The Safety Profile of FDA-Approved Epithelium-Off Corneal Cross-Linking in a US Community-Based Healthcare System

Purpose: To determine the occurrence of early post-operative complications following FDA-approved epithelium-off corneal cross-linking in the United States.

Materials and methods: This multicenter, retrospective cohort study identified patients who underwent epithelium-off (epi-off) corneal cross-linking (CXL) for keratoconus and post-refractive keratectasia within the Kaiser Permanente Northern California healthcare system between 2016 and 2018. Post-operative complications including delayed epithelial healing, infection, and loss of visual acuity were recorded.

Results: The study included 878 eyes of 654 patients. The mean age was 27±9.4 years (range 7-71). Five hundred ninety-nine patients (91.6%) had keratoconus while 55 had post-refractive corneal ectasia (8.4%). Forty-seven eyes had prolonged follow-up because of the occurrence of complications in the early post-operative period. The respective rates of delayed epithelial healing, and keratitis were 3.9% (95% CI 2.7-5.3%), and 1.5% (95% CI 0.8-2.5%). Four approaches for management of delayed epithelial healing were compared; epithelium healing duration was the longest in the repeat bandage contact lens (BCL) group (23.8 days) and the shortest in the antibiotic ointment group (14.3 days), with statistically significant differences (p < 0.05) in the healing time between these 2 groups.

Conclusion: The concern for early clinical complications after epi-off CXL often leads to delayed CXL intervention and further keratoconus progression with increased economic burdens. A large retrospective review of 878 eyes found that FDA-approved epi-off CXL protocol appears to be safe with low occurrence rates of early post-operative complications. The recommended management for delayed epithelial healing is using antibiotic ophthalmic ointment.