Since the conception of the Dresden protocol (Wollensak et al. 2003a), corneal collagen cross-linking (CXL) has been considered as a viable treatment option for reducing the progression of keratoconus. As technological advancements in corneal topography measurements are likely to facilitate the earlier detection and diagnosis of keratoconus, more patients are likely to choose to undergo CXL treatment in the near future. The ‘traditional’ Dresden protocol requires debridement of the corneal epithelium, which initially results in reduced vision and varying degrees of pain during the process of re-epithelialisation. Consequently, a number of studies have suggested technical refinements to the treatment protocol, to facilitate CXL without the need for epithelial debridement; this methodology is typically known as ‘transepithelial’ CXL.

This review outlines the current state of knowledge regarding the latest developments in refining the transepithelial CXL procedure, including the use of multiple permeability enhancers and iontophoresis. As transepithelial CXL is still in its infancy, more large-scale, randomised clinical trials are required to understand better the efficacy, safety and permanency of this treatment.