Jeffrey Brett G, Cukras Catherine A, Vitale Susan, Turriff Amy, Bowles Kristin, Sieving Paul A
National Eye Institute, National Institutes of Health, Bethesda, MD.
Current address: College of Optometry, University of Houston, TX ; National Eye Institute, National Institutes of Health, Bethesda, MD.
Transl Vis Sci Technol. 2014 Oct 3;3(5):5. doi: 10.1167/tvst.3.5.5. eCollection 2014 Sep.
To examine the variability of four outcome measures that could be used to address safety and efficacy in therapeutic trials with X-linked juvenile retinoschisis.
Seven men with confirmed mutations in the gene were evaluated over four visits spanning 6 months. Assessments included visual acuity, full-field electroretinograms (ERG), microperimetric macular sensitivity, and retinal thickness measured by optical coherence tomography (OCT). Eyes were separated into Better or Worse Eye groups based on acuity at baseline. Repeatability coefficients were calculated for each parameter and jackknife resampling used to derive 95% confidence intervals (CIs).
The threshold for statistically significant change in visual acuity ranged from three to eight letters. For ERG a-wave, an amplitude reduction greater than 56% would be considered significant. For other parameters, variabilities were lower in the Worse Eye group, likely a result of floor effects due to collapse of the schisis pockets and/or retinal atrophy. The criteria for significant change (Better/Worse Eye) for three important parameters were: ERG b/a-wave ratio (0.44/0.23), point wise sensitivity (10.4/7.0 dB), and central retinal thickness (31%/18%).
The 95% CI range for visual acuity, ERG, retinal sensitivity, and central retinal thickness relative to baseline are described for this cohort of participants with X-linked juvenile retinoschisis (XLRS).
A quantitative understanding of the variability of outcome measures is vital to establishing the safety and efficacy limits for therapeutic trials of XLRS patients.
研究四种可用于评估X连锁青少年视网膜劈裂症治疗试验安全性和有效性的结果指标的变异性。
对7名确诊该基因有突变的男性进行了为期6个月、分4次就诊的评估。评估内容包括视力、全视野视网膜电图（ERG）、微视野黄斑敏感度以及通过光学相干断层扫描（OCT）测量的视网膜厚度。根据基线时的视力将眼睛分为较好眼组或较差眼组。计算每个参数的重复性系数，并采用刀切法重采样得出95%置信区间（CI）。
视力有统计学意义的显著变化阈值为3至8个字母。对于ERG a波，振幅降低超过56%将被视为显著变化。对于其他参数，较差眼组的变异性较低，这可能是由于视网膜劈裂腔塌陷和/或视网膜萎缩导致的下限效应。三个重要参数（较好眼/较差眼）有显著变化的标准为：ERG b/a波比值（0.44/0.23）、逐点敏感度（10.4/7.0 dB）和中心视网膜厚度（31%/18%）。
描述了该组X连锁青少年视网膜劈裂症（XLRS）参与者相对于基线的视力、ERG、视网膜敏感度和中心视网膜厚度的95%CI范围。
对结果指标变异性的定量理解对于确定XLRS患者治疗试验的安全性和有效性限度至关重要。
