玻璃体内注射抗血管内皮生长因子类药物的并发症

玻璃体内注射抗血管内皮生长因子(VEGF)类药物治疗是目前视网膜脉络膜新生血管性疾病研究的热点.临床应用时应重视由于玻璃体内注射本身、药物对眼组织的毒性作用、药物全身吸收后副作用等原因可产生一些眼部(如眼内炎、晶状体损伤、视网膜脱离、视网膜色素上皮撕裂等)及全身并发症(如血压升高、视幻觉、过敏反应等).     

玻璃体内注射贝伐单抗治疗早产儿视网膜病变的临床进展

血管内皮细胞生长因子(VEGF)在早产儿视网膜病变(ROP)的发生过程中发挥重要作用.在ROP的新生血管增生阶段,应用抗VEGF类药物抑制VEGF可以阻断视网膜血管的异常增生.本文就抗VEGF类药物贝伐单抗(Avastin)单纯玻璃体内注射、玻璃体内注射联合视网膜光凝或玻璃体切除手术等不同方式治疗ROP的临床研究进行回顾,并就贝伐单抗治疗ROP的安全性评价进行汇总.     

抗VEGF治疗在儿童眼底病中的应用

血管内皮生长因子(VEGF)是胚胎时期眼球发育过程中血管形成的关键介质,也是在多种眼科疾病中引起视网膜新生血管形成和血管通透性改变的重要因子。随着抗VEGF治疗在成人的应用逐渐成熟,越来越多的研究关注于抗VEGF治疗在儿童眼底病的应用,包括早产儿视网膜病变(ROP)、Coats病、家族性渗出性玻璃体视网膜病变(FEVR)、色素失禁症相关视网膜病变、镰状细胞视网膜病、视网膜母细胞瘤及各种病因引起的脉络膜新生血管等。本文将对抗VEGF在这些眼底病中的应用现状作一综述。     

抗血管内皮生长因子药物治疗糖尿病视网膜病变的研究现状

糖尿病可引起眼内血管内皮生长因子（vascularendothelialgrowthfactor,VEGF）水平病理性升高,导致眼内新生血管形成、黄斑水肿的发生。抗VEGF药物最早被用于湿性年龄相关性黄斑变性,现也被试验性地用于糖尿病视网膜病变（diabeticretinopathy,DR）。VEGFl65选择性拮抗剂Pe—gaptanib与VEGF—A单抗Ranibizumab被批准玻璃体内注射,且对DR有较好的疗效;VEGF．A全长抗体Bevacizumab被标示外用于玻璃体内注射治疗DR,也能达到较好的效果;重组融合蛋白Aflibercept针对DR的疗效也得到一些试验的支持。玻璃体内注射抗VEGF药物治疗DR已被证实短期有效且安全,但其长期的疗效与安全性有待更多的大规模临床试验来验证。     

自体视网膜色素上皮-脉络膜薄片移植术治疗年龄相关性黄斑变性

目前对于渗出性年龄相关性黄斑变性（AMD）的治疗主要有温热疗法、光动力疗法和玻璃体内注射抗血管内皮生长因子等疗法。手术彻底去除脉络膜新生血管（CNV）不可避免地会造成视网膜色素上皮（RPE）、Bruch膜和脉络膜毛细血管的损伤。黄斑转位术虽可使RPE维持黄斑中心凹光感受器的功能，但由于增生性玻璃体视网膜病变、黄斑水肿和复视等并发症的发生率较高而限制其应用。     

血管内皮生长因子抑制剂在糖尿病性视网膜病变中的应用

眼部新生血管是糖尿病性视网膜病变致盲的主要病理改变,而血管内皮生长因子（vascular endothelial growth factor,VEGF）在新生血管形成过程中起关键性刺激作用。VEGF抑制剂主要通过与VEGF结合并阻断其生物活性而起作用,从而达到抑制眼部新生血管生成的目的,在糖尿病性视网膜病变血管渗漏及新生血管形成的治疗中取得了显著的成绩。Bevacizumab（Avastin）是VEGF抑制剂之一,属于重组人源化单克隆抗体,因其疗效良好、价格低廉已被广泛应用于临床。现将VEGF抑制剂（尤其是Avastin）治疗糖尿病性视网膜病变的相关应用进展作一综述。     

