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Updated: Oct 9, 2026

Three Different Protocols of Corneal Collagen Crosslinking in Keratoconus: Conventional, Accelerated and Iontophoresis
Published on: November 12, 2015
Epithelium-on Corneal Cross-linking Using a Modified Penetration Enhancer Without Supplemental Oxygen or
Farhad Hafezi1,2,3,4,5, M Enes Aydemir1, Mark Hillen1
1ELZA Institute, Dietikon, Switzerland.
Purpose:
To present the 1-year results of a novel epitheliumon corneal cross-linking (epi-on CXL) protocol for the treatment of progressive keratoconus that does not require supplemental oxygen or iontophoresis and that involves the use of a modified penetration enhancer solution to enable riboflavin to saturate the corneal stroma transepithelially.
Methods:
Thirty-eight eyes from 29 patients with progressive keratoconus were included. Patients were treated with epi-on CXL using accelerated pulsed high-fluence ultraviolet-A irradiation. The main outcome measures included the thinnest corneal thickness, the anterior radius of curvature in the 3-mm zone centered on the thinnest location of the cornea (ARC3mm), demarcation line depth, the final deviation value D of the Belin/Ambrósio Enhanced Ectasia Display (D), maximum anterior keratometry (Kmax), and the apical keratoscopy (Kfmax). The follow-up period was 1 month for the demarcation line depth and 1 year for all other parameters.
Results:
Differences before and after epi-on CXL were Δthinnest corneal thickness (-7.92 µm [445.29 µm, 437.37 μm], P = .28), ΔARC (-0.03 mm [6.80 mm, 6.77 mm], P = .57), demarcation line depth was 217.85 µm, ΔD (Belin/Ambrósio) (0.17 [9.96, 10.13], P = .68), ΔKmax (-0.01 D [56.12 D, 56.11 D], P = .99), ΔKfmax (-1.41 D [57.64 D, 56.23 D], P = .24).
Conclusions:
This new epi-on CXL approach demonstrated 12-month topographic stability in progressive keratoconus without requiring supplemental oxygen or iontophoresis. This simplification holds the potential to enable a practical, office-based approach to epi-on cross-linking.
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