玻璃体腔注射抗血管内皮生长因子单克隆抗体ranibizumab辅助微创玻璃体视网膜手术治疗严重增生型糖尿病视网膜病变的临床观察

目的 观察玻璃体腔注射抗血管内皮生长因子单克隆抗体ranibizumab（IVR）辅助微创玻璃体视网膜手术（VRS）治疗严重增生型糖尿病视网膜病变（PDR）的临床效果。方法 回顾性非随机临床对照研究。临床确诊为严重PDR的60例患者70只眼纳入研究。依据手术前是否行IVR治疗将患者分为IVR组和对照组。IVR组31例35只眼,对照组29例35只眼。IVR组于手术前3～4 d玻璃体腔注射10 mg/ml的ranibizumab 0.05 ml（含ranibizumab 0.5 mg）,然后行23G微创VRS。对照组直接行23G微创VRS。手术后随访3~12个月,平均随访时间（4.5±1.8）个月。对比分析两组患者最小分辨角对数（logMAR）最佳矫正视力（BCVA）、眼压、黄斑中心凹视网膜厚度（CRT）和视网膜复位及手术后并发症的发生情况。结果 IVR组患者均未发生与注射及药物相关的局部及全身不良反应。手术后1周,1、3个月,IVR组玻璃体积血（VH）发生率分别为8.6%、0.0%、0.0%,对照组VH发生率分别为28.6%、17.1%、8.6%。两组手术后各时间点VH发生率比较,手术后1周及1个月之间差异有统计学意义（χ²=4.63、4.56,P＜0.05）,手术后3个月之间差异无统计学意义（χ²=0.24,P＞0.05）。IVR组、对照组手术后平均logMAR BCVA分别为0.81±0.40、1.05±0.42,均较手术前提高。IVR组、对照组手术前后平均logMAR BCVA比较,差异有统计学意义（t=12.78、4.39,P＜0.05）。IVR组手术后平均logMAR BCVA较对照组提高,两组手术后平均logMAR BCVA比较,差异有统计学意义（t=-2.36,P＜0.05）。IVR组、对照组手术后平均CRT分别为（297.6±79.8）、（347.6±85.0） μm,两组平均CRT比较,差异有统计学意义（t=-2.53,P＜0.05）。IVR组、对照组手术后视网膜复位率分别为97.1%、94.3%,两组视网膜复位率比较,差异无统计学意义（χ²=0.35,P＞0.05）。IVR组、对照组一过性高眼压发生率分别为14.3%、34.3%,两组间一过性高眼压发生率比较,差异有统计学意义（χ²=4.79,P＜0.05）。IVR组、对照组视网膜前膜、新生血管性青光眼等并发症发生情况比较,差异也无统计学意义（χ²=0.97、0.51,P＞0.05）。结论 IVR辅助23G微创VRS治疗严重PDR能提高患者视力,降低手术后VH发生率,减小CRT。     

手术前玻璃体腔注射抗血管内皮生长因子单克隆抗体bevacizumab预防增生型糖尿病视网膜病变玻璃体切割手术后玻璃体积血的meta分析

目的 系统评价手术前玻璃体腔注射抗血管内皮生长因子单克隆抗体bevacizumab(IVB)预防增生型糖尿病视网膜病变(PDR)玻璃体切割手术后玻璃体积血(VH)的有效性和安全性.方法 随机对照试验(RCT)的Meta分析.计算机检索Medline、Embase、Cochrane图书馆、中国生物医学文献数据库和中国期刊全文数据库,并辅以手工检索相关书籍、期刊和会议论文及其参考文献.按照纳入和排除标准筛选评价手术前IVB预防PDR玻璃体切割手术后VH的RCT.对纳入的RCT进行数据提取后,采用Jadad评分量表进行质量评价.分析指标包括手术后VH发生率、最佳矫正视力(BCVA)、视网膜复位率和并发症发生率.统计学分析使用Stata/SE 11.2软件,连续变量采用加权平均差(WMD)及其95％可信区间(CI)表示,非连续变量采用比值比(OR)及其95％ CI表示,结果 共纳入7项符合标准的RCT,其中IVB组170例,对照组161例.纳入的RCT Jadad评分仅1项为5分,1项为3分,其余5项均为1分.手术后≤4周和手术后＞4周,IVB组VH发生率低于对照组,差异均具有统计学意义(OR=3.28,95％ CI:1.58～6.82,P=0.00;OR=2.51,95％ CI:1.21～5.22,P=0.01).手术后3个月和手术后6个月,IVB组VH发生率与对照组比较,差异均无统计学意义(OR=2.52,95％ CI:0.74～8.57,P=0.14;OR=3.26,95％ CI:0.50～21.45,P=0.22).IVB组手术后BCVA优于对照组,差异具有统计学意义(WMD=0.29,95％ CI:0.13～0.44,P=0.00).IVB组手术后视网膜复位率与对照组比较,差异无统计学意义(OR=0.39,95％ CI:0.10～1.59,P=0.19).IVB组手术后视网膜再脱离发生率与对照组比较,差异无统计学意义(OR=2.36,95％ CI:0.74～7.56,P=0.15);IVB组手术后新生血管性青光眼发生率与对照组比较,差异无统计学意义(OR=1.47,95％ CI:0.28～7.71,P=0.65).结论 手术前IVB能够有效预防PDR玻璃体切割手术后VH,且相对较为安全,但仍需高质最、多中心、大样本、长期随访的RCT进一步研究证实.     

