Abstract：
OBJECTIVE: 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.
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.
摘要：
目的：研究USH2A视网膜病变中椭球区（EZ）宽度的长期自然史。
方法：光学相干断层扫描的EZ宽度测量来自55例分子证实为双等位基因USH2A视网膜病变的参与者的110只眼。我们使用分层贝叶斯方法来构建和比较描述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，指数下降最好地代表了基于偏差信息准则得分的EZ宽度的长期损失。对数变换的EZ宽度在30年的推断疾病持续时间内线性下降（中位数：0.063（IQR：0.040-0.086）log（µm）/年）。与原始EZ宽度下降率相比，对数变换的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对73名参与者).LogEZ宽度下降率与基线EZ宽度（Spearmanρ=-0.18，p=0.06）和年龄（ρ=-0.10，p=0.31）脱钩。患有Usher综合征的眼睛表现出黄斑EZ宽度丢失的中位发病年龄较早（18.8（IQR：13.1-24.7）vs28.1（IQR：18.5-35.8），p<0.001），但具有可比性的logEZ宽度下降率（0.060（IQR：0.035-0.100）vs0.065（IQR：0.050-0.079）log（µm）/年；p=0.42）。
结论：EZ宽度跟随USH2A视网膜病变的指数下降。与原始EZ宽度下降率相比，对数变换的EZ宽度下降率可能是临床试验的最佳终点。综合征眼表现出黄斑EZ宽度损失的较早发作，但进展速度与非综合征眼相当。
方法：光学相干断层扫描的EZ宽度测量来自55例分子证实为双等位基因USH2A视网膜病变的参与者的110只眼。我们使用分层贝叶斯方法来构建和比较描述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，指数下降最好地代表了基于偏差信息准则得分的EZ宽度的长期损失。对数变换的EZ宽度在30年的推断疾病持续时间内线性下降（中位数：0.063（IQR：0.040-0.086）log（µm）/年）。与原始EZ宽度下降率相比，对数变换的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对73名参与者).LogEZ宽度下降率与基线EZ宽度（Spearmanρ=-0.18，p=0.06）和年龄（ρ=-0.10，p=0.31）脱钩。患有Usher综合征的眼睛表现出黄斑EZ宽度丢失的中位发病年龄较早（18.8（IQR：13.1-24.7）vs28.1（IQR：18.5-35.8），p<0.001），但具有可比性的logEZ宽度下降率（0.060（IQR：0.035-0.100）vs0.065（IQR：0.050-0.079）log（µm）/年；p=0.42）。
结论：EZ宽度跟随USH2A视网膜病变的指数下降。与原始EZ宽度下降率相比，对数变换的EZ宽度下降率可能是临床试验的最佳终点。综合征眼表现出黄斑EZ宽度损失的较早发作，但进展速度与非综合征眼相当。
