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Updated: Oct 27, 2025
Three Different Protocols of Corneal Collagen Crosslinking in Keratoconus: Conventional, Accelerated and Iontophoresis
Published on: November 12, 2015
Progression of Pediatric Keratoconus After Corneal Cross-Linking: A Systematic Review and Pooled Analysis
Asaf Achiron1,2, Omar El-Hadad1,3, Duncan Leadbetter1
1Bristol Eye Hospital, University Hospitals Bristol NHS Foundation Trust, Bristol, United Kingdom.
Insights
Corneal collagen cross-linking (CXL) for pediatric keratoconus (KC) shows a nearly 10% progression risk. The most common progression metric is a ≥1.0 diopter increase in Kmax, Kmean, or Ksteep.
Area of Science:
- Ophthalmology
- Corneal Surgery
- Pediatric Eye Care
Background:
- Corneal collagen cross-linking (CXL) is established for adult keratoconus (KC).
- Efficacy in pediatric KC is suggested, but progression criteria and systematic analysis are lacking.
- This study addresses the need for standardized progression assessment in children post-CXL.
Purpose of the Study:
- To define common criteria for pediatric KC progression after CXL.
- To systematically review and pool data on pediatric KC progression post-CXL.
- To assess the risk of KC progression in children treated with CXL.
Main Methods:
- Systematic literature review of full-length studies on pediatric KC treated with CXL.
- Analysis of methods used to report progression.
- Pooled analysis of progression rates based on identified criteria.
Main Results:
- Thirty-seven studies (2078 eyes) were analyzed.
- Increased Kmax, Kmean, or Ksteep by ≥1.0 diopter was the most frequent progression criterion (78.3%).
- The pooled progression rate after epithelium-off CXL was 9.9% (95% CI: 6.1%–14.6%), with significant heterogeneity (I² = 86.48%).
Conclusions:
- Pediatric KC progression after CXL, defined by a ≥1.0 diopter increase in specific corneal measurements, occurs in approximately 10% of cases.
- Standardized quantitative reporting of KC progression is crucial for future CXL efficacy studies in children.
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.
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