抗血管内皮生长因子在辅助增生性糖尿病视网膜病变手术治疗中的应用

增生性糖尿病视网膜病变(PDR)是糖尿病患者严重眼部并发症之一,是导致患者失明的主要原因.玻璃体切除术(PPV)是治疗严重玻璃体积血、增生性糖尿病视网膜病变的有效方法.但是由于PDR患者眼内血管内皮生长因子(VEGF)浓度异常增高,使得玻璃体腔内和视网膜表面存在大量的新生血管,极易渗漏、出血,术中常常出现活动性出血而降低手术野的清晰度,降低操作精准度进而影响手术进程.在较严重活动性出血的情况下,继续进行气/液交换可导致血小板的残留,术后再次出现机化膜的概率非常高,严重影响手术的成功率.另外,新生血管可引起术后前房出血、再次玻璃体积血以及视网膜表面出血等,炎症、积血造成的术后高眼压,机化膜再次牵拉视网膜脱离等并发症也将随之而来,严重影响其术后视功能的恢复和远期预后.随着近几年抗VEGF药物的广泛临床应用,研究发现PPV前玻璃体腔注射抗VEGF药物可抑制新生血管的活动性,显著减少术中及术后出血的发生,降低手术难度,缩短手术时间,有效提高手术成功率.本文就抗VEGF辅助PPV治疗增生性视网膜病变的分子机制、临床应用、有效性及安全性等进行综述.     

阿柏西普治疗眼底新生血管性疾病

眼底新生血管性疾病的预后主要取决于新生血管的形成情况.目前认为血管内皮生长因子(vascular endothelial growth factor,VEGF)是促新生血管生成最重要的诱导因子,也是抗新生血管治疗中重要的治疗靶点.阿柏西普是最新一代的抗VEGF药物,可以与VEGF-A、VEGF-B、血小板源性生长因子(platelet-derived growth factor,PDGF)所有亚型相结合,与VEGF有更高的亲和力,用于治疗湿性年龄相关性黄斑变性、视网膜静脉阻塞、糖尿病视网膜病变及息肉样脉络膜血管病变,能够提高患者最佳矫正视力和减少中央视网膜厚度,同时在某些其他抗VEGF无应答患者的治疗中亦获得较好效果.     

抗VEGF时代激光光凝治疗糖尿病视网膜病变的再认识

增生性糖尿病视网膜病变（proliferative diabetic retinopathy,PDR）是糖尿病致盲的主要原因。全视网膜光凝（panretinal photocoagulation,PRP）是目前治疗PDR的标准方法,但是存在加重黄斑水肿、导致周边视野缺失等不良反应。玻璃体注射抗血管内皮生长因子（vascular endothelial growth factor,VEGF）药物可有效抑制视网膜和视盘新生血管,改善糖尿病视网膜病变的严重程度,展示了替代PRP治疗糖尿病视网膜病变的良好前景。正确认识抗VEGF药物的临床价值,探索PRP联合抗VEGF疗法的模式和方法有助于改善PDR的治疗预后。     

玻璃体内注射雷珠单抗联合激光光凝治疗早产儿视网膜病变疗效观察

目的　观察激光光凝联合玻璃体内注射雷珠单抗治疗早产儿视网膜病变（retinopathy of prematurity,ROP）的安全性及有效性。方法　对32例（64眼）ROP患儿行玻璃体内注射雷珠单抗治疗,观察附加病变、嵴、嵴上新生血管的消退情况以及周边视网膜,其中12例（24眼）附加病变、嵴及嵴上新生血管不完全消退者进行激光光凝治疗。结果　32例64眼ROP患儿中,经玻璃体内注射雷珠单抗治疗病变完全消退者20例40眼,占62.5%;12例24眼病变复发,经联合激光光凝治疗病情稳定,占37.5%。病变复发的24眼中,包括急进型后极部ROP 14眼,阈值期ROP 6眼,阈值前期ROP 4眼。所有患儿视网膜病变不同程度消退。给予玻璃体内注射雷珠单抗治疗后新生血管及出血吸收,血管继续发育至锯齿缘或病变瘢痕化。12例（24眼）病变复发者联合视网膜光凝治疗后病变完全消退。32例ROP患儿眼部及全身未见不良反应。结论　玻璃体内注射雷珠单抗治疗ROP效果好,不但可以使嵴、嵴上新生血管及附加病变完全消退,而且还可使视网膜血管继续生长,对于病变不能完全消退的患儿联合视网膜激光光凝治疗后也可获得较好疗效。     

