Deep Phenotyping of PDE6C-Associated Achromatopsia
Deep Phenotyping of PDE6C-Associated Achromatopsia
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DOI：
10.1167/iovs.19-27761
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发表时间：
2019-12-01
影响因子：
4.4
通讯作者：
Michaelides, Michel
中科院分区：
文献类型：
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作者：
Georgiou, Michalis;Robson, Anthony G.;Michaelides, Michel
目的.对PDE 6C色盲患者进行深层表型分析并检查疾病自然史。详细评估了8例PDE 6C致病变异的受试者，包括临床表型、最佳矫正视力、眼底自发荧光和光学相干断层扫描。6名受试者还进行了共焦和非共焦自适应光学扫描光检眼镜检查、眼轴长度、国际标准模式和全视野视网膜电图（ERG）、短波长闪光（S-锥）ERG和色觉测试。所有受试者均表现为早发性眼球震颤，最佳矫正视力、光敏感度下降，严重色觉丧失，其中5例为高度近视。我们确定了三种新的致病变异，并首次提供了与九种变异相关的表型数据。没有受试者有中心凹发育不全或在中心凹中心的残留椭圆体区（EZ）;一个没有EZ，三个有低反射区，四个有外视网膜萎缩。基线时光学相干断层扫描显示的中心EZ病变的平均宽度为1923 μ m。EZ病变大小的平均每年增加为48.3 μ m。眼底自发荧光显示中央低自发荧光，周围环信号增加（n = 5）。基线时的平均低自发荧光面积为3.33 mm（2），平均每年增加0.13 mm（2）。非共焦自适应光学扫描光检眼镜发现残留的中心凹锥，只有一个两例。全视野ERG与严重的全身性视锥系统功能障碍一致，但S视锥敏感性相对保留。PDE 6C视网膜病变是一种严重的视锥细胞功能障碍综合征，通常表现为典型的全色盲，但没有中心凹发育不全。近视和缓慢进行性黄斑病变是常见的特征。在老年人中，很少（如果有的话）有剩余的中央凹视锥用于干预。
PURPOSE. To perform deep phenotyping of subjects with PDE6C achromatopsia and examine disease natural history.METHODS. Eight subjects with disease-causing variants in PDE6C were assessed in detail, including clinical phenotype, best-corrected visual acuity, fundus autofluorescence, and optical coherence tomography. Six subjects also had confocal and nonconfocal adaptive optics scanning light ophthalmoscopy, axial length, international standard pattern and full-field electroretinography (ERG), short-wavelength flash (S-cone) ERGs, and color vision testing.RESULTS. All subjects presented with early-onset nystagmus, decreased best-corrected visual acuity, light sensitivity, and severe color vision loss, and five of them had high myopia. We identified three novel disease-causing variants and provide phenotype data associated with nine variants for the first time. No subjects had foveal hypoplasia or residual ellipsoid zone (EZ) at the foveal center; one had an absent EZ, three had a hyporeflective zone, and four had outer retinal atrophy. The mean width of the central EZ lesion on optical coherence tomography at baseline was 1923 mu m. The mean annual increase in EZ lesion size was 48.3 mu m. Fundus autofluorescence revealed a central hypoautofluorescence with a surrounding ring of increased signal (n = 5). The mean hypoautofluorescent area at baseline was 3.33 mm(2) and increased in size by a mean of 0.13 mm(2)/year. Nonconfocal adaptive optics scanning light ophthalmoscopy revealed residual foveal cones in only one of two cases. Full-field ERGs were consistent with severe generalized cone system dysfunction but with relative preservation of S-cone sensitivity.CONCLUSIONS. PDE6C retinopathy is a severe cone dysfunction syndrome often presenting as typical achromatopsia but without foveal hypoplasia. Myopia and slowly progressive maculopathy are common features. There are few (if any) residual foveal cones for intervention in older adults.