Advanced transepithelial corneal collagen crosslinking

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PROJECT SUMMARY Keratoconus is an eye disease where the cornea is mechanically weakened, leading to progressive thinning, distortion, and degradation of vision. In severe cases, corneal transplantation may be required to restore vision. Corneal collagen crosslinking (CXL) is a procedure that uses riboflavin, oxygen and ultraviolet (UV) light to produce a chemical reaction that strengthens collagen fibers in the cornea stroma. CXL has been shown to halt keratoconus progression over the long term. A problem with the standard CXL procedure is that the surface epithelial cells must be removed first so that riboflavin, oxygen, and UV can easily enter the corneal stroma. It is common for epithelial healing to be delayed after CXL. This increases the chance that the cornea may become hazy. It also increases the risk of infections that can lead to scarring and loss of vision. To avoid these problems, some doctors perform CXL without removing the epithelium. This is called “transepithelial CXL” in contrast to the standard “epi-off CXL” procedure. Unfortunately, as currently practiced, transepithelial CXL is far less effective in strengthening the cornea. We have developed an advanced transepithelial CXL technology (Casey CXL) that overcomes the epithelial barrier to riboflavin, oxygen, and UV delivery. A computational finite- element model (FEM) of diffusion and reaction kinetics showed that Casey CXL can significantly exceed the performance of standard epi-off CXL. We propose to validate the advantages of Casey CXL in ex vivo experiments using both rabbit and human eye bank corneas: 1. Construct an oxygen-UV delivery system to enrich oxygen to >90% in the ambient air over the corneal surface during UV irradiation. 2. Measure oxygen concentration in the corneal stroma during CXL. We will use a fiber-optics oximetry probe to measure oxygen in the anterior and mid-stroma during UV irradiation. We will test the hypothesis that by using oxygen enrichment and pulsed UV, Casey CXL allows greater oxygen penetration to the mid-stroma than standard epi-off CXL. The FEM predicts a more than 2-fold advantage for Casey CXL, which would greatly improve the depth of corneal strengthening. 3. Use optical coherence tomographic elastography, a nondestructive testing technology, to measure cornea stiffness before and after experimental CXL. This would test the hypothesis that Casey CXL can stiffen the cornea more than standard epi-off CXL, as predicted by the FEM. These experiments would validate the Casey CXL protocol, including the drug formulation, procedure steps, and oxygen-UV delivery device, to prepare for clinical trials in human patients.