抗血管内皮生长因子单克隆抗体bevacizumab玻璃体腔注射治疗增生型糖尿病视网膜病变的研究现状

抗血管内皮生长因子单克隆抗体bevacizumab(商品名Avastin)玻璃体腔注射(IVB)能减少增生型糖尿病视网膜病变(PDR)患者视网膜血管渗出性并发症、阻止视网膜新生血管的发展、减少玻璃体积血、减少黄斑水肿导致的视力减退.全视网膜激光光凝术以及玻璃体切割手术联合IVB提高了PDR的治疗效果,降低了治疗风险和并发症.但bevacizumab以及IVB本身也存在一些不良反应或副作用需要规避;针对不同病变情况的最佳有效剂量和治疗时机也值得进一步探索.     

玻璃体腔单次注射抗血管内皮生长因子单克隆抗体Bevacizumab治疗糖尿病性黄斑水肿

目的 观察玻璃体腔单次注射抗血管内皮生长因子单克隆抗体Bevacizumab治疗糖尿病性黄斑水肿（DME）的临床疗效和安全性。 方法 前瞻性非随机对照临床研究，共18例眼科常规检查以及荧光素眼底血管造影（FFA）和光相干断层扫描（OCT）检查确诊的DME患者的18只患眼纳入观察。患者年龄34～75岁，平均年龄（54±11）岁，无全身及局部手术禁忌症。治疗前平均logMAR最佳矫正视力(BCVA)为1.023±0.45，黄斑中心凹视网膜厚度486 μm。患眼玻璃体腔注射Bevacizumab 1.5 mg (0.06 ml)，治疗后随访观察12 ～20周，平均随访观察时间（16±4）周。对比观察治疗前后视力、眼压、OCT及FFA改变。 结果 18例患者治疗后1、4、12周的平均logMAR BCVA分别提高至0.864±0.48（P=0.001）、0.739 ±0.51（P=0.003）、0.792±0.50(P=0.015)，与治疗前比较，差异均有统计意义。治疗后12周，16只眼视力稳定或提高，占88.9％。其中，10只眼logMAR视力提高2行或以上，占55.6％；2只眼视力下降。OCT检查黄斑中心凹视网膜厚度，治疗后4周下降至413 μm，治疗后12周下降到383 μm，与治疗前比较，差异均有统计学意义 （P=0.002，P=0.001）。治疗后12周，黄斑水肿改善者13只眼，占72.2%。所有患者均未出现眼内或全身不良反应。 结论 玻璃体腔注射Bevacizumab治疗DME能明显改善患者视功能，减轻黄斑水肿，副作用少；但尚需进一步大样本、多中心的临床随机对照研究。 (中华眼底病杂志,2008,24:172-175)     

