兔眼玻璃体腔注射抗血管内皮生长因子单克隆抗体Bevacizumab的毒性观察

目的 观察不同剂量的抗血管内皮生长因子单克隆抗体Bevacizumab玻璃体腔注射后对兔眼角膜、房角、视网膜组织结构和功能的影响。 方法 24只健康新西兰大白兔分成3组，每组兔眼右眼分别注射Bevacizumab 1.25、2.50、5.00 mg；左眼为对照眼，注射相同体积的0.9％生理盐水。注射药物前后裂隙灯显微镜及直接检眼镜检查眼前段和眼底，监测眼压。注药前以及注药后1、4、8周行闪光视网膜电图（ERG）检查。8周时行角膜内皮计数后，摘除眼球行光学显微镜及透射电子显微镜检查。 结果 3组兔眼注射药物前后各时间点眼压、角膜内皮计数、ERG的a、b波振幅差异无统计学意义（P＞0.05）。光学显微镜检查，3组兔 眼角膜、房角、视网膜结构无明显变化。透射电子显微镜检查，视网膜超微结构亦无明显变化。 结论 玻璃体腔内注射1.25～5.00 mg Bevacizumab对正常兔眼组织没有明显毒性。 （中华眼底病杂志，2008，24：189-192）     

兔眼玻璃体腔注射抗血管内皮生长因子单克隆抗体Bevacizumab的视网膜毒性研究

目的 观察不同剂量抗血管内皮生长因子单克隆抗体Bevacizumab兔眼玻璃体腔注射的视网膜毒性作用。 方法 16只新西兰无色素兔的32只眼随机分为药物注射组和对照组，药物注射组又根据玻璃体腔注射药物剂量不同分为A、B、C组，玻璃体腔注射Bevacizumab剂量分别为0.05、0.10、0.25 ml，分别含Bevacizumab 1.25、2.50、6.25 mg。对照组玻璃体腔注射0.9％生理盐水0.10 ml。注药后1、2、4周行视网膜电图（ERG）检查。另外 ，在兔眼玻璃体腔注射Bevacizumab后1、2、4周，每组各摘除2只兔眼，行视网膜组织形态及超 微结构的光学显微镜和透射电子显微镜观察。 结果 兔眼玻璃体腔注射 Bevacizumab后1、2、4周，兔眼ERG各项反应波形均正常，振幅均未出现异常改变（P＞0.05）。光学显微镜下观察 ，药物注射组和对照组视网膜各层组织形态在各时间点均未见异常。透射电子显微镜观察， A、B组与对照组无明显差异；C组视网膜光感受器细胞出现部分线粒体损伤，发生肿胀和积 水变，4周时病变无缓解。 结论 单次兔眼玻璃体腔注射Bevacizumab 1.25 mg或2.50 mg是安全的。 （中华眼底病杂志，2008，24：193-196）     

