阿柏西普治疗眼底血管性疾病的临床研究新进展

阿柏西普是人血管内皮生长因子(vascular endothelial growth factor,VEGF)受体1和受体2胞外区结合域与人免疫球蛋白Fc段重组形成的融合蛋白,是一种新的抗VEGF药物,通过与VEGF紧密结合,降低血管通透性,进一步抑制新生血管的生成.多项大型Ⅲ期临床试验已验证了阿柏西普治疗湿性老年性黄斑变性、静脉阻塞黄斑水肿、糖尿病黄斑水肿和其他血管性眼底病的疗效,结果显示玻璃体内注射阿柏西普能够提高患者视力并且减轻眼底病变程度,为眼科医师提供了一种新的药物选择.本综述就阿柏西普的药理学特点以及它在眼底血管性疾病中的应用、疗效和安全性等方面进行论述.     

阿柏西普和雷珠单抗治疗糖尿病性黄斑水肿的疗效

目的:比较阿柏西普和雷珠单抗治疗糖尿病性黄斑水肿(DME)的疗效。方法:前瞻性随机对照试验。纳入2020-06/2021-09于我院确诊的非增殖期糖尿病视网膜病变合并DME的患者35例60眼,均采用3+PRN方案行玻璃体腔注射治疗,其中17例30眼接受阿柏西普治疗(阿柏西普组),18例30眼接受雷珠单抗治疗(雷珠单抗组)。随访12mo,观察两组患者中心凹厚度(CMT)和最佳矫正视力(BCVA)情况,记录玻璃体腔注射次数和并发症发生情况。结果:治疗后1、3、6、12mo,阿柏西普组CMT和BCVA均明显优于雷珠单抗组(均P<0.001)。随访期间,阿柏西普组玻璃体腔注射次数少于雷珠单抗组(4.23±0.86次vs 6.40±0.97次,P<0.05),两组患者均未出现药物相关不良反应、眼内感染、血管栓塞等严重并发症。结论:阿柏西普和雷珠单抗治疗DME均具有明确的疗效和安全性,相较于雷珠单抗,阿柏西普可能是DME患者更有效和方便的治疗选择。     

阿柏西普和雷珠单抗治疗视网膜分支静脉阻塞继发黄斑水肿患者的临床疗效对比

目的 对比分析阿柏西普(aflibercept)和雷珠单抗(ranibizumab)在治疗视网膜分支静脉阻塞(BRVO)继发黄斑水肿(ME)患者的临床疗效。方法 回顾性病例研究。收集2018年11月至2020年4月期间就诊的BRVO合并ME的患者41例(41只眼),根据其行玻璃体阿柏西普注药术和雷珠单抗注药术分为阿柏西普组和雷珠单抗组,详细观察分析两组间术前及术后1、3、6个月的各临床指标资料。结果 两组间患者术前最佳矫正视力(BCVA)、浆液性视网膜脱离(SRD)高度、黄斑中心凹陷(CSFT)比较无统计学差异(P <0.05),术后1个月,两组的BCVA,SRD高度和CSFT均优于术前,术后1、3、6个月,阿柏西普组较阿柏西普组的BCVA明显提高,SRD高度及CSFT明显降低,两者均有统计学差异(P <0.05)。6个月随访期间,阿柏西普组的平均注射针数较雷珠单抗组少,两组间比较有统计学差异(P <0.05)。结论 阿柏西普在治疗BRVO-ME方面对改善患者BCVA、SRD高度和CSFT方面效果显著,较雷珠单抗有更好的优势。     

曲安奈德联合阿柏西普治疗雷珠单抗应答不良的湿性年龄相关性黄斑变性

目的:比较阿柏西普玻璃体内注射联合曲安奈德后部眼球筋膜下注射治疗抗血管内皮生长因子(VEGF)药物雷珠单抗应答不良的湿性年龄相关性黄斑变性(ARMD)的效果及安全性。方法:回顾性队列研究。2018-06/2020-05对抗VEGF药物雷珠单抗治疗应答不良的难治性ARMD 60例60眼,随机分为阿柏西普对照组及曲安奈德联合阿柏西普观察组,每组30例30眼。两组患者每月1次分别行单纯阿柏西普玻璃体内注射或阿柏西普玻璃内注射联合曲安奈德后部眼球筋膜下注射,连续注射3次。分别于注射前和注射第3次后1、3、6mo进行复查视力(BCVA)、黄斑中心凹厚度(CMT)及眼压的改变。结果:两组患者在治疗后1、3、6mo的BCVA及CMT均明显好转(P<0.05)。观察组治疗后1mo平均眼压较前升高,但仍在正常范围,两组眼压比较有差异(17.50±4.60 vs 18.30±3.73mmHg,P<0.05)。结论:曲安奈德后部眼球筋膜下注射联合阿柏西普玻璃体内注射治疗湿性ARMD,有效地减轻黄斑区水肿并改善视力,更加安全可靠。     

