VEGF在糖尿病视网膜病变发病机制中的作用及抗VEGF靶向治疗新进展

糖尿病视网膜病变(diabetic retinopathy,DR)是糖尿病最常见的并发症之一。DR的发病机制十分复杂,至今尚未完全阐明。目前认为DR患者会出现视网膜毛细血管阻塞,可导致局部缺氧,由此引起促新生血管因子产生增多,其中包括VEGF。VEGF是促新生血管形成的主要因子之一,会降低血管内皮细胞间的紧密连接蛋白表达,参与血管炎症反应、增加血管通透性和促进新生血管形成。近年来有关DR的发病机制以及治疗的研究越来越深入。本文旨在阐述VEGF在DR发病机制中的作用,以及抗VEGF治疗策略的最新进展。     

抗VEGF药物治疗早产儿视网膜病变的研究进展

早产儿视网膜病变(retinopathy of prematurity,ROP)是目前全世界儿童致盲的主要原因之一[1]。以往对于阈值期和高危阈值前期的ROP采用激光或冷凝治疗,因激光和冷凝术均是破坏性的,不可避免地导致周边视野永久丧失,且并发症较多,术后仍有部分患儿病情无法控制,最终视力完全丧失。因此需要寻找新的治疗方法,近年来有较多的临床数据表明,玻璃体内注射抗血管内皮生长因子(anti-vascular endothelial growth factor,anti-VEGF)治疗ROP是一种有效的治疗方法。我们将对抗VEGF药物在ROP治疗的研究进展进行近期的文献综述。     

抗VEGF药物在PDR患者玻璃体切割手术前应用的临床研究

目的 探讨在增殖性糖尿病性视网膜病变患者进行玻璃体手术之前进行抗VEGF药物治疗对其手术难度、术中术后并发症及疗效情况等的影响.方法 选取安徽省立医院2018-08至2020-05诊断为增殖性糖尿病性视网膜病变(PDR)并拟予以23G玻璃体切割术进行治疗的患者43人50例患眼.将50例患眼分为眼内注药组与对照组,其中眼...     

抗血管内皮生长因子玻璃体内注射治疗不同区域早产儿视网膜病变的疗效观察

目的 观察抗血管内皮生长因子(vascular endothelial growth factor,VEGF)治疗不同区域早产儿视网膜病变的临床效果.方法 回顾性分析2013年4月至2014年4月在郑州儿童医院行玻璃体内注射抗VEGF药物的早产儿视网膜病变患儿24例(46眼),分为Ⅰ区病变组15例(28眼),Ⅱ区病变组9例(18眼).所有患者均在全身麻醉下行玻璃体内注射抗VEGF药物雷珠单抗,对患儿术后眼底进展情况进行观察,分析两组首次注射治愈和进展情况以及并发症发生情况.结果 两组间的出生孕周、出生体质量相比,差异均无统计学意义(均为P ＞0.05);手术矫正孕周相比,差异有统计学意义(P=0.001).24例(46眼)中,首次注射治愈21眼,病情继续发展25眼,治愈率为45.65％,治疗到治愈的时间间隔为2～12个月.Ⅰ区病变组首次注射治愈9眼,治愈率为32.14％,进展率为67.86％;Ⅱ区病变18眼中12眼首次注射治愈,6眼病情继续进展,治愈率为66.67％,进展率为33.34％.两组首次注射治愈率相比,差异有统计学意义(x2=5.263,P=0.022),Ⅰ区病变的首次注射治愈率明显低于Ⅱ区病变.两组进展率相比,差异有统计学意义(x2=-2.269,P=0.023),Ⅰ区病变的进展率明显高于Ⅱ区病变.随访中未发现与玻璃体内注射有关的白内障、眼内炎、视网膜裂孔等出现,仅有2例出现角膜水肿,4例出现结膜下出血,均未做特殊处理自愈.结论 玻璃体内注射抗VEGF药物对于Ⅰ区、Ⅱ区病变均有效,Ⅰ区病变手术成功率低,再次手术的几率大,但可为再次手术创造时间和条件.     