玻璃体腔重复注射抗血管内皮生长因子单克隆抗体bevacizumab对糖尿病大鼠视网膜的毒性观察

目的 观察玻璃体腔重复注射抗血管内皮生长因子(VEGF)单克隆抗体bevacizumab(商品名Avastin)对糖尿病大鼠视网膜的毒性作用.方法 40只健康成年雄性Sprague-Dawley大鼠随机分为正常组(A组)和糖尿病组,分别为10、30只.糖尿病组采用链脲佐菌霉素(STZ)尾静脉注射方法制作糖尿病动物模型.随机选取10只作为糖尿病视网膜病变(DR)组(B组),不作任何处理;其余20只大鼠左眼为实验组(C组),玻璃体腔注射25 mg/ml的bevacizumab 3 μ1,共注射3次,每次间隔10 d;右眼为实验对照组(D组),不给予任何处理.末次注射后20 d,采用闪光视网膜电图(F-ERG)对各组大鼠行视网膜功能检测;溴化乙锭(EB)染色视网膜铺片,荧光显微镜观察各组大鼠视网膜血管变化情况;苏木精-伊红(HE)染色,光学显微镜观察大鼠视网膜形态学变化;免疫组织化学染色法观察大鼠视网膜各层Thy-1及VEGF阳性表达情况.结果 F-ERG检测显示,A、B、C、D 4组暗适应a、b波潜伏期,暗适应b波振幅及振荡电位(Ops)总振幅比较,差异均有统计学意义(F=33.165,36.162,19.955,23.243;P值均=0.000);A、B、C、D4组暗适应a波振幅比较,差异无统计学意义(F=0.097,P=0.961).荧光显微镜观察发现,A组大鼠视网膜血管走行良好,B组大鼠视网膜血管走行纡曲、扩张,C组大鼠视网膜血管走形规则、变细,D组大鼠视网膜可见微血管瘤.光学显微镜观察发现,A组大鼠视网膜层次结构整齐分明,B组大鼠视网膜各层细胞结构排列紊乱,C组大鼠视网膜各层细胞排列整齐,D组大鼠视网膜各层细胞排列不整齐.免疫组织化学染色发现,Thy-1阳性表达主要位于神经节细胞层(GCL),极少数位于内丛状层、内核层.VEGF阳性表达主要定位于GCL,少量位于神经纤维层、内核层及视网膜色素上皮层.结论 玻璃体腔重复注射bevacizumab对糖尿病大鼠视网膜有一定毒性作用.

Abstract：

Objective To observe the retinal toxicity of repeated intravitreal injection with bevacizumab(Avastin)in diabetic rats.Methods Forty male Sprague Dawley(SD)rats were randomly divided into normal group(Group A,10 rats)and diabetes mellitus group(30 rats).The rats in diabetes mellitus group were induced with streptozotocin injection for diabetic retinopathy model.And then randomly divided into diabetic retinopathy(DR)group(Group B,10 rats),the rats were not intervened;the left eyes of the other 20 rats were intravitreal injected with bevaeizumab 3 μ1(25 mg/m1)for 3 times as experimental group(Group C);the right eyes of the 20 rats were not intervened as experimental control group(Group D),20 days after last intravitreal injection,retinal function was measured by Flicker Electroretinogram (F-ERG);retinal vascular pattern was determined by fluorescence microscopy of ethidium bromide(EB)stained retinal flat mounts;retinal morphological changes were determined by light microscope on hematoxylin-eosin (HE) stained sections;Thy-1 and VEGF expression was measured by immunohistochemistry staining.Results F-ERG showed that-the differences of a-and b-waves-the b-wave amplitude and the Ops-wave amplitude in the implicit time between group A,B,C and D were significant (F=33.165,36.162,19.955,23.243;P=0.000);the differences of a-wave amplitude between group A,B,C and D was not significant(F=0.097,P=0v961).Retinal blood vessel pattern was normalin Group A;retinal vascular vessels were tortuous and irregularly expanded in Group B:retinal vascular vessels of Group C were regular and thinner than Group A;microaneurysm were showed in Group D.Light microscope displayed that the layers of the rat retina of Group A were regular,the retinal architectures of Group B were irregular,the retinal layers were regular in Group C,the retinal layers were irregular in Group D.Immunohistochemistry staining discovered that Thy-1 and VEGF were mainly expressed in ganglion cell layer(GCL).Conclusion Repeated intravitreal injection of bevacizumab iS toxic tO retina of diabetes mellitus rats.     

