Accelerated Corneal Collagen Cross-Linking Protocols for Progressive Keratoconus: Systematic Review and Meta-analysis

Purpose: The aim of this study was to compare the outcomes of 18 mW/cm2 (5 minutes) versus 9 mW/cm2 (10 minutes) accelerated corneal collagen cross-linking protocols in patients with progressive keratoconus. Methods: A systematic review and meta-analysis were performed according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines, and electronic information was searched to identify studies comparing the outcomes of 5- versus 10-minute protocols in patients with progressive keratoconus. Mean changes in uncorrected visual acuity, best-corrected visual acuity, cylinder (diopters), thinnest corneal thickness, corneal keratometry values (K1 and K2), corneal high-order aberration (HOA), spherical aberration, coma, and trefoil were the primary outcome measures. Secondary outcome measures included the mean change in central corneal thickness and postoperative complications. Random effects modeling was used for the analysis. Results: Four studies that enrolled 329 eyes were included. The 10-minute protocol had significantly improved outcomes compared with the 5-minute protocol for the mean changes in K1 and K2 (P < 0.00001), corneal total HOA (P = 0.0002), and corneal coma (P = 0.00001). However, no statistically significant differences were found between the 2 protocols in uncorrected visual acuity, best-corrected visual acuity, cylinder, thinnest corneal thickness, spherical aberration, or trefoil. The 5-minute protocol was associated with a significantly lower mean change in the central corneal thickness for secondary outcomes. In addition, no significant differences were found between the 2 protocols for postoperative complications. Conclusions: The 10-minute protocol had better K1, K2, and HOA outcomes than the 5-minute protocol, but no statistically significant differences in the other outcomes.