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J. E. Chan, T. A. Pridgen, K. G. Csaky; Role of the Choroidal Blood Flow in the Elimination of Sodium Fluorescein (NaFl) Delivered by an Episcleral Implant. Invest. Ophthalmol. Vis. Sci. 2009;50(13):5955.
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Drug delivery via an episcleral implant is an attractive approach for the therapy of chronic diseases. However evidence to date suggests this approach allows for only limited drug penetration to the posterior segment due in part to rapid choroidal blood flow resulting in efficient elimination of drug. In this study, we sought to determine the extent of elimination by choroidal blood flow of hydrophilic drug delivery by an episcleral implant.
Sprague-Dawley rats were injected with intravenous indocyanine green (ICG) and the large penetrating vessel surrounding the optic nerve in one eye was photocoagulated using a diode (810 nm) laser to achieve choroidal nonperfusion. Ablation of the choroidal vasculature was verified by the use of intravenous concanavalin A and examination of choroidal and retinal flatmounts. Following laser photocoagulation, implants containing 2% NaFl were placed episclerally in the superotemporal quadrant of both eyes. After various time points after complete dissolution of the implants, both eyes were enucleated and the retina and conjunctiva/choroid/sclera complex (CCSC) were dissected. A novel method of tissue dissolution, extraction and quantitation of NaFl from the various ocular tissues using a spectrophotometer was performed.
A standard curve of varying concentrations of NaFl in the corresponding eye tissues was generated and demonstrated linearity over a range of 4.7 ng/mL to 470 ng/mL while the efficiency of extraction was found to be >98%. The elimination curve of NaFl in untreated control eyes demonstrated a concentration of 25.3 ng of NaFl per mg of wet tissue weight in the CCSC at 3 hrs with a reduction of 93.9% of drug at 3 hrs (n=5) while only 0.65% of NaFl partitioned into the retina. Following ICG-directed choroidal occlusion, concanavalin A flatmounts demonstrated complete nonperfusion of >90% of the choroid and retina. The elimination curve of NaFl in laser-treated eyes demonstrated a concentration of 16.6 ng of NaFl per mg of wet tissue weight in the CCSC at 3 hrs with a reduction of 94.8% of drug at 3 hrs (n=2) while only 0.50% of NaFl partitioned into the retina.
These findings show that selective ablation of the choroidal vasculature does not significantly alter episcleral elimination of drugs, suggesting that the choroidal vasculature is likely not the major elimination route for episclerally delivered drugs.
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