A newly published review in the journal International Ophthalmology offers a comprehensive overview of transepithelial corneal cross-linking (TE-CXL)—a less invasive alternative to the standard treatment for keratoconus.1

The review, led by a team of international ophthalmic researchers, synthesizes existing clinical evidence on TE-CXL—often called “epi-on” cross-linking—where the corneal surface is left intact during treatment.

Key takeaways from the review:

  • Improved comfort and safety: Because TE-CXL preserves the epithelium, patients generally experience less pain, faster visual recovery, and lower rates of infection and corneal haze compared with epithelium-off cross-linking (S-CXL).

  • Weaker biomechanical effects: The intact epithelium limits riboflavin penetration and oxygen diffusion, resulting in reduced corneal stiffening compared to the standard protocol. This can translate into lower effectiveness at halting keratoconus progression in many cases.

  • Technological innovations: Recent advancements—including novel riboflavin formulations, iontophoresis-assisted delivery systems, optimized UV-A settings, and experimental “theranostic” approaches that dynamically monitor riboflavin levels—show promise in narrowing the gap between TE-CXL and traditional methods.

  • Variability in outcomes: Differences in how TE-CXL is performed, both in riboflavin delivery and light protocols, contribute to inconsistent results across clinics. Larger, standardized clinical trials are still needed to establish best practices and long-term stability.

Experts say that while TE-CXL won’t replace S-CXL as the gold standard anytime soon, it could become an attractive option for certain patients, particularly those for whom epithelial removal poses extra risk or discomfort. Further refinement and validation of emerging technologies could enhance its uptake in clinical practice.

Reference

1. Zhou, W., Subasinghe, S. K., March de Ribot, F., Ogbuehi, K. C., & Dias, G. J. (2026). Transepithelial corneal cross-linking: a review. International Ophthalmology, 46, Article 62. https://doi.org/10.1007/s10792-025-03928-1