Corneal Biomechanical Property Changes Following Corneal Collagen Cross- linking in Keratoconus: A Systematic Review and Meta-regression Analysis

Purpose: To evaluate the changes in corneal biomechanical properties following corneal collagen cross-linking (CXL) in keratoconus patients and determine factors influencing measurement sensitivity through systematic review and meta-regression analysis. Methods: A systematic search identified 11 studies (2009-2024) evaluating biomechanical changes after CXL, with sample sizes ranging from 10-200 participants and follow-up periods of 3 months to 4 years. Studies were assessed for risk of bias using ROBINS-I. Random-effects meta-analysis was performed, with pre-specified subgroup analyses by measurement device and meta-regression to identify significant moderators of reported outcomes. Publication bias was evaluated using funnel plot, Egger's regression test, and trim-and-fill analysis. Results: The pooled effect size was 0.56 (95% CI: 0.26-0.87), indicating moderate positive biomechanical effects after CXL, with substantial heterogeneity (I² = 88.6%, p < 0.0001). Corvis ST detected biomechanical changes more consistently (in 88% of studies) than ORA (40% of studies). Meta-regression identified measurement device type (coefficient: 0.248), publication year (0.0161 per year), and sample size (0.0024 per patient) as significant predictors of reported outcomes. Dynamic parameters (V1, V2, L2) and custom metrics demonstrated higher sensitivity to post-CXL changes than standard measurements. Evidence of publication bias was found, with adjusted effect size after trim-and-fill analysis of 0.62 (95% CI: 0.45-0.79). Conclusion; CXL effectively improves corneal biomechanical properties in keratoconus patients, with Corvis ST demonstrating superior sensitivity in detecting these changes compared to ORA. Dynamic parameters appear more valuable than standard metrics for clinical assessment of post-CXL biomechanical changes. Despite publication bias and inter-study heterogeneity, the significant positive effect supports CXL's clinical efficacy. Standardized measurement protocols and parameters are needed for better comparison of biomechanical outcomes across different CXL techniques and patient populations.