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V. H. Barocas, R. K. Balachandran; Estimation of Inward and Outward Permeability of the Blood-Vitreous Barrier to Fluorescein via a Detailed Model of Intravitreal Transport. Invest. Ophthalmol. Vis. Sci. 2007;48(13):5815.
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To use the large body of experimental data on intravitreal fluorescein pharmacokinetics, in conjunction with a detailed model of intravitreal transport, to determine the parameters that govern fluorescein transport into and out of the vitreous.
A detailed finite-element model of intravitreal transport was employed. The model accounts for diffusion of fluorescein in the vitreous, convection of fluorescein by posterior aqueous humor flow, transfer of fluorescein between the vitreous and the choroidal circulation, and loss of fluorescein to the surrounding tissue. The model was applied to various published studies in which fluorescein was delivered intravitreally, orally, or intravenously, and optimal model parameters were calculated by nonlinear least squares regression.
The data of Palestine and Brubaker (IOVS 21:542, 1981), the most thorough study of blood-to-vitreous transport, were analyzed and gave a value of 9.9 x 10-6 s-1 for the transport coefficient (per unit volume of choroid) between the vitreous and the blood, and a value of 9.9 x 10-6 cm/s for the transport coefficient (per unit surface area) at the scleral surface. Calculations based on these parameters generally showed good agreement with other published experimental work (e.g., Lund-Anderson et al., IOVS 26:698, 1985), but in some cases the active transport of fluorescein, which was not included in the model, may have been significant.
The coefficient calculated by our regression is somewhat smaller than that used in previous models of intravitreal drug transport, suggesting that choroidal losses may not be as severe a factor in transscleral drug delivery as previously feared. The active transport of fluorescein or of drugs may be an important consideration, but its significance remains unclear.
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