Abstract
Corneal collagen cross-linking (CXL) is widely used to halt the progression of keratoconus by biomechanically strengthening the corneal stroma; however, its potential effects on retina and choroid remain unclear. This systematic review and meta-analysis synthesized current evidence on structural and microvascular changes in the posterior segment following CXL in patients with keratoconus, assessed by optical coherence tomography (OCT) and OCT angiography (OCTA). A comprehensive search of PubMed, EMBASE, and Web of Science was performed up to May 24, 2025. Random-effects meta-analysis using Hedges' g was applied to pool quantitative data. In addition, studies that met the eligibility criteria but lacked sufficient data for quantitative synthesis were qualitatively assessed and included in the descriptive analysis. Ten studies involving 233 eyes from 215 keratoconus patients were included. Meta-analysis demonstrated no significant change in central macular thickness at 1 month (Hedges's g = -0.15; 95% confidence interval [CI]: -0.44 to 0.13; p = 0.30) or 6 months (Hedges's g = -0.12; 95% CI: -0.47 to 0.22; p = 0.48). Subfoveal choroidal thickness also remained unchanged at 1 month (Hedges's g = -0.14; 95% CI: -0.45 to 0.17; p = 0.37). Sensitivity analyses confirmed the robustness of these results. In the qualitative synthesis, parameters demonstrated overall stability, aside from a few exceptions. In conclusion, current evidence suggests that CXL does not result in clinically meaningful changes in posterior segment structure or microvasculature in keratoconus patients. These findings support the posterior segment safety of CXL.