卵黄样黄斑营养不良基因三个新的点突变与散发性Best病表现型关系的分析

Best病又称Best卵黄样黄斑营养不良(BVMD),是一种不规则的常染色体显性遗传性疾病,也有一些散发病例;临床特征是幼年或青年时期双眼黄斑部视网膜出现卵黄状的脂质样沉积物,而视力一般不受影响.随着病情发展,卵黄样物质逐渐吸收,开始出现视力波动.患者常在40岁左右时常发展为视网膜色素上皮(RPE)萎缩,黄斑部视网膜纤维瘢痕形成,以及继发性脉络膜新生血管(CNV)形成和视网膜下出血,最终出现视力严重的不可逆性损害.     

卵黄样黄斑营养不良的光学相干断层扫描影像学特征

目的探讨卵黄样黄斑营养不良各病变阶段光学相干断层扫描(optical coherence tomography,OCT)的影像学特征。方法回顾性分析6例(8眼)卵黄样黄斑营养不良患者的OCT图像特征,并与眼底特征、眼底荧光血管造影进行对照分析。结果卵黄样病变期患者眼底检查可见黄斑区卵圆形隆起病灶,OCT可见视网膜色素上皮层和光感受器层之间有一中等密度反射区域,随病变进展,沉积物厚度增高。萎缩期患者黄斑区见萎缩灶,OCT表现为视网膜色素上皮层脉络膜复合体弥漫性增厚,神经感觉层变薄,合并脉络膜新生血管形成时可见高反射的新生血管膜。结论详细的病史资料、眼底检查、眼底荧光血管造影以及OCT的联合应用,有助于更科学的分析卵黄样黄斑营养不良的临床特征和病理改变。     

鸟枪弹样视网膜脉络膜病变的诊断与治疗

鸟枪弹样视网膜脉络膜病变(BSR)是一 种双眼弥漫性后葡萄膜炎，病因与发病机制不清。眼底特征性病变为散在多发性黄白色斑点状渗出性病灶，后期为脱色素性脉络膜视网膜瘢痕灶，犹如鸟枪弹一样；伴有轻度前葡萄膜炎、玻璃体炎、视网膜血管炎、黄斑囊样水肿和视盘水肿；并伴有视野改变和电生理改变。常因黄斑囊样水肿、黄斑瘢痕或脉络膜新生血管使视力严重受损。糖皮质激素和免疫抑制剂是常用治疗方法。（中华眼底病杂志，2004，20：130-132）     

卵黄样黄斑变性与黄斑蝶形色素上皮变性

卵黄样黄斑变性(Best)病和黄斑蝶形色素上皮变性(Deutman)一直被描述为二种单独遗传性变性疾病,二者均影响视网膜色素上皮和外层视网膜。本文报告一例右眼为卵黄样黄斑变性,左眼为蝶状黄斑色素上皮变性病例。此一情况说明二种罕见的疾病可能是同一遗传性疾病的不同表现。患者女性22岁,无自觉症状及眼病史。双眼视力6/6。眼底检查:双视神经乳头、视网膜血管及周边眼底均正常。右眼黄斑区有一3/4PD大小,境界清楚的卵圆     

外周渗出性出血性脉络膜视网膜病变诊断及治疗研究进展

外周渗出性出血性脉络膜视网膜病变(PEHCR)是以视网膜下出血和(或)视网膜色素上皮下出血或渗出为主要特征的周边视网膜疾病, 常被误诊为老年性黄斑变性、息肉样脉络膜血管病变或脉络膜黑色素瘤等。随着多模式影像学发展, PEHCR在B型超声、荧光素眼底血管造影、光相干断层扫描等检查中表现出不同特征, 据此可与上述疾病鉴别。该病治疗方法包括激光光凝治疗、玻璃体腔注射抗血管内皮生长因子药物和玻璃体切割手术等, 但目前尚无统一治疗标准。未来仍需进一步深入了解PEHCR临床特征、治疗方案及预后, 最大程度避免临床漏诊与误诊, 提高治疗效率。     

