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局限性脉络膜凹陷的临床研究进展

The clinical progress of focal choroidal excavation

来源期刊: 眼科学报 | 2023年7月 第38卷 第7期 512-517 发布时间: 收稿时间:2023/9/7 10:45:10 阅读量:3405
作者:
关键词:
局限性脉络膜凹陷发病机制光学相干断层扫描临床表现
focal choroidal excavation pathogenesis OCT clinical manifestations
DOI:
10.12419/2210210001
局限性脉络膜凹陷(focal choroidal excavation,FCE)是表现为光感受器细胞层、视网膜色素上皮层向脉络膜层凹陷的眼底病变。发病机制多认为是先天脉络膜发育异常、炎症或感染。基于光学相干断层扫描(optical coherence tomography,OCT),可将FCE从光感受器尖端与视网膜色素上皮层是否分离、形态特征或中央脉络膜厚度三种方式对其进行分类。FCE常合并脉络膜新生血管等疾病。该文对FCE的临床研究现状做一综述。
Focal choroidal excavation (FCE) is a retinopathy, expressing with a depression in photoreceptor cell layer and retinal pigment layer towards the choroidal layer. The pathogenesis is recongized as congenital choroidal developmental abnormalities, inflammation, or infection. Based on optical coherence tomography (OCT), FCE can be classified by three methods: the situation of photoreceptor separating from the retinal pigment upper cortex, morphological features, or central choroidal thickness. FCE is usually associated with other diseases such as choroidal neovascularization. This article reviews the current clinical research on FCE.
局限性脉络膜凹陷(focal choroidal excavation,FCE)是表现为光感受器细胞层、视网膜色素上皮层(retinal pigment epithelium,RPE)向脉络膜层凹陷的眼底病变,但不合并巩膜扩张和后巩膜葡萄肿,多位于黄斑区。随着OCT的发展和普及,越来越多的FCE被发现,且临床证实FCE并非长期稳定,可合并脉络膜新生血管(choroidal neovascularization,CNV)、中心性浆液性脉络膜视网膜病变(central serous chorioretinopathy,CSC)、年龄相关性黄斑变性(age-related macular degeneration,AMD)等疾病。目前,国内对FCE的报道较少,FCE并发症的发病机制并未明确,故本文将结合国内外文献报道,对FCE的研究进展进行综述。

1 FCE的命名

1959年,Klien[1]首次报道在病理组织切片中发现了脉络膜缺损的存在。2006年,Jampol等[2]通过OCT观察到黄斑区特殊的脉络膜视网膜变化,并首次以“脉络膜凹陷”对该病变进行命名。OCT征象表现为视网膜神经上皮层下有与浆液反射一致的透明空间,局部脉络膜组织凹陷。2011年,Margolis等[3]正式提出局限性脉络膜凹陷的病名,提出该病变无明显种族差异,可双眼发病,并根据OCT征象将其分为贴服型(confirming type)和非贴服型(non confirming type)。

2 FCE的发病机制

FCE 的发病机制多有争议,早期因临床报道及研究较少,Margolis等[3]假设其是一种先天性后段畸形。2013年,Kumano等[4]报道FCE患者的吲哚菁绿血管造影显示多灶性强荧光和弱荧光,显示出脉络膜血管扩张、脉络膜血管高通透性的病理特征,推测FCE是由于脉络膜血管异常引起的对黄斑的向外牵拉;同时OCT图像显示病变区Bruch膜基底层与脉络膜上层明显粘连,认为FCE是由于脉络膜胚胎发育异常引起的脉络膜血管病变,而在中心凹的光感受器尖端与RPE之间的分离可能是导致视物变形的原因。但两种观点均不能解释FCE的进行性发展。而FCE与多种视网膜脉络膜疾病相关,2014年,Hashimoto等[5]通过研究一例白点综合征患者,推测外层视网膜和内层脉络膜的炎症病变导致RPE和Bruch膜受损,引起外层视网膜和脉络膜组织相互黏附。同时,纤维性脉络膜病变的收缩和眼压也会使视网膜组织向脉络膜突出。除此之外,部分研究者认为FCE是因为视网膜脉络膜组织局灶性炎症,引起脉络膜组织局灶性瘢痕,瘢痕组织牵拉脉络膜组织形成脉络膜凹陷[6-8]

