纤溶酶和透明质酸酶复合诱导兔眼完全性玻璃体后脱离的效果及其安全性

Efficacy and safety of plasmin and hyaluronidase in inducing completely posterior vitreous detachment in rabbit eyes

背景:完全性玻璃体后脱离可缓解、控制增生性玻璃体视网膜疾病的发展和预后。目前,解除玻璃体视网膜黏连的主要手段是玻璃体切割术,其存在黄斑、视盘的损伤,视网膜破裂、脱离及神经纤维层和神经节细胞撕脱等并发症。目的:联合应用纤溶酶和透明质酸酶诱导兔眼形成完全性玻璃体后脱离,评价其效果和安全性。设计、时间及地点:随机分组设计、动物对照实验,于2003-04/2004-09在内蒙古医学院实验室完成。材料:健康成年日本大耳白兔16只(32只眼),纤溶酶和透明质酸酶,平衡盐缓冲液。方法:采用玻璃体腔内注射,右眼为实验眼,注入1U纤溶酶+20U透明质酸酶0.1mL,左眼为对照眼,注入平衡盐缓冲液0.1mL。主要观察指标:注药后15,60min,1,3,5,7d裂隙灯、直接、间接检眼镜、+90DVOLK前置镜检查眼部情况。注药后1,3,7dB超检查玻璃体后脱离发生情况。注药后3d采用Topcon荧光造影机观察眼底形态、血管充盈时间、血管有无渗漏情况。注药前、注药后15,60min,1,3d进行闪光视网膜电图检查,计算同一眼注药前、后的b波的振幅值。注药后7d光镜下观察视网膜形态和结构,透射电镜下观察视网膜超微结构变化。结果:裂隙灯观察显示,对照眼无明显阳性表现。实验眼注药15min后,全部有明显的睫状充血,房闪、不同程度的玻璃体炎症反应,1d后发现3例白内障。B超观察显示,对照眼无明显改变,实验眼可见玻璃体程度不同的混浊,3d后开始有玻璃体后脱离形成(5/16),7d内全部形成。荧光造影机观察显示,实验眼视乳头周边神经纤维层完整,未见出血、水肿,造影动静脉充盈排空迅速、未见荧光渗漏。闪光视网膜电图检查发现实验眼b波在15min时下降,随着观察时间的延长b波在60min时恢复;对照眼无明显变化。组织学检查未发现形态和结构的异常。结论:1U纤溶酶+20U透明质酸酶可诱导形成兔眼完全性玻璃体后脱离,其对视网膜的功能有可逆性的影响,此剂量不足以引起视网膜组织结构的破坏。

BACKGROUND： Posterior vitreous detachment may relieve and control the development and prognosis of vitreoretinal disease. Presently, vitrectomy is the chief treatment of vitreoretinal synechia, but it induces the injures of macula lutea and optic papilla, as well some complications such as retinal rupture, detachment, nerve fiber layer and ganglion cell evulsion. OBJECTIVE： To evaluate the efficacy and safety of plasmin and hyaluronidase in inducing completely posterior vitreous detachment in the rabbit eyes. DESIGN, TIME AND SETTING： Randomized control experiments were performed in Inner Mongolia Medical College from April 2003 to September 2004. MATERIALS： Sixteen Japanese adult rabbits （32 eyes）, plasmin and hyaluronidase, balanced salt solution. METHODS： Sixteen rabbits received intravitreal injection （0.1 mL） of 1 U plasmin combined with 20 U hyaluronidase in right eye The fellow eyes were injected with a volumetric equivalent dose of balanced salt solution as controls. MAIN OUTCOME MEASURES： Slit lamp, ophthalmoscopy and ＋90DVOLK preset lens were applied at 15 minutes, 60 minutes and 1, 3, 5, 7 days after injection. B-ultrasonography was used to observe posterior vitreous detachment at 1, 3 and 7 days. Topcon fluorescein fundus angiography was performed at 3 days. Flash electroretinogram was performed before injection and 15 minutes, 60 mintltes, 1 day, 3 days after injection to assay the b-wave amplitude. Retinal morphous and structure were observed under light microscope on 7 days, and the ultrastructure was observed under transmission electron microscope. RESULTS： Slit lamp results displayed control eyes had no positive manifestation. Experimental eyes bad ciliary congestion, aqueous flare, vitreous inflammation at 15 minutes and cataract was observed in three cases on 1 day. B-ultrasonography showed that control eyes had no changes. After 3 days, posterior vitreous detachment could be observed in 5 cases, and all of them was observed on 7 days. Nerve fiber layer around discus opticus was complete, without hemorrhage or edema. The arteriovenous turgor and evacuation were observed to be rapid, no fluorescence leakage occurred. As for the experimental eyes, b-wave decreased at 15 minutes and recovered at 60 minutes by flash electroretinogram examination, while no changes were found in the control eyes. Histological detection showed no abnormalities of the morphology and structure. CONCLUSION： The combination of 1 U plasmin and 20 U hyaluronidase can induce completely posterior vitreous detachment in rabbit eyes, it has reversible effect on the function of retina, but the dose of medicine has no effect on retinal structure.