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H. F. Edelhauser, S. Lee, E. S. Kim, D. H. Geroski, B. E. McCarey; Pharmacokinetics of Intraocular Drug Delivery of Oregon Green 488 Labeled Triamcinolone by Subtenon Injection Using Ocular Fluorophotometry in Rabbit Eyes. Invest. Ophthalmol. Vis. Sci. 2008;49(13):3186. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
To evaluate the transscleral delivery of Oregon Green 488 labeled triamcinolone (OGTA) into the eye.
Ex vivo experiments were carried out using rabbit sclera and a Lucite block perfusion chamber. OGTA (200 ug/200 ul) was placed on the outer surface of the sclera and the concentration of OGTA that diffused through the sclera was measured using a fluorometer. Following the permeability study, the exposed sclera (n = 8) was removed from the chamber and divided into 2 pieces, one for a washout of OGTA and fluorometry test and the other frozen for immunofluorescein histopathology. OGTA (1 mg/0.2 ml) was also injected subtenon into one eye of anesthetized live rabbits (n = 6) and euthenatized rabbits (n = 3). OGTA concentrations in the choroid/retina, vitreous and anterior segment were measured using ocular fluorophotometry.
The permeability constant (mean ± SD) for the transscleral diffusion (Ktrans) of OGTA was 1.12 ± 0.08 x 10-9 cm/sec (n = 8) during the steady state perfusion between 13 and 21 hours. Scleral Washout showed higher OGTA concentration in the sclera exposed to OGTA fluorescence throughout the exposed sclera, as evidence of scleral penetration of OGTA. The maximum OGTA concentration (mean ± SD) in the retina/choroid after subtenon injection in vivo was 25.77 ± 10.26 ng/ml in the live rabbit at 3 hours and 84.68 ± 21.04 ng/ml in the euthanatized rabbits at 8 hours. The maximum vitreous concentrations in the live and euthanatized rabbit were 6.98 ± 2.09 ng/ml at 3 hours and 83.66 ± ng/ml at 8 hours, respectively.
OGTA is capable of diffusion across the isolated rabbit sclera and to the retina/choroid by transscleral diffusion from a subtenon depot. The high OGTA level in the choroid/retina appears to be determined the corresponding vitreous OGTA levels. Conjunctival and choroidal circulation affected transscleral drug delivery of OGTA.
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