CXL: Challenges and updates

Corneal cross‐linking (CXL) is a critical treatment for keratoconus that combines UVA light and riboflavin (vitamin B2). This procedure received FDA approval in 2016 based on studies by Sykakis et al. (2015) which indicated that CXL could stabilize keratoconus, prevent myopia progression, and improve uncorrected distance visual acuity (UDVA). Despite the promising results, the studies had potential biases and a low number of randomized controlled trials (RCTs). The two primary methods of CXL are epithelium‐off (epi‐off) and epithelium‐on (epi‐on or transepithelial). Epi‐off CXL involves removing the corneal epithelium to allow riboflavin penetration, whereas epi‐on CXL retains the epithelium, reducing patient discomfort but potentially being less effective. NG et al. (2021) found no significant difference in outcomes between these methods, though epi‐on showed fewer side effects such as corneal haze. Accelerated CXL protocols have been developed to increase efficiency. Karam et al. (2023) compared these protocols, revealing that a 10‐minute protocol with 9 mW/cm 2 UVA exposure provided better outcomes than a 5‐minute protocol with 18 mW/cm 2 . Accelerated methods are becoming more common due to their reduced treatment time. In pediatric cases, both conventional and accelerated CXL are effective, although the transepithelial method had a lesser impact, as concluded by Mahdavi Fard et al. (2020). Additionally, combined procedures known as CXL+ integrate CXL with other treatments like laser ablation. The Athens Protocol, developed by Dr. Kanellopoulos, combines topography‐guided laser ablation with CXL to address irregular astigmatism and coma in keratoconus patients. New riboflavin formulations and delivery methods, such as isotonic riboflavin and iontophoresis, have been developed to enhance riboflavin penetration and effectiveness. Glaukos' (Avedro) Mosaic System and the "sub400" protocol for ultrathin corneas are notable advancements, offering customized treatments based on individual corneal characteristics.