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

Reem O Nughays,1 Abdullah S Bazayd,1 Lujain A Alshamekh,2 Reemas A Alshammari,3 Mohammed A Alenezi,4 Hashem Y Dahlan,5 Jana A Alsubhi,6 Sara G Alshammri,7 Nouf A AlQurashi,8 Abdulaziz H Aldajani,9 Abdulrahman H Alrammah,9 Mariam N Alenezi,10 Areej Abdullah Almutairi,11 Abdulaziz F Alomayri,12 Saeed Alghamdi13 1College of Medicine, King Saud bin Abdulaziz for Health Sciences, Jeddah, Saudi Arabia; 2College of Medicine, Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabia; 3College of Medicine, Imam Mohammed bin Saud Islamic University, Riyadh, Saudi Arabia; 4College of Medicine, Northern Border University, Arar, Saudi Arabia; 5College of Medicine, Umm-Al Qura University, Makkah, Saudi Arabia; 6College of Medicine, University of Jeddah, Jeddah, Saudi Arabia; 7College of Medicine, Vision College, Riyadh, Saudi Arabia; 8College of Medicine, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia; 9College of Medicine, King Faisal University, Al-Hasa, Saudi Arabia; 10General Surgery Department, Farwaniya Hospital, Farwaniya, Kuwait; 11College of Medicine, Taif University, Taif, Saudi Arabia; 12College of Medicine, King Saud University, Riyadh, Saudi Arabia; 13Ophthalmology Department, King Abdulaziz Medical City, Jeddah, Saudi ArabiaCorrespondence: Reem O Nughays, College of Medicine, King Saud bin Abdulaziz for Health Sciences, Jeddah, Saudi Arabia, Tel +966543200330, Email [email protected] Saeed Alghamdi, Ophthalmology Department, King Abdulaziz Medical City, Jeddah, Saudi Arabia, Email [email protected]: 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.Keywords: corneal ectasia, corneal collagen cross-linking (CXL), epi-on, epi-off, keratoconus, maximal keratometry (Kmax), visual acuity, endothelial cell count (ECC)