Is it useful to cool the cornea during cross-linking?

The researchers at ELZA are constantly trying to improve corneal cross-linking. Back in 2013, we identified that oxygen is an essential component of the cross-linking reaction, and its availability limits the rate at which the cross-linking reaction proceeds [1]. But when we looked through the literature, we found an interesting phenomenon: lowering the temperature of the cornea, improves oxygen diffusion. This could solve a problem that exists when we try to accelerate the corneal cross-linking procedure by increasing the intensity of UV irradiation: oxygen gets consumed at a faster rate, limiting the effectiveness of the reaction. The original cross-linking reaction required 30 minutes of UV irradiation to stiffen the cornea, using 3 mW/cm² UV irradiation, but accelerating this reaction beyond 10 minutes (at 9 mW/cm² irradiation) starts to result in diminishing returns in terms of how effectively the cornea is strengthened.

To find out if this makes a difference, we performed some experiments [2]. We took 112 pig corneas obtained from an abattoir, soaked them in 0.1% riboflavin, and split them into 4 groups: two where we performed accelerated epi-off cross-linking, incubated at either 24°C, or 4°C for 10 minutes, and two non-cross-linked control groups, again, one at 4°C, and the other at 24°C, again for 10 minutes. We then performed some stress-strain measurements 

What did we find? Unsurprisingly, cross-linked corneas were stronger than non-cross-linked corneas. However, we did not observe any additional strengthening effect in the group of corneas cross-linked at 4°C over the corneas cross-linked at 24°C. 

This research was published this month in the journal, Eye and Vision.

Cooling the cornea corneal cross-linking - biomechanical effect of epithelium-off corneal cross-linking

 

 

References

  1. Richoz O, Hammer A, Tabibian D, Gatzioufas Z, Hafezi F. The biomechanical effect of corneal collagen cross-linking (Cxl) with riboflavin and UV-A is oxygen dependent. Transl Vis Sci Technol. 2013;2(7):6.
  2. Abdshahzadeh H, Abrishamchi R, Torres-Netto EA, et al. Impact of hypothermia on the biomechanical effect of epithelium-off corneal cross-linking. Eye Vis (Lond). 2021;8(1):4.2.