Efficacy And Safety Of Customized Corneal Cross-Linking For Keratoconus: A Systematic Review And Meta-Analysis

To evaluate the clinical outcomes and safety of customized corneal cross-linking (cCXL) for the treatment of keratoconus.

Systematic review and meta-analysis

Electronic databases were searched through May 1, 2025, yielding 394 records. Primary outcomes were 12-month changes in maximum keratometry (K_max), corrected distance visual acuity (CDVA), and thinnest corneal thickness (TCT). Secondary outcomes included additional keratometric indices, uncorrected distance visual acuity, spherical equivalent, higher-order aberrations, endothelial cell density, and demarcation line depth. Nineteen studies were included in the systematic review, with 14 studies eligible for meta-analysis. Both single-arm analyses of cCXL and comparative analyses versus non-customized CXL were performed. Subgroup analyses were conducted according to epithelial status and irradiation pattern.

At 12 months, cCXL significantly reduced K_max by −1.29 D (95% confidence interval (CI), −1.55 to −1.03) and achieved greater K_max flattening than non-customized CXL (additional −1.39 D; 95% CI, −1.82 to −0.95; p<0.001). CDVA improved by −0.10 logMAR (95% CI, −0.12 to −0.07; p<0.001), exceeding the improvement with non-customized CXL (p=0.031). TCT decreased modestly (−4.42 µm; 95% CI, −7.24 to −1.60; p=0.006). Significant reductions were observed in total higher-order aberrations (−0.24 µm; 95% CI, −0.37 to −0.11; p=0.016) and vertical coma (−0.25 µm; 95% CI, −0.49 to −0.00; p=0.049). Outcomes were comparable between epithelium-on and epithelium-off cCXL, and no significant endothelial cell loss or serious adverse events were reported.

Customized corneal crosslinking is a safe and effective treatment for keratoconus and provides superior topographic and visual outcomes compared with non-customized CXL through tailored energy delivery.