Abstract
Purpose To investigate oxygen kinetics during symmetrically pulsed and asymmetrically pulsed crosslinking (p-CXL) with and without supplementary oxygen at different irradiances and corneal depths.
Design Experimental, laboratory study
Methods In de-epithelialized porcine eyes, a femtosecond-laser generated tunnel was used to place a fibre-probe in corneal depths of 200 and 300 µm to measure the local oxygen concentration. After riboflavin imbibition, the corneas were irradiated at 9, 18 and 30 mW/cm2 for 10 seconds On and 10 seconds Off; while the oxygen concentration was continuously measured until oxygen levels depleted below the oxygen sensor’s threshold (1%) or until stabilized. All experiments were performed under normoxic (21%) and hyperoxic (>95%) conditions and the obtained data were used to identify parameters of a numerical algorithm for oxygen consumption and diffusion. Following the algorithm’s development, the suggested asymmetrical pulsing values were experimentally tested. For 9, 18 and 30 mW/cm2 the suggested tested pulsing schemes were 3 seconds On : 9 seconds Off, 2 seconds On : 9 seconds Off and 1 second On : 9 seconds Off respectively.
Results The minimum, available stromal oxygen for p-CXL in normoxic environment was decreasing <1% for 9, 18 and 30 mW/cm2 in 200 and 300 μm. Using optimized p-CXL, the minimum available oxygen increased to 3.8, 1.8 and 2.8 % at 200 μm, for irradiances of 9, 18 and 30 mW/cm2, respectively, where the periods exhibited an equilibrium state. At 300 μm, 1.1 % of oxygen was available for 30 mW/cm2. Using a hyperoxic environment, the oxygen concentration was 19.2% using 9 mW/cm2 in 200 μm, dropping to 17.0% in 300 μm. At 18 mW/cm2, the concentrations were 3.9% and 1% in 200 and 300 μm, respectively. Using 30 mW/cm2, all oxygen was depleted below the threshold limit (1% O2) for both depths. Using optimized pulsing in combination with hyperoxic environment, the oxygen concentration was 42.0% using 9 mW/cm2 in 200 μm and 43.3% in 300 μm. At 18 mW/cm2, the concentrations were 24.7% and 16.1% in 200 and 300 μm, respectively. Using 30 mW/cm2, the minimum oxygen availability was 25.7% and 13.7% in 200 and 300 μm, respectively.
Conclusion Supplementary oxygen during symmetrical and asymmetrical p-CXL increased the oxygen availability during corneal cross-linking. The pulsed irradiance and the hyperoxic environment potentially increased the efficacy of corneal cross-linking in deeper corneal layers and higher irradiances. The numerical algorithm for asymmetrical pulsing led to the quantification of “On” and “Off” times related to different scenarios such as irradiances.
Competing Interest Statement
The authors have declared no competing interest.
Footnotes
None of the authors has any financial interest