Test-Retest Variability of Functional and Structural Parameters in Patients with Stargardt Disease Participating in the SAR422459 Gene Therapy Trial.
Test-Retest Variability of Functional and Structural Parameters in Patients with Stargardt Disease Participating in the SAR422459 Gene Therapy Trial.
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参加 SAR422459 基因治疗试验的 Stargardt 病患者功能和结构参数的重测变异性。
DOI：
10.1167/tvst.5.5.10
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发表时间：
2016
影响因子：
3
通讯作者：
Wilson,DavidJ
中科院分区：
文献类型：
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作者：
Parker,MariaA;Choi,Dongseok;Erker,LauraR;Pennesi,MarkE;Yang,Paul;Chegarnov,ElviraN;Steinkamp,PeterN;Schlechter,CatherineL;Dhaenens,Claire-Marie;Mohand-Said,Saddek;Audo,Isabelle;Sahel,Jose;Weleber,RichardG;Wilson,DavidJ
目的：本分析的目的是确定参加SAR422459(NCT01367444)基因治疗临床试验的一组晚期Stargardt病(STGD)患者的功能和结构指标的重测变异性。方法：对参加SAR422459(NCT01367444)基因治疗临床试验的22名年龄在24岁到66岁之间、每条染色体上至少有一个致病ABCA4突变的晚期STGD患者进行了3次以上的筛查。功能视力评估包括：最佳矫正视力(BCVA)、糖尿病视网膜病变早期治疗研究(ETDRS)字母评分、使用I4e、III4e和V4e等参数值的半自动动态视野检查(SKP)、静态视野(SVF)计算视力山(HOV)。应用光谱域光学相干断层扫描(SD-OCT)评价黄斑中心厚度、黄斑体积等视网膜结构改变。结果：各参数的重复性系数(RC)和95%可信区间(CI)分别为：BCVA字母分(8个字母)、SKP等值线I4e、III4e和V4e(3478.85；2488.02和2622.46°2)、中心黄斑厚度和黄斑体积(分别为4.27μm和0.15 mm3)。结论：这一分析提供了重要的信息，以确定该队列中通常用于测量疾病进展的结构和功能评估是否发生了重大变化。此外，这些信息对未来评估STGD治疗的安全性和有效性的试验是有用的。翻译相关性：在STGD患者的治疗试验中，有必要确定STGD晚期参与者的功能和结构措施的变异性，以评估疗效和安全性。
Purpose: The goal of this analysis was to determine the test–retest variability of functional and structural measures from a cohort of patients with advanced forms of Stargardt Disease (STGD) participating in the SAR422459 (NCT01367444) gene therapy clinical trial.Methods: Twenty-two participants, aged 24 to 66, diagnosed with advanced forms of STGD, with at least one pathogenic ABCA4 mutation on each chromosome participating in the SAR422459 (NCT01367444) gene therapy clinical trial, were screened over three visits within 3 weeks or less. Functional visual evaluations included: best-corrected visual acuity (BCVA) Early Treatment Diabetic Retinopathy Study (ETDRS) letter score, semiautomated kinetic perimetry (SKP) using isopters I4e, III4e, and V4e, hill of vision (HOV) calculated from static visual fields (SVF) by using a 184n point centrally condensed grid with the stimulus size V test target. Retinal structural changes such as central macular thickness and macular volume were assessed by spectral-domain optical coherence tomography (SD-OCT). Repeatability coefficients (RC) and 95% confidential intervals (CI) were calculated for each parameter using a hierarchical mixed-effects model and bootstrapping.Results: Criteria for statistically significant changes for various parameters were found to be the following: BCVA letter score (8 letters), SKP isopters I4e, III4e, and V4e (3478.85; 2488.02 and 2622.46 deg 2, respectively), SVF full volume HOV (V TOT, 14.62 dB-sr), central macular thickness, and macular volume (4.27 μm and 0.15 mm 3, respectively).Conclusions: This analysis provides important information necessary to determine if significant changes are occurring in structural and functional assessments commonly used to measure disease progression in this cohort of patients with STGD. Moreover, this information is useful for future trials assessing safety and efficacy of treatments in STGD.Translational Relevance: Determination of variability of functional and structural measures in participants with advanced stages of the STGD is necessary to assess efficacy and safety in treatment trials involving STGD patients.