Pegaptanib sodium for the treatment of neovascular age-related macular degeneration

This article reviews pegaptanib sodium, a compound developed by Eyetech Pharmaceuticals Inc. and Pfizer Inc., for the treatment of neovascular age-related macular degeneration (AMD). Traditional treatment approaches to neovascular AMD have included destructive therapies such as thermal laser photocoagulation and photodynamic therapy; the use of pegaptanib sodium heralds a new treatment approach that is a non-destructive therapy based on the inhibition of vascular endothelial growth factor activity in the eye. This diminishes the neovascular drive in the pathologically hyperpermeable state of the diseased eye. Pegaptanib sodium is one of the first therapeutics belonging to the class of compounds known as aptamers. The chemistry, mechanism of action, pharmacokinetics and rationale for the clinical use of the drug are reviewed. The article highlights and summarises the results of the multi-centre, randomised, sham-controlled clinical trials with pegaptanib sodium to treat subfoveal choroidal neovascularisation in AMD. In addition, the safety profile is reviewed.     

抗VEGF联合视网膜光凝在治疗PDR中的相互影响和协同作用

目的：观察雷珠单抗联合激光在治疗增生期糖尿病视网膜病变(proliferative diabetic retinopathy, PDR)过程中的相互影响作用。

方法：2014-12/2015-08同期收治的增生期糖尿病视网膜病变合并黄斑水肿患者分为两组。雷珠单抗联合激光治疗组30例48眼,单纯激光组28例45眼。联合治疗组在玻璃体腔注射雷珠单抗后1wk,复查FFA,随后进行全视网膜光凝。单纯激光组仅行全视网膜光凝。观察和记录两组患者治疗后1、4、8wk时的最佳矫正视力,OCT测量黄斑厚度。

结果：治疗后1、4、8wk时,两组间最佳矫正视力、黄斑中心厚度差异均有统计学意义(P<0.05)。单纯激光组治疗后1wk后,视力有所下降,黄斑中心厚度增加。治疗后4、8wk时,视力逐渐改善,黄斑厚度降低。注药后1wk,FFA显示联合治疗组所有眼视网膜渗漏改善,新生血管膜不同程度退缩。未见眼内注射和眼底激光导致的相关并发症等情况。

结论：雷珠单抗联合激光治疗,早期即可改善患者视力,减轻黄斑水肿。抗VEGF治疗和激光光凝可在一定程度上起到协同作用。前者拮抗已经高表达的VEGF,改善黄斑水肿和微血管功能,增强激光疗效。有效的光凝又可进一步改善视网膜缺血缺氧状态,抑制VEGF的过多表达。     

玻璃体腔注射抗VEGF治疗的回顾性分析

目的：回顾分析佛山市第二人民医院眼科中心2013/2015年行玻璃体腔注射抗VEGF在眼底新生血管性疾病中的应用情况。
　　方法：回顾性分析2013-01/2015-12期间在佛山市第二人民医院眼科中心的住院患者,以手术方式为“玻璃体腔内注药术”为检索词查阅病历管理系统,排除玻璃体腔注射曲安奈德及抗生素药物的患者,就其相关疾病进行统计分析。同时查询相关疾病同年收住院患者资料并进行对比。
　　结果：3 a间共行239眼注射,男女比例接近,青年、中年及老年组间无统计学差异,3a间注射人数逐年增加。行抗VEGF( vascular endothelial growth factor )注射的相关疾病主要为脉络膜新生血管性疾病、视网膜静脉阻塞、糖尿病性视网膜病变及息肉状脉络膜血管病变,同一年度四类疾病及同种疾病不同年度行抗 VEGF 注射比率(注射/总数)有显著性统计学差异,其中脉络膜新生血管性疾病患者3a中接受注射程度最高,息肉状脉络膜血管病变则增长最快。
　　结论：抗VEGF玻璃体腔注射作为眼底新生血管性疾病新的治疗方式,正日益为患者接受。     

抗VEGF药物玻璃体内注射治疗视网膜血管样条纹继发脉络膜新生血管的远期观察

目的 探讨视网膜血管样条纹继发脉络膜新生血管(choroidal neovascularization,CNV)抗VEGF治疗的远期疗效.方法 回顾分析接受玻璃体内注射抗VEGF药物的视网膜血管样条纹继发CNV患者,观察至少3 a后患者视力改善情况、视网膜及脉络膜活动性病灶消退情况等指标.结果 纳入分析的21例(30眼)患者中,眼内注射次数6 ～18(10.0±2.4)次.随访36 ～54(39.5±2.2)个月.患者首次接受治疗时BCVA为(31.00±3.81)个字母数,观察终点时最佳矫正视力为(34.00±0.35)个字母数,总体差异无统计学意义(P=o.600).患者治疗前视网膜中央厚度为(406.21±21.23) μm,随访终末时为(251.16±36.36)μm,减少值为(150.21±24.43).μm,治疗前后视网膜中央厚度比较差异有统计学意义(P =0.002).30眼中16眼在初期治疗后视力明显提升,但随访中出现病变复发活跃后视力再次下降至基线水平;10眼在病变过程中出现不同程度黄斑下萎缩及瘢痕化改变,随访过程及随访终末视力与基线视力差异均无统计学意义(均为P ＞0.05);4眼由于初始CNV未累及黄斑区,在治疗随访过程中CNV稳定.结论 由于病变的高复发性及强活跃性,抗VEGF药物治疗血管样条纹继发CNV远期预后并不理想,治疗仅发挥了一定维持视功能的作用.     

