Abstract

BackgroundThe corneal cross-linking (CXL) photochemical reaction is essentially dependent on oxygen and hypothermia, which usually leads to higher dissolved oxygen levels in tissues, with potentially greater oxygen availability for treatment. Here, we evaluate whether a reduction of corneal temperature during CXL may increase oxygen availability and therefore enhance the CXL biomechanical stiffening effect in ex vivo porcine corneas.MethodsOne hundred and twelve porcine corneas had their epithelium manually debrided before being soaked with 0.1% hypo-osmolaric riboflavin. These corneas were equally assigned to one of four groups. Groups 2 and 4 underwent accelerated epithelium-off CXL using 9 mW/cm2 irradiance for 10 min, performed either in a cold room temperature (group 2, 4 °C) or at standard room temperature (group 4, 24 °C). Groups 1 and 3 served as non-cross-linked, temperature-matched controls. Using a stress-strain extensometer, the elastic moduli of 5-mm wide corneal strips were analyzed as an indicator of corneal stiffness.ResultsAccelerated epithelium-off CXL led to significant increases in the elastic modulus between 1 and 5% of strain when compared to non-cross-linked controls (P < 0.05), both at 4 °C (1.40 ± 0.22 vs 1.23 ± 0.18 N/mm) and 24 °C (1.42 ± 0.15 vs 1.19 ± 0.11 N/mm). However, no significant difference was found between control groups (P = 0.846) or between groups in which CXL was performed at low or standard room temperature (P = 0.969).ConclusionsAlthough initial oxygen availability should be increased under hypothermic conditions, it does not appear to play a significant role in the biomechanical strengthening effect of epithelium-off CXL accelerated protocols in ex vivo porcine corneas.

Highlights

  • The corneal cross-linking (CXL) photochemical reaction is essentially dependent on oxygen and hypothermia, which usually leads to higher dissolved oxygen levels in tissues, with potentially greater oxygen availability for treatment

  • Several elements suggest a potential dependency of oxygen availability on temperature: on the one hand, hypothermia leads to higher levels of dissolved oxygen in water [11] and the cornea is composed of more than 70% of water [12]

  • Accelerated epithelium-off CXL led to significant increases in the elastic modulus between 1 and 5% of strain when compared to non-cross-linked controls, both at 4 °C (1.40 ± 0.22 vs 1.23 ± 0.18 N/mm, P = 0.006) and 24 °C (1.42 ± 0.15 vs 1.19 ± 0.11 N/mm, P < 0.001)

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Summary

Introduction

The corneal cross-linking (CXL) photochemical reaction is essentially dependent on oxygen and hypothermia, which usually leads to higher dissolved oxygen levels in tissues, with potentially greater oxygen availability for treatment. Overall oxygen availability within corneal tissue can be described by Fick’s second law of diffusion; one dimension (i.e., along corneal depth x) can be expressed for a given time t as: ðx; tÞ 1⁄4 n0∙ erfcð2pxffiDffiffitffiÞ, where n0 is the oxygen concentration at the surface, and D the diffusion coefficient Applying this equation to estimate the oxygen concentration between 0 and 550 μm stromal depth, we noticed that after 20 min of diffusion, there is on average 7.39 mg/L oxygen available at 4 °C, but only

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