Efficiency And Safety Study Scleral Collagen Cross-linking By Using Ultraviolet A And Riboflavin

PURPOSE: Although the mechanism of myopia is not completely understood, it isbelieved that the sclera behaves as a “metabolic disorder”, causing it to become thinand expand under eye pressure, leading to eyeball shape deformation, because ofvarious inborn and postnatal factors. Scleral collagen cross-linking (CXL) byriboflavin/ultraviolet A (UVA) is a new technique that increases the mechanical andbiochemical stability of the sclera. The present pilot study was designed to investigatethe efficiency and safety of rabbit and donor human eyes with the general protocol ofscleral collagen cross-linking using riboflavin and UVA.METHODS: Scleral stress-strain measurement was performed to evaluate thebiomechanical efficiency of scleral collagen cross-linking using riboflavin and UVA.First of all, six donor human eyes in our study were randomly divided into two groups.The stress–strain behaviors of donor human equatorial and posterior scleral stripswere compared between cross-linked and un-CXL control groups. Then, twenty NewZealand adult albino rabbits were randomly divided into four groups. Thestress–strain behaviors of rabbit equatorial scleral strips were analysed amongun-CXL control,1w post-CXL,1m post-CXL and3m post-CXL groups by abiomaterial tester. Young modulus was calculated at8%strain. When the safety ofscleral collagen cross-linking using riboflavin and UVA was evaluated, Terminaldeoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) staining andtransmission electron microscopy (TEM) were performed on the equatorial sclerafrom six donor human eyes with/without CXL. Finally, twenty-five New Zealandadult albino rabbits were investigated pre-operation,1w,1m and3m post-operation todetect the latent danger of scleral CXL using dark-adapted electroretinography,TUNEL staining and transmission electron microscopy.RESULTS: No matter rabbit or human sclera, there was no statistically significantdifference between cross-linked specimens and untreated control specimens (P＞.05). Both rabbit and human scleral specimens exhibited nonlinear stress–strain behaviorwith an initial low Young modulus increasing gradually under higher stress. The stressand modulus of equatorial and posterior sclera after CXL gradually increased withriboflavin instillation before surgery. At the same strain levels, equatorial sclera withand without CXL exhibited higher Young modulus than that of posterior sclera. Thebiomechanical stability of the rabbit sclera was increased after CXL, which wassimilar with the cross-linked donor human sclera. The corresponding increases inrabbit scleral Young modulus were297%,253%and163%at1w,1m and3mpost-operation. In the donor human retina layers, there was no obvious differencebetween scleral CXL and un-CXL groups by TUNEL staining and TEM. Rabbitdark-adapted ERG amplitudes revealed a significant reduction1w and1mpostoperatively. The ultrastructural morphology of the rabbit retina has beenstructurally destroyed1week after scleral CXL.CONCLUSIONS: The protocol of UVA irradiation mentioned in the previous studiescan obviously increase the biochemical stability of rabbit and human scleral tissues.However, this protocol may not be safe enough, especially for the rabbit visualfunction and retinal cells.