The Epic Future of Epi-on
A look at what’s coming to cross-linking, both in and out of the FDA pipeline.
Excerpt Below
New cross-linking protocols are attempting to circumvent the shortcomings of the Dresden protocol, in particular by aiming to decrease treatment time and reduce postop pain, while producing comparable results.
“I’m excited by the latest developments in epi-on cross-linking,” says Farhad Hafezi, MD, PhD, chief medical officer of the ELZA Institute, Dietikon, Switzerland. “Given everything we’ve learned about cross-linking over the years, we’re now approaching a point where we can leverage that knowledge and combine it with molecules that act as penetration enhancers (to get riboflavin across the epithelium and into the stroma in clinically effective levels), pulsed UV light (that lets oxygen diffuse back into the cornea) and smart, individualized cross-linking protocols to get corneal stiffening effects on the same level as the epi-off gold standard Dresden protocol. At my institute, we’ve already moved over to epi-on cross-linking.”
Neera Singal, MD, FRCS(C), an assistant professor, chief of cornea and the head of the collagen cross-linking program in the department of ophthalmology and vision sciences at the University of Toronto, is also eager for epi-on cross-linking to come to the fore. “Dr. Stulting and colleagues recently reported the results of an epi-on technique with a new riboflavin formulation and UV light, which seems promising but isn’t available yet for prime time,”¹ she says. “With an efficacious epi-on technique, we’d virtually eliminate the risk of haze and have a significant improvement in postoperative pain. It’d also allow us to perform CXL on thinner corneas.”
Long-term studies are still needed to understand how all of these new protocols may affect corneal stability down the line,² but epi-on, accelerated and pulsed protocols show promise. Here, we’ll look at some epi-on treatments in the FDA pipeline, and other cross-linking protocols in use outside the United States.
The Epismart system uses a disposable wand to remove the mucin layer and promote epithelial permeability (top). A loading sponge is then placed on the cornea to maintain optimal drug concentration (bottom).
Epismart
EpiSmart (CXL Ophthalmics), an epi-on procedure developed by Roy S. Rubinfeld, MD, MA, is scheduled to begin Phase III trials in a few months. The treatment uses a proprietary riboflavin formulation that contains sodium iodide as its key active ingredient.³ “Sodium iodide enhances the penetration of riboflavin and helps to achieve homogeneous stromal loading,” explains Michael D. Webb, MA, MBA, president and CEO of EpiSmart. “It also scavenges hydrogen peroxide and converts it into oxygen. We apply the riboflavin solution, known as RiboStat, once at the initial outset of the procedure, rather than continually dropping riboflavin into the patient’s eyes.”
The EpiSmart procedure takes approximately 50 minutes from start to finish, with a 20-minute UVA exposure, and consists of three parts. First, a small wand-shaped tool is used to remove the mucin layer from the surface of the cornea. Next, the riboflavin solution is applied to a loading sponge that helps maintain drug concentration during stromal loading. Epismart uses a pulsing UVA device with two arms for bilateral treatment. It includes a fixation light and modulated compensating light to maintain the eye’s target focus.
“This is a true epi-on procedure,” Mr. Webb explains. “Generally, our patients go back to school or work the next afternoon with both eyes treated. We hope EpiSmart will help to move cross-linking toward a treatment paradigm that allows for treatment upon initial diagnosis, rather than waiting for significant vision loss.”
Sources
Stulting RD, Trattler WB, Woolfson JM, Rubinfeld RS. Corneal cross-linking without epithelial removal. J Cataract Refract Surg 2018;44:11:1363-1370.
Pasha H, Palazzolo L, Prakash G. Update on corneal collagen crosslinking for ectasia. Curr Opin Ophthalmol 2021;32:4:343-47.
Rubinfeld RS, Stulting RD, Gum GG, Talamo JH. Quantitative analysis of corneal stromal riboflavin concentration without epithelial removal. J Cataract Refract Surg 2018;44:2:237-242.