Purpose

To describe the earliest features of ABCA4-associated retinopathy.

Design

Case series.

Participants

Children with a clinical and molecular diagnosis of ABCA4-associated retinopathy without evidence of macular atrophy.

Methods

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.

Main Outcome Measures

Visual acuity, OCT, FAF, electroretinography, and AOSLO results.

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.

Conclusions

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.

中文翻译：

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ABCA4 相关视网膜病变中黄斑变性的早期模式

目的

描述ABCA4相关视网膜病变的最早特征。

设计

案例系列。

参与者

临床和分子诊断为ABCA4相关视网膜病变的儿童，没有黄斑萎缩的证据。

方法

视网膜表型的特征在于彩色眼底摄影、OCT、眼底自发荧光 (FAF) 成像、视网膜电图，以及 2 名患者的自适应光学扫描激光检眼镜 (AOSLO)。在所有患者中进行了ABCA4基因的测序。

主要观察指标

视力、OCT、FAF、视网膜电图和 AOSLO 结果。

结果

鉴定了8 名患有ABCA4相关视网膜病变但没有黄斑萎缩的儿童。等位基因变异体中ABCA4在所有患者中进行了鉴定。4 名儿童无症状，4 名报告 VA 丧失。患者年轻（中位年龄 8.5 岁；四分位距 6.8 岁），视力良好（中位数，最小分辨角 [logMAR] 的对数 0.155；四分位距，0.29 logMAR）。就诊时，黄斑看起来正常（n = 3），有轻微改变的中央凹反射（n = 4），或表现出明显的黄色细点（n = 1）。眼底自发荧光在 3 名患者的中央黄斑中识别出超自发荧光点，其中 2 名显示正常的眼底外观。只有 1 名儿童在就诊时有广泛的高度自发荧光视网膜斑点。OCT 成像在所有 8 名患者的外核层底部都发现了超反射。在外核体积明显减少的地方，这似乎优先发生在中心凹周围的位置。2 个人的纵向分裂探测器 AOSLO 成像证实，锥间距的最大变化发生在中央凹周围，而不是中央凹光感受器。视网膜电图显示 5 名接受测试的患者中有 3 名 B 波与 A 波的比值降低；在 2 名儿童中，录音清楚地显示了负电结果。

结论

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央凹，但不包括中央凹。在某些情况下，这些变化先于微小的、中央凹的、黄色的、超自发荧光点。外核层底部的超反射率，以前被描述为外界膜的增厚，可能代表中心凹锥体核水平的结构变化。视网膜电图表明视网膜功能障碍的初始部位可能发生在光转导之后。