Related Experiment Video
Updated: Apr 17, 2026
Three Different Protocols of Corneal Collagen Crosslinking in Keratoconus: Conventional, Accelerated and Iontophoresis
Published on: November 12, 2015
Transepithelial versus epithelium-off corneal cross-linking for the treatment of progressive keratoconus: a
Nienke Soeters1, Robert P L Wisse1, Daniël A Godefrooij1
1Utrecht Cornea Research Group, Department of Ophthalmology, University Medical Center Utrecht, Utrecht, Netherlands.
Purpose:
To compare the clinical effects and safety of transepithelial corneal cross-linking (CXL) to epithelium-off (epi-off) CXL in progressive keratoconus.
Design:
Randomized clinical trial (noninferiority).
Methods:
Patients received either transepithelial CXL with Ricrolin TE (n = 35) or epi-off CXL with isotonic riboflavin (n = 26) in 1 academic treatment center, using a simple unrestricted randomization procedure. The main outcome measure was clinical stabilization of keratoconus after 1 year, defined as a maximal keratometry (Kmax) increase <1 diopter (D).
Results:
Average Kmax was stable at all visits in the transepithelial group, while after epi-off CXL a significant flattening of 1.2-1.5 D was demonstrated from the 3-month follow-up onwards. The trend over time in Kmax flattening was significantly different between the groups (P = .022). Eight eyes (23%) in the transepithelial group showed a Kmax increase of >1 D after 1 year (range 1.3-5.4 D) vs none in the epi-off group (P = .017). There was significant different trend in corrected distance visual acuity (CDVA), with a more favorable outcome in the transepithelial group (P = .023). In the transepithelial group, no complications occurred and in the epi-off group, 4 eyes (15%) developed complications owing to healing problems (sterile infiltrate, herpes keratitis, central haze, and stromal scar).
Conclusion:
This study showed that although transepithelial CXL was a safe procedure without epithelial healing problems, 23% of cases showed a continued keratoconus progression after 1 year. Therefore, at this time, we do not recommend replacing epi-off CXL by transepithelial CXL for treatment of progressive keratoconus.
