Avastin在眼部应用的安全性研究

发布时间：2018-05-06 22:13

本文选题：Avastin + 角膜　；参考：《山东中医药大学》2010年硕士论文

【摘要】：目的：通过实验研究和临床研究,观察阿瓦斯汀(Avastin)在眼部应用的安全性。方法：给予兔眼玻璃体腔中注射不同剂量(1.25mg/0.05ml、2.5mg/0.1ml。5mg/0.2ml) Avastin和前房注射1.25mgAvastin,在注射前和注射后7天分别行角膜内皮镜、OCT和ERG检查,并在注射后7天摘除兔眼行光镜和透射电镜检查,对角膜内皮细胞密度、面积变异系数、OCT测得的视网膜厚度、ERGb波振幅数据进行统计分析。在临床上选取29例(30眼)糖尿病视网膜病变患者,给予玻璃体腔注射Avastinl.25mg/0.05ml。注射前、注射后3天、1周、1月、3月分别对其进行角膜内皮镜检查,以观察所选角膜区域的角膜内皮的细胞密度、面积变异系数、面积标准差、最大面积、最小面积等指标的变化；注射前和注射后1月行ERG、OCT和眼底荧光造影检查,以观察ERGb波振幅和峰时及视网膜黄斑部水肿的变化。对角膜内皮各项指标数据、ERG数据和OCT数据进行统计分析。结果：兔眼玻璃体腔及前房注药后,玻璃体腔注射5mg组和前房注射组角膜内皮细胞密度明显减小,细胞面积变异系数明显增大；1.25mg组和2.5mg组无明显变化。前房注射组角膜内皮细胞密度减少、面积变异系数增大与其他组相比差别有统计学意义(p0.05)。兔眼玻璃体腔注药后5mg组实验眼OCT测得的视网膜厚度明显变厚,差别有统计学意义(p0.05)；其余各组无明显变化,差别无统计学意义(p0.05)。兔眼玻璃体腔注药后各实验组ERGb波振幅在7天后下降明显,前房注射组和对照组变化不明显。5mg组实验眼ERG b波振幅下降明显低于其它三实验组和对照组。光学显微镜结果显示,前房注射组角膜内皮细胞形态不规则,六边形结构减少,细胞丢失较多,细胞核变长,核膜不连续,仍可见典型的六边形结构。其他组好于前房注射组。各组视网膜组织结构各层排列整齐,结构完整,均未见明显异常。透射电镜结果显示,前房注射组实验眼角膜内皮细胞胞质中细胞器稀疏,可见内质网短小并扩张,连接损伤明显。其他组实验眼均好于前房注射组。5mg组实验眼大部分视神经纤维的横断面空泡化,线粒体肿胀；较正常的突触连接结构很少,有的虽然有递质小泡,但突触后膜高密度板缺失,其他组未见明显异常。临床观察结果显示,所有患者角膜内皮细胞各项检测指标无明显改变,差别均无统计学意义(p0.05)。ERGb波和峰时无明显改变,差别无统计学意义(p0.05)。黄斑部水肿明显减轻,差别有统计学意义(p0.05)。视网膜新生血管显著消退,渗漏明显减少。结论：玻璃体腔注射5mg以下Avastin在短期内对动物视网膜组织结构和神经传导功能无显著影响。但是5mg组出现了视神经纤维的横断面空泡化,线粒体的肿胀,提示玻璃体腔注射Avastin单次剂量不易过大,间隔时间不易过短,以减少或避免Avastin积累对视网膜产生的毒副作用。临床上玻璃体腔注射Avastin 1.25mg是安全的。
[Abstract]:Objective: to observe the safety of Awa statin Avastin in ocular application through experimental and clinical studies. Methods: rabbit eyes were given different doses of 1.25mg / 0.05ml of 2.5 mg / 0.1ml.5mg / 0.2ml of Avastin and 1.25mgAvastin in anterior chamber. Oct and ERG were performed before and 7 days after injection, and the rabbit eyes were excised by light microscopy and transmission electron microscopy on the 7th day after injection. The ERGb wave amplitudes of retinal thickness measured by Oct were statistically analyzed. Twenty-nine patients with diabetic retinopathy were given intravitreal injection of Avastinl.25mg / 0.05ml. Corneal endothelium was examined before injection, 3 days after injection, 1 week, 1 month and 3 months after injection to observe the cell density, area variation coefficient, area standard deviation and maximum area of corneal endothelium in selected corneal area. ERGG Oct and fundus fluorescein angiography were performed before and after injection to observe the amplitude and peak of ERGb wave and macular edema. The corneal endothelium index data and OCT data were statistically analyzed. Results: after intravitreal and anterior chamber injection, the density of corneal endothelial cells in 5mg group and anterior chamber injection group decreased significantly, and the coefficient of variation of cell area increased significantly in 1.25mg group and 2.5mg group. In the anterior chamber injection group, the corneal endothelial cell density decreased and the area coefficient of variation increased, compared with the other groups, the difference was statistically significant (p 0.05). The retinal thickness measured by OCT in 5mg group after intravitreal injection was significantly thicker than that in other groups (P 0.05), but there was no significant difference in other groups (P 0.05). After vitreous injection, the amplitude of ERGb wave in each experimental group decreased significantly after 7 days, but the amplitude of ERG b wave in the anterior chamber injection group and control group was not significantly decreased compared with the other three experimental groups and control group. The results of optical microscope showed that the corneal endothelial cells in the anterior chamber injection group had irregular morphology, decreased hexagonal structure, more cell loss, longer nucleus and discontinuous nuclear membrane, and the typical hexagonal structure could still be seen. The other group was better than the anterior chamber injection group. The retinal tissue structure of each group was arranged neatly and the structure was intact, and no obvious abnormality was found. The results of transmission electron microscope showed that the cytoplasm of corneal endothelial cells in the anterior chamber injection group was sparse, the endoplasmic reticulum was short and dilated, and the injury of junction was obvious. The other experimental eyes were better than those in the anterior chamber injection group (group .5mg). Most of the optic nerve fibers in the experimental eyes were vacuolated and mitochondria were swollen. There were few synaptic junctions in the normal group, some of them had transmitter vesicles, but the high density plate of the postsynaptic membrane was absent. No obvious abnormality was found in other groups. The results of clinical observation showed that there were no significant changes in the corneal endothelial cells in all the patients, but there was no significant difference in the peak and p0.05 waves of corneal endothelium, and there was no significant difference in the changes between the two groups (P 0.05). Macular edema was alleviated significantly (P 0.05). Retinal neovascularization subsided significantly and leakage decreased significantly. Conclusion: intravitreal injection of Avastin below 5mg has no significant effect on retinal tissue structure and nerve conduction function. However, in 5mg group, the optic nerve fibers were vacuolated and mitochondria swelled, suggesting that the single dose of Avastin injected into the vitreous body was not too large and the interval was not too short, in order to reduce or avoid the toxic side effects of Avastin accumulation on the retina. Clinically, intravitreal injection of Avastin 1.25mg is safe.
【学位授予单位】：山东中医药大学
【学位级别】：硕士
【学位授予年份】：2010
【分类号】：R77

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