Olsen Timothy W, Feng Xiao, Wabner Kathy, Conston Stanley R, Sierra David H, Folden David V, Smith Morton E, Cameron J Douglas
University of Minnesota, Department of Ophthalmology, Minneapolis, Minnesota 55455-0501, USA.
Am J Ophthalmol. 2006 Nov;142(5):777-87. doi: 10.1016/j.ajo.2006.05.045. Epub 2006 Sep 20.
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.
Animal study.
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.
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.
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.
通过在灵长类动物和猪动物模型中对脉络膜上腔进行微插管，描述、测试和评估一种新型眼后段给药系统（PDS）的药代动力学。
动物研究。
使用一只恒河猴（猕猴）（n = 1）和猪模型（n = 93）来评估PDS，这是一种将药物输送通道与光纤照明及最佳过渡特性相结合的微插管。研究了手术技术、安全性、组织病理学、视网膜和脉络膜血流、示踪染料注射以及曲安奈德药代动力学。进行了术前和术后使用荧光素和吲哚菁绿（ICG）成像的高速视频共焦扫描激光眼科检查（cSLO）以及广域眼底成像研究。摘除眼球用于组织病理学或药代动力学研究。
94只动物中有93只进行了插管。并发症包括：眼内炎（1/94）、脉络膜撕裂（1/94）、脉络膜血流异常（4/94）、术后炎症（6/94）、巩膜扩张（4/94）、伤口脓肿（1/94）等。组织病理学显示未出现并发症的病例解剖结构正常。曲安奈德在局部眼组织中至少保留120天，在体循环中可检测到极低水平。
通过使用精细的手术技术，微插管系统可以安全且可重复地进入脉络膜上腔。应避免PDS尖端用力撞击黄斑和视神经区域的结缔组织。曲安奈德的药代动力学具有独特性，表明其在局部组织中的水平长期较高而全身水平较低。PDS进入脉络膜上腔代表了一种新型给药方法，适用于多种针对黄斑、视神经和后极部的药物治疗。
