Glaukos' Epioxa maintains corneal flattening and visual gains through 3 years in keratoconus

Glaukos has reported 3-year topline results from a long-term phase 3 extension study of Epioxa, its epithelium-on (epi-on) corneal cross-linking therapy for keratoconus, suggesting that the corneal flattening and visual gains seen after a single treatment persist well beyond the 12-month pivotal end point.¹

The extension study, GLK-202-03, followed a cohort of patients who received cross-linking in the company's second phase 3 pivotal trial, GLK-202-02, and tracked them for up to 3 years after treatment. Efficacy assessments focused on changes in corneal curvature and visual acuity. A total of 38 study eyes from 35 participants were enrolled, and 92% of eyes completed the year 3 visit, according to the company.¹

Sustained Kmax flattening and visual acuity gains

At 3 years, treated eyes showed a sustained 1.9 D improvement in Kmax from baseline, which Glaukos characterized as meaningful long-term corneal flattening and stabilization. No additional treatment was administered during the extension period.¹

Visual outcomes followed a similar pattern. At year 3, 29% of eyes had gained 2 or more lines of BCVA from baseline, and 20% had gained 3 or more lines.¹

The figures build on the parent trial's 12-month results. In October 2024, Glaukos reported that GLK-202-02 met its primary efficacy endpoint, with a least squares mean Kmax treatment effect of –1.0 D for Epioxa vs a sham/placebo control at month 12 (P < .0001).² Eyes in that trial were randomly assigned in a 2:1 ratio to Epioxa or placebo with a sham procedure.²

Clinicians reading the new data should note the difference between the 2 measures. The 12-month figure was a placebo-adjusted treatment effect from a randomized, double-masked trial, whereas the 3-year figure is a change from baseline in treated eyes only, from an extension cohort without a control arm. Even so, a Kmax improvement that holds, and appears to deepen, between years 1 and 3 is the kind of durability signal that cornea specialists have wanted to see from an epi-on approach.

Safety through 3 years

Through the 3-year follow-up, treated eyes had no serious adverse events, no treatment-related adverse events, and no discontinuations due to adverse events.¹ Glaukos chairman and CEO Thomas Burns said the data “reinforce the potential of Epioxa to provide durable clinical benefits” for patients with keratoconus.¹

According to the prescribing information, the most common adverse reaction in clinical studies was conjunctival hyperemia (31%). Other reactions, reported in 5% to 25% of eyes, included corneal haze, photophobia, punctate keratitis, eye pain and irritation, and corneal epithelial defects.¹

Why durability matters for epi-on cross-linking

Conventional epithelium-off (epi-off) cross-linking has been a mainstay for halting keratoconus progression since its FDA approval in 2016. However, as Kenneth Beckman, MD, FACS, noted at the World Cornea Congress IX, removing the epithelium carries risks of infection, scarring, delayed wound healing, and prolonged visual recovery.³ The challenge for epi-on techniques has been delivering enough riboflavin, UV light, and oxygen through an intact epithelium to achieve efficient cross-linking. Glaukos’ approach addresses the oxygen problem with supplemental oxygen delivered via sealed goggles, maintaining a concentration above 90% during treatment.³

Presenting phase 3 results at the 2025 American Academy of Ophthalmology annual meeting, Beckman said that, based on the data, essentially any patient who would have been a candidate for cross-linking would also be a candidate for the epi-on procedure.⁴ Three-year data add weight to that view, because long-term durability has historically been the central question hanging over epi-on cross-linking.

Regulatory and commercial context

The FDA approved Epioxa HD/Epioxa in October 2025, making it the first corneal cross-linking therapy that does not require epithelium removal.⁵ The approval was based on 2 prospective, randomized, multicenter, double-masked phase 3 trials that enrolled more than 400 patients.⁶ Glaukos announced commercial availability in March 2026.⁶

Epioxa HD (riboflavin 5'-phosphate ophthalmic solution) 0.239% and Epioxa (riboflavin 5'-phosphate ophthalmic solution) 0.177% are applied sequentially and are indicated for epi-on corneal collagen cross-linking in adults and pediatric patients aged 13 years and older, in conjunction with the O2n System and Boost Goggles.⁶

References

1. Glaukos announces positive three-year Epioxa results demonstrating durable clinical outcomes in keratoconus. News release. Glaukos Corporation. October 7, 2026. Accessed October 8, 2026. https://investors.glaukos.com/news/news-details/2026/Glaukos-Announces-Positive-Three-Year-Epioxa-Results-Demonstrating-Durable-Clinical-Outcomes-in-Keratoconus/default.aspx

2. Hutton D. Glaukos reports positive phase 3 results for Epioxa. Ophthalmology Times. October 16, 2024. Accessed October 8, 2026. https://www.ophthalmologytimes.com/view/glaukos-reports-positive-phase-3-results-for-epioxa

3. World Cornea Congress IX: epi-on and accelerated crosslinking with Kenneth Beckman, MD. Ophthalmology Times. March 27, 2025. Accessed October 8, 2026. https://www.ophthalmologytimes.com/view/world-cornea-congress-ix-epi-on-and-accelerated-crosslinking-with-kenneth-beckman-md

4. AAO 2025: Ken Beckman discusses trial demonstrating safety and efficacy of epithelium-on CXL. Ophthalmology Times. October 18, 2025. Accessed October 8, 2026. https://www.ophthalmologytimes.com/view/aao-2025-ken-beckman-discusses-trial-demonstrating-safety-and-efficacy-of-epithelium-on-cxl

5. FDA approves Glaukos' Epioxa incision-free keratoconus therapy. Ophthalmology Times. October 20, 2025. Accessed October 8, 2026. https://www.ophthalmologytimes.com/view/fda-approves-glaukos-epioxa-incision-free-keratoconus-therapy

6. Glaukos announces commercial availability of Epioxa for the treatment of keratoconus. Ophthalmology Times. March 20, 2026. Accessed October 8, 2026. https://www.ophthalmologytimes.com/view/glaukos-announces-commercial-availability-of-epioxa-for-the-treatment-of-keratoconus