Epi-On Corneal Crosslinking Procedure Arrests Keratoconus Progression

Epi-on CXL is a safe, non-invasive method for cross-linking with minimal adverse events.

Epi-on corneal crosslinking may improve visual acuity and maximum corneal curvature (Kmax) without altering minimum corneal thickness or creating significant serious adverse events (AEs) in patients with keratoconus, according to a study published in Cornea.

Researchers enrolled 2228 patients with corneal ectatic disease (70% men or boys; mean age, 32 years; keratoconus, 86.3% ) at 9 clinical sites in a prospective, randomized, controlled, open-label trial and randomly assigned them to 1 of 3 UVA treatment modalities which included 2.4 J/cm2 over 20 minutes, 3.6 J/cm2 over 20 minutes, or 3.6 J/cm2 over 30 minutes. Logarithm of the minimum angle of resolution (logMAR) corrected distance visual acuity (CDVA) was the primary endpoint, while logMAR uncorrected distance visual acuity (UCVA), Kmax, and minimum corneal thickness were the secondary endpoints. These parameters were assessed at baseline and at 1-day, 6-month, and 12-month postoperative follow-up visits.  

Individuals with keratoconus demonstrated significant improvements in CDVA, UCVA, and Kmax at 6 and 12 months with no change in minimum corneal thickness. Overall, 81% of patients with keratoconus maintained or improved their vision. Patients younger than 21 years tended to experience greater CDVA improvements, and 89% of these patients maintained or improved their vision. Overall, 14% of patients with keratoconus gained 3 lines or more of CDVA, according to the report.

A mild corneal epithelial defect was reported in 31 cases (1.4%) and was the only AE reported in more than 1% of participants. No serious AEs were related to treatment protocol. No treatment arm demonstrated superiority in efficacy or safety compared with the others.

The results support our contention that this represents a safer, noninvasive crosslinking to arrest the progression of keratoconus.

“Robust improvements were observed in visual acuity sustained over 12 months in a keratoconus population (not known to spontaneously regress), including a large subset of young subjects 21 years old or younger, with minimal AEs,” according to the researchers. “The results support our contention that this represents a safer, noninvasive crosslinking to arrest the progression of keratoconus.”

Study limitations include an overrepresentation of men and boys in the study sample and the lack of a control group.


Epstein RJ, Belin MW, Gravemann D, Littner R, Rubinfeld RS. EpiSmart® crosslinking for keratoconus: a phase 2 study. Cornea. Published online September 29, 2022. doi:10.1097/ICO.0000000000003136