Biomechanical assessments of high-fluence corneal cross-linking with supplemental oxygen using optical coherence...

Epithelium-off corneal collagen cross-linking (CXL) has drawbacks related to epithelial removal. Earlier epithelium-on approaches without supplemental oxygen showed limited efficacy due to inadequate permeation of the photoenhancer and oxygen into the corneal stroma. Improved epithelium-on CXL with improved photoenhancer permeation and supplemental oxygen has demonstrated effective cross-linking in two phase 3 trials.

The study aims to evaluate the effect of supplemental oxygen during epithelium-on CXL in an ex vivo animal study mirroring the clinical CXL procedure, using an in-house built optical coherence elastography (OCE) system that measures biomechanical changes (stiffness) in the cornea.

Epithelium-on CXL was performed on two groups of ex vivo rabbit eyes at a UV fluence of $10J/{\mathrm{cm}}^2$ and irradiance of $30\mathrm{mW}/{\mathrm{cm}}^2$ . Eyes in Group 1 were treated under normoxic (ambient air, 21% oxygen) conditions, whereas eyes in Group 2 were treated under hyperoxic ( $>90\%$ oxygen) conditions.

Forty eyes treated under hyperoxic conditions and pulsed illumination exhibited a statistically significant greater increase ( $p<0.0001$ ) in shear modulus (81% larger increase), as a measure of stiffness, compared with eyes treated under normoxic conditions.

These results strongly suggest that the use of supplemental oxygen during epithelium-on CXL produces stronger inter-corneal collagen cross-links and greatly improves corneal stiffness, potentially lessening or preventing the risk of vision loss for patients with keratoconus.