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Updated: Jul 2, 2026

Three Different Protocols of Corneal Collagen Crosslinking in Keratoconus: Conventional, Accelerated and Iontophoresis
Published on: November 12, 2015
Regional Biomechanical and Topographic Changes after Transepithelial vs. Epithelium-off Continuous Accelerated
BangXun Mao1,2, ChangChang He1, Qian Ye1
1National Clinical Research Center for Ocular Diseases, Eye Hospital, WenZhou Medical University, Wenzhou, China.
Purpose:
To compare regional biomechanical and topographic outcomes between transepithelial (Epi-on) and epithelium-off (Epi-off) continuous accelerated corneal cross-linking (ACXL) in keratoconus.
Design:
A retrospective cohort study.
Subjects:
Seventy-seven keratoconic eyes were included: 45 with Epi-on ACXL and 32 with Epi-off ACXL.
Methods:
All eyes underwent ACXL (10 mW/cm2, 7.2 J/cm2). Pentacam HR and Corvis ST measurements were obtained preoperatively (pre), and at 1 month (pos1m), and 6 months (pos6m) postoperatively. The SSIv2m, M, and J0, J45 were evaluated across central (0-3 mm), paracentral (3-6 mm), and peripheral (6-9 mm) regions. Correlated measurements were analyzed using generalized estimating equations for regional and longitudinal data, and generalized linear models for intergroup comparisons, with both absolute (Δ) and relative changes (Δ%) evaluated.
Main Outcome Measures:
Regional changes in SSIv2m, M, J0, and J45 were analyzed across central (0-3 mm), paracentral (3-6 mm), and peripheral (6-9 mm) regions preoperatively and at 1 and 6 months postoperatively.
Results:
At 6 months, SSIv2m increased significantly in all regions of the Epi-off ACXL group (greatest centrally), whereas the Epi-on group showed no consistent change. ΔSSIv2m between preoperative and pos6m was significantly greater in Epi-off ACXL than Epi-on ACXL across all regions (central: P < 0.01; paracentral and peripheral: P < 0.05). Central flattening (negative ΔM) was significant in the Epi-off ACXL group (P < 0.001) and exceeded that in Epi-on ACXL (P < 0.001). No significant changes were detected in J0 or J45. Δ%SSIv2m exceeded Δ%M in the paracentral and peripheral (paracentral: P < 0.01; peripheral: P < 0.05) regions after Epi-off ACXL.
Conclusions:
Epi-off ACXL induces stronger and more durable biomechanical stiffening and central flattening than Epi-on ACXL. Biomechanical parameters, particularly SSIv2, were more sensitive than curvature-based metrics for detecting regional treatment effects.
Financial Disclosures:
Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

