A novel bioerodible deep scleral lamellar cyclosporine implant for uveitis
A novel bioerodible deep scleral lamellar cyclosporine implant for uveitis
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DOI：
10.1167/iovs.05-1540
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发表时间：
2006-06-01
影响因子：
4.4
通讯作者：
Robinson, MR
中科院分区：
文献类型：
--
作者：
Gilger, BC;Salmon, JH;Robinson, MR
目的.目的：探讨巩膜外层或深层缓释环孢霉素（CsA）装置在自然发生的葡萄膜炎动物模型中的可行性、安全性和有效性。一个两室灌注室被用来评估在体外人类和马的巩膜渗透性的荧光素，地塞米松荧光素，或CsA。设计了一种可生物降解的CsA基质贮库型植入剂，并测定了CsA的体外释放速率。测量植入眼的组织CsA水平。患有马复发性葡萄膜炎（ERU）的马接受了巩膜上或深层巩膜板层CsA植入，并进行了长达3年的监测。地塞米松-荧光素和CsA穿透体外马巩膜差;然而，低但可检测水平的CsA检测眼内在体内。植入物放置在巩膜外层未能控制ERU的炎症发作。CsA植入物放置在邻近脉络膜上腔的深层巩膜中，导致大多数眼组织中的CsA水平较高。在临床马ERU患者中，葡萄膜炎发作的频率显着降低后，植入深层巩膜板层CsA植入物。CsA从巩膜外间隙穿过巩膜的扩散不是将药物递送至马眼的可行方法。然而，将深层巩膜板层CsA植入物放置在脉络膜上腔附近可有效达到治疗性眼部药物浓度并控制ERU马的葡萄膜炎。
PURPOSE. To determine the feasibility, safety, and effectiveness of an episcleral or deep scleral lamellar sustained release cyclosporine (CsA) device in a naturally occurring animal model of uveitis.METHODS. A two-compartment perfusion chamber was used to assess in vitro human and equine scleral permeability of fluorescein, dexamethasone-fluorescein, or CsA. A biodegradable, matrix-reservoir CsA implant was designed, and release rates of CsA were determined in vitro. Tissue CsA levels were measured in eyes with the implant. Horses with equine recurrent uveitis (ERU) received episcleral or deep scleral lamellar CsA implants and were monitored for up to 3 years.RESULTS. Dexamethasone-fluorescein and CsA penetrated the in vitro equine sclera poorly; however, low but detectable levels of CsA were detected intraocularly in vivo. The implant placed episclerally failed to control inflammatory episodes in ERU. CsA implants placed in the deep sclera adjacent to the suprachoroidal space resulted in high levels of CsA in most ocular tissues. In clinical equine patients with ERU, frequency of uveitic flare-ups was significantly decreased after implantation of a deep scleral lamellar CsA implant.uCONCLUSIONS. Diffusion of CsA across the sclera from the episcleral space was not a feasible method of drug delivery to the equine eye. However, placing a deep scleral lamellar CsA implant adjacent to the suprachoroidal space was effective in achieving therapeutic ocular drug concentrations and controlling uveitis in horses with ERU.