光相干断层扫描血管成像在眼底疾病诊断研究中的应用

光相干断层扫描血管成像(OCTA)通过对同一体素多次扫描信号间的差异进行处理,得到视网膜与脉络膜血流信息.OCTA因其无创、三维显示、分辨率高等优点,可用于眼底疾病的检查.OCTA能发现眼底疾病的血流改变,可以清晰显示正常眼底与年龄相关性黄斑变性、糖尿病视网膜病变、视网膜血管阻塞等疾病的视网膜与脉络膜毛细血管血流.本文就OCTA的基本原理及其在正常眼、年龄相关性黄斑变性与脉络膜新生血管、糖尿病视网膜病变、特发性黄斑中心凹旁毛细血管扩张症2型、视网膜血管阻塞、中心性浆液性脉络膜视网膜病变、息肉样脉络膜血管病变等眼底疾病诊断中的应用进行综述.     

卵黄样黄斑营养不良的OCT表现

卵黄样黄斑营养不良(Best病)作为常染色体显性遗传性黄斑疾病,其临床表现常分5期:0期:卵黄病变前期;Ⅰ期:卵黄期;Ⅱ期:假性前房积脓期;Ⅲ期:卵黄囊肿破裂期;Ⅳ期:萎缩期.相干光断层扫描(OCT)可快速获得较高分辨率眼底断层图像,为研究此病的病变特征、病情演变和分期提供了进一步的认识.本文主要综述了卵黄样黄斑营养不良不同阶段的OCT表现.     

黄斑囊样水肿

黄斑囊样水肿 (cystoid macularedema,CME)是眼底的常见病 ,但它不是一种独立的特发性疾病 ,而是很多眼底疾病在黄斑区的表现。引起黄斑囊样水肿最常见的疾病有 :视网膜静脉阻塞、糖尿病性视网膜病变、视网膜血管炎、黄斑区视网膜前膜、视网膜毛细血管扩张症、视网膜色素变性、葡萄膜炎、白内障或其它内眼手术后、黄斑区脉络膜的新生血管 ,以及少见的特发性黄斑囊样水肿、烟酸中毒、青年性视网膜劈裂、Gold-mann- Favre综合症等多种疾病。Gass指出 :在正常的生理情况下 ,眼内的液体和电解质是从玻璃体通过视网膜和脉络膜引流到血循环中的…     

视网膜血管瘤样增生性病变的眼底光学影像学特征观察及意义

目的观察视网膜血管瘤样增生性病变（RAP）在眼底彩色照相、眼底荧光血管造影（FFA）、吲哚青绿血管造影（ICGA）及光相干断层扫描（OCT）的图像特征改变及意义。方法回顾性分析2008年1月至2014年3月在河北省眼科医院就诊的11例14只眼RAP患者的临床资料,重点观察患眼病变部位在眼底彩色照相、FFA、ICGA及OCT图像中的改变特征。结果I期RAP3只眼,眼底表现为黄斑中心凹旁有1个斑点状或结节状黄红色血管瘤样病灶分布,其在FFA及ICGA中均表现为对应的强荧光,且病灶两端有视网膜小动脉和小静脉相连,呈“发夹”状外观。OCT表现为病灶对应处视网膜内有斑点状或囊状强反光物质分布。Ⅱ期RAP6只眼,眼底检查显示黄斑区视网膜水肿增厚,并有较多出血及硬性渗出分布。FFA及ICGA均显示黄斑区有1—2个斑片状或结节状强荧光灶出现,并有多支视网膜小血管与其吻合。OCT检查显示病灶对应部位神经上皮内或神经上皮下有团块状强反光物质分布,伴有神经上皮层囊样水肿增厚、局限性脱离以及严重的PED。BI期RAP5只眼,眼底表现为黄斑区中央视网膜深层有黄红色盘状或片状新生血管样病灶分布。FFA及ICGA检查显示病灶呈强荧光改变,并均能观察到多支视网膜血管与其吻合。OCT显示病灶对应处神经上皮下有团块状强反光物质分布,并与向上隆起的Bruch膜与脉络膜复合体相连。结论各期RAP病变在各种光学影像学检查中有特征性改变,熟练掌握这些改变特征将有助于临床医师对其做出正确的诊断和分期,并指导治疗。     