糖尿病性黄斑水肿抗VEGF治疗对视网膜毛细血管影响的研究进展

抗血管内皮生长因子(vascular endothelial growth factor,VEGF)药物对于治疗视网膜疾病,比如渗出性年龄相关性黄斑变性、糖尿病视网膜病变(diabetic retinopathy,DR)、视网膜静脉阻塞具有革命性意义。玻璃体腔内注射抗VEGF药物后能明显减轻黄斑水肿,但同时是否也会破坏视网膜微循环、加快视网膜毛细血管闭塞？本文通过相干光断层扫描血流成像(optical coherence tomography angiography,OCTA)和超广角眼底血管造影(ultra-widefield fluorescein angiography,UWFA)技术观察糖尿病性黄斑水肿(diabetic macular edema,DME)患者抗VEGF治疗对视网膜毛细血管的影响,从黄斑无血管区面积、无灌注区大小及血流密度三方面进行综述。     

抗VEGF药物在视网膜血管性疾病围手术期的应用

血管内皮生长因子（VEGF）与新生血管性眼病密切相关,是有效的治疗靶点.抗VEGF药物能减少新生血管形成,降低血管通透性,为新生血管性眼病的治疗带来重大变革.目前雷珠单抗在国内已被批准用于湿性年龄相关性黄斑变性的治疗,在美国被批准用于糖尿病性黄斑水肿和视网膜静脉阻塞后黄斑水肿的治疗.抗VEGF药物也作为适应证外治疗药物用于其他新生血管性眼病的治疗,如增生性糖尿病视网膜病变、其他视网膜血管性疾病和新生血管性青光眼等.抗VEGF药物辅助手术治疗显示出明显的疗效,可减少术中、术后的并发症和疾病的复发率.就贝伐单抗和雷珠单抗等抗VEGF药物在视网膜血管性疾病围手术期的应用情况进行综述.     

Effect of anti-VEGF treatment on nonperfusion areas in ischemic retinopathy

In recent years, retinal ischemia such as that which occurs in diabetic retinopathy (DR) and retinal vein occlusion (RVO) has become a hotspot of ischemic retinopathy research. High levels of vascular endothelial growth factor (VEGF) are recognized as a major cause of macular edema (ME) in DR and RVO. High concentrations of VEGF in the vitreous can lead to serious retinal ischemia and hypoxia and form retinal nonperfusion areas (NPAs). Different levels of retinal ischemia can represent disease severity and progression. Anti-VEGF therapy as the first-line treatment for ME has been found to be effective in improving vision, but there are still disputes about whether anti-VEGF therapy could improve retinal ischemia and achieve reperfusion of previously developed retinal NPAs. Here, we review and summarize studies of the effects of anti-VEGF drugs on retinal ischemia, especially NPAs.     

Fundus fluorescein angiography imaging of retinopathy of prematurity in infants: A review

Fluorescein angiography in retinopathy of prematurity is increasingly utilized over the past decade. The development of ultra-wide-field imaging combined with fluorescein angiography has allowed improved visualization of the peripheral retinal vasculature. Patient cooperation in the pediatric population is particularly challenging, but hand-held digital retinal photography has shown promise and can visualize the infant retina without the need for anesthesia and intravenous access. Many features of retinopathy of prematurity and its response to laser and anti-VEGF treatment can be either exclusively or better visualized on fluorescein angiography compared to indirect ophthalmoscopy or color fundus photography. Disease treatment is gradually shifting from laser photocoagulation to intravitreal anti-VEGF agents, the latter being associated with late-onset vision-threatening sequelae. The role of fluorescein angiography in retinopathy of prematurity monitoring will continue to increase with the longer follow-up required and different clinical behavior seen with anti-VEGF treatment. We highlight the utility, safety, and importance of fluorescein angiography in the diagnosis, treatment, and follow-up of retinopathy of prematurity.     

