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U. Pinninti, R. V. Jones, Y. Shayesteh, J. F. Rubinson, S. E. Mansour; Enhanced Scleral Permeability With Ovine Hyaluronidase. Invest. Ophthalmol. Vis. Sci. 2007;48(13):3190.
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An in vitro study to determine the effect of ovine hyaluronidase (Vitrase®) on the permeability of bovine and human sclera to exogenous drugs. If scleral permeability increases with Vitrase, this would allow increased intraocular drug concentrations without the use of intravitreal injections. This would be beneficial in the treatment of vitreoretinopathies such as diabetic retinopathy and macular degeneration. The aim of these experiments is to establish an effective dose range for Vitrase, and determine the extent of increased penetration of relevant therapeutic drugs (eg. Avastin, Kenalog) to the posterior segment when used with Vitrase as a subtenons injection.
32 enucleated calf eyes were incubated in 0, 17U/ml, 34U/ml, 77U/ml, 155U/ml, 310U/ml, and 620U/ml of Vitrase for 6hrs. The eyes were stained with methylene blue dye for 30min and the posterior sclera was then examined histopathologically for the extent of penetration of the dye, and integrity of the sclera. Samples of vitreous were analyzed with HPLC to determine the concentrations of therapeutic drugs in the vitreous when administered with Vitrase as a subtenons injection. We are currently incubating 39 enucleated calf eyes in 155U/ml, 310U/ml and 620U/ml of hyaluronidase to compare the transport efficiency for triamcinolone and avastin in the presence/absence of Vitrase. Analyses for the three are being carried out by reversed phase HPLC, ELISA, and a UV-vis kinetic methods, respectively. The optimal concentration of Vitrase will be used in a human clinical trial of diabetics with clinically significant macular edema about to undergo cataract surgery. They receive triamcinolone and Vitrase as a posterior sub-tenons injection a week prior to cataract extraction. At the time of cataract extraction a vitreous biopsy is done to determine the concentration of medication. The patients are followed and evaluated for relative effect of triamcinolone as an intravitreal injection versus delivered sub-tenons with Vitrase.
We found that at concentrations below 155U/ml, there was minimal penetration of the sclera by the dye and above 310U/ml there was significant disintegration of the outer sclera. A comparison of the transcleral permeability for subtenons triamcinolone and avastin in the presence/absence of Vitrase is underway.
310U/ml of ovine Vitrase is a safe and effective concentration and likely enhances penetration of coadministered drugs into the posterior segment.
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