Abstract
Keratoconus (KC) incidence is on the increase. The advent of corneal-collagen cross-linking (CXL) has revolutionized the management of KC. This systematic review looks at the efficacy and complications of two novel treatments within CXL: Epithelial-On (Epi-On) and CXL-plus procedures. Two separate literature searches were carried out up until July 1, 2021. Articles only published in the last two years were included to ensure that only the most recent articles were reviewed. A total of 15 articles were selected for this review. There were varied results regarding the efficacy of Epi-On. No significant difference was found between Epi-On and standard Epithelial-Off (Epi-Off) CXL. However, it was found that Epi-On was inferior to standard CXL in terms of reducing K(MAX). There was a higher risk of progression in patients treated with Epi-On CXL, with an increased rate of patients requiring re-treatment due to the advancement of their KC. While some studies report CXL-plus procedures demonstrate long-term efficacy and safety, a considerable number of studies advise caution, reporting a significant deterioration in corrected distance visual acuity (CDVA). Consequently, a question persists regarding the safest and most efficacious approach, given the lack of robust large randomized controlled trials (RCTs) in the current literature.