A review of anti-VEGF agents for proliferative diabetic retinopathy

Previous research has implicated vascular endothelial growth factor (VEGF) in the pathogenesis of diabetic retinopathy (DR). Although many studies reviewed the use of anti-VEGF for diabetic macular oedema, little has been written about the use of anti-VEGF for proliferative diabetic retinopathy (PDR). This study is a review of relevant publications dealing with the use of anti-VEGF for the treatment of PDR. The articles were identified through systematic searches of PUBMED and the Cochrane Central Register of Controlled Trials. At the end of each section, we summarized the level of evidence of the scientific literature. Off-label use of anti-VEGF agents was found to be beneficial in PDR, especially in cases with neovascular glaucoma, persistent vitreous haemorrhage, and before vitrectomy. The disadvantages of the use of anti-VEGF are its short-effect duration, causing tractional retinal detachment in cases with pre-existing pre-retinal fibrosis and endophthalmitis in rare cases. There is no conclusive evidence from large randomized trials regarding the efficacy of anti-VEGF treatment in PDR. However, numerous case series, sound biochemical mechanism of action, and increasing experience with using anti-VEGF drugs can be used to support the ongoing use of this treatment modality in selected patients.     

抗VEGF时代激光视网膜光凝在视网膜静脉阻塞临床管理中的价值

视网膜静脉阻塞(retinal vein occlusion, RVO)是仅次于糖尿病视网膜病变的常见视网膜血管疾病,其视力损害的主要原因是黄斑水肿(macular edema,ME)和眼部新生血管(neovascularition,NV)并发症,尤其是新生血管性青光眼(neovascular glaucoma,NVG)。虽然激光视网膜光凝治疗ME、NV和NVG的疗效早已明确,但抗VEGF治疗可有效改善RVO患者的视力预后,已成为RVO-ME的一线治疗方法,也有助于治疗NV和NVG。近期研究表明,增加激光治疗并不能增加抗VEGF治疗RVO-ME的视力收益,也不能降低抗VEGF注射次数;抗VEGF治疗不能阻止,但可延迟缺血性RVO发生NV并发症。播散性激光视网膜光凝仍是治疗NV并发症的核心方法,但不鼓励预防性激光治疗。(眼科,2022,31:165-168)     

抗VEGF时代激光光凝治疗糖尿病视网膜病变的应用进展

糖尿病视网膜病变(DR)是糖尿病患者最普遍和最严重的眼部并发症,也是成人失明的主要原因之一。近年来,以抗血管内皮生长因子(VEGF)制剂为代表的药物治疗已成为DR的一线疗法,但不能逆转视网膜无灌注区、微动脉瘤和毛细血管异常扩张,不能按时接受治疗者有病情进展风险。激光疗法的广泛应用已有40多年历史,可通过消除毛细血管无灌注区,有效降低致盲率,其中广泛视网膜光凝治疗(PRP)一直是DR的主要治疗方法。激光技术不断改进和发展,在保持疗效的基础上,实现了视网膜损害与副作用最小化的目标。通过联合抗VEGF制剂,可实现优势互补,达到更佳疗效。加深对激光及激光联合抗VEGF制剂治疗DR的临床研究,有助于建立符合我国国情的个性化治疗方案。本文就抗VEGF时代激光在DR治疗中的应用进展进行简要综述。     

Adverse events and complications associated with intravitreal injection of anti-VEGF agents: a review of literature

Intravitreal injection of anti-vascular endothelial growth factor (VEGF) agents is increasingly used for the treatment of a wide variety of retinal diseases, including age-related macular degeneration, diabetic retinopathy and retinal vascular occlusions, and retinopathy of prematurity. Despite encouraging results in halting the disease and improving the vision, intravitreal injection of anti-VEGF agents may be associated with systemic adverse events and devastating ocular complications. In this review, we provide an overview of safety data for intravitreal injection of common anti-VEGF agents.