息肉样脉络膜血管病变的临床特征与手术治疗进展

息肉样脉络膜血管病变(polypoidal choroidal vasculopathy,PCV)是一组以脉络膜异常分支血管网及末端息肉样血管扩张病灶为特征的眼底疾病,临床治疗较为棘手。大面积视网膜黄斑下出血(submacular hemorrhage,SMH)甚至玻璃体腔出血是PCV的严重并发症,往往需要手术干预。其手术治疗包括气体填充和/或组织型纤溶酶原激活物(tPA)注射、玻璃体切割联合视网膜切开或外路引流等。本文就目前国内外关于PCV的临床特征、并发症及手术治疗新进展等内容进行综述。     

ISCEV Symposium Author Index

Purpose

Abnormalities in the BEST1 gene have recently been recognised as causing autosomal recessive bestrophinopathy (ARB). ARB has been noted to have a variable phenotypic presentation, distinct from that of autosomal dominant Best vitelliform macular dystrophy (BVMD). Both conditions are associated with deposits in the retina, a reduced or absent electro-oculography (EOG) light rise, and the risk of developing angle-closure glaucoma. Herein, we describe the clinical and genetic characteristics of a young male diagnosed with ARB associated with angle-closure glaucoma resulting from a novel homozygous mutation in BEST1.

Methods

All research involved in this case adhered to the tenets of the Declaration of Helsinki. The proband underwent slitlamp examination, retinal autofluorescence imaging and optical coherence tomography after presenting with deteriorating vision. The findings prompted genetic testing with bi-directional DNA sequencing of coding and flanking intronic regions of BEST1. The proband’s family members were subsequently screened.

Results

A provisional diagnosis of ARB was made based on the findings of subretinal and schitic lesions on fundoscopy and retinal imaging, together with abnormal EOG and electroretinography. Genetic testing identified a novel homozygous mutation in BEST1, c.636+1 G>A. Family members were found to carry one copy of the mutation and had no clinical or electrophysiological evidence of disease. The proband was additionally diagnosed with angle-closure glaucoma requiring topical therapy, peripheral iridotomies and phacoemulsification.

Conclusions

Phenotypic overlap, reduced penetrance, variable expressivity and the ongoing discovery of new forms of bestrophinopathies add to the difficulty in distinguishing these retinal diseases. All patients diagnosed with ARB or BVMD should be examined for narrow angles and glaucoma, given their frequent association with these conditions.     

成年人型卵黄样黄斑营养不良的临床特征

目的研究成年人型卵黄样黄斑营养不良的临床和影像学特征。设计回顾性病例系列。研究对象北京同仁医院9例（13眼）成年人型卵黄样黄斑营养不良患者。方法分析患者的眼底表现、荧光素眼底血管造影（FFA）、相干光断层扫描（OCT）和自体荧光检查结果。主要指标FFA及OCT特征。结果所有患者均无家族史。视力在0．3及以上者8／13眼（61．5％）。所有患者均表现为黄斑区圆形卵黄样微隆起、边界清楚的、不超过1PD的视网膜下病变。FFA显示病变处呈遮蔽荧光,其旁无或显现荧光,在吸收过程中,荧光相应增加。OCT显示在视网膜色素上皮（RPE）光带前见一梭形均匀的高反射区,在吸收过程中,高反射区出现不均匀,或有小的无光反射暗区。结论黄斑区圆形卵黄样不超过1PD的视网膜下病变,无明显视网膜脱离及无病变破裂分层是本病的特点。FFA和OCT检查相结合有助于成年人型卵黄样黄斑营养不良的诊断。     

