PURPOSE: To describe, test, and evaluate the pharmacokinetics of a novel posterior drug delivery system (PDS) by means of microcannulation of the suprachoroidal space in both the primate and pig animal model. DESIGN: Animal study. METHODS: A rhesus macaque (Macaca mulatta) (n = 1) and pig model (n = 93) were used to evaluate the PDS, a microcannula that combines a drug delivery channel with a fiber-optic illumination and optimal transition properties. The surgical technique, safety profile, histopathology, retinal and choroidal blood flow, injection of tracer dyes, and triamcinolone pharmacokinetics were studied. Pre- and postsurgical high-speed video confocal scanning laser ophthalmoscopy (cSLO) that used fluorescein and indocyanine green (ICG) imaging and wide-field fundus imaging studies were performed. Globes were enucleated for either histopathology or pharmacokinetics. RESULTS: Cannulation was performed in 93 of 94 animals. Complications included: endophthalmitis (1/94), choroidal tear (1/94), choroidal blood flow irregularities (4/94), postoperative inflammation (6/94), scleral ectasia (4/94), wound abscess (1/94), and others. Histopathology demonstrated normal anatomy in uncomplicated cases. Triamcinolone remains in the local ocular tissue for at least 120 days, and measurable at very low levels in the systemic circulation. CONCLUSIONS: Accessing the suprachoroidal space by the microcannulation system can be performed in a safe and reproducible manner by using careful surgical technique. Forceful PDS tip impact into connective tissues in the macular and optic nerve regions should be avoided. Triamcinolone pharmacokinetics are unique and suggest long-term local tissue levels with low systemic levels. PDS access to the suprachoroidal space represents a novel drug delivery method, applicable to a wide variety of pharmacotherapies to the macula, optic nerve, and posterior pole.
PURPOSE: To describe, test, and evaluate the pharmacokinetics of a novel posterior drug delivery system (PDS) by means of microcannulation of the suprachoroidal space in both the primate and pig animal model. DESIGN: Animal study. METHODS: A rhesus macaque (Macaca mulatta) (n = 1) and pig model (n = 93) were used to evaluate the PDS, a microcannula that combines a drug delivery channel with a fiber-optic illumination and optimal transition properties. The surgical technique, safety profile, histopathology, retinal and choroidal blood flow, injection of tracer dyes, and triamcinolone pharmacokinetics were studied. Pre- and postsurgical high-speed video confocal scanning laser ophthalmoscopy (cSLO) that used fluorescein and indocyanine green (ICG) imaging and wide-field fundus imaging studies were performed. Globes were enucleated for either histopathology or pharmacokinetics. RESULTS: Cannulation was performed in 93 of 94 animals. Complications included: endophthalmitis (1/94), choroidal tear (1/94), choroidal blood flow irregularities (4/94), postoperative inflammation (6/94), scleral ectasia (4/94), wound abscess (1/94), and others. Histopathology demonstrated normal anatomy in uncomplicated cases. Triamcinolone remains in the local ocular tissue for at least 120 days, and measurable at very low levels in the systemic circulation. CONCLUSIONS: Accessing the suprachoroidal space by the microcannulation system can be performed in a safe and reproducible manner by using careful surgical technique. Forceful PDS tip impact into connective tissues in the macular and optic nerve regions should be avoided. Triamcinolone pharmacokinetics are unique and suggest long-term local tissue levels with low systemic levels. PDS access to the suprachoroidal space represents a novel drug delivery method, applicable to a wide variety of pharmacotherapies to the macula, optic nerve, and posterior pole.
Authors: Samirkumar R Patel; Damian E Berezovsky; Bernard E McCarey; Vladimir Zarnitsyn; Henry F Edelhauser; Mark R Prausnitz Journal: Invest Ophthalmol Vis Sci Date: 2012-07-01 Impact factor: 4.799
Authors: Henry F Edelhauser; Cheryl L Rowe-Rendleman; Michael R Robinson; Daniel G Dawson; Gerald J Chader; Hans E Grossniklaus; Kay D Rittenhouse; Clive G Wilson; David A Weber; Baruch D Kuppermann; Karl G Csaky; Timothy W Olsen; Uday B Kompella; V Michael Holers; Gregory S Hageman; Brian C Gilger; Peter A Campochiaro; Scott M Whitcup; Wai T Wong Journal: Invest Ophthalmol Vis Sci Date: 2010-11 Impact factor: 4.799
Authors: Raghu Raj Singh Thakur; Steven J Fallows; Hannah L McMillan; Ryan F Donnelly; David S Jones Journal: J Pharm Pharmacol Date: 2013-10-16 Impact factor: 3.765
Authors: Timothy W Olsen; Xiao Feng; Kathy Wabner; Karl Csaky; Stefan Pambuccian; J Douglas Cameron Journal: Invest Ophthalmol Vis Sci Date: 2011-07-01 Impact factor: 4.799