Department of Ophthalmology, Columbia University, New York, New York; Division of Ophthalmology, Department of Visual Sciences, Nihon University School of Medicine, Tokyo, Japan.
Department of Ophthalmology, Columbia University, New York, New York.
Ophthalmology. 2018 Jan;125(1):89-99. doi: 10.1016/j.ophtha.2017.07.019. Epub 2017 Sep 22.
To characterize patients affected by a uniquely severe, rapid-onset chorioretinopathy (ROC) phenotype of ABCA4 disease.
Comparative cohort study.
Sixteen patients were selected from a large clinically diagnosed and genetically confirmed cohort (n = 300) of patients diagnosed with ABCA4 disease.
Phenotypic characteristics were assessed on color fundus photographs, short-wavelength autofluorescence (488-nm), and near-infrared autofluorescence (NIR-AF, 787-nm) images. Subfoveal thickness measurements were obtained from enhanced-depth imaging OCT. Generalized retinal function was determined with full-field electroretinogram (ffERG) testing, and lipofuscin accumulation was assessed by quantitative autofluorescence (qAF).
All patients exhibited advanced disease features, including pigment migration in the macula and retinal vessel attenuation at an early age, and reported a symptomatic onset, on average, at 7.4 years (average for ABCA4 disease is 21.9 years, P < 0.0001). Deterioration of the macula was observed to begin with an intense, homogeneous signal on short-wavelength autofluorescence, which corresponds to an attenuated NIR-AF signal and progresses to a patchy, coalescing pattern of chorioretinal atrophy within the subsequent decade. Measurement of choroidal thickness revealed a more rapid thinning of choriocapillaris with age of Sattler's layer compared with the rate in most other patients with ABCA4 disease (P < 0.001). Levels of qAF in the macula before atrophy were above both the 95% confidence intervals for healthy individuals and patients with Stargardt disease (STGD1) (>1000 qAF units). Severe attenuation of cone responses and notable decreases in rod responses were detected by ffERG. Sequencing of the ABCA4 gene revealed exclusively deleterious, null mutations, including stop codons; frameshift deletions; variants in canonical splice sites, which completely abolish splicing; and known deleterious missense alleles.
The ROC phenotype is a unique classification of ABCA4 disease, which is caused by deleterious null biallelic ABCA4 mutations and is characterized by the rapid deterioration of retinal pigment epithelium and photoreceptor layers in the macula and significant choroidal thinning within the first 2 decades of life.
描述一种独特的、快速发作的脉络膜视网膜病变（ROC）表型的 ABCA4 病患者的特征。
比较队列研究。
从一个大型的临床诊断和基因确诊的 ABCA4 病患者队列（n=300）中选择了 16 名患者。
在眼底彩色照片、短波自动荧光（488nm）和近红外自动荧光（NIR-AF，787nm）图像上评估表型特征。从增强深度成像 OCT 获得中心凹下厚度测量值。全视野视网膜电图（ffERG）测试确定视网膜整体功能，定量自动荧光（qAF）评估脂褐素积累。
所有患者均表现出晚期疾病特征，包括黄斑区色素迁移和视网膜血管萎缩，且发病年龄较早，平均发病年龄为 7.4 岁（ABCA4 病的平均发病年龄为 21.9 岁，P＜0.0001）。在短波自动荧光上，最初观察到一个强烈的、均匀的信号，这与 NIR-AF 信号的衰减相对应，随后的 10 年内，信号逐渐发展为脉络膜视网膜萎缩的斑片状融合模式。脉络膜厚度的测量显示，与大多数其他 ABCA4 病患者相比，Sattler 层的脉络膜毛细血管在年龄增长时的变薄速度更快（P＜0.001）。在萎缩发生之前，黄斑区的 qAF 值高于健康个体和 Stargardt 病（STGD1）患者的 95%置信区间（＞1000 qAF 单位）。ffERG 检测到锥细胞反应严重衰减和杆细胞反应明显下降。ABCA4 基因测序显示，完全缺失功能的双等位基因突变，包括终止密码子、移码缺失、经典剪接位点的变异导致完全剪接缺失以及已知的有害错义等位基因。
ROC 表型是 ABCA4 病的一种独特分类，由有害的纯合缺失 ABCA4 突变引起，其特征是在生命的头 20 年内黄斑部的视网膜色素上皮和感光细胞层迅速恶化，以及显著的脉络膜变薄。
