家族性渗出性玻璃体视网膜病变研究进展

家族性渗出性玻璃体视网膜病变(familial exudative vitreoretinopathy,FEVR)是一种罕见的先天性视网膜血管发育异常性疾病,主要表现为周边部视网膜无血管灌注区.其临床表现多样,轻者可无明显症状而漏诊;中重度者视力极差或失明,可表现为视网膜周边无灌注区伴新生血管形成,视网膜渗出,镰状皱褶,黄斑异位和视网膜脱离等.已发现FEVR相关的突变基因包括FZD4、LRP5、NDP、TSPAN12、ZNF408和KIF11基因,涉及常染色体显性遗传、常染色体隐性遗传、X连锁遗传等多种遗传方式.本文就该病的发病机制、临床特点和分期、致病基因研究进展和鉴别诊断与治疗等方面进行综述.     

家族性渗出性玻璃体视网膜病变

家族性渗出性玻璃体视网膜病变(FEVR)是一种遗传性眼科疾病，是 导致青少年视网膜脱离的原因之一。遗传方式有：常染色体显性遗传、常染色体 隐性遗传或X性连锁遗传。目前与FEVR相关的致病基因有EVR1，EVR2，EVR3，EVR4。临床表 现 多种多样，其眼底特征表现为周边视网膜无灌注和新生血管形成。荧光素眼底血管造影检查 有助于诊断。需与早产儿视网膜病变、Norrie病、视网膜母细胞瘤、Coat's病等相鉴别。 通过筛查发现早期患者可使用激 光光凝或者冷凝治疗周边无血管区；对于晚期患儿主要行巩膜扣带术或玻璃体切割术，但预 后较差。近年来随着对本病分子遗传学和分子生物学研究的深入进展，希望能够找到更加有 效的治疗方法，或者通过早期筛查、早期发现早期治疗，使因为FEVR失明的患者越来越少。      

家族性渗出性玻璃体视网膜病变的诊断与治疗

家族性渗出性玻璃体视网膜病变(familial exudative vitreoretinopathy, FEVR)是一种罕见的遗传性视网膜血管发育异常性疾病,目前已发现的致病基因有FZD4、NDP、LRP5、TSPAN12、ZNF408、KIF11。其临床表现多样,轻者无临床症状,重者可出现视网膜周边无灌注区、新生血管形成、视网膜渗出、玻璃体积血、视网膜褶皱、视网膜脱离等。荧光素眼底血管造影(FFA)检查能发现早期无症状者,可明确病变范围和预示病情发展,指导治疗。患者病变程度不同,治疗方法各异,主要包括：视网膜激光光凝术、巩膜外垫压术、玻璃体切割术及抗-VEGF药物的辅助治疗。随着本病基因研究的进展,有望在分子水平对本病进行诊断,获得更有效的治疗方法。     

家族性渗出性玻璃体视网膜病变

家族性渗出性玻璃体视网膜病变（familialexudative vitreoretinopathy，FEVR）是一种较少见的常染色体显性遗传性眼病，主要表现有玻璃体混浊、周边部视网膜血管异常和新生血管、黄斑异位和牵拉性视网膜脱离等。首先由Criswick和Schepens于1969年报告，国内于1992年和1995年有陆续报告。我们近年来收集6例患者的临床资料，现总结如下。     

家族性渗出性玻璃体视网膜病变相关视网膜脱离的手术治疗及进展

家族性渗出性玻璃体视网膜病变(FEVR)是一种遗传性视网膜血管疾病,最典型的临床特征是周边无血管区,病情进展可导致视网膜脱离,晚期可继发白内障、青光眼、角膜混浊甚至眼球萎缩,是亚洲儿童、青少年视网膜脱离的主要原因之一。FEVR相关视网膜脱离主要通过手术治疗,包括玻璃体切除术、巩膜扣带术,有时联合视网膜光凝术、抗血管内皮生长因子(VEGF)治疗等。手术方式选择有赖于详细的术前、术中评估,包括患眼分型、分期、纤维增殖情况和眼前段并发症等,不同分期患眼解剖及视功能预后大不相同。孔源性视网膜脱离成年患者的手术复位率较为理想,而牵拉性视网膜脱离儿童患者手术复位率相对较低。低龄、晚期患者手术难度大、预后不良,手术治疗策略存在争议。本文就FEVR相关视网膜脱离的手术治疗效果与进展进行综述。     

家族性渗出性玻璃体视网膜病变3例

家族性渗出性玻璃体视网膜病变(familial exudative vitreoretinopathy,FEVR)是一种以玻璃体视网膜病变为主的遗传性疾病,大多数为常染色体显性遗传。主要表现为周边部视网膜血管发育异常、新生血管形成及其继发性眼病如玻璃体混浊、牵拉性视网膜脱离等。临床上较少见,且临床表现差异大,可无症状或因继发眼病而就诊,极易造成漏诊或误诊。我们近来收集3例患者的临床资料现总结如下。     

