28 EyeWorld Asia-Pacific | March 2025 REFRACTIVE SURGERY for its EpiSmart system in 2021 and began a Phase 3 clinical trial in October 2023. Michael W. Belin, MD, Chief Medical Officer for Epion Therapeutics, said recruitment for the Phase 3 trials should be completed by the end of 2024/early 2025. The EpiSmart, Phase 3 trials, instead of using Kmax as a metric, which Dr. Rubinfeld said is not correlated with vision, uses visual acuity as its efficacy metric. The two concurrent Phase 3 trials will enroll 800 subjects at 20 investigational sites in the U.S., with patients receiving bilateral, simultaneous treatment when indicated, according to the company’s press release. Dr. Belin said the EpiSmart system is unique in riboflavin concentration (“up to 5x more concentrated” than some other systems), its proprietary riboflavin loading sponge, which provides constant contact of the drug to the corneal surface, and with the addition of sodium iodine, which he said enhances penetration of the drug through the epithelium. “It stabilizes the riboflavin once it gets into the stroma so we don’t drop during the UV application and …. [contributes] oxygen back into the cycle,” Dr. Belin said, adding later, “the other thing that I think is unique about our protocol is that we have the ability to treat both eyes simultaneously if both eyes qualify for entrance into the study.” Dr. Rubinfeld, one of the physicians at the forefront of the epithelium-on crosslinking technology, said having a crosslinking system in the U.S. that can be performed upon initial diagnosis of keratoconus (not needing to wait for documented progression) and in a transepithelial manner will greatly benefit patients. Dr. Beckman agreed, though he said, for now, the approved epithelium-off procedure remains the gold standard, and he would perform it on his own child, if he needed it. “Once epi-on is approved, if it is even close to epi-off, no one will be doing epi-off, they’ll be doing full-time epion,” he said, noting that this would likely be due to a more favorable risk-benefit profile. “I think it will be the first line because of safety, but that doesn’t mean it’s better. If your goal is stopping progression, and epi-off gives you a diopter of flattening and epi-on gives you a third of a diopter of flattening, both of them have stopped progression, but you might say the risk is so much less with epi-on, I’d much rather do that. I do think it’s the way of the future, and I do think that once it’s there it will be everyone’s first line, assuming you’re allowed and have the access.” Dr. Belin said a transepithelial procedure will likely have a better risk-benefit ratio, allowing physicians to intervene at the earliest possible stages. “I think that will ultimately be the benefit of epithelium-on crosslinking, allowing us to not wait until there is permanent loss of vision but to intervene in patients with true disease at the earliest point of diagnosis,” Dr. Belin said. Dr. Trattler said a transepithelial procedure could provide a better patient experience because there is no epithelial defect and lead to quicker visual recovery, but he also said these procedures are looking to increase efficacy as well through pulsed light and other methods to increase oxygen availability. “Pulsing of UV light (as compared to continuous UV light), in our experience, has worked well to strengthen the cornea. You’re achieving a stronger effect when the three critical components to the crosslinking reaction are present: riboflavin, UV light, and oxygen. When the UV light is on, the oxygen in the cornea depletes, so techniques that allow for increased oxygen availability in the cornea can help provide a more efficient crosslinking reaction. Both the Glaukos and Epion Therapeutics clinical trials for epithelial-on crosslinking use pulsed UV light to increase oxygen availability. Glaukos also has an eye mask that delivers additional oxygen to the corneal surface. With more oxygen, the crosslinking reaction is more effective,” Dr. Trattler said. About the Physicians Brandon Ayres, MD | Cornea Service, Wills Eye Hospital, Philadelphia, Pennsylvania | bayres@willseye.org Kenneth Beckman, MD | Director of Corneal Surgery, Comprehensive Eyecare of Central Ohio, Westerville, Ohio | kenbeckman22@aol.com Michael W. Belin, MD | Professor of Ophthalmology and Vision Science, University of Arizona College of Medicine, Chief Medical Officer, Epion Therapeutics, Tucson, Arizona | mwbelin@epiontx.com Roy Rubinfeld, MD | Clinical Professor, Georgetown University, Medical Center, Medical Director, ReVision, Washington, D.C., and Rockville, Maryland | rsrubinfeld@gmail.com William Trattler, MD | Director of Cornea, Center for Excellence in Eye Care, Miami, Florida | wtrattler@gmail.com Reference 1. Hafezi F, et al. Individualized corneal cross-linking with riboflavin and UV-A in ultrathin corneas: the sub400 protocol. Am J Ophthalmol. 2021;224:133–142. Relevant Disclosures Ayres: Glaukos Beckman: Glaukos Belin: Epion Therapeutics Rubinfeld: Epion Therapeutics, www.CXLUSA.com Trattler: Epion Therapeutics, Glaukos This article originally appeared in the December 2024 issue of EyeWorld. It has been slightly modified and appears here with permission from the ASCRS Ophthalmic Services Corp.
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