Comparative antiproliferative and cytotoxic profile of bevacizumab (Avastin), pegaptanib (Macugen) and ranibizumab (Lucentis) on different ocular cells

Aim To compare the antiproliferative and cytotoxic properties of bevacizumab (Avastin), pegaptanib (Macugen) and ranibizumab (Lucentis) on human retinal pigment epithelium (ARPE19) cells, rat retinal ganglion cells (RGC5) and pig choroidal endothelial cells (CEC). Methods Monolayer cultures of ARPE19, RGC5 and CEC were used. Bevacizumab (0.1–0.3 mg/ml), pegaptanib (0.025–0.08 mg/ml) or ranibizumab (0.04–0.125 mg/ml) diluted in culture medium were added to the cells. Expression of VEGF-receptors (VEGFR1 and VEGFR2) and von Willebrand factor (a marker for endothelial cells) were analysed by immunohistochemistry. CEC cells were stimulated with VEGF. Cellular proliferative activity was monitored by BrdU-incorporation into cellular DNA. For cytotoxicity assays cells were grown to confluence and then cultured in a serum-depleted medium to ensure a static milieu. MTT-test was performed after one day. Results CEC and ARPE19 cells stained positively for VEGFR1 and VEGFR2. More than 95% of the CEC cells were positive for von Willebrand factor. Ranibizumab reduced CEC cell proliferation by 44.1%, bevacizumab by 38.2% and pegaptanib by 35.1% when the drugs were used at their established clinical doses. The differences, however, between the three drugs in respect to cell growth inhibition were not statistically significant. Only a mild antiproliferative effect of bevacizumab or pegaptanib on ARPE19 cells could be observed. Ranibizumab did not alter ARPE19 cell proliferation. No cytotoxicity on RGC5, CEC and ARPE19 cells could be seen. Conclusions Bevacizumab, pegaptanib and ranibizumab significantly suppress choroidal endothelial cell proliferation. However, when used at the currently established doses none of the drugs was superior over the others in respect to endothelial cell growth inhibition. The biocompatibility of all three drugs — including the off-label bevacizumab — seems to be excellent when used at the currently recommended intravitreal dose. This work is presented on behalf of the Tuebingen Bevacizumab Study Group.     

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.     

康柏西普与雷珠单抗治疗视网膜中央静脉阻塞继发黄斑水肿的疗效及安全性分析

目的 比较康柏西普与雷珠单抗治疗视网膜中央静脉阻塞（central retinal vein occlusion,CRVO）继发黄斑水肿的效果和安全性。方法 将陕西省杨凌示范区医院自2015年6月-2017年1月纳入的CRVO继发黄斑水肿患者102例作为研究对象,随机分为两组,即使用康柏西普治疗的A组50例（50眼）,使用雷珠单抗治疗的B组52例（52眼）,观察治疗后1、3、6个月时患者视力恢复情况和黄斑部视网膜厚度变化情况,评价不同药物的治疗效果和安全性。结果 治疗6个月后A组患者视力提高率（52.00%）高于B组（30.77%）,差异具有统计学意义（P<0.05）;两组患者的黄斑部视网膜厚度的改善A组优于B组,且各个复诊时间点比较,差异均具有统计学意义（P<0.05）。两组不良反应发生率分别为8.00%和11.54%,差异无统计学意义。结论 康柏西普治疗CRVO继发黄斑水肿的临床效果优于雷珠单抗,但二者的安全性差异不显著,有待于进一步长期大样本研究证实。     

雷珠单抗治疗黄斑 CNV疾病的临床观察

目的：探讨雷珠单抗（ Ranibizumab）玻璃体腔注射治疗黄斑脉络膜新生血管（ CNV）疾病的临床疗效与安全性。方法收集2013年3月到2015年7月间在我院门诊诊断为活动性黄斑下CNV疾病的患者共59例（60只眼）,男性26例（27只眼）,女性33例（33只眼）,年龄19～78岁,分为三组,分别为湿性老年性黄斑变性组23例（24只眼）,中心性渗出性视网膜脉络膜病变组20例（20只眼）,病理性近视继发黄斑CNV 组16例（16只眼）。于治疗前、治疗后第1天,0．5、1、3、6个月时对患者进行最佳矫正视力（ BCVA）的检査、相干光断层扫描（ OCT）、眼底彩照检查,治疗前、治疗后6个月眼底血管造影（ FFA及ICGA）,进行效果评价。结果三组治疗后1、3、6个月,分别与治疗前相比,BCVA显著提高,且差异有统计学意义（均为P ＜0．05）;三组治疗后0．5、1、3、6个月,分别与治疗前相比,黄斑中心视网膜厚度（CMT）显著降低,且差异有统计学意义（均为P ＜0．05）;并发症方面,6．8％（11／161注射次数）注射后出现球结膜出血,1．2％（2／161注射次数）在治疗后第1天出现高眼压。结论玻璃体腔内注射雷珠单抗治疗黄斑CNV疾病疗效显著,且安全性很好。     

