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34 | EYEWORLD DAILY NEWS | MAY 5, 2019 ASCRS SYMPOSIA ASCRS ASOA ANNUAL MEETING by Ellen Stodola EyeWorld Senior Staff Writer/ Meetings Editor another variable when considering the variability of stiffening as well. Dr. Dupps also suggested that epi-on approaches should not be lumped together because there are differences in riboflavin concen- tration. Though he did acknowledge some of the sight-threatening complications that some may use as a rationale for epi-on, Dr. Dup- ps said that epithelial disruption can still occur with epi-on. In conclusion, he said that transepithelial techniques should ideally pass the equivalency test for long-term stability or show sufficient safety advantages that repeat treatment is as safe and as effective as one-time epi-off treat- ment. Epi-on needs to be vetted in comparative effectiveness trials, where epi-off is still the gold stan- dard, Dr. Dupps said. Editors' note: Dr. Belin has finan- cial interests with Avedro, CXLO, and Oculus. Dr. Dupps has financial interests with Avedro. Dr. Rubinfeld has financial interests with CurveRight, CXLO, and CXLUSA. He first discussed his hierar- chy of factors to prioritize in the ideal crosslinking experience: • Effective (stability through stiff- ening) • Low risk of sight threatening complications • Patient comfort/experience • Cost effective and sustainable in practice • Minimized treatment duration He then flipped around Dr. Rubinfeld's argument and asked: Why are we even interested in epi-on? And which of the above characteristics could be improved? He said epi-on could potentially produce a lower risk profile of complications and could potential- ly offer more patient comfort/a better experience. Dr. Dupps went on to discuss a comparison of epi-off and epi- on, first looking at effectiveness, which he defined as "stability through stiffening." He noted the riboflavin, UV, and oxygen penetration are essential for cross- linking effect, and the epithelium inhibits penetration. Epi-off elim- inates the possibility of reduced stromal reaction, he said, adding that the epithelium presents The session also featured sev- eral point/counterpoint presenta- tions. Roy Rubinfeld, MD, Wash- ington, D.C., argued in favor of epi-on crosslinking in his presen- tation titled "Epi-on is the future." He started by questioning why all crosslinking isn't epi-on. There was no formulation/technology available when crosslinking was first created to load the stroma through the epithelium. So the epithelium was removed because it blocked stromal loading. Dr. Rubinfeld pointed out current complications of epi-off crosslinking: corneal edema, sterile infiltrates, infectious keratitis, delayed epithelial healing, corneal haze, persistent ocular surface issues, and stromal scars. Nearly all of these are a result of epithelial removal. It's not a new idea to come up with epi-on crosslinking, Dr. Rubinfeld said; the co-inventors of crosslinking initially tried but couldn't get it to work, and there have been multiple epi-on at- tempts over the years. But how do you get the riboflavin in? Dr. Rubinfeld said that one way is to rough up the epithelium. There's currently limited evi- dence for epi-on, but Dr. Rubin- feld pointed out a meta-analysis published in the Journal of Cataract and Refractive Surgery in December 2018. Dr. Rubinfeld said that for crosslinking, you need UVA light, riboflavin, and oxygen in the same place at the same time, and the epithelium can potentially block all of these things. Dr. Rubinfeld then referenced several studies, including some in the works, to look at epi-on crosslinking. In general, treatments evolve toward being less invasive, he concluded. On the other side of the issue, William Dupps, MD, Cleveland, argued that epi-off is the future. O n Saturday afternoon, a symposium focused on the consensus and controversy relating to keratoconus. The session was moderated by Elmer Tu, MD, Chicago, and Anthony Aldave, MD, Los Angeles. Michael Belin, MD, Tucson, Arizona, shared an update on the status of corneal crosslinking in the U.S. Crosslinking, he said, was first reported in 1997, and human trials started in 2003 (the Dresden protocol). However, it was only approved in the U.S. in 2016. Dr. Belin said Avedro's crosslinking approval was a major benefit for both patients and physicians. However, he also noted that the cost of the device and drug are vastly higher than outside the U.S., and insurance carriers limit treatment based on the FDA study design. Dr. Belin said he thinks the goal of crosslinking should be the prevention of sequelae, not just the stabilization after loss of function. This, he said, requires earlier intervention than currently covered by most carriers. He also commented on the status of crosslinking outside the U.S., noting that there are multiple riboflavin formulations, multiple UVA delivery systems, accelerated crosslinking, modified delivery for corneas thinner than 400 microns, combined treatments, and epi-on crosslinking. There are no combined treat- ments approved in the U.S. Dr. Belin further commented on epi-on crosslinking, noting that it remains controversial. Standard riboflavin does not cross the ep- ithelial barrier, but he added that epi-on studies are ongoing. Keratoconus the focus of Saturday afternoon symposium Dr. Tu and Dr. Aldave moderate a symposium on keratoconus.

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