Accelerated versus conventional corneal collagen cross-linking for keratoconus: A meta-analysis of randomized controlled trials.

Purpose: To systematically compare the effectiveness of conventional corneal collagen cross-linking (CCXL) protocols and accelerated corneal collagen cross-linking (ACXL) protocols in cases with progressive keratoconus.

Methods: The Cochrane library, EMBASE, MEDLINE, PubMed, and Web of Science databases were searched for randomized controlled trials (RCTs). Outcomes were clinical results and changes in corneal properties. Standardized mean differences (SMD) and 95% confidence interval (CI) were used to estimate the clinical consequences. All outcomes were distributed by different follow-up durations (6 months, 12 months, and > 12 months). We also compared maximum keratometry (Kmax) and best spectacle-corrected visual acuity (BCVA) in subgroups, which were categorized by the discrepant impregnation time period of riboflavin.

Results: We included 14 RCTs that met the eligibility criteria in this meta-analysis. At the last follow-up, CCXL was superior in postoperative change in demarcation line (SMD: -1.573; 95% CI: -2.897 to -0.248) and in Kmax (SMD:0.302; 95% CI: 0.071 to 0.533), whereas ACXL provided a significantly lower reduction in central corneal thickness (SMD: 0.498; 95% CI: 0.125 to 0.871). No differences in the changes in uncorrected visual acuity, BCVA, manifest refraction spherical equivalent, corneal biomechanical properties, and the endothelial cell density were found among both groups.

Conclusion: CCXL was superior to ACXL in greater corneal flattening and deeper demarcation line, while ACXL seemed to cause less reduction in CCT and allow for earlier UDVA stability. To clearly define the comparative safety and clinical consequences of the different regimens of CXL, more RCTs are required.