早产儿视网膜病变抗VEGF治疗进展

早产儿视网膜病变(retinopathy of prematurity, ROP)是发生于早产儿的一种未成熟视网膜血管增生性眼病,是发展中及发达国家儿童致盲的主要因素。ROP的传统治疗方法是视网膜激光光凝或冷冻治疗,但凝固治疗可导致视网膜永久性破坏,存在发生视野缺损、高度近视等并发症风险。玻璃体腔注射抗血管内皮细胞生长因子(VEGF)药物治疗ROP后视网膜功能的发育比凝固治疗更趋向正常,再加上操作简便、耗时短等优点,玻璃体腔注射抗VEGF药物逐渐成为ROP的重要治疗方式; 在Ⅰ区ROP、Ⅱ区后部ROP和急进型ROP治疗中为首选治疗方式。但是抗VEGF药物治疗ROP所致的严重系统并发症、最低有效剂量及后期复发情况等问题尚待进一步研究。本文将对ROP抗VEGF治疗现状进行综述。     

VEGF在糖尿病性视网膜病变发病机制中的作用及抗VEGF治疗新进展

糖尿病性视网膜病变是世界新发致盲因素之一。血管内皮生长因子（ｖａｓｃｕｌａｒｅｎｄｏｔｈｅｌｉａｌｇｒｏｗｔｈｆａｃｔｏｒ,ＶＥＧＦ）是糖尿病性视网膜病变发病机制中的关键因子,成为近年研究的热点。近年来,抗ＶＥＧＦ药物成为新生血管性及血管性眼底疾病的重要治疗药物,本文就ＶＥＧＦ在糖尿病性视网膜病变病理进程中的作用及抗ＶＥＧＦ治疗新进展作一综述。     

早产儿视网膜病变抗血管内皮生长因子药物治疗新进展

早产儿视网膜病变（retinopathy of prematurity,ROP）是一种进行性视网膜血管异常生长、病理性新生血管形成的致盲性眼病。传统一线治疗激光光凝,存在治疗相对滞后、不可逆周边视野缺损等局限性。近年来,以哌加他尼钠、贝伐单抗、雷珠单抗、阿柏西普和康柏西普等为代表的抗血管内皮生长因子药物已广泛用于眼底新生血管性疾病,尤其在ROP治疗中不断取得新的进展,并成为其基础和临床研究的焦点和热点。     

玻璃体腔注射抗VEGF药物治疗早产儿视网膜病变的研究进展

早产儿视网膜病变(ROP)是发生于早产儿的一种未成熟视网膜血管增殖性眼病,是一种严重的儿童致盲性眼病。视网膜激光光凝术是治疗ROP的经典方法,然而激光治疗是破坏性的,尤其是在ROP Ⅰ区病变的情况下,视网膜激光光凝治疗会引起严重的并发症。研究表明,血管内皮细胞生长因子(VEGF)在ROP发生及发展过程中具有关键作用,而玻璃体腔注射抗VEGF药物不仅能有效控制ROP,并且为视网膜继续发育争取了机会。本文就玻璃体腔内注射抗VEGF药物治疗ROP的治疗指征、药物筛选、注射部位、给药剂量、疗效观察以及并发症对其进行综述。     

VEGF和PEDF在增殖性糖尿病视网膜病变中的研究进展

增殖性糖尿病视网膜病变( proliferative diabetic retinopathy,PDR)是一种以眼内新生血管形成为特征的糖尿病并发症。眼内新生血管的形成是当今世界主要致盲原因之一。血管内皮生长因子( vascular endothelial growth factor,VEGF)与色素上皮衍生因子( pigment epithelium-derived factor,PEDF)作为眼内新生血管形成最主要的细胞因子,近年来成为研究热点。本文就VEGF和PEDF在PDR中的研究进展进行综述。     

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.     

