Corneal biomechanical property changes following corneal collagen cross-linking in keratoconus: a systematic review and meta-regression analysis

Abstract

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 comprehensive literature search was conducted across PubMed, Scopus, Cochrane Library, and Google Scholar, identifying 8139 records. After duplicate removal and screening, 12 eligible studies (2009-2024) involving various CXL protocols and measurement tools (Corvis ST, Ocular Response Analyzer [ORA], and Ambrsio Relational Thickness [ART]) were included. Risk of bias was assessed using ROBINS-I and the NIH Quality Assessment Tool. Effect sizes were synthesized using random-effects meta-analysis, and heterogeneity was quantified using I² statistics. Meta-regression was performed to evaluate associations between corneal stiffness and visual acuity outcomes. Publication bias was assessed through funnel plots, Egger's test, and trim-and-fill analysis.

Results: CXL significantly improved corneal biomechanical properties, particularly when assessed with Corvis ST, which detected changes in 75% of studies, compared to 25% using ORA. Dynamic parameters such as V1, V2, and L2 were more sensitive than standard metrics. Meta-regression revealed a significant correlation between corneal stiffness and visual acuity for Corvis ST (p = 0.02 and p = 0.04, respectively), but not for ORA. The pooled effect size for biomechanical change was 0.74 (95% CI 0.59-0.89), reduced to 0.62 after Trim-and-Fill adjustment, suggesting 16.2% potential publication bias. Egger's test confirmed small-study effects (p = 0.024). Heterogeneity was high (I² = 98.3%), attributed to variability in protocols and study designs.

Conclusions: CXL leads to sustained improvements in corneal biomechanical properties in keratoconus patients, with stronger and more consistent detection using dynamic and device-specific metrics, particularly with Corvis ST. While findings support the long-term efficacy of CXL, variability in measurement protocols underscores the need for standardization. Meta-regression confirms the clinical relevance of biomechanical improvements, especially their correlation with visual function.

Keywords: Biomechanical properties; Corneal collagen cross-linking; Keratoconus; Meta-analysis.