阿柏西普与雷珠单抗治疗湿性黄斑变性的效果比较

目的:比较阿柏西普与雷珠单抗玻璃体内注射治疗湿性年龄相关性黄斑变性(AMD)的临床效果。方法:前瞻性随机对照研究。收集2019年4至6月郑州市第二人民医院湿性AMD 79例(79眼)随机分为两组。阿柏西普组,39例(39眼),玻璃体内注射阿柏西普;雷珠单抗组,40例(40眼),玻璃体内注射雷珠单抗。术后6个月及12个月...     

阿柏西普与雷珠单抗治疗湿性黄斑变性的效果比较

目的比较阿柏西普与雷珠单抗玻璃体内注射治疗湿性年龄相关性黄斑变性(AMD)的临床效果。方法前瞻性随机对照研究。收集2019年4至6月郑州市第二人民医院湿性AMD 79例(79眼)随机分为两组。阿柏西普组, 39例(39眼), 玻璃体内注射阿柏西普;雷珠单抗组, 40例(40眼), 玻璃体内注射雷珠单抗。术后6个月及12个月随访观察, 比较两组的治疗效果。结果术后6个月及12个月, 两组视力均优于术前(t=5.680, 5.310;均P<0.001), 但两组间差异无统计学意义(t=1.420, 1.066;P=0.160, 0.290)。两组术后黄斑中心区厚度(CMT)均低于术前(t=6.900, 7.499;均P<0.001), 但两组间差异无统计学意义(t=0.262, 0.412;P=0.794, 0.681)。阿柏西普组的平均注射次数(7.63±1.25)次, 少于雷珠单抗组的(8.72±1.62)次(t=-3.342, P=0.002)。结论玻璃体内注射阿柏西普或雷珠单抗治疗湿性AMD均能降低CMT, 提高视力, 阿柏西普注射次数较少。     

玻璃体腔内注射阿柏西普或雷珠单抗治疗糖尿病视网膜病变疗效的Meta分析

目的:采用Meta分析系统评估玻璃体腔内注射阿柏西普或雷珠单抗治疗糖尿病视网膜病变(DR)的疗效。方法:使用PubMed、MEDLINE、Web of Science、Cochrane、Nature Series、ScienceDirect、ESI等数据库进行数据检索。共纳入10项研究行玻璃体腔内注射阿柏西普或雷珠单抗治疗,1240例糖尿病性视网膜病变(DR)患者。使用RevMan 5.3进行Meta分析。结果:合并结果显示IVA组(IVA,玻璃体腔内注射阿柏西普)黄斑中心厚度(CMT)显著降低(P<0.00001);与IVR组(IVR,玻璃体内注射雷珠单抗)相比,最佳矫正视力(BCVA)和视力(VA)没有明显改善。结论:研究表明IVA和IVR对治疗DR均有成效。但阿柏西普有利于改善CMT,而雷珠单抗更有利于提高BCVA或VA。     

视网膜分支静脉阻塞继发黄斑水肿的治疗进展

黄斑水肿（macular edema， ME）是视网膜分支静脉阻塞（branch retinal vein occlusion，BRVO）的常见并发症，也是导致视力下降的主要原因。目前，BRVO继发ME的治疗主要包括黄斑格栅样激光光凝和玻璃体内注射激素或抗血管内皮生长因子药物。激素类药物主要包括曲安奈德和地塞米松玻璃体植入剂，抗血管内皮生长因子药物包括雷珠单抗、贝伐单抗、阿柏西普、康柏西普。玻璃体切割术是BRVO继发ME一种有前景的治疗方法。     

玻璃体内注射阿柏西普治疗顽固性糖尿病黄斑水肿的疗效

目的研究玻璃体内注射阿柏西普治疗顽固性糖尿病黄斑水肿的短期效果。方法收集2018年6月至2019年6月来我院眼科就诊的顽固性糖尿病黄斑水肿患者30例(30眼),行玻璃体内注射阿柏西普治疗。治疗前所有患者均接受过至少3次的玻璃体内注射雷珠单抗治疗,随访期为1个月。在术前及术后1个月时,检查患者最佳矫正视力(best corrected vision acuity,BCVA)和眼压,并行黄斑区光学相干断层成像检查,记录黄斑中心区厚度(central macular thickness,CMT)。比较治疗前后各组数据差异。结果 BCVA从阿柏西普治疗前的(0.61±0.26)logMAR提升至治疗后1个月的(0.51±0.19)logMAR,差异有统计学意义(P=0.016)。治疗前CMT为(441.77±108.09)μm,治疗后1个月CMT为(354.47±83.93)μm,差异有统计学意义(P<0.001)。治疗前及治疗后1个月眼压相比,差异无统计学意义(P>0.05)。在随访期间未发现任何眼部及全身相关并发症。结论对于雷珠单抗不应答的顽固性糖尿病黄斑水肿患者,转为阿柏西普...     