Mutations in the NDP gene: contribution to Norrie disease, familial exudative vitreoretinopathy and retinopathy of prematurity

Background: To examine the contribution of mutations within the Norrie disease (NDP) gene to the clinically similar retinal diseases Norrie disease, X‐linked familial exudative vitreoretinopathy (FEVR), Coat’s disease and retinopathy of prematurity (ROP). Methods: A dataset comprising 13 Norrie‐FEVR, one Coat’s disease, 31 ROP patients and 90 ex‐premature babies of <32 weeks’ gestation underwent an ophthalmologic examination and were screened for mutations within the NDP gene by direct DNA sequencing, denaturing high‐performance liquid chromatography or gel electrophoresis. Controls were only screened using denaturing high‐performance liquid chromatography and gel electrophoresis. Confirmation of mutations identified was obtained by DNA sequencing. Results: Evidence for two novel mutations in the NDP gene was presented: Leu103Val in one FEVR patient and His43Arg in monozygotic twin Norrie disease patients. Furthermore, a previously described 14‐bp deletion located in the 5′ unstranslated region of the NDP gene was detected in three cases of regressed ROP. A second heterozygotic 14‐bp deletion was detected in an unaffected ex‐premature girl. Only two of the 13 Norrie‐FEVR index cases had the full features of Norrie disease with deafness and mental retardation. Conclusion: Two novel mutations within the coding region of the NDP gene were found, one associated with a severe disease phenotypes of Norrie disease and the other with FEVR. A deletion within the non‐coding region was associated with only mild‐regressed ROP, despite the presence of low birthweight, prematurity and exposure to oxygen. In full‐term children with retinal detachment only 15% appear to have the full features of Norrie disease and this is important for counselling parents on the possible long‐term outcome.     

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。     

伴有严重渗出性视网膜病变的Coats病1例

Coats病是散发的非遗传性疾病,不伴有系统性异常,常单眼发病。我们报道1例27岁俄罗斯Coats病女患者。眼底检查显示左眼下方视网膜血管瘤样改变,血管迂曲扩张、呈串珠状,伴有严重的浆液性视网膜脱离。中心凹亦脱离,有成簇的白色沉积物。     

[In Press] Paediatric retinal detachment: a review

Paediatric retinal detachment (PRD) is an uncommon and challenging disease; it differs from adult detachments in etiology, anatomical characteristics, management and prognosis. PRDs can be particularly challenging, even for the most expert paediatric surgeons due to the higher prevalence of total retinal detachments, late diagnosis and bilateral involvement with respect to those which occur in adulthood. Moreover, the anatomical success, when achieved, is frequently not related to a functional recover. Postsurgical adverse events, refractive errors and amblyopia may additionally undermine the final outcome. Up to date there are few reviews regarding the approach of retinal detachment in children, mainly dealing with rhegmatogenous retinal detachment. In this review, rhegmatogenous, ROP-related and Coats’-related PRDs were considered. The available literature from the last decades werereviewed and summarized. Epidemiology, etiology and clinical presentation, together with therapeutic approaches and outcomes have been reviewed and discussed.     

RNA干扰技术在视网膜疾病治疗中的研究进展

RNA干扰(RNA interference,RNAi)是一种在动物中广泛存在的、通过双链RNA分子在mRNA水平上诱导特异性序列基因沉默的过程。作为一种阻断基因表达的新手段,RNAi技术日趋成熟完善,开辟了一条基因治疗的新途径。RNAi技术能够有效阻止视网膜新生血管的形成,抑制增生性玻璃体视网膜病变的发生和发展,诱导视网膜母细胞瘤细胞的凋亡。现将RNAi技术在上述视网膜病变中的研究进展作一综述。     

Fluorescein angiography of retinal vascular involution after intravitreal injection of ranibizumab for retinopathy of prematurity