玻璃体腔重复注射抗血管内皮生长因子单克隆抗体bevacizumab对糖尿病大鼠视网膜的毒性观察

Objective To observe the retinal toxicity of repeated intravitreal injection with bevacizumab(Avastin)in diabetic rats.Methods Forty male Sprague Dawley(SD)rats were randomly divided into normal group(Group A,10 rats)and diabetes mellitus group(30 rats).The rats in diabetes mellitus group were induced with streptozotocin injection for diabetic retinopathy model.And then randomly divided into diabetic retinopathy(DR)group(Group B,10 rats),the rats were not intervened;the left eyes of the other 20 rats were intravitreal injected with bevaeizumab 3 μ1(25 mg/m1)for 3 times as experimental group(Group C);the right eyes of the 20 rats were not intervened as experimental control group(Group D),20 days after last intravitreal injection,retinal function was measured by Flicker Electroretinogram (F-ERG);retinal vascular pattern was determined by fluorescence microscopy of ethidium bromide(EB)stained retinal flat mounts;retinal morphological changes were determined by light microscope on hematoxylin-eosin (HE) stained sections;Thy-1 and VEGF expression was measured by immunohistochemistry staining.Results F-ERG showed that-the differences of a-and b-waves-the b-wave amplitude and the Ops-wave amplitude in the implicit time between group A,B,C and D were significant (F=33.165,36.162,19.955,23.243;P=0.000);the differences of a-wave amplitude between group A,B,C and D was not significant(F=0.097,P=0v961).Retinal blood vessel pattern was normalin Group A;retinal vascular vessels were tortuous and irregularly expanded in Group B:retinal vascular vessels of Group C were regular and thinner than Group A;microaneurysm were showed in Group D.Light microscope displayed that the layers of the rat retina of Group A were regular,the retinal architectures of Group B were irregular,the retinal layers were regular in Group C,the retinal layers were irregular in Group D.Immunohistochemistry staining discovered that Thy-1 and VEGF were mainly expressed in ganglion cell layer(GCL).Conclusion Repeated intravitreal injection of bevacizumab iS toxic tO retina of diabetes mellitus rats.     

玻璃体腔重复注射抗血管内皮生长因子单克隆抗体bevacizumab对糖尿病大鼠视网膜的毒性观察

Objective To observe the retinal toxicity of repeated intravitreal injection with bevacizumab(Avastin)in diabetic rats.Methods Forty male Sprague Dawley(SD)rats were randomly divided into normal group(Group A,10 rats)and diabetes mellitus group(30 rats).The rats in diabetes mellitus group were induced with streptozotocin injection for diabetic retinopathy model.And then randomly divided into diabetic retinopathy(DR)group(Group B,10 rats),the rats were not intervened;the left eyes of the other 20 rats were intravitreal injected with bevaeizumab 3 μ1(25 mg/m1)for 3 times as experimental group(Group C);the right eyes of the 20 rats were not intervened as experimental control group(Group D),20 days after last intravitreal injection,retinal function was measured by Flicker Electroretinogram (F-ERG);retinal vascular pattern was determined by fluorescence microscopy of ethidium bromide(EB)stained retinal flat mounts;retinal morphological changes were determined by light microscope on hematoxylin-eosin (HE) stained sections;Thy-1 and VEGF expression was measured by immunohistochemistry staining.Results F-ERG showed that-the differences of a-and b-waves-the b-wave amplitude and the Ops-wave amplitude in the implicit time between group A,B,C and D were significant (F=33.165,36.162,19.955,23.243;P=0.000);the differences of a-wave amplitude between group A,B,C and D was not significant(F=0.097,P=0v961).Retinal blood vessel pattern was normalin Group A;retinal vascular vessels were tortuous and irregularly expanded in Group B:retinal vascular vessels of Group C were regular and thinner than Group A;microaneurysm were showed in Group D.Light microscope displayed that the layers of the rat retina of Group A were regular,the retinal architectures of Group B were irregular,the retinal layers were regular in Group C,the retinal layers were irregular in Group D.Immunohistochemistry staining discovered that Thy-1 and VEGF were mainly expressed in ganglion cell layer(GCL).Conclusion Repeated intravitreal injection of bevacizumab iS toxic tO retina of diabetes mellitus rats.     

