Efficacy Outcome Measures for Clinical Trials of USH2A Caused by the Common c.2299delG Mutation
Efficacy Outcome Measures for Clinical Trials of USH2A Caused by the Common c.2299delG Mutation
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DOI：
10.1016/j.ajo.2018.06.017
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发表时间：
2018-09-01
影响因子：
4.2
通讯作者：
Jacobson, Samuel G.
中科院分区：
文献类型：
--
作者：
Calzetti, Giacomo;Levy, Richard A.;Jacobson, Samuel G.
目的：了解USH2A基因c.2299delG突变患者视力和视网膜结构的变化，为临床治疗试验做准备。设计：回顾性观察性病例系列。方法：对18例携带USH2A基因c.2299delG突变的纯合子或复合杂合子患者的视力、动态视野、适应黑暗和光线的静态视野、光学相干断层扫描（OCT）和自身荧光（AF）成像进行研究。根据所分析的参数，至少有一半的患者可获得串行数据。结果：USH2A这种特定分子形式的疾病进展动力学在测量参数之间存在差异。视力可以保持正常几十年。动态和适应光线的静态视野在整个视野范围内的下降速度与基于杆的视野的下降速度相似。通过黄斑的水平OCT扫描显示，内段/外段线宽的收缩率与共定位AF成像和基于锥的光适应灵敏度相似。杆状体在同一区域的敏感度收缩速度是锥状体的两倍。结论：在USH2A基因c.2299delG突变的患者中，杆状光感受器比视锥细胞更早表达疾病，且更具侵袭性。为了及时完成临床试验，在中央或外中央-外周视网膜区域进行基于棒的视觉测量是必要的。(C) 2018 Elsevier Inc.版权所有。)
PURPOSE: To determine the change in vision and retinal structure in patients with the common c.2299delG mutation in the USH2A gene in anticipation of clinical trials of therapy.DESIGN: Retrospective observational case series.METHODS: Eighteen patients, homozygotes or compound heterozygotes with the c.2299delG mutation in USH2A, were studied with regard to visual acuity, kinetic perimetry, dark- and light-adapted static perimetry, optical coherence tomography (OCT), and autofluorescence (AF) imaging. Serial data were available for at least half of the patients, depending on the parameter analyzed.RESULTS: The kinetics of disease progression in this specific molecular form of USH2A differed between the measured parameters. Visual acuity could remain normal for decades. Kinetic and light-adapted static perimetry across the entire visual field had similar rates of decline that were slower than those of rod-based perimetry. Horizontal OCT scans through the macula showed that inner segment/outer segment line width had a similar rate of constriction as co-localized AF imaging and cone-based light-adapted sensitivity extent. The rate of constriction of rod-based sensitivity extent across this same region was twice as rapid as that of cones.CONCLUSIONS: In patients with the c.2299delG mutation in USH2A, rod photoreceptors are the cells that express disease early and more aggressively than cones. Rod-based vision measurements in central or extracentral-peripheral retinal regions warrant monitoring in order to complete a clinical trial in a timely manner. ((C) 2018 Elsevier Inc. All rights reserved.)