The FDA's October 2025 approval of EPIOXA HD / EPIOXA (riboflavin 5-phosphate ophthalmic solution 0.239% / 0.177%, Glaukos), the first epithelium-on corneal cross-linking therapy, removes the recovery burden that has long delayed referral and treatment.
Vance Thompson, MD, of Vance Thompson Vision, hosted a conversation on interventional keratoconus with William Trattler, MD; Elise Kramer, OD, FAAO, FSLS; and Mitch Ibach, OD, FAAO.
Dr. Trattler is a cornea, cataract, and refractive surgeon in Miami, Dr. Kramer specializes in specialty contact lenses and ocular surface disease at her Miami and Weston practices, and Dr. Ibach practices alongside Thompson, managing anterior segment disease across cornea, cataract, and refractive surgery.
“We all know that keratoconus leads to irreversible corneal damage, and it's our job to recognize it early. In my opinion, we don't want to just wait and observe.”
Keratoconus fast facts
- Keratoconus is a progressive corneal ectatic disorder, not a dystrophy, meaning the disease process has already begun by the time keratoconus is clinically diagnosed.1
- Subclinical keratoconus, corneal changes that precede a formal diagnosis, shows up in roughly 1 in 4 eyes undergoing cataract surgery in published data, while manifest keratoconus in that same population runs closer to 2%.2
- Dr. Trattler's own experience tracks with that pattern: In a screening analysis of 1,000 eyes from cataract surgery candidates in their 60s to 80s, his group found keratoconus in 3.3% of eyes, most previously undiagnosed.
- In October 2025, the FDA approved EPIOXA, the first epithelium-on corneal cross-linking therapy, eliminating the need for epithelial debridement.3
- A phase 3 pivotal trial of 312 eyes found EPIOXA produced a statistically significant 1.0D treatment effect in maximum corneal curvature (Kmax) at 12 months compared with sham treatment (P<0.0001).4
- EPIOXA’s labeling does not require documented progression prior to treatment, lowering the threshold for early referral.4
- Corneal cross-linking (CXL) is FDA-approved for patients 13 years and older, though off-label treatment in younger children has been reported.3
The diagnostic gap in keratoconus
Dr. Trattler's patients are not always diagnosed on the first—or even the second—visit. One patient had already been evaluated by three board-certified ophthalmologists, including two within his own practice, before a routine corneal topography performed during a refractive surgery evaluation revealed keratoconus. No one had previously obtained corneal imaging.
This case illustrates a broader challenge. Because corneal topography is not routinely included in a standard comprehensive eye examination, keratoconus can remain undetected—even in patients evaluated by experienced ophthalmologists. As a result, patients may be told that their vision loss is due to another cause when the underlying diagnosis has simply not been imaged.
“Topography is not something that's done under standard of care for a comprehensive eye exam, and so a lot of decrease in vision may be incorrectly attributed to amblyopia or other things—and that's where keratoconus could be missed.”
Key data from EPIOXA's phase 3 trial
That diagnostic gap is exactly why EPIOXA matters. For most of cross-linking's history in the United States, epithelium-off treatment was the only FDA-approved option, and scraping the epithelium means pain, weeks of recovery, and a delay before patients can go back to their contact lenses.
EPIOXA skips that step: a riboflavin formulation built to penetrate an intact epithelium, paired with supplemental oxygen delivered through specialized goggles during UV-A treatment.3
The phase 3 pivotal trial behind the FDA approval randomized 312 eyes 2:1 to EPIOXA or sham. At 12 months, treated eyes improved 0.5D in Kmax while sham eyes worsened 0.4D, a 1.0D between-group difference that was both statistically significant and clinically meaningful.4 There were no serious ocular adverse events and no treatment-related discontinuations.4
The importance of stabilizing the cornea before vision correction
Because epithelium-on cross-linking produces minimal immediate structural change, Dr. Trattler noted that patients can be fit for scleral lenses the same week and keep wearing the pair they already own without the fit going stale.
Dr. Kramer emphasized that while specialty contact lenses play a critical role in visual rehabilitation, they should not be viewed as a substitute for disease stabilization. "Even if a patient sees well in a scleral lens, we still want the cornea stabilized first with CXL whenever appropriate. Specialty lenses restore vision, but they don't stop keratoconus from progressing,” she added.
Once the cornea is stable, Dr. Ibach put it plainly, calling cross-linking “the key that unlocks the refractive toolbox” for everything that follows, from scleral lenses to corneal tissue addition keratoplasty (CTAK) to topography-guided photorefractive keratectomy (PRK). “After a patient is cross-linked, now we’ve opened up all of these different options,” he added.
Key takeaways
- Keratoconus diagnosis should trigger immediate referral for cross-linking evaluation, not a period of watchful waiting.
- Dr. Kramer flags any patient with increasing myopic astigmatism or vision that no longer corrects to 20/20 as reason enough for a topography referral.
- EPIOXA’s phase 3 data support earlier intervention, since the treatment no longer requires waiting to document progression.4
- CXL stabilizes the cornea first; visual rehabilitation with scleral lenses, CTAK, PRK, or implantable collamer lens (ICL) follows once the cornea has been strengthened.
- Collaboration between optometry and ophthalmology, from diagnosis through vision rehabilitation, remains the backbone of modern keratoconus care.
Conclusion
Keratoconus shows up more often in everyday practice than a standard exam is built to detect, but the tools for catching it early keep getting better. And the mindset is changing to one of an interventional nature.
“Catching patients early, treating them early, and prevention of worsening is the key to managing patients with keratoconus.”
For the full conversation on diagnosis triggers, referral timing, and where EPIOXA fits into a modern treatment plan, watch the complete discussion. For more on evolving CXL technology dive into the article A Look at the Latest Technology in Corneal Cross-Linking!
This article was written by Keren Beki based on the recorded conversation between Drs. Thompson, Trattler, Kramer, and Ibach.
