Recombinant Human Hyaluronidase Facilitates Dexamethasone Penetration Into the Posterior Ocular Segment After Xub–Tenon's Injection

Abstract

Abstract: : Purpose:Trans–scleral drug delivery to the posterior segment of the eye would be a useful and minimally invasive delivery route in the treatment of choroidal neovascularization, macular degeneration, and other diseases limited to this area, which typically are treated via an intravitreal injection. Steroids may be useful in choroidal neovascularization as are other drugs. We therefore designed experiments to examine the extent to which recombinant human hyaluronidase can enhance trans–scleral penetration of retrobulbar dexamethasone into the posterior pole choroid, retina and vitreous of rabbit eye. Methods: New Zealand red male rabbits were used for the study. Under general anesthesia (ketamine and xylazine hydrochloride) a 1.5 ml sub–Tenon's injection of either dexamethasone with hyaluronidase or dexamethasone alone were injected. After euthanasia the choroid, retina and vitreous samples were extracted at 1,2,3 and 6 hours post–injection. Mass spectrometry was used to assess dexamethasone levels in tissues with the minimum quantifiable limits on the order of 5.00 ng/ml. Results: The choroidal, retinal and vitreous dexamethasone levels of rabbits treated with dexamethasone alone reached peak concentrations 1 hour after injection. The choroidal and retinal concentrations of dexamethasone in rabbits treated with dexamethasone + hyaluronidase) were higher and reached peak levels 2 hours after injection. Peak choroidal, retinal and vitreous concentrations of dexamethasone were 10x, 5x and 8x higher, respectively, than in samples without hyaluronidase. Conclusions: Significantly higher choroidal, retinal and vitreous levels of dexamethasone can be detected after sub–Tenon's injection of dexamethasone in combination with recombinant human hyaluronidase compared to dexamethasone alone. Addition of hyaluronidase significantly enhances trans–scleral drug delivery to posterior segment of the eye.

Keywords: choroid: neovascularization • age-related macular degeneration • retina