AIM: To describe the involution patterns of vessel growth of retina through fluorescein angiography (FA) of children, who had been under treatment up to 1y previously intravitreal ranibizumab (IVR) as monotherapy for retinopathy of prematurity (ROP). METHODS: This is a retrospective study. The medical information and FA of 17 children (34 eyes) whose area of avascular retina from the ora serrata was more than two disc diameters (DD) were analyzed. RESULTS: Among 34 eyes, all were the presence of finger-shaped vessels and arteriolar-venular shunts (100%, 34/34 eyes). Popcorn abnormalities were found in most of the eyes (94.1%, 32/34 eyes). Furthermore, in many cases (23.5%, 8/34 eyes), there were leakage persisting in the region of the junction between avascular and vascular retina. In contrast, just 2 eyes (5.9%) showed damage of retinal capillary bed and 3 eyes (8.8%) showed large area of retinal pigment epithelium (RPE) atrophy. CONCLUSION: Although IVR can be very effective in ROP, we should remain cautious as infants may remain avascular peripheral retinas and abnormal vessel. FA allows accurate visualization of vessel abnormalities in eyes with ROP, which will be helpful to affect assessment of disease activity and therapeutic effect.     

Clinical features and treatment outcomes of intraocular lymphoma: a single-center experience in China

AIM:To investigate the clinical manifestations,diagnostic approaches,treatments,and outcomes of intraocular lymphoma.METHODS:In this retrospective study,16 patients(28 eyes)with intraocular lymphoma were recruited in the Department of Ophthalmology,Peking Union Medical College Hospital,from 2004 to 2019.All patients underwent comprehensive ophthalmic examinations.Vitreous specimens of 13 patients were sent for cytopathology examination and other adjunctive diagnostic procedures.Three patients were diagnosed with intraocular lymphoma according to analysis of the histopathological results of systemic lymphoma by one clinician.Twenty-three eyes were treated with intravitreal administration of methotrexate,4 eyes could not receive ocular treatment due to life-threatening lymphoma,and 1 eye did not require ocular treatment because the fundus lesions regressed after systematic chemotherapy.RESULTS:In 28 eyes,25 eyes were diagnosed with vitreoretinal lymphoma,and 3 eyes were diagnosed with ciliary body lymphoma,all of which were non-Hodgkin diffuse large B cell lymphomas.The final visual acuity improved in 15 eyes(54%),remained unchanged in 5 eyes(18%),and decreased in 8 eyes(29%).Anterior segment inflammation disappeared or reduced in 8 and 5 eyes,respectively;and 15 eyes had no anterior segment reaction.Twenty eyes had mild vitreous opacity,1 eye had mild vitritis,and 7 eyes had pars plana vitrectomy combinedwith silicone oil tamponade.Fundus lesions disappeared in 9 eyes and were relieved in 5 eyes;4 eyes showed no changes,and the remaining 10 eyes’fundus were normal.CONCLUSION:The clinical manifestations of intraocular lymphoma are diverse,and the misdiagnosis rate is high.Cytopathological analysis of vitreous is one of the gold standards for the diagnosis.Immunohistochemistry,gene rearrangement and flow cytometric immunophenotypic analysis can improve the diagnostic rate.Ocular chemotherapy or radiotherapy regimens may preserve visual acuity,and a multidisciplinary team can provide individualized treatment for the patients.     

Transpupillary thermotherapy (TTT) for age-related macular degeneration

Purpose. To review the results of transpupillary thermotherapy (TTT) on choroidal neovascular membranes associated with age-related macular degeneration (AMD). Materials and Methods. 35 eyes of 35 patients with AMD and choroidal neovascularization and exudation were treated with TTT and had fundus photographs and fluorescein angiography (FA) before and at least six months after TTT. 28 eyes had predominantly occult lesions as seen on FA, while 7 demonstrated primarily classic lesions. All were treated with 650 mw power or less using the 810 nm diode laser (3000 micron spot, duration of 60 seconds). Visual acuity, lesion size, and amount of subretinal fluid were determined by results of examination and review of photographs and fluorescein angiograms. Results. A 50% reduction in subretinal fluid was achieved in 67% of treated eyes overall, with stabilization of vision (less than three lines of visual acuity lost) in 86%. Complications from treatment were infrequent (9%) and involved hemorrhage noted in the region of treatment upon follow-up. Conclusion. TTT promotes resolution of subretinal fluid and appears to stabilize visual acuity in patients with exudative AMD.