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April 27, 2026—Glaukos today announced the online publication of a Phase 3, confirmatory pivotal trial for Epioxa in Ophthalmology and Therapy. In this paper, Beckman et al. shared the results of the prospective, Phase 3, multicenter, sham procedure/placebo controlled, double-masked, randomized clinical trial evaluating the safety and efficacy of Epioxa, the first and only FDAapproved, epithelium-on, oxygen-enriched corneal cross-linking therapy for the treatment of keratoconus.
As reported in the published paper, Epioxa met its primary endpoint, showing a statistically significant and clinically meaningful improvement in Kmax at Month 12 (-0.5 D improvement in Epioxa-treated eyes versus +0.4 D worsening in the sham group).1 The difference between the two groups was a statistically superior -1.0 D (95% CI -1.3, -0.6; p < 0.0001). Keratoconus was slowed or halted in treated eyes, while sham/placebo eyes continued to show steepening, with consistent trends across age, sex, race, and baseline severity subgroups, including eyes with mild keratoconus.
In addition, the safety profile was favorable with no serious ocular adverse events and mild, transient treatment-emergent events. No clinically meaningful changes were observed in corneal thickness, endothelial cell count, intraocular pressure, or macular thickness, supporting the procedure’s tolerability and safety.
To summarize, in this pivotal study, Epioxa met its primary efficacy endpoint, halting or slowing disease progression, and helped to improve corneal integrity and maintain visual function. In addition, safety was favorable with mild side effects that were temporary. Notably, both eyes of a subject could be enrolled in the Epioxa trial with the second eye treated as early as one week after the first eye. The efficacy endpoint (1.0 D difference in Kmax at Month 12) was the same as in the Photrexa/Photrexa Viscous Phase 3 pivotal trials.2
These data support early intervention in keratoconus management, suggesting that a “watch and wait” approach carries real risk of disease worsening. Early treatment offers the greatest opportunity to preserve corneal integrity.
Additional details from the study are provided below:
• The study was conducted at 28 U.S. clinical sites.
• Patients enrolled in the study ranged from age 13 to age 51.
• Key inclusion/exclusion criteria:
o Axial topography consistent with KC and central or inferior steepening on Pentacam and clinical signs of KC (ie., Fleischer ring, Vogt striae, corneal thinning, corneal scarring, and/or scissoring of the retinoscopic reflex) and Kmax ≥47.00 D
o Corneal thickness ≥325 µm
o No prior corneal surgery or other ocular conditions and no history of or risk for delayed epithelial healing
• Eyes were randomized 2:1 to Epioxa treatment or sham/placebo control
o Randomization was stratified by baseline severity (mild vs. moderate/severe) and by age (<30 vs. ≥30 years) within each site
o Epioxa treated eyes (N=200) received Epioxa HD (riboflavin 5’-phosphate ophthalmic solution 0.239%) and Epioxa (riboflavin 5-phosphate ophthalmic solution 0.177%), and underwent UV-A pulsed irradiation (1 second on/1 second off) with supplemental oxygen delivered via Boost Goggles®
o Control eyes (N=112) received placebo drops and underwent a sham irradiation procedure
• The primary efficacy endpoint was the between-group difference in least squares (LS) mean change from baseline in maximum corneal curvature (Kmax ) at month 12
• Eyes initially randomized to sham/placebo were crossed over to receive Epioxa treatment after 12 months and followed for an additional 6 months.
References
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. Ophthalmol Ther 2026;Online ahead of print.
2. Hersh PS SR, Muller D. United States multicenter clinical trial of corneal collagen crosslinking for keratoconus treatment. Ophthalmology. 2017;124(9):1259-1270.
As reported in the published paper, Epioxa met its primary endpoint, showing a statistically significant and clinically meaningful improvement in Kmax at Month 12 (-0.5 D improvement in Epioxa-treated eyes versus +0.4 D worsening in the sham group).1 The difference between the two groups was a statistically superior -1.0 D (95% CI -1.3, -0.6; p < 0.0001). Keratoconus was slowed or halted in treated eyes, while sham/placebo eyes continued to show steepening, with consistent trends across age, sex, race, and baseline severity subgroups, including eyes with mild keratoconus.
In addition, the safety profile was favorable with no serious ocular adverse events and mild, transient treatment-emergent events. No clinically meaningful changes were observed in corneal thickness, endothelial cell count, intraocular pressure, or macular thickness, supporting the procedure’s tolerability and safety.
To summarize, in this pivotal study, Epioxa met its primary efficacy endpoint, halting or slowing disease progression, and helped to improve corneal integrity and maintain visual function. In addition, safety was favorable with mild side effects that were temporary. Notably, both eyes of a subject could be enrolled in the Epioxa trial with the second eye treated as early as one week after the first eye. The efficacy endpoint (1.0 D difference in Kmax at Month 12) was the same as in the Photrexa/Photrexa Viscous Phase 3 pivotal trials.2
These data support early intervention in keratoconus management, suggesting that a “watch and wait” approach carries real risk of disease worsening. Early treatment offers the greatest opportunity to preserve corneal integrity.
Additional details from the study are provided below:
• The study was conducted at 28 U.S. clinical sites.
• Patients enrolled in the study ranged from age 13 to age 51.
• Key inclusion/exclusion criteria:
o Axial topography consistent with KC and central or inferior steepening on Pentacam and clinical signs of KC (ie., Fleischer ring, Vogt striae, corneal thinning, corneal scarring, and/or scissoring of the retinoscopic reflex) and Kmax ≥47.00 D
o Corneal thickness ≥325 µm
o No prior corneal surgery or other ocular conditions and no history of or risk for delayed epithelial healing
• Eyes were randomized 2:1 to Epioxa treatment or sham/placebo control
o Randomization was stratified by baseline severity (mild vs. moderate/severe) and by age (<30 vs. ≥30 years) within each site
o Epioxa treated eyes (N=200) received Epioxa HD (riboflavin 5’-phosphate ophthalmic solution 0.239%) and Epioxa (riboflavin 5-phosphate ophthalmic solution 0.177%), and underwent UV-A pulsed irradiation (1 second on/1 second off) with supplemental oxygen delivered via Boost Goggles®
o Control eyes (N=112) received placebo drops and underwent a sham irradiation procedure
• The primary efficacy endpoint was the between-group difference in least squares (LS) mean change from baseline in maximum corneal curvature (Kmax ) at month 12
• Eyes initially randomized to sham/placebo were crossed over to receive Epioxa treatment after 12 months and followed for an additional 6 months.
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References
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. Ophthalmol Ther 2026;Online ahead of print.
2. Hersh PS SR, Muller D. United States multicenter clinical trial of corneal collagen crosslinking for keratoconus treatment. Ophthalmology. 2017;124(9):1259-1270.