3 FCE的OCT分型及其影像学特征

早期根据光感受器尖端与视网膜色素上皮层是否分离将FCE分为贴服型和非贴服型[3],且随着病情变化,非贴服型可转化为贴服型。Matsubara等[9]报道一例白点综合征患者,初期OCT表现为RPE与Bruch膜分离,中央凹视网膜下高反射信号,治疗3个月后视网膜下液吸收,非贴服型FCE转化为贴服型,推测炎症导致RPE与Bruch膜功能紊乱,脉络膜厚度逐渐减少,在眼内压的作用下,受损的RPE与Bruch膜向脉络膜凹陷,随着炎症的改善,RPE功能逐渐恢复,视网膜下液被吸收,使非贴服型的FCE变成贴服型。
Shinojima[10]等通过增强深度成像光学相干断层扫描(enhanced depth imaging optical coherence tomography, EDI-OCT)将FCE在形态上进一步分为锥形、碗状和混合型,且碗状FCE的RPE层多不规则,在荧光血管造影和ICGA上均表现为萎缩。国内一项研究提示紧密型与碗型凹陷临床多见[11]。现根据中央脉络膜厚度可分为3种亚型[12]:1)1型为近视型,中央脉络膜厚度<100 μm;2)2型为疑似先天型,无相关脉络膜视网膜病变,中央脉络膜厚度为100~200 μm;3)继发型或获得型,并发相关脉络膜视网膜疾病,中央脉络膜厚度>200 μm,此分型对临床有着较大的指导意义,因为3型FCE中多与中心性浆液性脉络膜视网膜病变等脉络膜疾病相关,且脉络膜新生血管在3型FCE中更为常见。
眼底检查中,因脱色素的程度不同,FCE可表现为中心凹处或其周围轻微的色素紊乱至黄白色斑块[13],当出现CNV等并发症时,可有视网膜下出血等征象[14]。在FCE检测中,SD-OCT提供了形态学特征,而近红外自发荧光(near-infrared autofluorescence,NIA)可有效检测病变范围,提供较为精确的FCE面积数据。大多数情况下,色素变化与眼底自发荧光(fundus autofluorescence,FAF)图像上的低自发荧光区域相对应,红外成像中则表现为不均匀、低反射信号。而FCE在荧光素血管造影(fundus fluorescein angiography,FFA)和吲哚菁绿造影(indocyanince green angiography,ICGA)检查中的表现各异,无明显特异性。在FFA检查中,FCE及其周围可表现为窗样缺损(图1)及不规则的强荧光或弱荧光。Chen等[14]认为FFA中荧光的变化与CNV引起的RPE功能紊乱、视网膜下出血和视网膜下积液等病理变化有关。在ICGA检查中,FCE表现为弱荧光,透见脉络膜血管,晚期显示斑块状或点状强荧光等染色异常,并发CNV时出现荧光素的渗漏。然而FAF和ICGA荧光的改变与FCE的边缘无明显的关系[13-14]
图1 一例左眼FCE患者眼底照相、OCT及FFA检查结果
Figure 1 Images of fundus color photo, OCT and FFA in the left eye of a patient with Focal choroidal excavation
(A)眼底图显示黄斑中心凹轻微色素紊乱;(B)OCT显示锥型非贴服型FCE;(C、D)FFA造影早期、晚期,FCE均显示窗样缺损。
(A) Corlor fundus of the left eye showed pigment irregularity in the macular area; (B) The contour of cone-shaped of unconfirming type FCE; (C&D) Early- and late-phase FFA images showed patches of window defects corresponding to FCE.

