FDA-Approved Epi-On CXL for Keratoconus

For patients with keratoconus, corneal cross-linking has long been one of the most effective tools for stopping disease progression. An FDA-approved significant advancement in how that treatment is delivered was approved in October 2025, and Chicago Cornea Consultants is now offering it.

Chicago Cornea Consultants Now Offers FDA-Approved Epi-On CXL

Epithelium-on corneal cross-linking, known as Epi-On CXL, has received FDA approval under the brand name Epioxa, developed by Glaukos Corporation. This marks the first time an epi-on corneal cross-linking therapy has received full FDA approval in the United States, and Chicago Cornea Consultants is proud to be among the first practices in Illinois to bring it to patients.

This is not a new area for our team. Chicago Cornea Consultants has been at the forefront of cross-linking since 2010, and the path to this FDA approval runs directly through our clinical work.

What Is Keratoconus and Why Does CXL Matter?

Keratoconus is a progressive eye condition in which the cornea, the clear front surface of the eye, gradually thins and begins to bulge outward into a cone-like shape. This structural change distorts the way light enters the eye, leading to blurred vision, increasing astigmatism, glare, and light sensitivity.

In mild cases, glasses or soft contact lenses can manage symptoms. As the condition progresses, rigid scleral or gas-permeable contact lenses may become necessary to provide adequate vision correction. Without intervention to stop progression, some patients eventually require a corneal transplant.

Keratoconus most commonly develops in adolescence or early adulthood and tends to progress most rapidly in younger patients. It can affect one or both eyes and often runs in families, though it can also occur with no family history. Early detection is important, as CXL is most effective when performed before the disease reaches an advanced stage.

Corneal cross-linking was developed specifically to halt progression. The procedure strengthens the cornea by creating new bonds between the collagen fibers that give the cornea its shape and stability. Rather than correcting vision directly, CXL addresses the underlying structural problem, helping prevent the disease from advancing to a point where transplantation becomes necessary.

How Traditional Epi-Off CXL Works

The original FDA-approved form of CXL, approved in 2016 and known as epithelium-off (Epi-Off) CXL, follows a specific sequence.

First, the epithelium, the thin outer layer of the cornea, is removed. Riboflavin (Vitamin B2) eye drops are then applied to the exposed corneal surface. Once the riboflavin has saturated the tissue, ultraviolet-A light is applied, triggering a photochemical reaction that forms new cross-links between corneal collagen fibers and stiffens the cornea.

Epi-Off CXL is clinically proven and effective. However, removing the epithelium comes with a recovery period. Patients typically experience several days of discomfort, light sensitivity, and blurred vision while the surface heals. There is also a small but real risk of infection, corneal haze, and other wound-healing complications during that window.

What Makes Epi-On CXL Different

Epi-On CXL achieves the same goal of strengthening the cornea but takes a fundamentally different approach to getting the riboflavin where it needs to go.

Instead of removing the epithelium, Epioxa uses a specially formulated, oxygen-enriched riboflavin solution designed to penetrate the intact epithelial layer on its own. The treatment is then activated with UV light in an oxygen-rich environment, which intensifies the cross-linking reaction and allows effective strengthening of the cornea without any surface disruption.

Because the epithelium remains intact throughout the procedure, patients benefit from:

• Shorter recovery time with faster return to normal activities
• Significantly less discomfort during and after the procedure
• Reduced risk of infection, since the corneal surface is never opened
• Reduced risk of corneal haze or scarring
• The ability to treat both eyes on the same day

For many patients, Epi-On CXL means returning to daily life within a day or two, rather than waiting a week or more for recovery.

The Clinical Data Behind Epioxa

FDA approval of Epioxa was based on data from two prospective, randomized, multicenter, double-masked Phase 3 clinical trials involving more than 400 patients combined. The trials evaluated Epioxa against a sham procedure in patients with progressive keratoconus.

Results demonstrated a clinically meaningful and statistically significant improvement in maximum corneal curvature (Kmax) at 12 months compared to the control group, meeting the primary efficacy endpoint. Treatment was well tolerated, with 91.5% of patients completing the full 12-month trial.

The approval of Epioxa on October 20, 2025, made it the first and only FDA-approved epithelium-on corneal cross-linking therapy on the market.

Chicago Cornea Consultants' History With Epi-On CXL

Chicago Cornea Consultants has been involved in epi-on CXL long before FDA approval made it widely available. Our practice participated in the CXL-USA clinical trial from 2010 to 2019, successfully performing epi-on CXL on more than 2,000 eyes with excellent outcomes. That trial was among the largest and longest-running investigational studies of epi-on cross-linking in the United States.

Our team was the first practice in Illinois to perform CXL, beginning in 2010, years ahead of the 2016 FDA approval of the standard epi-off procedure. Since then, Chicago Cornea Consultants has performed more corneal cross-linking procedures than any other practice in the metro Chicago area, with over 3,000 eyes treated in total.

Patients are referred to us for CXL from throughout the Midwest.

When the FDA approved Epioxa in October 2025, our team was already deeply familiar with the procedure, its results, and the patients it is best suited to treat. We were the first in Illinois to offer it following FDA approval.

Who Is a Candidate for Epi-On CXL?

Epi-On CXL is indicated for patients with progressive keratoconus. Candidates are typically those who have documented evidence of corneal progression and who still have sufficient corneal thickness to undergo the procedure safely.

Epi-On CXL may be particularly well suited for:

• Patients concerned about recovery time associated with traditional epi-off CXL
• Those who need both eyes treated and want to do so in a single visit
• Younger patients with progressive disease who want to act early
• Patients who have postponed treatment due to concerns about discomfort or downtime

Not every patient with keratoconus is automatically a candidate. A thorough evaluation at Chicago Cornea Consultants, including corneal topography and thickness measurements, is needed to determine whether Epi-On CXL, traditional Epi-Off CXL, or another approach is the right choice for your specific case.

Schedule a CXL Consultation at Chicago Cornea Consultants

If you have been diagnosed with keratoconus or have been told your cornea is changing, the team at Chicago Cornea Consultants can assess your situation and walk you through all available options, including FDA-approved Epi-On CXL.

During your consultation, we will review your corneal topography, measure corneal thickness, evaluate the rate of progression, and recommend the cross-linking approach best matched to your eyes and lifestyle.

With over 15 years of cross-linking experience, more procedures performed than any practice in the Chicago area, and direct involvement in the clinical trials that led to FDA approval, our team brings a depth of expertise that is difficult to match.

Contact Chicago Cornea Consultants today to schedule your consultation.