阿柏西普与雷珠单抗治疗糖尿病性黄斑水肿的疗效比较

目的：分析阿柏西普和雷珠单抗对糖尿病性黄斑水肿治疗的疗效。

方法：前瞻性研究。选择2019-11/2020-02于邢台市人民医院眼科首次就诊的糖尿病性黄斑水肿(DME)的患者纳入研究,随机按治疗方式分为阿柏西普组与雷珠单抗组,采用3+PRN(pro re nata)的治疗方案,两次注射时间间隔至少4wk,所有患者均先注射3次,随访时根据患者的最佳矫正视力(BCVA)及黄斑部中心凹视网膜厚度(CFT)的大小决定是否再次注射,患者均完成12mo随访,记录治疗前后两组患者的BCVA、CFT、眼压以及注射次数的变化。

结果：两组患者的BCVA、CFT在术前及术后随访中均有差异(P<0.05),两组间BCVA及CFT随访期间均无差异(P>0.05)。随访结束时,阿柏西普组平均注射次数为6.094±0.689次,雷珠单抗组为7.231±0.652次,比较无差异(t=-6.403,P<0.05)。所有患者均未出现眼部并发症以及全身不良反应。

结论：与玻璃体腔注射雷珠单抗比较,注射阿柏西普注射液治疗DME能取得相似的治疗效果,且注射次数更少。     

新型双特异性单抗Faricimab治疗糖尿病性黄斑水肿及年龄相关性黄斑变性的研究进展

糖尿病性黄斑水肿(DME)和年龄相关性黄斑变性(ARMD)是世界范围内视力损害和失明的主要原因，二者共同的病理特征是血管通透性增加和异常新生血管，血管内皮生长因子(VEGF)及血管生成素-2(Ang-2)等细胞因子在其中起着重要作用。抗VEGF制剂玻璃体内注射显著改变了DME和ARMD的临床管理，但无反应病例的存在、频繁注射带来的治疗负担及风险等局限性需要克服。Faricimab是一种同时靶向阻断VEGF-A和Ang-2的新型双特异性单抗，可有效降低血管通透性、减少新生血管数量和减轻视网膜水肿。注册临床研究显示Faricimab可有效改善视力和消退视网膜积液，相较于阿柏西普和雷珠单抗具有非劣效性，能维持较长的给药间隔，同时具有较高的安全性。本文就Faricimab在DME和ARMD治疗中的最新进展做一综述。     

Riss des retinalen Pigmentepithels durch intravitreale Aflibercept-Injektion

Development of tears in the retinal pigment epithelium (RIP) has been described as a possible complication following anti-vascular endothelial growth factor (VEGF) antibody therapy with substances which have been available for years when treating pigment epithelium detachment (PED) in eyes affected by age-related macular degeneration (AMD). Aflibercept has become available for the treatment of exsudative AMD since December 2012. This case report describes a further patient in addition to the only other case published so far who developed RIP after aflibercept treatment for PED. Patients have to be thoroughly informed about this potential side effect before initiation of intravitreal aflibercept injection therapy.     

Treatment of Retinitis Pigmentosa-Associated Cystoid Macular Oedema Using Intravitreal Aflibercept (Eylea) despite Minimal Response to Ranibizumab (Lucentis): A Case Report

BackgroundWe present an interesting case of bilateral retinitis pigmentosa (RP)-associated cystoid macular oedema that responded on two separate occasions to intravitreal injections of aflibercept, despite previously demonstrating only minimal response to intravitreal ranibizumab. This unique case would support a trial of intravitreal aflibercept for the treatment of RP-associated cystoid macular oedema.ConclusionsThis is the first case report to demonstrate a reduction of RP-associated CMO following intravitreal aflibercept, despite inadequate response to ranibizumab on two separate occasions. Aflibercept may provide superior action to other anti-VEGF medications due to its intermediate size (115 kDa) and higher binding affinity. This is worthy of further investigation in a large prospective cohort over an extended time to determine the safety and efficacy of intravitreal aflibercept for use in this condition.Key Words: Aflibercept, Cystoid macular oedema, Eylea, Retinitis pigmentosa     

Aflibercept for diabetic macular oedema: a Meta-analysis of randomized controlled trials