4 FCE的常见并发症

目前临床报道的FCE患者年龄以40~60岁多见,Park等[15]统计了在儿童眼科和神经眼科就诊的1 697例患者(年龄<40岁),其中仅有3例为FCE患者,但低发病率是否反映FCE与后天获得性相关有待进一步考证。FCE患者多为单眼发病,但也有报道提示部分患者可双眼患病[13]。FCE患者大多因视物变形、视力下降等症状就诊。同时也有研究者在脉络膜新生血管[6]、脉络膜骨瘤[16]等疾病的治疗随访过程中发现脉络膜凹陷的形成。局灶性脉络膜凹陷是多种脉络膜视网膜疾病的常见征象[17],当FCE并发CNV、CSC、AMD等疾病,对患者视力影响较大,且随着治疗的进展,FCE的形态将发生进一步的改变。根据其并发症的不同,总结如下。

4.1 FCE与脉络膜新生血管

脉络膜新生血管是由于异常生长的脉络膜毛细血管穿过Bruch膜,进入视网膜色素上皮下或神经视网膜下,按病因可分为变性疾病(如AMD)、炎症性疾病、外伤性疾病、特发性CNV等。因其管壁高通透性,易出血或渗出,临床多采用玻璃体腔注射抗VEGF药物治疗[18]。CNV并发FCE患者经抗VEGF治疗后,CNV病变消退,视网膜下液体逐渐吸收,而脉络膜凹陷内的液体最后吸收,且少数患者深部脉络膜凹陷内可见残余积液[19]
在Zheng等[13]对18例(25眼)非获得性FCE患者的长期随访中,有4眼出现CNV。Sato[7]报道了一例贴服型FCE,在随访过程中继发2型CNV,根据其对侧眼CNV病史及其长期吸烟史,结合患者年龄,推测FCE与局灶性炎症或其他原因导致的Bruch膜的损伤有关,且脉络膜毛细血管的损伤可诱导FCE的CNV发展。除此之外,临床也有FCE并发炎性脉络膜病变继发CNV的报道,例如点状内层脉络膜病变(punctate inner choroidopathy,PIC)[20]。根据Rajabian等[21]对FCE的OCTA研究,FCE患者病变区域脉络膜厚度较正常人薄,且深层毛细血管和脉络膜毛细血管丛改变明显。Zhu等[20]推测凹陷处局灶性脉络膜缺血、RPE改变以及视网膜神经上皮层与RPE层的分离可能是CNV发生的易感因素。而继CNV后出现的FCE与治疗后局部瘢痕收缩有着密切的关系[6,22]

4.2 FCE与中心性浆液性脉络膜视网膜病变

    FCE属于肥厚脉络膜谱系疾病,脉络膜厚度是否增厚仍有争议。Ellabban等[8]认为FCE并发CSC患者的脉络膜厚度大于正常人眼睛。然而,Suzuki等[23]观察到FCE并发CSC患者中心凹下脉络膜厚度(subfoveal choroidal thickness,SFChT)与对眼脉络膜厚度无明显差异。因此,Wang[24]等认为脉络膜厚度可能不是导致FCE发病的关键因素。研究中发现FCE凹陷区脉络膜毛细血管层OCTA表现为暗色血流信号缺失区域,周围环绕高灌注区域。FFA提示[23, 25-26]FCE边缘可见渗漏点,晚期呈强荧光点,进一步提示脉络膜循环障碍和RPE层萎缩是其发病的关键因素;而CSC系视网膜外屏障被破坏,脉络膜毛细血管内的液体通过RPE病变处渗漏。FCE与CSC似乎均与脉络膜高通透性有关。在Docherty等[27]的病例报道中,FCE的类型可以在贴服型和非贴服型之间相互转化,推测大多数情况下FCE类型可能取决于视网膜神经上皮下液体的积聚与吸收之间的平衡,非贴服型FCE中的透明空间可能是脉络膜高通透性导致的持续性视网膜下液体。

