In October of 2025, the U.S. Food & Drug Administration (FDA) approved Epioxa, ushering in a novel cross linking procedure for patients with keratoconus. This is especially exciting news since clinical trials for epi-on crosslinking were performed right here at CLEI! In just a few months time, this procedure will become available to patients commercially, so now is a good time to be informed on what Epioxa is and how it differs from existing corneal cross linking procedures.
What is Epioxa?
Epioxa (technically two formulations: Epioxa HD 0.239% and Epioxa 0.177%) is a topical drug therapy designed for use in epithelium-on corneal collagen cross-linking for keratoconus, in conjunction with a specialized UV-activation system. In simpler terms: instead of surgically removing the outer layer of the cornea (the epithelium) and applying riboflavin and UV as in the classic “epi-off” cross-linking procedure, Epioxa allows treatment while the epithelium remains intact (“epi-on”), thus reducing invasiveness. It is the first FDA-approved incision-free, topical cross-linking therapy for keratoconus.
Why this matters (and how it differs from traditional cross-linking)
Traditional corneal cross-linking (CXL) involves the application of riboflavin (vitamin B2) to the cornea, removal of the epithelium (epi-off) so that riboflavin penetrates, followed by UV-A light exposure to create additional cross-links in the stromal collagen. The goal is to stiffen the cornea, slow or halt progression of keratoconus, and reduce risk of corneal ectasia. While effective, the epi-off approach has downsides: risk of infection, a longer healing period, complications from wound healing, and patient discomfort during recovery.
Enter Epioxa:
- No epithelium removal ― The “epi-on” approach preserves the outer corneal layer, meaning less trauma, less pain and quicker recovery.
- Topical and oxygen-enriched formulation ― The treatment uses riboflavin 5′-phosphate solutions plus a UV-activation step in an oxygen-enriched environment (via the companion device system).
- Faster, smoother recovery and lower risk profile (expected) ― Because the procedure is less invasive, patients may expect less downtime, fewer complications and a more comfortable postoperative period. Physicians quoted in the announcement emphasized improved comfort and minimized recovery time.
- First of its kind approval ― Epioxa represents a shift: the first FDA-approved epithelium-on, incision-free cross-linking therapy for keratoconus.
Who is eligible and when will it be available?
According to the prescribing information, Epioxa is indicated for adults and pediatric patients aged 13 years and older with keratoconus, for epithelium-on corneal collagen cross-linking. The company behind Epioxa, Glaukos Corporation, expects commercial availability in Q1 2026 (early 2026). It’s important to note: since this is newly approved, many providers are still preparing for adoption, insurance coverage, device installations, and patient awareness — so while the approval is official, real-world access may lag slightly.
What are the benefits for patients?
For patients:
- Reduced pain and discomfort after the procedure (because no epithelium removal)
- Shorter recovery period and quicker return to daily activities
- Lower risk of infection or complications associated with open corneal surface
Considerations and what we still don’t know
While the approval is exciting, there are some caveats:
- Since Epioxa is newly approved, long-term real-world outcomes (beyond the clinical trial horizon) are still accumulating.
- Access and reimbursement may vary regionally. Patients may face delays while providers adopt devices or insurers develop policies.
- While the “epi-on” approach is less invasive, it may not be appropriate for all keratoconus cases (for example very advanced disease) — standard “epi-off” CXL may still have a place depending on the case.
- The treatment requires a specific device system (O₂n™ System + Boost Goggles®) in conjunction with the drug formulations. Clinics will need to invest accordingly.
If you’re a patient with keratoconus (or suspect it), now is a good time to be proactive: ask your ophthalmologist or corneal specialist whether you’re a candidate for cross-linking, and mention the upcoming Epioxa option.
In addition, if you’re interested in epi-on crosslinking and don’t want to wait for the newly approved technology to become commercially available, you may be able to access this treatment sooner by joining CLEI’s ongoing FDA clinical trial. Participating gives you the opportunity to receive epi-on CXL under the care of a dedicated corneal team, with close monitoring and support throughout the process. If you’d like to know whether you qualify or simply want to learn more about what participation involves, reach out to our team.
Here at CLEI, we would be happy to discuss your options and determine whether you’re a good candidate for this innovative new treatment. Our team is committed to providing the most advanced, evidence-based care available, and we’re here to guide you through every step — from diagnosis to treatment planning to long-term vision stability. If you’re interested in learning more about Epioxa or exploring all available cross-linking options, we invite you to schedule a consultation with our specialists.