23G和25G+玻璃体切割手术治疗增生型糖尿病视网膜病变的疗效对比观察

目的 对比观察23G和25G+玻璃体切割手术治疗增生型糖尿病视网膜病变(PDR)的临床效果。方法 前瞻性随机对照研究。行玻璃体切割手术治疗的PDR患者57例75只眼纳入研究。所有患者均行视力、眼压、前置镜、眼B型超声等检查。采用随机数字表法将患者分为23G手术组和25G+手术组,前者30例39只眼,后者27例36只眼。分别行23G玻璃体切割手术和25G+玻璃体切割手术。记录手术时间,并观察手术中医源性损伤的发生情况。23G手术组、25G+手术组手术后平均随访时间分别为10.0、8.5个月。以手术后3个月为疗效判定时间点,观察视力、眼压及并发症的发生情况。结果 23G手术组、25G+手术组平均手术时间分别为（53.35±7.42）、（49.16±5.17） min,两组平均手术时间比较,差异有统计学意义（t=4.37,P＜0.05）。23G手术组、25G+手术组手术中发生医源性损伤者分别为11、5只眼,两组手术中发生医源性损伤的眼数比较,差异有统计学意义（χ²=4.93,P＜0.05）。23G手术组、25G+手术组手术后视力均较手术前明显提高,两组手术前后视力比较,差异均有统计学意义（χ²=16.81、18.29,P＜0.05）。两组手术后视力≥0.05的眼数比较,差异无统计学意义（χ²=0.13,P＞0.05）。23G手术组、25G+手术组发生早期低眼压分别为7、3只眼,两组发生早期低眼压的眼数比较,差异有统计学意义（χ²=5.67,P＜0.05）。结论 与23G玻璃体切割手术比较,25G+玻璃体切割手术治疗PDR可缩短手术时间,减少手术中医源性损伤的发生,降低手术后早期低眼压发生率。     

玻璃体腔注射抗血管内皮生长因子单克隆抗体bevacizumab对增生型糖尿病视网膜病变纤维血管膜中整合素链接激酶表达的影响

目的 观察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)对增生型糖尿病视网膜病变(PDR)纤维血管膜中整合素链接激酶(ILK)表达及视网膜血管内皮细胞数量的影响.方法 玻璃体切割手术中取出的24例PDR患者的视网膜前纤维血管膜,其中12例患者手术前1周玻璃体腔单次注射bevaei...     

增生型糖尿病视网膜病变玻璃体切割手术前后生存质量比较

玻璃体视网膜手术是治疗增生型糖尿病视网膜病变(PDR)的重要手段[1,2].PDR患者的视网膜缺血等病变程度决定了手术后视功能,同时手术并发症也在很大程度影响手术的效果以及患者的生存质量[3].生存质量是在医学模式更新背景下提出的一套衡量人类健康的指标体系,对于评价药物疗效,延缓疾病进展,指导患者进行心理和生活调节均有重要意义[4].目前国外有关PDR玻璃体切割手术前后患者生存质量的研究大多随访时间较短,而且用的量表多是Visual Function Questionnaire (VFQ-25)[5,6],所测条目与国人的文化和生活方式有偏差,据此我们设计了适合国人的调查表,观察了一组在我院行玻璃体切割手术并能跟踪随访的PDR患者治疗前后的各项生存质量指标,以比较PDR患者手术治疗前后的生活质量.现将结果报道如下.     

玻璃体腔注射抗血管内皮生长因子单克隆抗体bevacizumab对增生型糖尿病视网膜病变纤维血管膜中整合素链接激酶表达的影响

Objective To observe the effect of intravitreal injection of bevacizumab(Avastin,IVB)on the expression of integrin-linked kinase(ILK)in fibrovascular membranes and the number of vascular endothelial cells(VECs)in proliferative diabetic retinopathy(PDR).Methods Twenty-four fibrovascular membrane samples were collected during pars plana vitrectomy in 24 patients with PDR.1 2 PDR patients had received a single 1.25 mg IVB 7 days preoperatively(bevaeizumab group),the other 1 2 patients(nonbevacizumab group)had not received lVB.For each of 24 fibrovascular membranes specimen.the number of VECs in the membranes were counted after staining with hematoxylin-eosin and yon willebrand factor.Expressions of ILK in the fibrovascular membranes were detected through immunohistochemistry analysis.Results Immunohistochemistry revealed that ILK was highly expressed in all of 24 fibrovaseular membranes of PDR.The average optieal density of ILK expression level in bevacizumab and non-bevaeizumab group were(127.78±15.08)and(129.03±16.26)respectively.the difference was not statistically significant (t=0.330,P=0.745).The number of VECs in ftbrovascular membranes in bevacizumab and nonbevaeizumab group were 21.50±3.94 and 41.33±7.44 respectively,the difference was statistically significant(t=3.872,P=0.003).Condusiom ILK was expressed in fibrovascular membranes of PDR.IVB can decrease the number of VECS during the process of PDR,but it can not affect the expression of ILK protein.     