雷珠单抗联合玻璃体切割术治疗增生性糖尿病视网膜病变合并Ⅰ、Ⅱ期青光眼临床观察

目的：探讨雷珠单抗联合玻璃体切割术( PPV)对增生性糖尿病视网膜病变( PDR)合并Ⅰ、Ⅱ期新生血管性青光眼( NVG)的临床效果。方法回顾性分析2011年6月—2014年6月眼科确诊为PDR合并Ⅰ、Ⅱ期NVG患者60例(60只眼)的临床资料,根据术前有无注射雷珠单抗分为观察组34例(34只眼)和对照组26例(26只眼),均行23G PPV,观察组术前注射雷珠单抗,对照组术前未注射雷珠单抗。观察两组手术时间、新生血管平均出血次数、电凝使用次数、术中及术后6个月并发症发生率;术前、术后1个月测定最佳修正后视觉灵敏度( BCVA)、房水中血管内皮细胞生长因子( VEGF)、色素上皮衍生因子( PEDF)及术后1个月黄斑中心凹视网膜厚度( CRT)值。结果观察组手术时间短于对照组,新生血管出血次数、电凝使用次数少于对照组( P<0．05);观察组术前、术后房水VEGF、PEDF低于对照组,术后BCVA高于对照组(P<0．01);观察组术中医源性视网膜裂孔、术中大量出血及术后一过性高眼压、玻璃体出血发生率均低于对照组( P<0．05)。结论雷珠单抗联合PPV治疗PDR合并NVG,可降低房水VGEF、PEDF,提高BCVA水平,降低术中及术后并发症发生率。     

雷珠单抗治疗视网膜静脉阻塞继发黄斑水肿的疗效及其影响因素

目的：研究玻璃体腔注射雷珠单抗治疗视网膜静脉阻塞(RVO)继发黄斑水肿的疗效及其影响因素。

方法：回顾性病例研究。收集2020-04/2021-02于我院治疗的RVO继发黄斑水肿患者61例61眼,其中BRVO患者30例30眼,CRVO患者31例31眼。所有患者均完成了3次雷珠单抗(0.5mg)玻璃体腔注药治疗,部分患眼进行了视网膜激光治疗。治疗(首次玻璃体腔注药)后随访3mo,观察治疗后视力、眼压及黄斑中心凹厚度(CRT)情况,并记录眼部及全身并发症发生情况。

结果：纳入患者治疗后视力均较治疗前显著改善,CRT均较治疗前显著降低(P<0.01),且BRVO和CRVO患者中治疗前视力≤1(LogMAR)的患者3次玻璃体腔注药后视力均优于治疗前视力>1的患者(P<0.01),但CRT无差异(均P>0.05)。BRVO和CRVO患者中分别有12、8眼在3次玻璃体腔注药期间进行了病变区激光治疗,BRVO和CRVO患者中激光治疗和未激光治疗的患者3次玻璃体腔注药后视力和CRT均无差异(P>0.05)。随访期间未发现眼部及全身严重并发症的发生。

结论：雷珠单抗治疗RVO继发黄斑水肿具有良好的疗效和安全性,但基线视力可能对疗效具有一定影响。     

Anti-VEGF-refractory Exudative Age-related Macular Degeneration: Differential Response According to Features on Optical Coherence Tomography

Purpose

To describe optical coherence tomography (OCT) characteristics of neovascular age-related macular degeneration (AMD) patients refractory to intravitreal anti-vascular endothelial growth factor (VEGF) injections (ranibizumab, bevacizumab) and their responses to alternative anti-VEGF agents or photodynamic therapy (PDT).

Methods

A retrospective review of 267 neovascular AMD patients treated with intravitreal anti-VEGF injections.