家族性渗出性玻璃体视网膜病变的荧光素眼底血管造影分析

目的分析家族性渗出性玻璃体视网膜病变的眼底表现及荧光素眼底血管造影(FFA)特征。方法收集我院诊治的家族性渗出性玻璃体视网膜病变患者,进行眼底照相及FFA检查,进行对比分析。结果眼底特征性表现为,视盘颞侧一条索样皱襞,该部分视网膜血管分支密集、数目较多,终止与周边视网膜。周边视网膜检查可见一边界清晰的片状灰白色病灶,此处视网膜血管迂曲扩张。FFA特征为:周边视网膜FFA显示血管分支增多、迂曲扩张,呈"树枝样"改变,走行平直。血管末端发生吻合、呈扇形终止,此部分血管渗漏。结论眼底检查、FFA结合患者病史、家族史可明确诊断家族性渗出性玻璃体视网膜病变。     

家族性渗出性玻璃体视网膜病变致病基因的研究进展

家族性渗出性玻璃体视网膜病变(FEVR)是一种严重的临床和遗传异质性视网膜疾病,以周边视网膜血管发育异常为特征。FEVR的临床表型较多,典型的特征是视网膜皱褶; FEVR的遗传方式也较多,具有很高的遗传异质性,包含常染色体隐性遗传,X染色体隐性遗传,常染色体显性遗传以及其他的散在遗传方式。迄今为止已经证实9个FEVR致病基因：NDP、FZD4、LRP5、CTNNA1、TSPAN12、ZNF408、KIF11、CTNNB1、JAG1基因。这些基因主要参与Wnt、Notch和Norrin-β-catenin等信号通路。本文从上述9个FEVR致病基因及其信号通路等方面进行综述。     

家族性渗出性玻璃体视网膜病变临床表型的相关因素分析

目的观察并分析家族性渗出性玻璃体视网膜病变(FEVR)不同临床表型的相关因素。方法回顾性系列病例研究。2012年1月至2021年12月于北京大学人民医院眼科检查确诊的FEVR患者42例84只眼以及家系中一级亲属68名纳入研究。患者来自42个无血缘关系家庭。患者中, 男性31例, 女性11例;首诊年龄(16.6±33.7)个月。外院转诊21例, 均为眼底筛查发现病变;首诊本院21例。早产儿、足月儿分别为4、38例。有FEVR阳性家族史2例。均为FEVR分期1～5期。年龄<5岁者, 全身麻醉后广角数码儿童视网膜成像系统行荧光素眼底血管造影(FFA)检查;≥5岁者, 行常规FFA检查。来自28个家系的一级亲属68名均行常规眼底检查及FFA检查。行基因检测26个家系, 其中先证者26例, 一级亲属57名。对已知参与FEVR的基因共受体低密度脂蛋白受体相关蛋白5(LRP5)、Wnt受体卷曲蛋白4(FZD4)、Norrie病(NDP)、四旋蛋白12(TSPAN12)、连环蛋白β1(CTNNB1)基因进行高通量测序和分子遗传学分析。观察患者临床表现及FEVR的基因型与临床表型相关性。结果 42...     

早产儿家族性渗出性玻璃体视网膜病变的临床特征

目的:探讨6例早产儿家族性渗出性玻璃体视网膜病变(FEVR)的临床特征.方法:收集2018-08/2019-01在上海交通大学附属新华医院眼科就诊的FEVR早产儿6例,均于全身麻醉下行荧光素眼底血管造影(FFA)检查确诊,回顾性分析患儿的病例资料及病情特点.结果:患儿6例均有明确的早产病史,初始诊断为早产儿视网膜病变(...     

Retinal vascular pattern in familial exudative vitreoretinopathy

We evaluated the retinal vascular pattern in 133 eyes (77 cases) with familial exudative vitreoretinopathy (FEVR). A wide variety of retinal vascular abnormalities were observed in the extreme fundus periphery, particularly in the temporal retinal sector. They included: presence of an avascular zone in the extreme periphery, vasodilation and arteriovenous anastomosis in the peripheral vascularized retina, v-shaped avascular zone along the temporal meridian, and neovascularization. A grading system into five types was proposed with these features as parameters. Macular ectopia, falciform retinal fold and vitreoretinal adhesion appeared to be secondary to retinal vascular abnormalities. The presence of sporadic FEVR is postulated.     

Atypical Adams-Oliver syndrome with typical ocular signs of familial exudative vitreoretinopathy

AIM: To report an atypical Adams-Oliver syndrome (AOS) family with typical ocular signs of familial exudative vitreoretinopathy (FEVR). METHODS: A patient with visible avascular area and obvious non-perfusion zone in the peripheral retina with systemic signs of AOS was reported. Familial and personal characteristics were collected for the patient and his sister. Gene sequencing and ophthalmic examinations including fluorescein angiography were all performed for the whole family. RESULTS: Two novel mutations of DOCK6 (c.1396C>T and c.4796G>A) were identified in the proband and his family, and two compound heterozygous mutations were revealed in the proband and his sister. The patient and his sister showed physical deformities and mental abnormalities while FEVR mimicking retinal disorder can also be defined. No remarkable ocular or systemic abnormality can be observed for their parents. Peripheral retinal non-perfusion area, obvious abnormal vascularization or even retinal fold were observed in the proband and his sister, while only small avascular zone was identified for their parents. CONCLUSION: This is the first genetic authenticated AOS case mimicked as FEVR with genetic sequencing of a family. For the patients with ocular phenotype of FEVR, further examination should be performed if the systemic or mental abnormalities exist.     