玻璃体腔注射抗血管内皮生长因子药物治疗早产儿视网膜病变的研究现状

与冷冻及激光光凝治疗比较,玻璃体腔注射抗血管内皮生长因子（VEGF）药物治疗早产儿视网膜病变（ROP）可减少对视网膜解剖结构的破坏,促使周边视网膜继续血管化,降低视网膜脱离、视野缺损及高度近视的发生。在ROP 1区病变及屈光间质混浊等激光光凝难以施行的患眼中有其独特优势。选择合理的药物和剂量,掌握最佳治疗时间,注意避免局部并发症及全身安全性等方面的问题,对进一步提高玻璃体腔注射抗VEGF药物治疗ROP的应用水平具有重要意义。     

玻璃体腔重复注射抗血管内皮生长因子单克隆抗体bevacizumab对眼压的影响

玻璃体腔注射抗血管内皮生长因子单克隆抗体bevacizumab(商品名Avastin)不仅是治疗视网膜、脉络膜新生血管(CNV)相关疾病的有效方法之一~([1,2]),而且对视网膜静脉阻塞(RVO)及糖尿病视网膜病变(DR)伴发的黄斑水肿(ME)也有明显的治疗作用~([1,2]).     

抗血管内皮生长因子单克隆抗体bevacizumab抑制大鼠脉络膜新生血管

目的　观察玻璃体腔注射抗血管内皮生长因子（VEGF）单克隆抗体bevacizumab（商品名Avastin）抑制激光诱导的实验性脉络膜新生血管（CNV）的效果及特点。方法　12只雄性棕色挪威（BN）大鼠平均分为bevacizumab组和对照组,每组6只。每一只大鼠随机选取1只眼为实验眼,采用半导体激光围绕其视盘激光光凝8点后,bevacizumab组和对照组玻璃体腔立即分别给予2.00 μl bevacizumab和乳酸林格注射液。激光光凝后7、14、21 d两组行荧光素眼底血管造影（FFA）和吲哚青绿血管造影（ICGA）动态观察CNV的形态及渗漏情况。激光光凝后21 d摘除实验眼作石蜡切片行苏木精-伊红染色,比较两组CNV的高度,同时行VEGF免疫组织化学染色,观察CNV斑块中VEGF的表达情况。结果　激光光凝后7 d,ICGA检查结果显示,bevacizumab组和对照组均有CNV生成。FFA检查结果显示,bevacizumab组的渗漏强度始终比对照组弱,但bevacizumab组渗漏强度随时间推移逐渐增强。bevacizumab组CNV平均厚度比对照组低。免疫组织化学检查结果显示,bevacizumab组VEGF表达阴性。结论　激光光凝后立即玻璃体腔注射2.00 μl bevacizumab可以降低CNV厚度并抑制其渗漏,但不能阻止CNV的生成,抑制CNV渗漏的效果不能长时间保持。     

玻璃体腔注射抗血管内皮生长因子单克隆抗体Bevacizumab的不良反应三例

抗血管内皮生长因子(VEGF)单克隆抗体Bevacizumab应用于眼科治疗脉络膜新生血管(CNV)、视网膜及虹膜新生血管均显示出良好疗效[1],但是其不良反应报告不多[2].我们从2007年7月开始使用Bevacizumab进行玻璃体腔注射,临床工作中遇到一些可能与药物有关的不良反应或是难以解释的现象,现报道如下.     

玻璃体腔注射抗血管内皮生长因子单克隆抗体bevacizumab后视功能的变化

玻璃体腔注射抗血管内皮生长因子单克隆抗体bevacizumab(商品名：Avastin)后,患眼功能改善或稳定,疗效和安全性良好。其中,视功能变化表现为视力显著提高,对比敏感度稳定不变或明显改善,视网膜电图（ERG）未出现显著改变,多焦视网膜电图（mfERG）反应稳定或改善,眼电图(EOG)和视觉诱发电位(VEP)与治疗前相比无明显改变,视野保持稳定或轻微改善,色觉保持不变。但重复注射、bevacizumab联合其它治疗后的视功能变化以及长期疗效及安全性仍需更加充分的评估依据进行大样本长时间随访研究。     

