**6. Other applications of intraoperative OCT for corneal collagen cross-linking**

OCT has been used for in vivo evaluation of the riboflavin penetration to the stroma during CXL.

Riboflavin penetration of the cornea is associated with a hyper-reflective signal change in the corneal stroma. Although the correlation between the band's intensity and riboflavin stromal concentration has not been directly investigated, it is speculated that a higher OCT reflectivity should be positively correlated with riboflavin concentration.

Mahotra et al. evaluated the depth of hyper-reflective band (representing penetration of riboflavin) in the anterior corneal stroma after riboflavin saturation of the stroma in 20 patients undergoing CXL with either complete epithelial removal or grid-like epithelial removal (leaving behind intact islands of epithelium) using hand-held spectral domain OCT. In the complete removal group, the hyper-reflective band was homogenous, extending to a mean depth of 54.2 ± 5.2 μm in the stroma. However, the hyper-reflective band was uneven in the grid pattern epithelial removal [26].

Vinciguerra et al. measured the depth of hyper-reflective band after riboflavin saturation of the stroma using two different methods (epithelium-off and iontophoresis method) in six patients. In the conventional epi-off group, after 30 minutes of riboflavin instillation, a homogeneous hyper-reflective band without fading was measured at a mean depth of 80 μm. In the iontophoresis group, a less homogeneous but deeper hyper-reflective band with a fading effect was observed extending through the anterior 200 μm of the cornea [27].

Pahuja et al. used a microscope-integrated real-time spectral domain optical coherence tomography (ZEISS OPMI LUMERA 700 and ZEISS RESCAN 700) to compare the penetration of riboflavin between epithelium-on and epitheliumoff methods in keratoconus patients undergoing accelerated CXL. The mean depth of the hyper-reflective stromal band was 149.39 and 191.04 microns in the epithelium-on and epithelium-off groups, respectively. These results are compatible with enhanced riboflavin corneal penetration with the epithelium-off method [28].