Vitelliform maculopathy: Diverse etiologies originating from one common pathway

Vitelliform lesions (VLs) are associated with a wide array of macular disorders but are the result of one common pathway: retinal pigment epithelium (RPE) impairment and phagocytic dysfunction. VLs are defined by the accumulation of yellowish subretinal material. In the era of multimodal advanced retinal imaging, VLs can be further characterized by subretinal hyperreflectivity with optical coherence tomography and hyperautofluorescence with fundus autofluorescence. VLs can be the result of genetic or acquired retinal diseases. In younger patients, VLs usually occur in the setting of Best disease. Additional genetic causes of VL include pattern dystrophy or adult-onset vitelliform macular dystrophy. In older patients, acquired VLs can be associated with a broad spectrum of etiologies, including tractional, paraneoplastic, toxic, and degenerative disorders. The main cause of visual morbidity in eyes with VLs is the onset of macular atrophy and macular neovascularization. Histopathological studies have provided new insights into the location, nature, and lifecycle of the vitelliform material comprised of melanosomes, lipofuscin, melanolipofuscin, and outer segment debris located between the RPE and photoreceptor layer. Impaired phagocytosis by the RPE cells is the unifying pathway leading to VL development. We discuss and summarize the nature, pathogenesis, multimodal imaging characteristics, etiologies, and natural course of vitelliform maculopathies.     

Photodynamic therapy with verteporfin for subfoveal choroidal neovascularization in best disease

PURPOSE: To describe the effects of photodynamic therapy using verteporfin for the treatment of subfoveal choroidal neovascularization (CNV) in Best vitelliform macular dystrophy. DESIGN: Interventional case report. METHODS: A 43-year-old patient with confirmed Best vitelliform macular dystrophy complicated with subfoveal CNV received a single photodynamic therapy session with verteporfin. The patient was prospectively followed with fluorescein angiography and optical coherence tomography. RESULTS: A regression of the neovascular lesion and resolution of the exudative manifestations was observed 3 weeks after treatment; at that time, visual acuity had improved from 20/60 to 20/25. Optical coherence tomography disclosed restoration of normal macular architecture due to fluid resolution and lesion contraction. Up to 2 years from this single treatment, no further change was observed. CONCLUSIONS: Regression of CNV and resolution of subretinal hemorrhage as well as exudative manifestations occurred after photodynamic therapy with verteporfin. Verteporfin therapy may be a viable treatment for subfoveal neovascular lesions in Best vitelliform macular dystrophy.     

Optical coherence tomography study of adult vitelliform macular detachment in a patient with basal laminar drusen

To report the morphological data of adult vitelliform macular detachment in a patient with basal laminar drusen using optical coherence tomography (OCT-3) as an observational case report. A 70-year-old man presented with adult vitelliform macular detachment and basal laminar drusen underwent fundus biomicroscopy, fundus fluorescein angiography and OCT-3. Fundus examination showed bilateral yellow subretinal macula deposits with associated basal laminar drusen. Examination with OCT revealed areas of hyper-reflectivity compatible in size with the subretinal deposits below and elevating the photoreceptor layer. This was accompanied by underlying disruption of the OCT signal from retinal pigment epithelium (RPE) in the more affected left eye. In adult vitelliform macular detachment and basal laminar drusen, OCT may demonstrate that the yellow material is located predominantly below RPE in early disease and between the photoreceptor layer and the retinal pigment epithelium in later disease.     

