Eyeworld

EW FEATURE 52 Crosslinking playbook • January 2019 "Some of these agents absorb light at different wavelengths, such as rose bengal, which mainly absorbs green light. This is interesting but may present a different challenge for retinal safety compared to ribo- flavin. The ability of any crosslink- ing compound to effectively cross the epithelium is a very important property that remains to be evaluat- ed with these new molecules." None of these alternative com- pounds have been evaluated in large enough studies to give a clear idea of their potential advantages and disadvantages. "For the time being, riboflavin is the gold standard for clinical use due to its excellent clinical track record and well-known safety and efficacy properties," Dr. Thompson said. Dr. Alió doesn't see riboflavin being replaced in the near future. "Probably in the future new CXL Substitutions Research is also currently underway to find alternatives to different com- ponents of the current procedure. "Crosslinking will benefit in the future from the advances that will substitute the ultraviolet light, with its proven toxic effects, for other types of energies or biochemical products or nanosubstances," Dr. Alió said. "We have been working for several years in the application of nanotechnology to the treatment of keratoconus, 1 which seems to be, in my opinion, a very promising technique. Other non-light depen- dent systems are being developed worldwide." The substitution of riboflavin, however, while possible, seems unlikely. "Several other photoactive compounds have been described in the literature as alternatives to riboflavin," Dr. Thompson said. accelerated protocols are applied in epi-on treatments," Dr. Thompson said. "Avedro is currently enrolling patients in a multicenter, sham-con- trolled Phase 3 clinical study in the United States to evaluate the use of supplemental oxygen, pulsed high irradiance light, and a transepithelial riboflavin formulation in progressive keratoconus patients." Dr. Alió thinks these "accelerat- ed" or "fast protocols" will be used more in the future, making the pro- cedure more effective and reducing treatment time. Meanwhile, Dr. Parker noted, "Modifications and alternatives to the original Dresden protocol are pouring in." "If some method for enabling 'epi-on' crosslinking to achieve the same effect as the standard 'epi- off' technique could be found, that would decisively change the way the procedure is performed," he said. Crosslinking with Avedro KXL device is the only FDA-approved therapy to slow the progression of ectasia. Crosslinking has become a new standard of care for patients diagnosed with progressive keratoconus. substances will appear when a total change in paradigm in the treatment of keratoconus appears, knowing better how to deal with the collagen fibers to strengthen them in a different way," he said. "Riboflavin is so effective, and so well studied, there may be little motivation to find an alternative chemical solution, aside from the price of the riboflavin itself, which is more a function of corporate pricing decisions than 'production cost' of the solution," Dr. Parker said. Expanding indications Experience with CXL has also led to some expanding indications. "I have been following the development of refractive applications of CXL with interest, particularly the PiXL proce- dure," Dr. Thompson said. "Prelim- inary studies from international colleagues have demonstrated that Future continued from page 50

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