4.3 FCE与卵黄样黄斑营养不良

FCE并发卵黄样黄斑营养不良(best vitelliform macular dystrophy,BVMD)的临床报道最早见于2014年,并认为卵黄样物质与FCE有着一定的关系[28],后有研究者在对BVMD患者的长期随访中发现卵黄样病变和FCE可长期保持稳定[29]。2018年,Kuma等[30]对19例(38眼)BVMD患者进行研究,用频域光学相干断层成像(spectral-domain optical coherence tomography,SD-OCT)观察纤维化柱与FCE的形态关系,其中6例患者(8眼)并发FCE,研究结果提示除萎缩期外的7眼可见低反射性视网膜下间隙,有4眼的FCE位于圆柱形纤维化柱的正下方。研究者认为卵黄样物质是由于神经感觉层与RPE层分离所致,不一定是FCE引起的,且BVMD的局限性脉络膜凹陷多见于卵黄期,在FCE的形成过程中纤维性支柱发挥着重要的作用,但需进一步验证。

4.4 FCE与白点综合征

Matsubara等[9]报道了一例白点综合征,1名40岁妇女感冒后出现左眼视物模糊,SD-OCT显示RPE和Bruch膜中断分离,中央凹下的外层视网膜可见高反射病变,中心凹旁可见椭圆体带的缺失,脉络膜可见异常的高反射病变。经糖皮质激素治疗后4周后OCT显示中心凹下脉络膜凹陷的形成,脉络膜凹陷中心和边缘的脉络膜厚度分别为183 μm和228 μm。3个月后,视网膜下液体已完全吸收,最终形成FCE,FCE中心和边缘的脉络膜厚度改变为147 μm和200 μm。由此可见轻度炎症可能会引起Bruch膜和RPE层损伤变薄,随着炎症改善,引起压力比例失调,导致Bruch膜和RPE层向后凹陷。

4.5 FCE与脉络膜骨瘤

脉络膜骨瘤是一种由成熟骨逐渐取代脉络膜组织的良性肿瘤,其病程包括肿瘤的成长、钙化与脱钙化,常并发CNV[31]。脉络膜骨瘤并发FCE多以临床病例报道为主要,据Bernabei等[32]的临床病例报道,其眼底征象无明显特异性,多表现为黄橙色隆起性病变。OCT显示脉络膜骨瘤对应的高反射海绵状结构,以及中央凹的局灶脉络膜凹陷,病灶脉络膜的上缘陡坡,沿其顶端挤压视网膜内层。但此例患者缺乏长期随访,据Rajabian等[33]在对一例脉络膜骨瘤患者进行5年的随访过程中发现,后期脉络膜骨瘤病变区域明显扩大,在FCE附近形成广泛的CNV,伴随周围视网膜下出血、积液、视网膜下高反射以及干叉征(pitchfork sign)的形成,而这些都是炎症反应的标准。炎症反应是否为脉络膜骨瘤患者发生FCE的重要驱动因素,有待考证。

5 结语

FCE的发病机制极其复杂,OCT研究是当前研究焦点。根据OCT形态可将其分为不同类型,病变并非长期稳定,凹陷下脉络膜厚度、凹陷宽度可能是FCE患者并发症发生的危险因素,其中FCE并发CSC和CNV较为常见,对视力的影响也较大。对于FCE临床尚无特殊治疗手段,所以,我们希望通过总结相关病例的临床表现,为其治疗和预后提供一定的帮助。

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1、成都中医药大学“杏林学者”学科人才科研提升计划(YXRC2018013)。
This work was supported by the Discipline Innovation Team of Chengdu University of Traditional Chinese Medicine (YXRC2018013).()
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