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Epithelium-on Corneal Cross-linking Using a Modified Penetration Enhancer Without Supplemental Oxygen or Iontophoresis

Farhad HafeziUSC Roski Eye Institute, University of Southern California, Los Angeles, California;M. Enes AydemirELZA Institute, Dietikon, SwitzerlandMark HillenELZA Institute, Dietikon, SwitzerlandLéonard KollrosELZA Institute, Dietikon, SwitzerlandNikki L. HafeziDepartment of Ophthalmology, New York University Grossman School of Medicine, New York University, New York;Nan‐Ji LuWest China Hospital of Sichuan UniversityShady T. AwwadDepartment of Ophthalmology, American University of Beirut Medical Center, Beirut, Lebanon;ShiHao ChenEye Hospital of Wenzhou Medical University, Wenzhou, ChinaEmilio A. Torres-NettoELZA Institute, Dietikon, Switzerland
2026en
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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 (K max ), and the apical keratoscopy (K f max ). 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), ΔK f max (−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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