Transepithelial corneal cross-linking: a review

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.

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.

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.

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.