AIM: To evaluate the relative efficacy and safety of aflibercept for treatment of diabetic macular oedema (DMO). METHODS: A comprehensive search in MEDLINE, CENTRAL and EMBASE was undertaken for randomized controlled trials (RCTs) comparing intravitreal anti-vascular endothelial growth factor (anti-VEGF) versus another treatment. Primary outcome measures were proportion of patients with at least 15 letters of gain or loss on a logMAR visual acuity chart, and change in best corrected visual acuity (BCVA) and central macular thickness (CMT) from baseline. Safety outcomes were rates of death, thromboembolic events and any systemic or ocular serious adverse events. The final search was performed on November 2017. RESULTS: Four RCTs were included. Only one trial compared efficacy and safety of aflibercept with bevacizumab and ranibizumab over 1 or 2y. Three trials were included for Meta-analysis comprising 661 patients (331 in the aflibercept, and 330 in the photocoagulation group). Aflibercept was more efficacious compared to photocoagulation in the proportion of patients with at least 15 letters of improvement and worsening, and in improvement of BCVA and reduction in CMT at 1 or 2y. The safety estimates at 1 or 2y did not differ statistically. CONCLUSION: Aflibercept offers superior benefits over photocoagulation in improving and preserving vision, with no differences in safety. Further comparative effectiveness trials between aflibercept and other anti-VEGF agents will aid ophthalmologists in treatment decisions.     

Zytokinbestimmung aus Glaskörperproben bei retinalen Gefäßerkrankungen

Purpose

The aim of this study was to determine cytokine levels from vitreous samples of treatment-naive patients with diabetic retinopathy (DRP), retinal vein occlusion (RVO) and exudative age-related macular degeneration (ARMD).

Methods

In this study 187 patients (median age 67 years, 101 males) were treated with a combined drug therapy including a 23-gauge core vitrectomy. Interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1) and intravitreal vascular endothelial growth factor (VEGF-A) levels were determined a using cytometric bead assay (CBA) and compared to those of the control group.

Results

Compared to the control group all diseases had significantly elevated cytokine levels, except VEGF in ARMD. In DRP samples of patients with diffuse diabetic macula edema (DME) higher VEGF-A and MCP-1 levels were found than in patients with focal DME. Ischemic DRP had higher VEGF levels than non-ischemic DRP. All measured cytokines were significantly higher in central retinal vein occlusion (CRVO) than in branch retinal vein occlusion (BRVO).

Conclusions

Differences in intravitreal cytokine levels in DRP, RVO and ARMD could be demonstrated. The knowledge of depicted specific characteristic dysregulation of cytokines could allow more targeted future therapies.     

新生血管性年龄相关性黄斑变性治疗进展

年龄相关性黄斑变性是西方国家65岁以上人群视力损害和视力丧失的重要原因,是目前我国第三大致盲性眼病,主要影响中心视力。血管内皮生长因子在新生血管性年龄相关性黄斑变性的发病机制中起着重要的作用,目前抗血管内皮生长因子治疗已成为临床一线治疗方法。但仍有一部分患者需反复注射或不应答,因此需探索新的治疗方式进一步完善当前治疗,为今后新生血管性年龄相关性黄斑变性的治疗提供新思路。     

Detection of inducible nitric oxide synthase and vascular endothelial growth factor in choroidal neovascular membranes

Vascular endothelial growth factor (VEGF) is among the cytokines which have been implicated in the pathogenesis of choroidal neovascularization secondary to age-related macular degeneration (ARMD). There is, however, evidence that intercellular signaling molecules, such as nitric oxide (NO), are involved in this process. NO is synthesized via the inducible isoform of NO synthase (iNOS), which is expressed after induction by cytokines. In the current study, we investigated whether VEGF and iNOS are coexpressed in choroidal neovascular membranes (n = 7) from patients with ARMD. Immunohistochemistry was performed on cryosections with anti-iNOS and anti-VEGF. Moderate to intense immunostaining for iNOS and VEGF was observed in retinal pigment epithelial cells, macrophages, and in spatial relation to vessel walls. As scored by light microscopy, we found a significant correlation between immunoreactivity for VEGF and iNOS (p < 0.0341) in vascular endothelial cells. Our study supports a significant role for iNOS in the pathogenesis of neovascularization and membrane growth in ARMD. Moreover, our findings suggest a possible relationship between NO and VEGF in the regulation of pathologic angiogenesis in this disease.     

阿柏西普对葡萄膜黑色素瘤细胞的作用及其机制研究

目的 探索阿柏西普对葡萄膜黑色素瘤细胞的作用及其机制.方法 将B16F10细胞(葡萄膜黑色素瘤细胞)分为实验组和对照组,对照组不使用药物处理,实验组分别用0.2 g·L-1、2.0 g·L-1、4.0 g·L-1阿柏西普进行干预.通过实时细胞电子分析系统(RT-CES)、CCK-8法探讨不同剂量的阿柏西普对葡萄膜黑色素...