Oxygen Kinetics During Corneal Cross-linking With and Without Supplementary Oxygen

To measure and simulate oxygen kinetics during corneal cross-linking at different irradiances with and without supplementary oxygen.

Experimental, laboratory study.

In de-epithelialized porcine eyes, a femtosecond-laser-generated tunnel was used to place a fiber probe in corneal depths of 100, 200, and 300 μm to measure the local oxygen concentration. After riboflavin imbibition, the corneas were irradiated at 3, 9, 18, and 30 mW/cm² while the oxygen concentration was measured. All experiments were performed under normoxic (21%) and hyperoxic (>95%) conditions. The obtained data were used to identify parameters of a numerical model for oxygen consumption and diffusion.

The equilibrium stromal oxygen concentration under atmospheric oxygen at 3 mW/cm² was 2.3% in 100 μm decreasing to <1% in 300 μm. With 9, 18, and 30 mW/cm², no oxygen was available in 200 μm, respectively, 100 μm or deeper. Using a hyperoxic environment, the concentration was 50% using 3 mW/cm² in 100 μm, decreasing to 40% in 300 μm. At 9 mW/cm², the concentrations were 5%, 3%, and 1% in 100, 200 and 300 μm, respectively. Using 18 and 30 mW/cm², all oxygen was depleted at 100 μm; however, oxygen half-lives were longer at 18 mW/cm² than at 30 mW/cm². The oxygen model was able to reproduce the experiments and indicated an exponential decay with increasing distance to the anterior surface.

Supplementary oxygen increases the oxygen availability during corneal cross-linking. At higher irradiances, supplementary oxygen is beneficial and eliminates the bottleneck of oxygen allowing a potentially more efficient cross-linking. The calibrated numerical model can quantify the spatial oxygen concentration related to different scenarios such as irradiance or environmental oxygen concentration.