预测视网膜静脉阻塞继发黄斑水肿抗VEGF治疗后视力的形态学指标分析

目的 评价视网膜静脉阻塞（RVO）继发黄斑水肿（ME）患者抗VEGF治疗基线荧光血管造影（FFA）及相干光断层扫描（OCT）指标与患者治疗后最佳矫正视力（BCVA）的关系。设计 回顾性病例系列。研究对象 北京同仁医院连续抗VEGF治疗应答良好的125例125眼RVO继发ME患者。方法 所有患者均接受每月1次玻璃体注射雷珠单抗0.05 ml,直至ME完全消退。所有患者均采用Spectralis HRA+OCT进行FFA及OCT检查,半自动分析患者基线FFA及OCT形态学指标。采用Logtistic回归分析评价各分析因素与患者治疗后BCVA的关系。主要指标 BCVA,黄斑旁中心凹毛细血管灌注,黄斑中心视网膜厚度,黄斑中心视网膜容积,视网膜各层的完整性。结果125眼中,7眼（5.6%）基线BCVA≥0.5,抗VEGF治疗后43眼（34.4%）BCVA≥0.5。患者基线黄斑旁中心凹毛细血管无灌注（P=0.01,OR=0.213）、 内丛状层结构模糊（P=0.005,OR=0.225）、外界膜破坏（P=0.001,OR=0.160）是阻碍治疗后获得良好视力预后的主要影响因素。结论 基线FFA显示黄斑中心凹毛细血管无灌注或OCT显示黄斑中心凹区视网膜内丛状层结构模糊或外界膜破坏提示抗VEGF治疗RVO继发ME的视力预后不佳。（眼科,  2018,  27：111-115）     

Effect of antivascular endothelial growth factor treatment on the intratumoral uptake of CPT-11

Promising preclinical activity with agents blocking the function of vascular endothelial growth factor (VEGF) has been observed in various cancer types, especially with combination therapy. However, these drugs decrease microvessel density, and it is not known whether this reduced vessel density (VD) results in decreased delivery of concomitantly administered classical anticancer drugs. We designed an in vivo study to investigate the relation between VEGF-blocking therapy, tumoral blood vessels, and intratumoral uptake of anticancer drugs. Nude NMRI mice bearing colon adenocarcinoma (HT29) were treated with the anti-VEGFmAb A4.6.1 or placebo. After 1 week, CPT-11 was administered 1 h prior to killing the animals. In A4.6.1 treated tumours, there was a significant decrease in VD, more pronounced with potentially functional large vessels than endothelial cords. Interestingly, a trend to increased intratumoral CPT-11 concentration was observed (P=0.09). In parallel, we measured an increase in tumour perfusion, as estimated by high-performance liquid chromatography determination of intratumoural Hoechst 33342 concentration. In the growth delay study, CPT-11 was at least equally effective with or without pretreatment with A4.6.1. These data suggest that tumour vascular function and tumour uptake of anticancer drugs improve with VEGF-blocking therapy, and indicate the relevance for further investigations.     

VEGF对大鼠50%肝脏移植术后血清HGF、IL-6浓度的影响

目的 探讨血管内皮生长因子(vascular endothelial growth factor,VEGF)对大鼠部分肝移植术后血清肝细胞生长因子(hepatocyte growth factor,HGF)、白细胞介素-6(interleukin-6,IL-6)浓度的影响.方法 建立大鼠50%部分肝移植模型.实验动物分3组:VEGF治疗组、anti-VEGF组、对照组.分别于术后注射鼠重组VEGF、 anti-VEGF、生理盐水.在术后不同时相点(0、12、24、72、168 h)测血清中HGF、IL-6 含量及肝脏生化指标.结果 VEGF组血清HGF、IL-6水平较对照组明显增高,anti-VEGF组较对照组明显降低,有显著差异.anti-VEGF 组天冬氨酸转氨酶(aspartate aminotransferase,AST)、丙氨酸转氨酶(alanine aminotransferase,ALT)较VEGF组及对照组明显升高,有显著差异.结论 VEGF治疗能明显促进大鼠部分肝脏移植术HGF、IL-6的释放.     