4期早产儿视网膜病变玻璃体视网膜手术前玻璃体腔注射抗血管内皮生长因子单克隆抗体bevacizumab的安全性和有效性

目的 观察4期早产儿视网膜病变（ROP）玻璃体视网膜手术前玻璃体腔注射抗 血管内皮生长因子单克隆抗体bevacizumab（商品名Avastin）的安全性和有效性。 方法 回顾性病例研究。临床确诊为4期ROP并接受玻璃体腔注射bevacizumab治疗的8例患儿16只眼纳入本研究。所有患儿于表面麻醉下给予双眼玻璃体腔注射bevacizumab 0.625 mg。注药后第5天,采用间接检眼镜和二代广角数码视网膜成像系统（RetCam Ⅱ）观察并记录患眼眼底情况,评估血管活动性;观察有无与玻璃体腔注射bevacizumab相关的不良反应。所有患儿在全身麻醉状态下行玻璃体切割手术;其中,14只眼行保留晶状体的玻璃体切割手术,2只眼行晶状体切除联合玻璃体切割手术。玻璃体切割手术后3个月,观察所有患眼视网膜复位情况以及行保留晶状体玻璃体切割手术的14只眼的晶状体透明度。结果注药后第5天,所有患眼视网膜动脉纡曲及静脉扩张程度明显减轻,新生血管膜变白并有不同程度萎缩。无1例患儿发生眼内炎、眼内压增高、眼内新鲜出血、胃肠道反应等与玻璃体腔注射bevacizumab相关的不良反应。玻璃体切割手术后3个月,视网膜完全复位15只眼,占93.75%;视网膜部分复位1只眼,占6.25%。所有保留的晶状体都保持透明。结论4期ROP患儿玻璃体视网膜手术前行玻璃体腔注射bevacizumab能安全、有效地减轻ROP血管活动性。     

玻璃体腔注射乳酸环丙沙星对视网膜 影响的研究

目的探讨玻璃体腔注射乳酸环丙沙星治疗方法对视网膜组织的安全性。方法24只兔随机分为4组，每组6只。玻璃体腔内分别注入0.1 ml不同浓度的乳酸环丙沙星，浓度分别为：2 500 、5 000、10 000 μg/ml；对照组注射生理盐水0.1 ml。手术后观察眼底表现，分别行光学显微镜、透射电子显微镜等组织学检查和视网膜电图（ERG）视网膜功能检查。结果250、500 μg组光学显微镜检查结果未见异常，超微结构大致正常；1 000 μg 组光学显微镜下可见视网膜内外核层排列不规则，神经节细胞水肿变性或脱失，透射电子显微镜下可见超微结构改变。视网膜功能检查显示，各组ERG的a～b波波幅注药前后无明显差别。结论玻璃体腔注射国产乳酸环丙沙星安全、抗菌谱广，500 μg以下是较为安全的眼内应用剂量。(中华眼底病杂志,2005,21:180-182)     

抗肿瘤坏死因子-α单克隆抗体治疗实验性自身免疫性葡萄膜视网膜炎的研究

目的 观察抗肿瘤坏死因子-α单克隆抗体（TNF-α MCAb）对于实验性自身免疫性葡萄膜视网膜炎（EAU）的治疗作用。方法 合成光感受器间维生素A类结合蛋白（IRBP）R16多肽片段，联合免疫佐剂诱导EAU动物模型。按照注射次数不同将大鼠分为2组，分别于IRBP R16免疫后的第6天和第4、6、8天自大鼠尾静脉注入TNF-α MCAb，裂隙灯显微镜观察其眼部临床表现，同时设未治疗组大鼠作为对照。于IRBP R16免疫后第13天测量迟发型超敏反应（DTH），并于第14天处死大鼠，取眼球行组织病理检查。应用酶联免疫吸附试验（ELISA）检测抗体注射后14 d 时大鼠血清中Th1类细胞因子γ-干扰素（IFN-γ）、Th2类细胞因子白细胞介素-4（IL-4）水平以及房水中IFN-γ水平。测量引流淋巴结细胞的抗原特异性淋巴细胞增生反应。结果 TNF-αMCAb治疗组大鼠的眼部炎症较未治疗组明显减轻，病理分级下降；房水和血清中IFN-γ水平降低，血清中IL-4增高；DTH反应下降；引流淋巴结细胞对IRBP R16多肽刺激的增生反应下降，差异均有统计学意义（P＜0.01）。与单次注射相比，3次注射的治疗效果更显著（P＜0.05）。结论 TNF-αMCAb能够有效减轻EAU大鼠眼部的炎症反应和特异性细胞免疫反应，改变Th1/Th2细胞因子平衡；多次应用作用更显著。     

