Small-Incision Lenticule Extraction with Prophylactic Cross-Linking: A Systematic Review and Meta-Analysis

Keratorefractive lenticule extraction (KLEx) treats myopia and myopic astigmatism while preserving corneal biomechanics better than flap-based procedures. KLEx with prophylactic accelerated corneal cross-linking (KLEx-CXL) has been proposed for thinner corneas, higher myopia, or borderline tomography, but its incremental value remains uncertain.

KLEx-CXL may reduce biomechanical instability, but adds operative time, cost, and protocol variability. Comparative evidence is needed to determine whether it improves outcomes over KLEx alone.

MEDLINE, Embase, Scopus, Web of Science, CENTRAL, and CINAHL were searched to July 2, 2026. Comparative adult studies with at least 6 months' follow-up reporting refractive or visual outcomes were included. Two reviewers extracted data, assessed risk of bias, and rated certainty using GRADE. Random-effects meta-analyses pooled mean differences.

Nine studies included 730 eyes: 386 KLEx and 344 KLEx-CXL. Residual MRSE was similar overall (MD 0.03 D; 95% CI, -0.01 to 0.06; P=0.17), with no consistent timepoint-specific difference. A small residual difference was confined to moderate-myopia cohorts (0.09 D; 95% CI, 0.04 to 0.15) and absent in high myopia. KLEx showed a 1-month advantage in uncorrected distance vision (MD -0.04 logMAR), safety index (MD 0.07), and efficacy index (MD 0.08), resolving by 12 months. Corrected vision was similar throughout. Biomechanical measures favored KLEx-CXL. Early haze was transient; no ectasia occurred. Certainty was low.

KLEx and KLEx-CXL achieved similar residual refraction and corrected visual acuity. KLEx-CXL produced measurable biomechanical reinforcement but transiently delayed early uncorrected visual recovery. Current evidence supports reserving prophylactic cross-linking for higher-risk eyes.