Progression of Pediatric Keratoconus After Corneal Cross-Linking: A Systematic Review and Pooled Analysis

Purpose: Corneal collagen cross-linking (CXL) is an effective treatment to slow down keratoconus (KC) progression in adults. Several studies have also shown efficacious outcomes in pediatric populations, yet no systematic analysis has been performed and no accepted definition for progression is available in children after CXL. This study aimed to establish the most commonly used criteria for progression and to conduct a systematic review of the literature with pooled analysis to assess children's keratoconus progression after CXL. Methods: A systemic literature review combined with pooled analysis was performed on full-length studies of KC after CXL treatment in a pediatric population and the methods used to report progression were analyzed. Results: Thirty-seven studies (2078 eyes) were identified on the rates of KC progression after CXL. The most common method to report progression was increased Kmax, Kmean, or Ksteep by ≥1.0 diopter (78.3% of studies). Using these criteria, the mean pooled progression rate after epithelium-off CXL was 9.9% (95% confidence interval: 6.1% –14.6%, total pooled sample size: 1508 eyes) with high heterogeneity between studies [I 2 = 86.48% (95% confidence interval: 80.98 – 90.39), P < 0.0001]. Conclusions: When considering KC progression after CXL in children, with an increase in Kmax, Kmean, or Ksteep ≥ 1.0 diopter, the progression risk was roughly 10%. We encourage clear quantitative reporting of KC progression in future studies evaluating CXL efficacy in pediatric populations.