Results

Twenty patients (7.5%) were refractory to anti-VEGF injections (stationary or increased retinal exudation despite three or more monthly injections). They were grouped into either the extensive intraretinal fluid group (IRF group, 9 patients) or the subretinal fluid only group (SRF group, 11 patients) according to OCT findings. In the IRF group, response rates to subsequent treatment were 0% (0 / 7) for bevacizumab, 50% (3 / 6) for ranibizumab and 50% (3 / 6) for PDT ± anti-VEGF. Three out of four bevacizumab-refractory patients showed response to ranibizumab as a secondary treatment. In the SRF group, response rates were lower with 0% (0 / 7) for bevacizumab, 22.2% (2 / 9) for ranibizumab and 28.6% (2 / 7) for PDT ± anti-VEGF. One out of four bevacizumab-refractory patients responded to ranibizumab. The visual outcome was worse in the IRF group (median 20 / 1,000) than in the SRF group (median 20 / 100).

Conclusions

In anti-VEGF-refractory neovascular AMD, patients with extensive IRF refractory to bevacizumab can be responsive to ranibizumab while patients with SRF may be refractory to both, suggesting a different pathophysiology and intraocular pharmacokinetics.     

Ranibizumab治疗老年黄斑变性合并脉络膜新生血管短期临床观察

目的观察Ranibizumab（Lucentis）治疗渗出型老年黄斑变性（Aga-Related Macular Degeneration,AMD）合并脉络膜新生血管（Choroidal Neovascularization,CNV）的短期治疗效果。方法经荧光素眼底血管造影（Fundus Fluorescein Angiography,FFA）、吲哚青绿血管造影（Indocyanine Geen Angiography,ICGA）和光学相干断层成像术（Optic Coherence Tomography,OCT）等检查确诊30例渗出型AMD患者的30只患眼行每月1次Lucentis治疗,共3次,剂量为0.5mg（0.05ml）;玻璃体腔注入,治疗前和治疗后1周,1、3个月的临床资料,以视力、眼压、FFA、ICGA、OCT检查结果为观察指标,评价Lucentis对渗出型AMD的短期治疗效果。结果 30例治疗后1个月视力稳定19例（63.3%）,视力提高11例（36.7%）;3个月30例视力稳定16例（55.2%）,视力提高13例（44.8%）,1例治疗后2月时发生脑梗停止治疗。30例治疗后1h有4例眼压升高〉20mmHg（1mmHg=0.133kPa）,最高23.8mmHg;1d、1个月眼压均在正常范围内。FFA和ICGA检查显示均有不同程度渗漏减轻或消退。OCT检查显示视网膜水肿和浆液性脱离明显好转。治疗后无明显不良反应,仅有轻微眼部局限性结膜充血、结膜下出血、眼前小暗影;个别眼压轻微升高等,一般5d内恢复正常。结论 Lucentis玻璃体腔注射治疗渗出型AMD安全有效。     

雷珠单抗治疗慢性中心性浆液性脉络膜视网膜病变合并CNV的疗效及其影响因素

目的:应用多模式影像观察玻璃体腔抗血管内皮生长因子(VEGF)注射在慢性中心性浆液性脉络膜视网膜病变(CCSC)合并脉络膜新生血管(CNV)的治疗效果,探讨评估其影响因素。方法:回顾性分析30例30眼确诊为CCSC合并CNV患者的资料。所有患者均行最佳矫正视力(BCVA)、频域相干光断层扫描(SD-OCT)的增强深度成像(EDI)模式,荧光素眼底血管造影(FFA)、吲哚菁绿血管造影(ICGA)及光学相干断层扫描血管成像(OCTA)血流扫描检查。对存在黄斑区视网膜下积液(SRF)以及CNV的患眼行玻璃体腔雷珠单抗(IVR)注射治疗,采取1+PRN方案,随访时间为注药治疗后1wk, 1mo,末次注药治疗后3mo。观察指标为最佳矫正视力(BCVA,LogMAR)、黄斑中心凹厚度(CMT)、黄斑中心凹下脉络膜厚度(SFCT)以及CNV血流面积。结果:所有患眼在基线、眼内注药治疗后1wk, 1mo,末次治疗后3mo时各时间点CMT有差异(F=62.06,P<0.01);治疗后各时间点CMT与治疗前比较均有差异(t=3.08、6.57、4.90,P=0.01、0.02、<0.01),其...