Aims To investigate the long-term natural history of ellipsoid zone (EZ) width in USH2A -retinopathy. Methods EZ width measurements from optical coherence tomography were retrospectively obtained from 110 eyes of 55 participants with molecularly confirmed biallelic USH2A -retinopathy. We used a hierarchical Bayesian method to construct and compare different mathematical models describing the long-term decline of EZ width. Results Compared with linear and quadratic models, exponential decline best represented the long-term loss of EZ width based on the deviance information criterion score. Log-transformed EZ width declined linearly over 30 years of inferred disease duration (median: 0.063 (IQR: 0.040–0.086) log (µm)/year). Compared with the raw EZ width decline rate, the log-transformed EZ width decline rate required 48% fewer patients to achieve an identically powered 1-year trial (38 vs 73 participants). Log EZ width decline rate was uncoupled from baseline EZ width (Spearman ρ=−0.18, p=0.06) and age (ρ=−0.10, p=0.31). Eyes with Usher syndrome exhibited earlier median onset ages of macular EZ width loss (18.8 (IQR: 13.1–24.7) vs 28.1 (IQR: 18.5–35.8) years, p<0.001) but comparable log EZ width decline rates (0.060 (IQR: 0.035–0.100) vs 0.065 (IQR: 0.050–0.079) log (µm)/year; p=0.42). Conclusions EZ width follows an exponential decline in USH2A -retinopathy. Compared with raw EZ width decline rate, log-transformed EZ width decline rate may be a superior endpoint for clinical trials. Syndromic eyes exhibit an earlier onset of macular EZ width loss but progress at comparable rates to non-syndromic eyes. Data are available on reasonable request. Data used in this study were previously published in Toms et al , 2020 (PMID: 31998945).

中文翻译：

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USH2A-视网膜病变中椭圆体区宽度的长期自然史


目的 研究 USH2A 视网膜病变中椭圆体区 (EZ) 宽度的长期自然史。方法通过光学相干断层扫描对 55 名患有分子证实的双等位基因 USH2A 视网膜病变的参与者的 110 只眼睛进行回顾性测量。我们使用分层贝叶斯方法构建并比较了描述 EZ 宽度长期下降的不同数学模型。结果与线性和二次模型相比，指数下降最能代表基于偏差信息标准得分的 EZ 宽度的长期损失。对数转换的 EZ 宽度在推断疾病持续时间的 30 年内呈线性下降（中位数：0.063 (IQR: 0.040–0.086) log (μm)/年）。与原始 EZ 宽度下降率相比，对数转换的 EZ 宽度下降率需要减少 48% 的患者才能实现相同功效的 1 年试验（38 名受试者与 73 名受试者）。对数 EZ 宽度下降率与基线 EZ 宽度（Spearman ρ=−0.18，p=0.06）和年龄（ρ=−0.10，p=0.31）无关。患有 Usher 综合征的眼睛表现出黄斑 EZ 宽度减少的中位发病年龄较早（18.8（IQR：13.1-24.7）与 28.1（IQR：18.5-35.8）岁，p<0.001），但对数 EZ 宽度减少率具有可比性（0.060（IQR： 0.035–0.100) vs 0.065 (IQR: 0.050–0.079) log (μm)/年；p=0.42)。结论 EZ 宽度随着 USH2A 视网膜病变呈指数下降。与原始 EZ 宽度下降率相比，对数转换的 EZ 宽度下降率可能是临床试验的更好终点。综合征眼表现出黄斑 EZ 宽度损失较早发生，但进展速度与非综合征眼相当。可根据合理要求提供数据。本研究中使用的数据先前发表于 Toms 等人，2020 年（PMID：31998945）。