Metformin therapy as a strategy to compensate anti-VEGF resistance in patients with diabetic macular edema

Diabetic macular edema (DME) is the complication of diabetic retinopathy, the leading cause of vision loss among diabetic patients. Metformin is the main antidiabetic treatment. It is preferable for its great anti-angiogenic and anti-inflammatory effects. Anti-vascular endothelial growth factor (VEGF) therapy is the preferable treatment for DME despite its lack of convincing results in some patients. To assess whether the combination of metformin and anti-VEGF drugs may decrease the risk of anti-VEGF resistance among DME patients. We included DME patients with a central retinal thickness (CRT) ≥ 250 μm who consecutively underwent at least 3 anti-VEGF therapies from January 1, 2020, to December 30, 2021. Anti-VEGF resistance was defined as persistent macular edema with decreased CRT ≤ 25% after 3 anti-VEGF injections. 109 patients were considered for this research, of whom 65 (59.6%) were resistant to anti-VEGF therapy. The mean CRT of the non-metformin group decreased from 344.88 ± 129.48 to 318.29 ± 123.23 (20.85%) and from 415.64 ± 144.26 to 277.11 ± 99.25 (31.51%) (P = .031) in the metformin group. Moreover, the metformin group had fewer resistant patients than the non-metformin, 24 (45.3%) versus 41 (73.2%). Furthermore, a considerable gain in visual acuity was observed in both groups, with a BCVA gain of 40.41% in the metformin group and 39.9% in the non-metformin group. Metformin may be combined with an anti-VEGF drug to minimize the risk of anti-VEGF resistance among DME patients. Moreover, it can serve to design effective therapeutic deliveries.     

外层视网膜管型在nARMD中的发生率及其对抗VEGF治疗注射次数的影响

目的：探索抗血管内皮生长因子(VEGF)治疗的渗出性年龄相关性黄斑变性(nARMD)患眼中出现外层视网膜管型(ORT)的比例,及ORT出现前后抗VEGF治疗的频率。

方法：回顾性分析,共纳入按3+PRN方案治疗的nARMD患者54例60眼,基线时患者进行荧光素眼底血管造影(FFA)、眼底彩照(CFP)、最佳矫正视力(BCVA)及黄斑相干光断层扫描成像(OCT)检查,以后每月随访查BCVA、眼底彩照及黄斑OCT。记录患者OCT上视网膜下高反射物质(SHRM)的比例及随访中出现ORT结构的时间及比例,比较出现ORT前后玻璃体腔注射的平均次数。比较出现ORT眼及未出现ORT眼两组的BCVA及中心视网膜厚度(CRT)。

结果：在基线及随访至6、12、24mo时,ORT出现的比例分别为15.0%、21.7%、25.0%及46.7%。出现ORT后抗VEGF每月平均注射次数减少(P<0.05)。基线时有78.3%患眼出现SHRM,其中66.0%最后出现ORT,而在基线时不存在SHRM的13眼中仅23.1%眼出现ORT,相对风险值为2.86(P<0.01)。出现ORT眼较未出现ORT眼的BCVA更差及CRT更厚。

结论：ORT随着病程延长逐渐增加,ORT出现后抗VEGF再治疗的频率下降。     

抗VEGF与激光治疗1型早产儿视网膜病变的Meta分析

目的:系统评价抗VEGF与激光治疗1型早产儿视网膜病变(ROP)的疗效分析。方法:通过计算机检索PubMed、EMbase、CBM、The Cochrane Library、WanFang Data、CNKI和VIP数据库,收集比较抗VEGF与激光用于治疗1型ROP疗效的随机对照试验(RCT),检索时限均从建库至2020-01-06,按照纳入与排除标准提取资料,行质量评价后,采用RevMan 5.3软件进行Meta分析。结果:共纳入6个RCT。Meta分析结果显示:抗VEGF与激光组相比,复发率无差异[RR=0.94,95%CI(0.17~5.23),P=0.94];亚组分析Ⅰ区有差异[RR=0.17,95%CI(0.05~0.62),P=0.007];Ⅱ区无差异[RR=2.20,95%CI(0.07~73.48),P=0.66]。与激光组相比,再治疗率无差异[RR=2.36,95%CI(0.70~7.99),P=0.17],亚组分析Ⅰ区无差异[RR=0.33,95%CI(0.01~7.50),P=0.49];Ⅱ区有差异[RR=13,95%CI(1.84~92.01),P=0.01]。两者不良反应发生率无差异[RR=0.87,95%CI(0.54~1.40),P=0.57]。结论:激光和抗VEGF疗效相当,但在降低Ⅰ区复发率方面抗VEGF则更有优势,降低Ⅱ区再治疗率方面激光更有优势。