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.

Abstract

To compare regional biomechanical and topographic outcomes between transepithelial (Epi-on) and epithelium-off (Epi-off) continuous accelerated corneal cross-linking (ACXL) in keratoconus. A retrospective cohort study. Seventy-seven keratoconic eyes were included: 45 with Epi-on ACXL and 32 with Epi-off ACXL. 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 (&#x394;) and relative changes (&#x394;%) evaluated. Regional changes in SSIv2_m, 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. 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. &#x394;SSIv2_m between preoperative and pos6m was significantly greater in Epi-off ACXL than Epi-on ACXL across all regions (central: <i>P</i> &lt; 0.01; paracentral and peripheral: <i>P</i> &lt; 0.05). Central flattening (negative &#x394;M) was significant in the Epi-off ACXL group (<i>P</i> &lt; 0.001) and exceeded that in Epi-on ACXL (<i>P</i> &lt; 0.001). No significant changes were detected in J₀ or J₄₅. &#x394;%SSIv2_m exceeded &#x394;%M in the paracentral and peripheral (paracentral: <i>P</i> &lt; 0.01; peripheral: <i>P</i> &lt; 0.05) regions after Epi-off ACXL. 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. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.