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

Krungkraipetch et al., 2025 | Int Ophthalmol | Meta Analysis

Citation

Krungkraipetch Luksanaporn, Assawaboonyadech Angkhana, Supajitgulchai Dutdao. Corneal biomechanical property changes following corneal collagen cross-linking in keratoconus: a systematic review and meta-regression analysis. Int Ophthalmol. 2025-Jun-28;45(1):270. doi:10.1007/s10792-025-03617-z

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.

Key Findings

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),

Outcomes Measured

Requires manual extraction

Population

Field	Value
Population	See abstract
Sample Size	See abstract
Age Range	See abstract
Condition	See abstract

MeSH Terms

Humans
Keratoconus
Collagen
Cross-Linking Reagents
Cornea
Biomechanical Phenomena
Photochemotherapy
Photosensitizing Agents
Visual Acuity
Ultraviolet Rays
Riboflavin
Elasticity
Corneal Cross-Linking

Evidence Classification

Level: Meta Analysis
Publication Types: Journal Article, Systematic Review, Meta-Analysis
Vertical: collagen

Provenance

PMID: 40580225
DOI: 10.1007/s10792-025-03617-z
PMCID: Not in PMC
Verified: 2026-04-09 via PubMed E-utilities API

Source extracted via PubMed E-utilities API on 2026-04-09