儿童遗传性视网膜疾病的眼底自身荧光表现

目的 观察儿童遗传性视网膜疾病的眼底自身荧光(FAF)特征.方法 回顾性分析22例临床资料完整、年龄5～14岁之问的遗传性视网膜疾病患儿的FAF检查结果.其中,Best卵黄样病变8例16只眼,Stargardt病3例6只眼,视锥细胞营养不良3例6只眼,原发性视网膜色素变性(RP)5例10只眼,X连锁青少年型视网膜劈裂症3例6只眼.仔细询问现病史及家族史,行视力、裂隙灯显微镜眼前节检查,间接眼底镜检查,彩色眼底像和FAF照相,其中部分患儿接受了荧光素眼底血管造影(FFA)、视网膜电流图、眼电图、光相干断层扫描检查.对上述患儿的FAF结果特征进行归纳总结,并与其眼底照相和/或FFA结果进行比较分析.结果 3例Stargardt病患儿的6只眼及3例视锥细胞营养不良患儿的6只眼FAF检查显示黄斑区可见对称性的圆形、近圆形弱荧光或荧光缺如区,2例视锥细胞营养不良患儿的4只眼及1例Stargardt病患儿的2只眼可见弱荧光或荧光缺如区外缘环以强荧光;Best卵黄样病变患儿黄斑区可见一个强度均匀或不均匀的强FAF病灶;RP患儿后极部视网膜FAF增强,黄斑区周围可见宽度不等的环形强荧光带,拱环区FAF正常;3例X连锁青少年型视网膜劈裂症患儿中5只眼中心凹部位FAF检查可见蜂窝或颗粒状强荧光.结论 Stargardt病及视锥细胞营养不良患儿黄斑区为近圆形弱荧光,部分病变区外缘环以强荧光;Best卵黄样病变患儿黄斑区为强度均匀或不均匀的强FAF病灶;RP患儿后极部视网膜FAF增强,拱环区FAF正常,黄斑区周围可见宽度不等的环形强荧光带;X连锁青少年型视网膜劈裂症患儿中心凹部位为蜂窝或颗粒状强荧光.

Abstract：

Objective To observe the autofluorescence (AF) manifestation in children with hereditary retinal diseases. Methods The clinical data of 22 children (aged from 5 to 14 years) with hereditary retinal diseases were retrospectively analyzed. There were 8 children (16 eyes) with Best vitelliform macular dystrophy, 3 children (6 eyes) with Stargardt macular dystrophy, 3 children (6 eyes) with macular cone dystrophy, 5 children (10 eyes) with primary retinitis pigmentosa, and 3 children (6 eyes) with X-linked juvenile retinoschisis. The routine clinical examinations included present history, family history, visual acuity, silt-lamp microscopy, indirect ophthalmoscopy, color fundus photography and fundus autofluorescence angiography (FAF). Some patients received fundus fluorescein angiography (FFA),electroretinogram (ERG), electrooculogram (EOG), and ocular coherence tomography (OCT). The characteristics of AF in all the children were analyzed, and were compared with the images of color fundus and/or FFA. Results Symmetry round macular fluorescent weak or absent area was found in all Stargardt disease and cone dystrophy. Weak AF area with surrounded circular increased AF was found in 2 children (4 eyes) with cone dystrophy and 1 child (2 eyes) with Stargardt macular dystrophy. A central round area with regular or irregular intense AF was observed in Best vitelliform macular dystrophy. RP children showed increased AF out of the macular region. Cellular or granular strong AF was found in the fovea of 3 children (5 eyes) with X-linked juvenile retinoschisis. Conclusion The children with hereditary retinal diseases had special AF changes.     

Multimodal fundus imaging in Best vitelliform macular dystrophy

Background  

Best vitelliform macular dystrophy (BVMD) is a rare autosomal dominant retinal disease of highly variable phenotypic expression. Interpretations of disease mechanisms based on histopathology, electrophysiology, genetic analysis, and retinal imaging are somewhat discordant in fundamental issues such as the location and extension of primary retinal changes. Herein we describe the morphological macular features in patients with BVMD undergoing simultaneous multimodal fundus imaging and compare to those of normal age-matched subjects.     

