Regional Biomechanical and Topographic Changes after Transepithelial vs. Epithelium-off Continuous Accelerated Corneal Cross-linking in Keratoconus: Updated Stress-Strain Index as a Superior Biomarker

Authors

• BangXun Mao, National Clinical Research Center for Ocular Diseases, Eye Hospital, WenZhou Medical University, Wenzhou 325027, China
• ChangChang He, National Clinical Research Center for Ocular Diseases, Eye Hospital, WenZhou Medical University, Wenzhou 325027, China
• Qian Ye, National Clinical Research Center for Ocular Diseases, Eye Hospital, WenZhou Medical University, Wenzhou 325027, China
• WeiJia Liu, University of Oxford
• Daniela Oehring, School of Health Professions
• YiQian Li, National Clinical Research Center for Ocular Diseases, Eye Hospital, WenZhou Medical University, Wenzhou 325027, China
• YuKe Zhang, National Clinical Research Center for Ocular Diseases, Eye Hospital, WenZhou Medical University, Wenzhou 325027, China
• XiaoMeng L, National Clinical Research Center for Ocular Diseases, Eye Hospital, WenZhou Medical University, Wenzhou 325027, China
• ChenHao Zhao, National Clinical Research Center for Ocular Diseases, Eye Hospital, WenZhou Medical University, Wenzhou 325027, China
• HongJie Hu, National Clinical Research Center for Ocular Diseases, Eye Hospital, WenZhou Medical University, Wenzhou 325027, China
• JiaWei Gong, National Clinical Research Center for Ocular Diseases, Eye Hospital, WenZhou Medical University, Wenzhou 325027, China
• HanHui Hou, National Clinical Research Center for Ocular Diseases, Eye Hospital, WenZhou Medical University, Wenzhou 325027, China
• YuFeng Ye, ZheJiang-United Kingdom Joint Laboratory on Ocular biomechanics
• ShiHao Chen, ZheJiang-United Kingdom Joint Laboratory on Ocular biomechanics
• YiYu Li, National Clinical Research Center for Ocular Diseases, Eye Hospital, WenZhou Medical University, Wenzhou 325027, China
• Ahmed Elsheikh, University of Liverpool
• FangJun Bao, Wenzhou Medical University

ORCID

• Daniela Oehring: 0000-0003-2954-0548

Document Type

Article

Abstract

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/cm ², 7.2 J/cm ²). Pentacam HR and Corvis ST measurements were obtained preoperatively (pre), and at 1 month (pos1m), and 6 months (pos6m) postoperatively. The SSIv2m, M, and J ₀, J ₄₅ 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 SSIv2 _m, M, J ₀, and J ₄₅ 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, SSIv2 _m increased significantly in all regions of the Epi-off ACXL group (greatest centrally), whereas the Epi-on group showed no consistent change. ΔSSIv2 _m 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 J ₀ or J ₄₅. Δ%SSIv2 _m 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.

DOI Link

10.1016/j.xops.2026.101246

Publication Date

2026-08-01

Publication Title

Ophthalmology Science

Volume

6

Issue

8

Acceptance Date

2026-01-01

Deposit Date

2026-05-28

Funding

This research was supported by the National Natural Science Foundation of China (82271049) and the Projects of Medical and Health Science Technology Program in Zhejiang Province (WKJ-ZJ-2542).

Additional Links

https://www.scopus.com/pages/publications/105048821411

Keywords

keratoconus, corneal cross-linking, ocular biomechanics, corneal shape, regional variation, Corneal shape, Keratoconus, Ocular biomechanics, Corneal cross-linking, Regional variation

Creative Commons License

This work is licensed under a Creative Commons Attribution-NonCommercial-No Derivative Works 4.0 International License.

Recommended Citation

Mao, B., He, C., Ye, Q., Liu, W., Oehring, D., Li, Y., Zhang, Y., L, X., Zhao, C., Hu, H., Gong, J., Hou, H., Ye, Y., Chen, S., Li, Y., Elsheikh, A., & Bao, F. (2026) 'Regional Biomechanical and Topographic Changes after Transepithelial vs. Epithelium-off Continuous Accelerated Corneal Cross-linking in Keratoconus: Updated Stress-Strain Index as a Superior Biomarker', Ophthalmology Science, 6(8). Available at: 10.1016/j.xops.2026.101246