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J. M. Stewart, O.-T. Lee, D. R. Lari; Optimization of Ultraviolet-A/Riboflavin Cross-Linking in an in vivo Rabbit Model. Invest. Ophthalmol. Vis. Sci. 2010;51(13):4989.
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© ARVO (1962-2015); The Authors (2016-present)
To evaluate the effects of various dosages of Ultraviolet-A (UVA) on wound healing and corneal stiffening in an in vivo rabbit model.
New Zealand White rabbits were used throughout this study. One eye was chosen at random for irradiation while the other served as its control. After removal of the central epithelium, eyes in the experiment group were treated with hypotonic 0.1% riboflavin solution every 5 minutes (beginning 30 minutes before irradiation) until the end of the 30 minute irradiation period. These corneas were irradiated with UVA light at one of five irradiance levels (5.0, 3.0, 2.0,1.2, and 0.6 mW/cm2) using a custom built UVA emitter ( = 370nm). Animals were euthanized at 1 week, 2 weeks and 3 weeks post operatively. The corneas of the enucleated eyes were evaluated with H&E stained light microscopy slides. Uniaxial mechanical testing of corneal strips isolated from a second group of treated eyes was performed using a custom tension tester, using clamps to grip the tissue, dual motors to stretch the sample, and a load cell to record stress values. An additional set of donor cadaver rabbit eyes was subjected to crosslinking at several irradiance levels, followed by mechanical testing.
At high irradiance (5 mW/cm2), there was significant endothelial cytotoxicity, resulting in non-healing epithelial defects, persistent corneal edema, and neovascularization. At the suggested irradiance levels used in other labs (3 mW/cm2), epithelial wound healing took 2-3 weeks but corneal edema and endothelial cytotoxicity was still noted. At irradiance levels of 2 mW/cm2, some corneas were healed by two weeks while others had persistent epithelial defects and edema. Irradiance levels lower than 2 mW/cm2 were better tolerated. Crosslinking of rabbit corneas in vivo resulted in mild stiffening. Uniaxial mechanical testing of donor rabbit corneas treated at 3, 2, or 1.2 mW/cm2 (n=3, each group) showed an increase in modulus compared to controls.
The standard dosage of irradiation used in human patients (3.0mW/cm2) is not tolerated well by rabbit corneas. The thinner corneas of rabbits necessitate lower irradiation levels for cross-linking treatments, and even these treatments require prolonged healing times. Rabbit corneas crosslinked at reduced irradiance show mild stiffening compared to controls. The treatment parameters identified in this study may comprise a suitable rabbit model for riboflavin/UV-A corneal crosslinking.
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