Tameesh Mohamed K, Lakhanpal Rohit R, Fujii Gildo Y, Javaheri Michael, Shelley Terry H, D'Anna Sam, Barnes Aaron C, Margalit Eyal, Farah Michel, De Juan Eugene, Humayun Mark S
Doheny Retina Institute, Doheny Eye Institute, Department of Ophthalmology, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.
Am J Ophthalmol. 2004 Nov;138(5):829-39. doi: 10.1016/j.ajo.2004.06.083.
To evaluate the feasibility, safety, and efficacy of local thrombolytic agents directly injected into occluded retinal veins in an experimental animal model.
Experimental animal study.
This experimental study was performed in two phases. In phase 1, 15 enucleated porcine eyes and 8 in vivo canine eyes were used for the development of the instrumentation and surgical technique required for retinal vein cannulation with prolonged intravascular infusion. In phase 2 of this study, experimental branch retinal vein occlusion was photo-chemically created using an intravenous injection of rose bengal followed by diode laser photocoagulation in eight eyes of eight dogs. Four eyes were treated by retinal vein cannulation and an injection of tissue plasminogen activator (t-PA) using a specifically designed microcatheter, while the remaining four eyes were untreated (control group). The total amount of t-PA injected intravenously ranged from 400 to 1000 mug, infused over a period ranging from 25 to 45 minutes with a mean pressure of 40 psi, resulting in a mean injection flow rate of 0.05 ml/min. The dogs underwent clinical examination, fluorescein angiography, and histologic examination. Main outcome measures were: Achievement of prolonged intravascular infusion of t-PA, changes in fundus appearance, fluorescein angiography, and histology.
A microcatheter instrument and a surgical technique for retinal vein cannulation with prolonged intravascular infusion were developed. Cannulation and t-PA infusion for a period of at least 30 minutes was achieved in all four treated eyes with experimental branch retinal vein occlusion. No complications were recorded in all treated eyes. One week and 1 month postoperatively, treated eyes exhibited marked decreases in retinal hemorrhages, retinal vein dilation, and tortuosity, whereas nontreated eyes exhibited persistence of these findings. Fluorescein angiography demonstrated improved circulatory flow in treated relative to nontreated eyes. Histologic analysis confirmed the presence of thrombi in nontreated eyes only.
Retinal vein cannulation with prolonged intravascular injection of t-PA is feasible and safe, and this may offer a new treatment option for retinal vein occlusion.
在实验动物模型中评估直接向闭塞的视网膜静脉注射局部溶栓剂的可行性、安全性和有效性。
实验动物研究。
本实验研究分两个阶段进行。在第一阶段,使用15只摘除眼球的猪眼和8只活体犬眼来开发视网膜静脉插管及长时间血管内输注所需的器械和手术技术。在本研究的第二阶段,通过静脉注射孟加拉玫瑰红,随后用二极管激光光凝,在8只犬的8只眼中光化学诱导实验性视网膜分支静脉阻塞。4只眼通过视网膜静脉插管并使用专门设计的微导管注射组织纤溶酶原激活剂(t-PA)进行治疗,其余4只眼不治疗(对照组)。静脉注射的t-PA总量为400至1000微克,在25至45分钟内输注,平均压力为40磅力/平方英寸,平均注射流速为0.05毫升/分钟。对犬进行临床检查、荧光素血管造影和组织学检查。主要观察指标为:t-PA长时间血管内输注的实现情况、眼底外观变化、荧光素血管造影和组织学情况。
开发了用于视网膜静脉插管及长时间血管内输注的微导管器械和手术技术。在所有4只患有实验性视网膜分支静脉阻塞的治疗眼中,实现了至少30分钟的插管和t-PA输注。所有治疗眼均未记录到并发症。术后1周和1个月,治疗眼的视网膜出血、视网膜静脉扩张和迂曲明显减少,而未治疗眼的这些表现持续存在。荧光素血管造影显示治疗眼相对于未治疗眼的循环血流有所改善。组织学分析仅在未治疗眼中证实存在血栓。
长时间血管内注射t-PA进行视网膜静脉插管是可行且安全的,这可能为视网膜静脉阻塞提供一种新的治疗选择。