Purpose: To compare the efficacy of four corneal cross-linking (CXL) protocols: standard epithelium-off (SCXL), accelerated epithelium-off (ACXL), transepithelial (TCXL), and accelerated transepithelial (A-TCXL) for pediatric keratoconus.Methods:A comprehensive literature search on the efficacy of SCXL, ACXL, TCXL and A-TCXL in treating keratoconus patients age 18-year or under was conducted using PubMed and EMBASE up to March 2020. Primary outcomes included uncorrected visual acuity (UCVA) and maximum keratometry (Kmax). Secondary outcomes included best-corrected visual acuity (BCVA), central corneal thickness (CCT), and mean refractive spherical equivalent (MRSE). Estimations were analyzed by weighted mean difference (WMD) and 95% confidence interval (95% CI) for the outcomes during observation periods from 6 to 36 months.Results:Eight papers involving total 704 eyes were enrolled. In pediatrics, ACXL resulted in significantly better postoperative UCVA than SCXL at 12-month observation (WMD = 0.08, 95% CI: 0.02 to 0.14, P = 0.007), while SCXL provided statistically better BCVA (WMD = -0.07, 95% CI: -0.12 to -0.01, P = 0.01) and MRSE (WMD = 0.31, 95% CI: 0.06 to 0.56, P = 0.01) than ACXL at 24 months. Furthermore, SCXL provided significantly improved BCVA compared with TCXL at 12- to 24-month observation. (WMD = -0.13, 95% CI: -0.21 to -0.05, P = 0.001). Conclusions:In pediatric keratoconus, although UCVA in short-term follow-up after ACXL was better than that after SCXL, the long-run results showed that SCXL may provide superior visual acuity than either ACXL or TCXL. Further investigation is required to compare the efficacy of different CXL protocols for the management of pediatric keratoconus.
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