A phase 3 randomized clinical trial evaluating Epioxa—an oxygen-enriched, epithelium-on corneal crosslinking procedure—has demonstrated statistically significant improvements in corneal curvature and a favorable safety profile in patients with keratoconus, according to results published in Ophthalmology and Therapy.

The multicenter, double-masked, sham-controlled study enrolled 312 eyes from 208 patients aged 13 to 51 years across 28 US sites. Eyes were randomized 2:1 to treatment (n=200) or sham/placebo (n=112). Patients met diagnostic criteria for keratoconus, including K_max of at least 47.0 D and characteristic topographic and clinical findings. Minimum corneal thickness was at least 325 µm.

The treatment protocol involved riboflavin 5′-phosphate ophthalmic solutions (0.239% and 0.177%), pulsed UV-A irradiation (30 mW/cm², 1 second on/1 second off), and supplemental oxygen delivery to achieve at least 90% oxygen concentration at the corneal surface. The epithelium was left intact during the procedure, which is a notable part of Epioxa’s introduction to the treatment armamentarium.

The primary endpoint was the between-group difference in change from baseline in maximum corneal curvature (K_max) at 12 months. The study results met this endpoint and demonstrated statistical significance and clinical relevance.

More specifically, at 12 months, the treatment group showed a mean improvement of −0.5 diopters (D) in K_max(95% CI −0.7 to −0.3; P<0.0001). The sham group showed a +0.4 D worsening¹ (95% CI 0.1 to 0.8; P=0.0045), and the between-group difference was −1.0 D (95% CI −1.3 to −0.6; P<0.0001). These findings indicate that keratoconus progression was slowed or halted in treated eyes, while untreated eyes continued to steepen, the study authors and an accompanying press release noted.

At 6 months, the treatment effect was also statistically significant: The between-group difference was −0.6 D (95% CI −0.9 to −0.2; P=0.0008) at this timepoint.

Subgroup analyses showed consistent treatment effects across age, sex, race, and baseline disease severity, and the researchers observed statistically significant improvements in most strata, particularly among patients who were younger than 30 years and those who had mild keratoconus.

No serious ocular adverse events were reported in either group. Ocular adverse events occurred in 30.5% of treated eyes vs 10.7% in the sham group, and most were mild and transient. The most common adverse event was punctate keratitis (6.5% vs 1.8%).

No clinically meaningful changes were observed in corneal thickness, endothelial cell count, intraocular pressure, or macular thickness, and the researchers found modest improvements in both best spectacle-corrected and uncorrected visual acuity.

According to the study researchers, corneal collagen crosslinking remains the only intervention shown to slow or halt keratoconus progression. They noted that traditionally, FDA-approved procedures have required epithelial debridement (epithelium-off), which is associated with risks including infection, delayed healing, and postoperative discomfort.

Epioxa combines epithelium-on treatment with supplemental oxygen to enhance crosslinking efficiency by promoting oxygen-dependent photochemical reactions within the corneal stroma. The study findings support the efficacy of this approach in stabilizing or improving corneal curvature in keratoconus across a broad patient population.OM

Reference:

1. Beckman KA, Parkhurst GD, Lee JH, et al. Randomized, controlled study to evaluate the safety and efficacy of oxygen‑enriched epithelium‑on corneal cross‑linking for the treatment of keratoconus. Opthalmol Ther. 2026;15:1463-1484. doi:10.1007/s40123-026-01364-7