家族性渗出性玻璃体视网膜病变基因研究进展

家族性渗出性玻璃体视网膜病变(FEVR)是以周边视网膜血管发育异常或不发育为特征的遗传性视网膜血管疾病,临床表现多样,遗传异质性明显.近年来发现数种与FEVR相关的致病基因,包括FZD4、LRP5、TSPAN12、NDP和ZNF408,致常染色体隐性遗传、常染色体显性遗传及X染色体连锁隐性遗传.FZD4编码卷曲蛋白4,与LRP5及TSPAN12蛋白组成受体复合物,结合Wnt或NDP编码的Norrin蛋白,参与活化典型Wnt或Norrin通路,在视网膜血管发育中起重要作用.ZNF408编码锌指蛋白,致常染色体显性遗传FEVR.本文就FEVR基因研究进展进行综述.     

Falciform Macular Folds and Chromosome 22q11.2: Evidence in Support of a Locus for Familial Exudative Vitreoretinopathy (FEVR)

Abstract

Background: Familial exudative vitreoretinopathy (FEVR) is a genetic disease caused by abnormal retinal vascular development. New additional genetic loci for FEVR have recently been identified. Microduplication of 22q11.2 has been reported with a heterogeneous phenotype and microdeletion of 22q11.2 has been associated with FEVR. We describe a case of a girl with microduplication of 22q11.2 and falciform macular folds.

Materials and Methods: The infant and first-degree relatives were examined. A dilated fundus examination was performed. Genetic screening was done by chromosomal microarray analysis and confirmed by fluorescent in situ hybridization (FISH).

Results: Bilateral macular folds were found with temporal fibrosis in the proband. A chromosomal microarray revealed a 2.21?Mb microduplication of the 22q11.2 region.

Conclusion: This is the first report to associate microduplication of 22q11.2 with macular folds, supporting the potential for a FEVR locus on chromosome 22q11.2. We encourage full ophthalmological examination for patients with microduplication of 22q11.2 to identify ocular associations.     

家族性渗出性玻璃体视网膜病变致病基因研究进展

家族性渗出性玻璃体视网膜病变（ｆａｍｉｌｉａｌｅｘｕｄａｔｉｖｅｖｉｔｒｅｏｒｅｔｉｎｏｐａｔｈｙ,ＦＥＶＲ）是一种罕见的遗传性视网膜血管发育异常的疾病,具有遗传异质性,遗传模式、表型和病程多样性的特点。ＦＥＶＲ遗传方式包括常染色体显性遗传、常染色体隐性遗传和Ｘ染色体隐性遗传。近年来,对ＦＥＶＲ致病基因的研究有了新的进展,目前已经发现的基因有ＦＺＤ４、ＬＲＰ５、ＮＤＰ、ＴＳＰＡＮ１２、ＺＮＦ４０８和ＫＩＦ１１,其中前４种基因被证实参与Ｎｏｒｒｉｎ／Ｆｒｉｚｚｌｅｄ-４信号通路,在视网膜血管生成过程中起重要作用。本文主要就ＦＥＶＲ致病基因的最新研究进展做一综述。     

Vitrectomy for rhegmatogenous or tractional retinal detachment with familial exudative vitreoretinopathy.

OBJECTIVE: To examine the anatomic features and surgical indications of familial exudative vitreoretinopathy (FEVR) complicated with rhegmatogenous or tractional retinal detachment. DESIGN: Retrospective noncomparative case series. PARTICIPANTS: Twenty-eight eyes of 25 patients who had either clinically suspected or fully diagnosed FEVR. Of these, 25 had rhegmatogenous retinal detachment, 2 had tractional retinal detachment, and 1 had tractional retinal detachment plus vitreous hemorrhage. INTERVENTIONS: The authors carefully observed the vitreoretinal interface during surgery, studied the clinical and anatomic features of FEVR, and then evaluated the surgical results. RESULTS: The vitreoretinal adhesions were so strong in the peripheral avascular area that iatrogenic retinal breaks easily occurred in 22 of 28 eyes. In all cases, the bimanual technique with vitreous scissors and forceps was required to dissect the posterior vitreous membrane from the retinal surface. The retina was reattached in 24 of 28 cases (85.7%), and visual acuity improved in 20 eyes (71.4%). CONCLUSION: Dissection of the vitreous in the peripheral avascular area is very difficult in FEVR, and those patients for whom this procedure was not successfully performed may have a poorer prognosis.