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Updated: Jun 17, 2026
Three Different Protocols of Corneal Collagen Crosslinking in Keratoconus: Conventional, Accelerated and Iontophoresis
Published on: November 12, 2015
Three-year outcomes of customized transepithelial corneal cross-linking with oxygen supplementation in keratoconus
Takashi Kojima1, Yingsong Lin2, Asahi Hishida2
1Nagoya Eye Clinic, Namiyose-cho 24-14, COLLECT MARK Kanayama 2F Atsuta-ku, Nagoya, Aichi, 456-0003, Japan. kojima@sanjogroup.jp.
Background:
Customized corneal cross-linking (CXL) has primarily been performed using the epithelium-off technique. Evidence on epithelium-preserving (transepithelial or epi-on) customized procedures remains limited, particularly with high oxygen concentrations (> 90%) beyond 1 year. We evaluated the 3-year clinical outcome and safety of customized transepithelial CXL (custom TE-CXL) with oxygen supplementation in patients with progressive keratoconus.
Methods:
This retrospective study included 74 individuals (90 eyes) with progressive keratoconus who underwent custom TE-CXL with oxygen supplementation and were followed for at least 3 years. Outcomes included visual acuity, keratometric parameters, corneal thickness, and total corneal higher-order aberrations (HOAs). Examinations were performed at baseline and at 1, 2, and 3 years postoperatively. Longitudinal changes were analyzed using a linear mixed-effects model adjusted for baseline values.
Results:
From 1 year onward, uncorrected visual acuity (UCVA) and maximum keratometry (Kmax) showed significant improvement compared with preoperative values. Least squares mean (LSMean) Kmax values decreased from 56.2 D at baseline to 54.9 D, 54.4 D, and 54.2 D at 1, 2, and 3 years, respectively (all P < 0.01). UCVA improved at 1 year and remained stable thereafter, whereas corrected distance visual acuity (CDVA) showed no significant changes. Total HOAs, including coma and spherical aberration, decreased progressively over time. Apical corneal thickness decreased gradually, and thinnest corneal thickness showed significant reductions from 1 year onward. No adverse events, such as infection or corneal haze, were observed during follow-up.
Conclusions:
This descriptive, non-comparative analysis showed that custom TE-CXL with oxygen supplementation may be associated with stabilization of keratoconus over a 3-year period without observed adverse events. Further randomized controlled studies are warranted to evaluate its comparative effectiveness.