Maximising corneal cross-linking effectiveness

Reviewed by Dr Theo G. Seiler, Jr.

Results from a laboratory study measuring oxygen kinetics during corneal cross-linking (CXL) indicate that supplementary oxygen has the potential to substantially increase the efficacy of the procedure, according to Dr Theo G. Seiler, Jr, senior physician in the Department of Ophthalmology at the University of Bern in Switzerland. The laboratory study, which was performed using de-epithelialised porcine eyes, measured local oxygen concentrations at varying corneal depths under atmospheric (21% O2) and hyperoxygenic (100% O2) conditions with different levels of ultraviolet (UV) irradiation.

The analyses showed that, compared with the atmospheric oxygen environment, supplementary oxygen increased the amount of oxygen available in the stroma during CXL. Dr Seiler noted that the benefit of the hyperoxygenic environment was particularly seen when using higher UV irradiances that are associated with increased oxygen consumption.

“The mechanism of action for CXL involves UV-induced activation of riboflavin, the photosensitiser, resulting in the generation of reactive oxygen species that induce formation of covalent bonds within the collagen fibrils and crosslink the proteoglycans between the fibrils,” he said. “Many previous studies have investigated the influence of varying the parameters for riboflavin imbibition and UV irradiation on CXL effectiveness.”

Dr Seiler said that the study was motivated by the limited research investigating the role of oxygen, which is the third crucial factor for achieving sufficient CXL. “Our findings show that providing supplementary oxygen is likely to be beneficial by increasing the aerobic reaction and allowing more efficient CXL in deeper corneal layers and at UV irradiance levels less than 3 mW/cm2,” he said.

Measurement of the oxygen concentration at different corneal depths was accomplished by inserting a fibre probe into channels created by a femtosecond laser at depths of 100 μm, 200 μm and 300 μm. Eyes were exposed to 0.1% riboflavin (Vibex Rapid, Avedro/Glaukos) for 10 minutes, and then the oxygen concentration was continually measured during irradiation at 3, 9, 18 and 30 mW/cm2. “In order not to alter the cornea during the measurements, the used fibre probe had a tip that was only around 50 μm in diameter,” Dr Seiler said.

Groups of eight eyes each were evaluated under each of the testing conditions while the oxygen concentration was continually measured. Under atmospheric oxygen and with irradiation at 3 mW/cm2, representing the conventional Dresden protocol, there was a surplus of oxygen available at all measured depths during the entire CXL procedure.

However, when the irradiance was increased to 9 mW/cm2, sufficient oxygen for CXL was available only at 100 μm and 200 μm. At UV irradiance above 9 mW/cm2, all oxygen was consumed within the anterior 100 μm, indicating that there was insufficient oxygen for achieving sufficient cross-linking in the profound cornea, Dr Seiler said.

When the testing was done in the hyperoxygenic environment, there was sufficient oxygen available for cross-linking at all measured depths when using the 3 mW/cm2 and 9 mW/cm2 irradiances. At higher UV irradiances, there was more oxygen available than under atmospheric conditions, although still not enough to provide sufficient oxygen through the entire corneal stroma. Additional analyses determining the consumption of oxygen showed that during the procedure, the half-lives were longer and the depletion rates higher with supplementary oxygen, suggesting a more efficient CXL than under atmospheric oxygen conditions, said Dr Seiler.

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Theo G. Seiler, Jr, MD

e: theo@seiler.tv

This article is based on a presentation given by Dr Seiler at the 2020 ESCRS Virtual Congress. The study was published (Seiler TG, Komninou MA, Nambiar MH, et al. Oxygen kinetics during corneal cross-linking with and without supplementary oxygen. Am J Ophthalmol. 2020;223:368-376). Dr Seiler has no relevant financial interests to disclose.

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