Department of Genetics, University College London Institute of Ophthalmology, University College London, London, United Kingdom; Medical Retina Service, Moorfields Eye Hospital, London, United Kingdom; Department of Ophthalmology, Leeds Institute of Molecular Medicine, St James's University Hospital, Leeds, United Kingdom.
Medical Retina Service, Moorfields Eye Hospital, London, United Kingdom.
Ophthalmology. 2018 May;125(5):735-746. doi: 10.1016/j.ophtha.2017.11.020. Epub 2018 Jan 6.
To describe the earliest features of ABCA4-associated retinopathy.
Case series.
Children with a clinical and molecular diagnosis of ABCA4-associated retinopathy without evidence of macular atrophy.
The retinal phenotype was characterized by color fundus photography, OCT, fundus autofluorescence (FAF) imaging, electroretinography, and in 2 patients, adaptive optics scanning laser ophthalmoscopy (AOSLO). Sequencing of the ABCA4 gene was performed in all patients.
Visual acuity, OCT, FAF, electroretinography, and AOSLO results.
Eight children with ABCA4-associated retinopathy without macular atrophy were identified. Biallelic variants in ABCA4 were identified in all patients. Four children were asymptomatic, and 4 reported loss of VA. Patients were young (median age, 8.5 years; interquartile range, 6.8 years) with good visual acuity (median, 0.155 logarithm of the minimum angle of resolution [logMAR]; interquartile range, 0.29 logMAR). At presentation, the macula appeared normal (n = 3), had a subtly altered foveal reflex (n = 4), or demonstrated manifest fine yellow dots (n = 1). Fundus autofluorescence identified hyperautofluorescent dots in the central macula in 3 patients, 2 of whom showed a normal fundus appearance. Only 1 child had widespread hyperautofluorescent retinal flecks at presentation. OCT imaging identified hyperreflectivity at the base of the outer nuclear layer in all 8 patients. Where loss of outer nuclear volume was evident, this appeared to occur preferentially at a perifoveal locus. Longitudinal split-detector AOSLO imaging in 2 individuals confirmed that the greatest change in cone spacing occurred in the perifoveal, and not foveolar, photoreceptors. Electroretinography showed a reduced B-wave-to-A-wave ratio in 3 of 5 patients tested; in 2 children, recordings clearly showed electronegative results.
In childhood-onset ABCA4-associated retinopathy, the earliest stages of macular atrophy involve the parafovea and spare the foveola. In some cases, these changes are predated by tiny, foveal, yellow, hyperautofluorescent dots. Hyperreflectivity at the base of the outer nuclear layer, previously described as thickening of the external limiting membrane, is likely to represent a structural change at the level of the foveal cone nuclei. Electroretinography suggests that the initial site of retinal dysfunction may occur after phototransduction.
描述 ABCA4 相关视网膜病变的最早特征。
病例系列。
没有黄斑萎缩证据的 ABCA4 相关视网膜病变的临床和分子诊断儿童。
通过眼底彩色照相、OCT、眼底自发荧光（FAF）成像、视网膜电图和 2 例患者的自适应光学扫描激光检眼镜（AOSLO）来描述视网膜表型。对所有患者进行 ABCA4 基因测序。
视力、OCT、FAF、视网膜电图和 AOSLO 结果。
确定了 8 名无黄斑萎缩的 ABCA4 相关视网膜病变儿童。所有患者均发现 ABCA4 双等位基因突变。4 名儿童无症状，4 名儿童视力丧失。患者年龄较小（中位年龄 8.5 岁；四分位间距 6.8 岁），视力较好（中位数 0.155 对数最小角分辨率[logMAR]；四分位间距 0.29 logMAR）。在发病时，黄斑区外观正常（n=3），黄斑区有轻微改变的光反射（n=4），或表现为明显的细小黄点（n=1）。3 名患者的眼底自发荧光显示中央黄斑区有高荧光点，其中 2 名患者眼底外观正常。只有 1 名儿童在发病时出现广泛的高荧光视网膜斑。OCT 成像在 8 名患者中均发现外核层底部高反射性。在外核层体积损失明显的情况下，这种情况似乎优先发生在外周。2 名患者的纵向分裂探测器 AOSLO 成像证实，在旁中心区而非中心凹，视锥细胞间距的变化最大。5 名接受测试的患者中有 3 名的视网膜电图 B 波到 A 波比值降低；在 2 名儿童中，记录明显显示负电结果。
在儿童期发病的 ABCA4 相关视网膜病变中，黄斑萎缩的最早阶段涉及旁中心区，而 spared 黄斑中心凹。在某些情况下，这些变化之前存在微小的、黄斑中心凹的、黄色的、高荧光点。以前描述为外节膜增厚的外核层底部的高反射性，可能代表在中心凹视锥细胞核水平的结构变化。视网膜电图提示视网膜功能障碍的初始部位可能发生在光转化之后。