Differential macular and peripheral expression of bestrophin in human eyes and its implication for best disease

PURPOSE: Best disease, or vitelliform macular degeneration, is an autosomal dominant form of macular degeneration that is caused by mutations in the gene encoding bestrophin. On clinical examination, Best disease is characterized by an elevated lesion beneath the neurosensory retina, resembling an egg yolk. The lesions in Best disease are primarily restricted to the macula, a small region of the retina responsible for central vision. The nature of the vitelliform material and the reason the development of such lesions is usually restricted to the macula are two unsolved questions in the pathogenesis of this disorder. METHODS: The expression of bestrophin protein and mRNA was evaluated by immunohistochemistry, Western blot, and quantitative PCR in a series of normal human eyes. The ultrastructure of the retinal pigment epithelium and the histopathology of two donors with clinically diagnosed Best disease were also examined. RESULTS: An eye from a Best disease donor with a T6R mutation was found to have deposits containing lipid and glycoconjugates within the central retinal scar. These deposits may be remnants of the vitelliform lesion. Immunohistochemical localization of bestrophin in a series of 22 unaffected eyes revealed a pattern in which macular labeling was less robust than labeling outside the macula in most (18/22) cases. This pattern was confirmed using quantitative PCR and Western blotting. CONCLUSIONS: Topographic differences in the levels of bestrophin protein may in part explain the propensity for the macula to develop lesions in Best disease.     

Vitelliform dystrophy and pattern dystrophy of the retinal pigment epithelium: concomitant presence in a family.

We describe three siblings presenting unusual pigmented dystrophic lesions of the fovea. The first sibling showed macroreticular dystrophy associated with butterfly shaped dystrophy in one eye and associated with vitelliform cyst in the other eye. The second showed the atrophic outcome of a vitelliform cyst with development of subretinal neovascular membrane in one eye and a radial pigmented macular dystrophy in the other eye. The third sibling had bilateral macular vitelliform lesions. This vitelliform patterned dystrophy of the retinal pigment epithelium may represent a new form that should be classified near Best's disease and the pattern dystrophies.     

常染色体隐性遗传性卵黄样营养不良并发闭角型青光眼临床特征分析

目的 总结常染色体隐性遗传性卵黄样营养不良（ARB）并发闭角型青光眼（ACG）/房角关闭（AC）患者的临床特征。设计 回顾性病例系列。研究对象 2017-2019年中山眼科中心经基因检测确诊ARB并发ACG/AC患者8例16眼。方法 回顾分析ARB并发ACG/AC患者临床发病特点、眼部改变。主要指标 发病特点，眼部生物学参数，视网膜、视神经及视功能改变。结果 ARB并发ACG/AC患者年龄15~34岁，平均（26.13±6.77）岁。男女各4例。最佳矫正视力0.1~0.8；眼压15~45 mmHg，平均（28.81±8.03）mmHg。平均前房深度（2.09±0.14）mm，平均眼轴（21.85±0.65）mm。房角关闭范围>180°者13眼，其平均垂直杯盘比（C/D） （0.9±0.10），平均视网膜神经纤维层厚度（62.53±149.06）μm，平均视野缺损值（-21.02±12.02）dB。房角关闭范围<180°者3眼，其平均垂直C/D（0.4±0.06），平均视网膜神经纤维层厚度（117±1.73）μm，平均视野缺损值（-5.56±1.53）dB。所有患眼眼底显示后极部多发大小不一、数量不等的视网膜下黄色物质沉积。相干光断层扫描显示后极部视网膜神经上皮层广泛浆液性浅脱离，光感受器外节延长，视网膜色素上皮层与Bruch膜间多灶大小不等高反射沉积物质。12眼（75%）视网膜层间劈裂腔形成，1眼局灶脉络膜下陷。8例眼电图（EOG）光峰／暗谷值（Ardent比）<1.55。结论 ARB并发ACG/AC患者发病年龄较轻，双眼房角狭窄或关闭同时伴有眼底散在卵黄样病灶及后极部视网膜神经上皮层广泛浆液性浅脱离。（眼科， 2020, 29： 370-374）