Efficacy and Safety of Epi-On vs Epi-Off Corneal Cross-Linking in Corneal Ectasia: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Corneal ectasias are progressive conditions that impair vision and quality of life. Corneal collagen cross-linking (CXL) aims to halt disease progression by strengthening the cornea. This review compares two CXL methods, epithelium-on (epi-on) and epithelium-off (epi-off), to assess their safety and effectiveness for managing corneal ectasia. A systematic search up to July 2024 of PubMed, Medline, Web of Science, Cochrane Central, Google Scholar, and Scopus identified 13 randomized controlled trials (RCTs) involving 872 patients and 1041 eyes. Data were analyzed following PRISMA guidelines using fixed-effects and random-effects models. The primary outcome was the change in maximal keratometry (Kmax) at 12 months, with secondary outcomes including safety profile, best-corrected visual acuity (BCVA), uncorrected visual acuity (UCVA), spherical equivalent (SE), and endothelial cell count (ECC). The findings revealed no statistically significant differences between epithelium-on (epi-on) and epithelium-off (epi-off) CXL in Kmax, BCVA, UCVA, SE, or corneal curvature parameters. However, epithelium-off (epi-off) CXL was associated with less endothelial cell loss and higher rates of side effects, including corneal haze and postoperative discomfort. The choice of treatment should be tailored to individual patient needs, balancing clinical goals and safety considerations. This review highlights the need for further studies to optimize CXL approaches and improve outcomes while minimizing complications.