玻璃体腔注射抗血管内皮生长因子单克隆抗体bevacizumab对增生型糖尿病视网膜病变纤维血管膜中整合素链接激酶表达的影响

Objective To observe the effect of intravitreal injection of bevacizumab(Avastin,IVB)on the expression of integrin-linked kinase(ILK)in fibrovascular membranes and the number of vascular endothelial cells(VECs)in proliferative diabetic retinopathy(PDR).Methods Twenty-four fibrovascular membrane samples were collected during pars plana vitrectomy in 24 patients with PDR.1 2 PDR patients had received a single 1.25 mg IVB 7 days preoperatively(bevaeizumab group),the other 1 2 patients(nonbevacizumab group)had not received lVB.For each of 24 fibrovascular membranes specimen.the number of VECs in the membranes were counted after staining with hematoxylin-eosin and yon willebrand factor.Expressions of ILK in the fibrovascular membranes were detected through immunohistochemistry analysis.Results Immunohistochemistry revealed that ILK was highly expressed in all of 24 fibrovaseular membranes of PDR.The average optieal density of ILK expression level in bevacizumab and non-bevaeizumab group were(127.78±15.08)and(129.03±16.26)respectively.the difference was not statistically significant (t=0.330,P=0.745).The number of VECs in ftbrovascular membranes in bevacizumab and nonbevaeizumab group were 21.50±3.94 and 41.33±7.44 respectively,the difference was statistically significant(t=3.872,P=0.003).Condusiom ILK was expressed in fibrovascular membranes of PDR.IVB can decrease the number of VECS during the process of PDR,but it can not affect the expression of ILK protein.     

玻璃体腔注射抗血管内皮生长因子单克隆抗体ranibizumab联合激光光凝治疗急进性后部型早产儿视网膜病变的疗效观察

目的 观察玻璃体腔注射抗血管内皮生长因子单克隆抗体ranibizumab（商品名Lucentis）联合激光光凝治疗急进性后部型早产儿视网膜病变（AP-ROP）的安全性和有效性。方法 经早产儿视网膜病变（ROP）筛查和临床检查确诊为AP-ROP的35例患儿70只眼纳入研究。所有患眼病变均位于后极部。其中,病变位于1区42只眼,病变位于2区28只眼。合并有虹膜新生血管或扩张的虹膜血管46只眼,合并玻璃体积血19只眼。所有患儿在确诊后12 h内接受玻璃体腔注射ranibizumab治疗。观察全身及眼部的不良反应情况。注药后1周,观察患眼眼底情况,比较玻璃体腔注射ranibizumab前后视网膜血管纡曲和扩张程度的变化。所有患眼均在玻璃体腔注射ranibizumab治疗后联合激光光凝治疗,激光治疗距离注药的时间间隔为1～10周,平均间隔时间（5.1±2.6）周。治疗后随访时间6～18个月,平均随访时间（10.3±3.9）个月。主要观察视网膜病变转归情况。对于随访过程中出现病情进展至4期或5期的患儿,行保留晶状体的玻璃体切割手术或玻璃体切割联合晶状体切除手术。结果 玻璃体腔注射ranibizumab后,无患儿发生眼部并发症及全身不良反应。出现新增的视网膜前出血12只眼,占所有患眼的17.1%;但出血均自行吸收。随访期间,所有的晶状体均保持透明,未发生医源性裂孔。玻璃体腔注射ranibizumab后1周,所有虹膜新生血管或扩张的虹膜血管均消退。玻璃体积血明显吸收16只眼,占合并有玻璃体积血患眼的84.2%。后极部血管纡曲、扩张明显消退61只眼,占所有患眼的87.1%;视网膜血管不同程度向周边生长59只眼,占所有患眼的84.3%。1区病变42只患眼中,血管发育至2区32只眼,占76.2%。2区病变28只患眼中,血管发育至2～3区交界处24只眼,占85.7%。玻璃体腔注射ranibizumab联合激光光凝治疗后,视网膜血管网或嵴消退、附加病变消退且视网膜平复62只眼,占所有患眼的88.6%。视网膜表面纤维增生膜持续加重,发生牵引性视网膜脱离8只眼,占所有患眼的11.4%。其中,进展至4期5只眼,占所有患眼的7.1%;进展至5期3只眼,占所有患眼的4.3%。接受保留晶状体的玻璃体切割手术4只眼,接受玻璃体切割联合晶状体切除手术4只眼。手术治疗后,视网膜完全复位5只眼,视网膜部分复位3只眼。结论 玻璃体腔注射ranibizumab联合激光光凝治疗AP-ROP安全、有效。     

