Transepithelial corneal cross-linking: a review

PURPOSE: This review aims to summarize the current understanding of transepithelial corneal cross-linking (TE-CXL) for treating keratoconus (KC). It focuses on how TE-CXL compares with the standard epithelium-off cross-linking (S-CXL) and discusses recent improvements intended to make it more effective. METHODS: Relevant studies were reviewed from PubMed and Google Scholar. The review focused on research about new riboflavin solutions, delivery techniques, ultraviolet-A (UV-A) light settings, oxygen supply methods, and recent new technologies designed to improve the results of TE-CXL. RESULTS: TE-CXL preserves the corneal epithelium, providing better patient comfort and fewer postoperative complications. However, its corneal stiffening effect is generally lower than S-CXL due to limited riboflavin penetration and UV photoactivation. Recent approaches, including chemical enhancers, iontophoresis-assisted delivery, optimized UV-A protocols, nanotechnology-based or ultrasound-assisted methods have demonstrated potential to improve biomechanical strengthening. In addition, theranostic-guided TE-CXL, which provides real-time monitoring of stromal riboflavin concentration and adaptive UV-A dosing, represents a promising advancement. Nevertheless, differences in treatment protocols and in oxygen and luminance parameters still lead to variability in clinical outcomes. CONCLUSIONS: TE-CXL is a promising and less invasive treatment for KC, offering better comfort and faster recovery. However, its long-term stability and biomechanical effect remain inferior to S-CXL. Future progress will depend on optimizing riboflavin and oxygen delivery, refining UV-A irradiation protocols, and validating newer technologies such as theranostic-guided CXL through large-scale clinical studies.