本文選題：Avastin + 角膜　； 參考：《山東中醫(yī)藥大學》2010年碩士論文

【摘要】：目的：通過實驗研究和臨床研究,觀察阿瓦斯汀(Avastin)在眼部應用的安全性。 方法：給予兔眼玻璃體腔中注射不同劑量(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天分別行角膜內(nèi)皮鏡、OCT和ERG檢查,并在注射后7天摘除兔眼行光鏡和透射電鏡檢查,對角膜內(nèi)皮細胞密度、面積變異系數(shù)、OCT測得的視網(wǎng)膜厚度、ERGb波振幅數(shù)據(jù)進行統(tǒng)計分析。在臨床上選取29例(30眼)糖尿病視網(wǎng)膜病變患者,給予玻璃體腔注射Avastinl.25mg/0.05ml。注射前、注射后3天、1周、1月、3月分別對其進行角膜內(nèi)皮鏡檢查,以觀察所選角膜區(qū)域的角膜內(nèi)皮的細胞密度、面積變異系數(shù)、面積標準差、最大面積、最小面積等指標的變化；注射前和注射后1月行ERG、OCT和眼底熒光造影檢查,以觀察ERGb波振幅和峰時及視網(wǎng)膜黃斑部水腫的變化。對角膜內(nèi)皮各項指標數(shù)據(jù)、ERG數(shù)據(jù)和OCT數(shù)據(jù)進行統(tǒng)計分析。 結(jié)果：兔眼玻璃體腔及前房注藥后,玻璃體腔注射5mg組和前房注射組角膜內(nèi)皮細胞密度明顯減小,細胞面積變異系數(shù)明顯增大；1.25mg組和2.5mg組無明顯變化。前房注射組角膜內(nèi)皮細胞密度減少、面積變異系數(shù)增大與其他組相比差別有統(tǒng)計學意義(p0.05)。兔眼玻璃體腔注藥后5mg組實驗眼OCT測得的視網(wǎng)膜厚度明顯變厚,差別有統(tǒng)計學意義(p0.05)；其余各組無明顯變化,差別無統(tǒng)計學意義(p0.05)。兔眼玻璃體腔注藥后各實驗組ERGb波振幅在7天后下降明顯,前房注射組和對照組變化不明顯。5mg組實驗眼ERG b波振幅下降明顯低于其它三實驗組和對照組。光學顯微鏡結(jié)果顯示,前房注射組角膜內(nèi)皮細胞形態(tài)不規(guī)則,六邊形結(jié)構(gòu)減少,細胞丟失較多,細胞核變長,核膜不連續(xù),仍可見典型的六邊形結(jié)構(gòu)。其他組好于前房注射組。各組視網(wǎng)膜組織結(jié)構(gòu)各層排列整齊,結(jié)構(gòu)完整,均未見明顯異常。透射電鏡結(jié)果顯示,前房注射組實驗眼角膜內(nèi)皮細胞胞質(zhì)中細胞器稀疏,可見內(nèi)質(zhì)網(wǎng)短小并擴張,連接損傷明顯。其他組實驗眼均好于前房注射組。5mg組實驗眼大部分視神經(jīng)纖維的橫斷面空泡化,線粒體腫脹；較正常的突觸連接結(jié)構(gòu)很少,有的雖然有遞質(zhì)小泡,但突觸后膜高密度板缺失,其他組未見明顯異常。臨床觀察結(jié)果顯示,所有患者角膜內(nèi)皮細胞各項檢測指標無明顯改變,差別均無統(tǒng)計學意義(p0.05)。ERGb波和峰時無明顯改變,差別無統(tǒng)計學意義(p0.05)。黃斑部水腫明顯減輕,差別有統(tǒng)計學意義(p0.05)。視網(wǎng)膜新生血管顯著消退,滲漏明顯減少。 結(jié)論：玻璃體腔注射5mg以下Avastin在短期內(nèi)對動物視網(wǎng)膜組織結(jié)構(gòu)和神經(jīng)傳導功能無顯著影響。但是5mg組出現(xiàn)了視神經(jīng)纖維的橫斷面空泡化,線粒體的腫脹,提示玻璃體腔注射Avastin單次劑量不易過大,間隔時間不易過短,以減少或避免Avastin積累對視網(wǎng)膜產(chǎn)生的毒副作用。臨床上玻璃體腔注射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.
【學位授予單位】：山東中醫(yī)藥大學
【學位級別】：碩士
【學位授予年份】：2010
【分類號】：R77

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