Comparison of Epithelium-Off Versus Transepithelial Corneal Collagen Cross-Linking for Keratoconus: A Systematic Review and Meta-Analysis

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Purpose:To systematically compare standard epithelium-off corneal collagen cross-linking (SCXL) and transepithelial corneal collagen cross-linking (TECXL) for treating keratoconus.Methods:PubMed, EMBASE, the Cochrane Library, the US trial registry (, VIP Database, Wanfang Databse, and China National Knowledge Infrastructure searches up to February 2017 were conducted. Primary outcomes were changes at 1 year in uncorrected distance visual acuity, maximum keratometry (Kmax), and mean keratometry (mean K). Secondary outcomes were changes at 1 year in corrected distance visual acuity, mean refractive spherical equivalent, central corneal thickness, endothelial cell density, and the occurrence of adverse events.Results:Eight studies with a total of 455 eyes were included. For primary outcomes, SCXL showed a greater reduction in mean K [standardized mean difference (SMD) 0.28; 95% confidence interval (CI), 0.03–0.53; P = 0.03] compared with TECXL. Subgroup analysis indicated that SCXL had a comparable effect on reducing mean K with TECXL protocols using chemical enhancers (SMD 0.05; 95% CI, −0.36 to 0.45; P = 0.82) but a greater reduction in mean K compared with TECXL with current iontophoretic protocols (SMD 0.43; 95% CI, 0.10–0.75; P = 0.01). For the other outcomes, there were no statistically significant differences.Conclusions:With the exception of less reduction in mean K with current iontophoretic protocols, analysis of the limited number of comparative studies available seems to demonstrate that SCXL and TECXL have a comparable effect on visual, refractive, pachymetric, and endothelial parameters at 1 year after surgery. Further follow-up is required to determine whether these techniques are comparable in the long-term.

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