Efficacy comparison of combining cross-linking and refractive laser ablation in progressive keratoconus: systematic review and meta-analysis

Objective: This study assessed the effect of combining corneal collagen cross-linking (CXL) with refractive laser ablation techniques for the treatment of keratoconus, a progressive corneal disorder. Methods: We performed a systematic review and meta-analysis to assess the effect of combined CXL and refractive techniques. We included all published clinical trials or observational studies published by September 1, 2023. We calculated and compared the standardized mean difference (SMD) between CXL alone and CXL plus laser ablation for uncorrected distance visual acuity, best-corrected distance visual acuity, spherical equivalent manifest refraction, sphere and cylinder, flat keratometry (K₁), steep keratometry (K₂), and central corneal thickness. Results: We identified 13 studies that fulfilled our inclusion and exclusion criteria. The average follow-up was 21.3 ± 11.8 months. The CXL plus laser ablation group showed improvement in uncorrected distance visual acuity logMAR (SMD, –0.35; 95% CI, –0.67 to –0.04; p = 0.029), best-corrected distance visual acuity logMAR (SMD, –0.17; 95% CI, –0.30 to –0.03; p = 0.014), spherical equivalent manifest refraction (SMD, –0.28; 95% CI, 0.06–0.50; p = 0.013), and change in maximal corneal curvature (K_max; SMD, –0.41; 95% CI, –0.69 to –0.13; p = 0.004) compared with CXL alone. However, central corneal thickness decreased further among patients who underwent CXL plus laser ablation (SMD, –0.37; 95% CI, –0.66 to –0.07; p = 0.016). No effect was observed in terms of sphere (p = 0.878), cylinder (p = 0.859), K₁ (p = 0.907), or K₂ (p = 0.169). Ectasia was not observed as an adverse effect resulting from the additional corneal ablation performed during the CXL treatments. Conclusions: This study showed that combining refractive laser ablation techniques with standard or accelerated CXL treatment improved visual and refractive outcomes and anterior corneal curvature values.