Parker Maria A, Choi Dongseok, Erker Laura R, Pennesi Mark E, Yang Paul, Chegarnov Elvira N, Steinkamp Peter N, Schlechter Catherine L, Dhaenens Claire-Marie, Mohand-Said Saddek, Audo Isabelle, Sahel Jose, Weleber Richard G, Wilson David J
Oregon Health & Science University, Casey Eye Institute, Portland, OR, USA.
Oregon Health & Science University, Casey Eye Institute, Portland, OR, USA ; OHSU-PSU School of Public Health, Oregon Health & Science University, Portland, OR, USA.
Transl Vis Sci Technol. 2016 Oct 1;5(5):10. doi: 10.1167/tvst.5.5.10. eCollection 2016 Oct.
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.
Twenty-two participants, aged 24 to 66, diagnosed with advanced forms of STGD, with at least one pathogenic 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.
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, respectively), SVF full volume HOV (V 14.62 dB-sr), central macular thickness, and macular volume (4.27 μm and 0.15 mm, respectively).
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.
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.
本分析的目的是确定参与SAR422459（NCT01367444）基因治疗临床试验的晚期Stargardt病（STGD）患者队列中功能和结构测量的重测变异性。
对22名年龄在24至66岁之间、被诊断为晚期STGD且每条染色体上至少有一个致病突变、参与SAR422459（NCT01367444）基因治疗临床试验的参与者，在3周或更短时间内进行了三次访视筛查。功能性视力评估包括：最佳矫正视力（BCVA）早期糖尿病视网膜病变研究（ETDRS）字母评分、使用I4e、III4e和V4e等视线的半自动动态视野检查（SKP）、通过使用带有V测试目标刺激大小的184n点中心浓缩网格从静态视野（SVF）计算的视力 hill（HOV）。通过光谱域光学相干断层扫描（SD-OCT）评估视网膜结构变化，如中心黄斑厚度和黄斑体积。使用分层混合效应模型和自抽样法为每个参数计算重复性系数（RC）和95%置信区间（CI）。
发现各参数具有统计学显著变化的标准如下：BCVA字母评分（8个字母）、SKP视线I4e、III4e和V4e（分别为3478.85；2488.02和2622.46度）、SVF全量HOV（V 14.62 dB-sr）、中心黄斑厚度和黄斑体积（分别为4.27μm和0.15mm）。
本分析提供了重要信息，有助于确定在该STGD患者队列中用于测量疾病进展的常用结构和功能评估中是否正在发生显著变化。此外，该信息对未来评估STGD治疗安全性和有效性的试验有用。
确定STGD晚期参与者功能和结构测量的变异性对于评估涉及STGD患者的治疗试验的疗效和安全性是必要的。