抗血管内皮生长因子单克隆抗体Bevacizumab预防非肥胖糖尿病小鼠视网膜微血管增生

目的 观察抗血管内皮生长因子单克隆抗体Bevacizumab眼内注射对非肥胖糖尿病小鼠视网膜微血管增生的预防作用。 方法 选取30只非肥胖糖尿病小鼠，左眼为实验眼，右眼为对照眼。实验眼眼内注入1 μl Bevacizumab(25 mg/1 ml)溶液， 对照眼眼内注入等量生理盐水。分别在注射后1周，1、2个月时随机各选取10只鼠，取出双侧眼球，行视网膜微血管内皮细胞超微结构观察以及视网膜CD34和血管内皮生长因子（VEGF）免疫组织化学测定，计算机图像分析对比两组间阳性染色密度的差异。 结果 VEGF和CD34阳性表达均为棕黄色着色，CD34的染色定位在血管内皮细胞上。在注射后1周、1个月时，两组间VEGF表达比较，差异有统计学意义（t=21.6, t=13.5; P＜0.01 ）；注射后2个月时，两组间VEGF表达比较，差异无统计学意义（t=0.9, P＞0.05）。注射后1周时，两组间CD34表达比较，差异无统计学意义（t=1.3, P＞0.05）；注射后1、2个月时，两组间CD34表达比较，差异有统计学意义（t= 3.2, P＜0.01; t=2.7, P＜0.05）。注射后各时间段，视网膜血管内皮细胞的微观结构都未发生明显改变。 结论 Bevacizumab眼内注射可预防非肥胖糖尿病小鼠视网膜微血管的异常增生。 （中华眼底病杂志，2008，24：180-183）     

玻璃体腔注射抗血管内皮生长因子单克隆抗体Ranibizumab治疗视网膜静脉阻塞继发黄斑水肿

视网膜静脉阻塞(RVO)继发的黄斑水肿是导致视力下降的常见原因,黄斑格栅样激光光凝是治疗黄斑水肿的常用方法,但是治疗后视力提高不明显[1].近年来应用玻璃体腔曲安奈德注射(IVTA)治疗RVO继发黄斑水肿具有一定效果[2,3],但仍有部分患者视力不提高.抗血管内皮生长因子(VEGF)单克隆抗体Ranibizumab是重组的人源化VEGF单克隆抗体片段,目前已获美国食品及药物管理局(FDA)批准,用于老年性黄斑变性脉络膜新生血管的治疗[4,5],最近又用于RVO继发黄斑水肿的治疗,并取得了肯定疗效[6].我们对15例RVO继发黄斑水肿患者进行了Ranibizumab玻璃体腔注射,现将结果报道如下.     

