re- search, to give their views. In addition, Dr. Stein, a very experienced CCL clinician in Canada, shares his insights. Edward J. Holland, M.D., cornea editor continued on page 28 Cornea editor's corner of the world

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