兔眼玻璃体内注射足叶乙苷对视网膜神经节细胞的毒性作用

目的 观察兔眼玻璃体内注射足叶乙苷对视网膜神经节细胞(RGC)的毒性作用.方法 采用随机数字法将24只健康新两兰大白兔随机分为正常组和0.0、1.5、15.0、150.0、375.0、750.0、1500.0μg 足叶乙苷组,每组3只兔,每只兔双眼用于实验.正常组不作任何处理,其余各组兔眼玻璃体内分别注射0.0、1.5、15.0、150.0、375.0、750.0、1500.0 μg足叶乙苷.注射后12 d,空气栓塞法处死所有兔.取眼球作常规病理检查,苏木精-伊红(HE)染色,光学显微镜观察视网膜形态变化、计数视网膜颞侧距视盘颞侧缘1 mm处400倍视野的RGC数量.取距视盘1 mm处颞上方1 mmX 1 mm大小视网膜行常规透射电子显微镜检查,观察视网膜超微结构变化情况.结果 光学显微镜和透射电子显微镜观察发现,正常组兔眼视网膜结构清晰规整,RGC呈球形或类球形;0.0、1.5、15.0、150.0μg足叶乙苷组兔眼视网膜各层结构与正常组相似;375.0、750.0、1500.0μg足叶乙苷组兔眼视网膜明显变薄,层次结构紊乱.正常组、0.0、1.5、15.0、150.0、375.0、750.0、1500.0μg足叶乙苷组兔眼RGC计数分别为(61.66±3.72)、(61.83±4.59)、(60.00±7.07)、(62.00±4.43)、(62.67±3.98)、(7.33±1.37)、0.00、0.00个,8组间差异有统计学意义(F=145.04,P=0.00).0.0、1.5、15.0、150.0μg足叶乙苷组兔眼RGC计数较正常组无明显变化,差异无统计学意义(F=0.244,P＞0.05);375.0μg足叶乙昔组兔眼RGC计数较正常组、0.0、1.5、15.0、150-0 μg 足叶乙昔组明显降低,差异有统计学意义(F=145.04,P＜0.05).结论 足叶乙苷对兔眼RGC有一定毒性作用,且该作用呈剂量依赖性.

Abstract：

Objective To observe the toxic effects of intravitreal injection of etoposide on retinal ganglion cells (RGC) in rabbit eyes. Methods Twenty-four healthy rabbits were divided into 8 groups randomly, including one normal group without any treatment, and 7 experimental groups with intravitreal injection of different dosages of etoposide (0.0, 1.5, 15.0, 150.0, 375.0, 750.0, 1500.0 μg). Twelve days after the injection, the animals were killed by air embolism, and the eyeballs were prepared for routine pathological examination with hematoxylin-eosin staining and transmission electron microscopy. Results Four experimental groups (0.0, 1.5, 15.0, 150.0 μg etoposide) had normal retinal structure and normal shape of ganglion cells while other 3 experimental groups with higher dosage of etoposide (375.0, 750.0 and 1500.0 μg) showed thinner and disorganized retina. The number of RGC of the normal group and 0.0, 1.5,15.0, 150.0, 375.0, 750.0, 1500.0 μg groups were 61.6±63.72, 61.83±4.59, 60.00±7.07, 62.00±4.43, 62.67±3.98, 7.33±1.37, 0.00 and 0.00 per 400 X visual field, with statistical difference among groups (F=145.04, P = 0.00). There was no statistical difference between the normal group and 0.0,1.5, 15.0, 150.0 μg groups (F=0.244,P＞0.05). The number of RGC of 375.0 μg group was decreased obviously compared with normal group and 0.0, 1.5, 15.0, 150.0 μg groups with statistical difference (F=145.04, P＜0.05). Conclusion Etoposide has a dosage-dependent toxicity on rabbit RGCs.     