23G和20G玻璃体手术治疗增生型糖尿病视网膜病变的对比观察

目的 对比观察20G和23G玻璃体手术治疗增生型糖尿病视网膜病变(PDR)的临床效果.方法 前瞻性随机对照研究.具有玻璃体手术指征的PDR患者126例142只眼纳入研究.所有患者均行视力、眼压、间接检眼镜、眼B型超声、泪膜破裂时间(BUT)、基础泪液分泌试验(SIT)以及角膜前后表面6 mm区域散光度、散光轴向检查.采用随机数字表法,将患者分为20G手术组和23G手术组,分别为66例74只眼和60例68只眼.手术后平均随访时间,20G手术组15.0个月,23G手术组12.5个月;以手术后6个月为评价两组疗效的时间点.对比分析两组患者手术中并发症、手术时间以及手术后视力、眼压、并发症及BUT、SIT、角膜前后表面散光度和散光轴向变化.结果 手术后6个月随访时,20G手术组74只眼中,视力≥0.05者49只眼,占本组患眼的66.2％;23G手术组68只眼中,视力≥0.05者47只眼,占本组患眼的69.1％.两组间视力≥0.05者比较,差异无统计学意义(x2=0.14,P＞0.05).20G手术组、23G手术组,手术中发生医源损伤18、7只眼,分别占本组患眼的24.3％、10.3％.两组间手术中医源性损伤发生率比较,差异有统计学意义(x2=4.81,P＜0.05).20G手术组、23G手术组平均手术时间分别为(69.0±8.2)、(51.0±6.3)min.两组间平均手术时间比较,差异有统计学意义(t=3.65,P＜0.05).手术后3d,20G手术组、23G手术组发生低眼压3、11只眼,分别占本组患眼的4.1％、14.7％.两组间低眼压发生率比较,差异有统计学意义(x2=5.85,P＜0.05).20G手术组、23G手术组发生高眼压或继发性青光眼24、14只眼,分别占本组患眼的32.4％、20.6％,两组间手术后高眼压或继发性青光眼发生率比较,差异无统计学意义(x2=2.54,P＞0.05).手术后1个月,20G手术组BUT、SIT长度、角膜前后表面散光度、散光轴向与手术前相应检测指标比较,差异均有统计学意义(t=3.35,4.12,-3.12,-3.22;P＜0.05);手术后3、6个月BUT、SIT长度、角膜前后表面散光度、散光轴向与手术前相应检测指标比较,差异均无统计学意义(3个月:t=0.45、0.98、-2.12、-1.02,P＞0.05;6个月:t=0.95、1.48、-1.02、-2.11,P＞0.05).手术后1、3、6个月,23G手术组BUT、SIT长度、角膜前后表面散光度、散光轴向与手术前相应检测指标比较,差异均无统计学意义(1个月:t=1.21、1.46、-2.32、-1.61,P＞0.05;3个月:t=1.45、2.21、-2.19、-1.89,P＞0.05;6个月:t=1.92、1.25、-1.75、-2.35,P＞0.05).结论 23G微创玻璃体手术治疗PDR安全有效,可缩短手术时间,减少手术并发症,减轻手术后眼表改变.     

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.     

玻璃体腔注射抗血管内皮生长因子单克隆抗体ranibizumab联合格栅样激光光凝治疗视网膜分支静脉阻塞合并黄斑水肿疗效观察

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ranibizumab(商品名Lucentis)联合黄斑格栅样激光光凝对视网膜分支静脉阻塞(BRVO)合并黄斑水肿的疗效.方法 临床确诊为BRVO合并黄斑水肿的46例患者46只眼纳入研究.所有患者均常规行矫正视力、裂隙灯显微镜、直接检眼镜、眼压、眼底彩色照相、荧光素眼底血管造影及光相干断层扫描检查.矫正视力检查采用糖尿病视网膜病变早期治疗研究(ETDRS)视力表进行.根据不同的治疗方法,将患者分为单纯玻璃体腔注射ranibizumab组(注射组)、玻璃体腔注射ranibizumab联合激光治疗组(联合组)及单纯激光光凝治疗组(激光光凝组),分别为18、17、11只眼.治疗后随访时间3～15个月,平均随访时间(8.0±3.2)个月.随访期间采用治疗前相同的设备和方法行相关检查.根据复诊情况,对注射组及联合组行重复注射治疗,比较两组重复注射次数.以末次随访为疗效判定时间点,对比分析3组患者治疗前后视力、黄斑中心视网膜厚度(CRT)的变化情况.同时观察与药物和治疗方式相关的眼部和全身不良反应发生情况.结果 注射组、联合组重复注射ranibizumab的平均次数分别为(5.4±0.4)、(3.2±0.6)次,二者比较,差异有统计学意义(t＝ 12.17,P＜0.05).随访期间所有患者均未发生与药物、玻璃体腔注射有关的眼部和全身严重不良反应.末次随访时,注射组、联合组及激光光凝组患者ETDRS视力较治疗前分别增加了(7.3±8.7)、(8.5±6.0)、(1.6±6.9)个字母.注射组、联合组治疗前后视力比较,差异有统计学意义(t＝3.58、5.78,P＜0.05);激光光凝组治疗前后视力比较,差异无统计学意义(f＝0.75,P＞0.05).注射组、联合组视力增加字母数比较,差异无统计学意义(t=0.45,P＞0.05);注射组、联合组视力增加字母数分别与激光光凝组视力增加字母数比较,差异均有统计学意义(t＝2.13、2.81,P＜0.05).注射组、联合组及激光光凝组患者CRT较治疗前分别减少了(110.6±43.1)、(125.5±35.2)、(50.7±19.7) μm,与治疗前CRT比较,差异均有统计学意义(t=-10.89、-14.70、8.55,P＜0.05).结论 玻璃体腔注射ranibizumab联合黄斑格栅样激光光凝治疗BRVO合并黄斑水肿可以减少重复注射次数,减轻黄斑水肿,提高视力.     

