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R.A. P. De Carvalho, M. Durst, M. Krause, J. Hanes, I. Maumenee, P. Campochiaro; Sealable Episcleral Drug Delivery Devices. The Effects of Sustained Release Formulations, Laser and Cryo on Ocular Pharmacokinetics of Tracers. . Invest. Ophthalmol. Vis. Sci. 2006;47(13):5111.
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After seal to the sclera, the targeted transscleral drug delivery system (TTDS) can provide unidirectional diffusion of drugs into the eye. In this study, we sought to characterize in vivo the effect of slow release formulations, cryopexy and laser photocoagulation in association with the TTDS on ocular pharmacokinetics of fluorescent tracers.
The TTDS was loaded with sodium fluorescein (NaF) in ethylene–vinyl acetate copolymers (EVAc) at different doses and implanted in White New Zealand rabbits. In vivo ocular fluorophotometry measured levels of NaF in the eye at baseline, 3, 6, 24 and 48 hours, 7, 14, 21, 30 and 45 days after implantation. In selected cases, fluorophotometry was performed up to 6 months. To eliminate the barrier induced by the RPE and possibly choroidal circulation, cryo was used in association with the implantation procedure (n=4), 3 weeks prior to it (n=3) and compared to animals receiving only implants (n=3). Laser was done immediately after device implantation (n=3) and compared to the fellow eye, which received the implant only. The area under the concentration–time curve (AUC, hour*mg/L) for the retina was computed. Results were reported in mean and standard error. Histology was carried out in all eyes. Diffusion patterns and pharmacokinetics parameters related to other ocular tissues were analyzed.
The EVAc polymer provided sustained release of NaF up to the last measured time point (6 months) in selected cases. Diode laser photocoagulation increased diffusion of tracers into the vitreous, but did not alter significantly the retinal fluorescence peak. Prior (AUC = 335668, +/– 67790) or concomitant cryopexy (AUC = 204558, +/– 40173) led to a statistically significant (p < 0.05) increase in the retinal fluorescence compared to eyes not exposed to cryo (AUC = 25307, +/– 5959). Histology demonstrated biocompatibility of the implants and confirmed the atrophic effects of the cryo and laser.
The TTDS can provide preferential diffusion of tracers through the sclera by avoiding periocular washout and reflux of tracers to the ocular surface. It results in increase of the bioavailability of tracers to the posterior segment, and decrease in systemic peak concentrations. Prior or concomitant cryopexy increases the intraocular diffusion of agents from the TTDS.
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