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R.A. P. De Carvalho, M.L. Krause, R.L. e Silva, I.H. Maumenee, P. Campochiaro; Transscleral Diffusion Patterns and Intraocular Tracer Kinetics of Sealable and Refillable Episcleral Drug Delivery Systems . Invest. Ophthalmol. Vis. Sci. 2005;46(13):3532.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: Transscleral–targeted delivery systems (TTDS) are proposed to prioritize drug diffusion through the sclera. This study aims to explore in vivo the intraocular kinetics of tracers as a function of different methods to accomplish a seal between the TTDS and the sclera. Methods: The TTDS were loaded with sodium fluorescein (NaF) at doses of 9.42 mg (+/– 0.16 mg) in compressed pellets, which rapidly dissolves after exposure to the sclera. In vivo ocular fluorophotometry measured the diffusion of NaF into the eye at baseline, 20 minutes, 1, 3, 6, 12, 24, 48, 96, and 156 hours after implantation. Blood was drawn at the same time points for plasma measurement. The devices were attached to the sclera by apposition (n=4) or indentation (n=4) into the scleral surface. Attachment was accomplished by the use of transscleral buckling sutures engaged by the implant. Eyes (n=3) receiving periocular injections NaF (9 mg) were used as control. Results (ng/ml, mean, SD) are reported in area under the concentration–time curve (AUC) and maximum concentration (Cmax) for posterior vitreous, and plasma maximum concentration (pCmax). Histology was carried out in all eyes. Results: In the periocular injection group the diffusion curve peaked in the anterior chamber (AC) at all time points, AUC = 779.8 (+/– 443.6), Cmax = 41.1 (+/– 12.8). For the indented implants the diffusion curve peaked in the retina/choroid and the AC concentration progressed as a function of the vitreous concentration, AUC = 3166.3 (+/– 1394.4), Cmax = 368.7 (+/– 292.2). In the apposition group a mixed pattern of diffusion was composed of a preferential diffusion into the AC followed by a predominantly high concentration in the vitreous, AUC = 4923.9 (+/– 4917.7), Cmax = 379.9 (+/– 182.2). The systemic absorption was higher for the periocular injection group, pCmax = 1206.8 (+/– 613.7), compared to the indentation group, pCmax = 301.7 (+/– 316.9), and to the apposition group, pCmax = 358.4 (+/– 156.9). Histology demonstrated biocompatibility of the implants. The use of other formulations is discussed. Conclusions: TTDS prioritizes the diffusion of tracers from the periocular space into the vitreous. Targeting transscleral drug delivery by tight scleral attachment can provide higher concentration of drugs to the posterior segment of the eye and potentially minimize systemic loss and periocular toxicity. Scleral indentation of implants can further improve selectiveness of the method by compressing the scleral tissue and minimizing the tangential diffusion through the sclera.
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