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.     

光动力疗法联合玻璃体腔注射抗血管内皮生长因子单克隆抗体ranibizumab治疗视网膜血管瘤样增生的疗效观察

视网膜血管瘤样增生(RAP)是近年来被认同的一种渗出型老年性黄斑变性( AMD)的特殊类型[1].其表现为深层视网膜内血管异常及视网膜-视网膜或视网膜-脉络膜血管吻合[2-5].RAP自然预后不良,其治疗也尚处于探索阶段.无论是对异常血管团直接激光光凝、激光光凝其滋养血管、光动力疗法(PDT)或经瞳孔温热疗法效果均不理想[6].我们采用PDT联合玻璃体腔注射抗血管内皮生长因子单克隆抗体ranibizumab(商品名Lucentis)对一组RAP患者进行了治疗.现将其结果报道如下.     

玻璃体腔注射抗血管内皮生长因子单克隆抗体ranibizumab治疗特发性脉络膜新生血管的临床观察

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ranibizumab(商品名Lucentis)治疗特发性脉络膜新生血管(ICNV)的临床疗效和安全性.方法 经临床检查确诊的ICNV患者54例54只眼纳入研究.其中,男性24例24只眼,女性30例30只眼;年龄21～49岁,平均年龄(32.57±7.06)岁;病程6 d～3个月.采用Snellen视力表行最佳矫正视力(BCVA)、早期糖尿病视网膜病变治疗研究(EDTRS)视力表行EDTRS视力检查,同时行间接检眼镜、荧光素眼底血管造影(FFA)、光相干断层扫描(OCT)等检查.患眼治疗前BCVA眼前手动～0.6,EDTRS视力平均字母数为(32.00±16.41)个.黄斑中心视网膜厚度(CRT)平均值为(337.31±76.91) μm.玻璃体腔注射10 mg/ml的ranibizumab 0.05 ml(含ranibizumab 0.5 mg).治疗后平均随访时间(15.56±6.54)个月.首次治疗后第1个月随访检查时如发现CNV病灶扩大或有新发CNV病灶,则行再次注射治疗.对比分析治疗前后BCVA、ETDRS视力、CRT及CNV病灶渗漏变化情况.结果 首次治疗后1个月,ETDRS视力平均字母数为(48.81±16.96)个,较治疗前平均字母数增加16.81个字母,差异有统计学意义(t=-11.991,P＜0.01).视力增加＞15个字母者25只眼,占46.30％;视力减少≥1个字母者2只眼,占3.70％.OCT检查显示,CRT平均值为(227.67±91.41)μm,与治疗前CRT平均值比较,差异有统计学意义(t=12.021,P＜0.01).末次随访检查时,患眼注射次数1～4次,平均注射次数(1.59±0.71)次.ETDRS视力平均字母数为(49.20±16.60)个,较治疗前平均字母数增加17.20个字母,差异有统计学意义(t=-11.390,P＜0.01).视力增加＞15个字母者27只眼,占50.00％;视力减少≥1个字母者3只眼,占5.56％.OCT检查显示,CRT平均值为(227.69±89.30) μm,与治疗前CRT平均值比较,差异有统计学意义(t=10.872,P＜0.01).CNV渗漏完全停止者35只眼,占64.81％;渗漏范围减少者11只眼,占20.37％;渗漏无明显变化或范围扩大者6只眼,占11.11％;出现新病灶者2只眼,占3.70％.随访中未见与注射及药物有关的眼部及全身不良反应.结论 玻璃体腔注射ranibizumab治疗ICNV安全有效,可提高患眼视力,减轻黄斑水肿;其远期疗效及安全性还有待进一步观察.