超声爆破微泡联合抗血管内皮生长因子单克隆抗体bevacizumab治疗激光诱导的兔眼脉络膜新生血管

目的　观察超声爆破微泡联合抗血管内皮生长因子（VEGF）单克隆抗体bevacizumab（商品名Avastin）对兔脉络膜新生血管（CNV）的治疗效果。方法 30只有色家兔60只眼通过氩绿激光视网膜激光光凝的方法建立CNV模型。激光光凝后21 d行荧光素眼底血管造影（FFA）,并于造影6~8 h后任意选择3只兔处死,摘取眼球,行苏木精-伊红（HE）染色组织学检查,判断CNV建模是否成功。于激光光凝后21 d,将27只CNV模型兔随机分成空白对照组、bevacizumb组及超声微泡+bevacizumb组,每组各9只兔。空白对照组不做任何处理,bevacizumab组玻璃体腔注射bevacizumab,超声微泡+bevacizumab组玻璃体腔注射超声微泡+bevacizumab。分别于处理后7、14、28 d对各组兔行FFA检查,观察CNV抑制情况并每组各处死3只兔取双眼行免疫荧光及蛋白质免疫印迹（Western blot）法检测视网膜、脉络膜VEGF蛋白的表达。以注射bevacizumab后28 d为疗效判断时间点,以FFA及组织蛋白学检测对比结果为疗效判断标准。结果　激光光凝后21 d组织病理学和FFA检查结果显示,CNV向视网膜内层增生,激光光凝区荧光渗漏明显。分组处理后28 d,FFA检查结果显示空白对照组有明显荧光渗漏,bevacizumab组荧光渗漏平均强度与空白对照组比较,差异有统计学意义（t=16.2952,P＜0.05）;超声微泡+bevacizumab组与bevacizumab组相比,差异有统计学意义（t=4.7955,P＜0.05）。各组荧光渗漏强度随时间变化均呈下降趋势。组织免疫荧光及Western blot检测结果显示,bevacizumab组VEGF蛋白表达与空白组和对照组相比,差异有统计学意义（t=7.0327,9.2596;P＜0.05）;超声微泡+bevacizumab组VEGF蛋白表达与bevacizumab组相比,差异有统计学意义（t=2.9724,17.1937;P＜0.05）。结论　超声微泡造影剂联合bevacizumab注射能够通过抑制VEGF的表达来增强CNV的治疗效果。     

玻璃体腔注射bevacizumab治疗年龄相关性黄斑变性的初步临床观察

目的初步探讨玻璃体腔内注射bevacizumab（Avastin）治疗湿性年龄相关性黄斑变性（ARMD）的临床效果。方法采用单中心非随机对照临床研究方法。收集经荧光素眼底血管造影检查（FFA）、相干光断层成像术（OCT）确诊存在黄斑中心凹下脉络膜新生血管（CNV）的ARMD患者5例,患眼最佳矫正视力均〈0．1,无全身和局部手术禁忌证。患眼行bevacizumab玻璃体腔内注射术,用量为1．5mg（0．06ml）,记录手术前、后患眼的视力、眼压、FFA和OCT的检查结果。术后随访时间4～6个月。结果全部患者均未出现眼内和全身不良反应。1例患者术后第3天出现一过性眼压升高,局部给予降眼压药物治疗后症状得到控制。1例患者术后1周视力由0．1上升至0．4;4例患者术后2个月视力提高1—6行,其中3例于术后4—6个月时视力保持稳定,1例视力下降。3例患者术后1个月黄斑水肿明显改善,黄斑中心凹视网膜厚度较术前减少5．9％～41．4％,3例患者FFA显示CNV渗漏较术前减轻。结论玻璃体腔内注射bevacizumab治疗湿性ARMD安全,副作用少,可改善患者的视功能,减轻黄斑水肿,减少CNV渗漏,有望成为药物治疗ARMD的新方法,但尚需进行多中心大样本临床随机对照研究。