Hamedani Ali G, Hauser Lauren A, Perlman Susan, Mathews Katherine, Wilmot George R, Zesiewicz Theresa, Subramony S H, Ashizawa Tetsuo, Delatycki Martin B, Brocht Alicia, Lynch David R
Department of Neurology (A.G.H., D.R.L.), University of Pennsylvania; Divisions of Neurology and Pediatrics (L.A.H., D.R.L.), Children's Hospital of Philadelphia, PA; Department of Neurology (S.P.), University of California at Los Angeles; Departments of Neurology and Pediatrics (K.M.), University of Iowa; Department of Neurology (G.R.W.), Emory University, Atlanta, GA; Department of Neurology (T.Z.), University of South Florida, Tampa Bay; Department of Neurology (S.H.S.), University of Florida, Gainesville; Department of Neurology (T.A.), Houston Methodist Hospital, TX; Murdoch Children's Research Institute (M.B.D.), Melbourne, Victoria, Australia; and Department of Neurology (A.B.), University of Rochester, NY.
Neurol Genet. 2018 Jul 23;4(4):e250. doi: 10.1212/NXG.0000000000000250. eCollection 2018 Aug.
To determine the natural history of contrast acuity in Friedreich ataxia.
In the Friedreich Ataxia-Clinical Outcome Measures Study, participants (n = 764) underwent binocular high- and low-contrast visual acuity testing at annual study visits. Mixed-effects linear regression was used to model visual acuity as a function of time, with random intercepts and slopes to account for intraindividual correlation of repeated measurements. A time-varying covariate was used to adjust for diabetes, and interaction terms were used to assess for effect modification by GAA repeat length, disease duration, and other variables.
Across a median of 4.4 years of follow-up, visual acuity decreased significantly at 100% contrast (-0.37 letters/y, 95% confidence interval [CI]: -0.52 to -0.21), 2.5% contrast (-0.81 letters/year, 95% CI: -0.99 to -0.65), and 1.25% contrast (-1.12 letters/y, 95% CI: -1.29 to -0.96 letters/year). There was a significant interaction between time and GAA repeat length such that the rate of decrease in visual acuity was greater for patients with higher GAA repeat lengths at 2.5% contrast ( = 0.018) and 1.25% contrast ( = 0.043) but not 100% contrast. There was no effect modification by age at onset after adjusting for GAA repeat length.
Low-contrast visual acuity decreases linearly over time in Friedreich ataxia, and the rate of decrease is greater at higher GAA repeat lengths. Contrast sensitivity has the potential to serve as a biomarker and surrogate outcome in future studies of Friedreich ataxia.
确定弗里德赖希共济失调患者对比敏感度的自然病程。
在弗里德赖希共济失调临床结局测量研究中，参与者（n = 764）在每年的研究访视时接受双眼高对比度和低对比度视力测试。采用混合效应线性回归将视力建模为时间的函数，使用随机截距和斜率来考虑重复测量的个体内相关性。使用时变协变量调整糖尿病，并使用交互项评估GAA重复长度、疾病持续时间和其他变量的效应修正。
在中位随访4.4年期间，100%对比度下视力显著下降（-0.37字母/年，95%置信区间[CI]：-0.52至-0.21），2.5%对比度下（-0.81字母/年，95%CI：-0.99至-0.65），以及1.25%对比度下（-1.12字母/年，95%CI：-1.29至-0.96字母/年）。时间与GAA重复长度之间存在显著交互作用，使得GAA重复长度较高的患者在2.5%对比度（P = 0.018）和1.25%对比度（P = 0.043）下视力下降速率更大，但在100%对比度下没有。在调整GAA重复长度后，发病年龄没有效应修正。
弗里德赖希共济失调患者的低对比度视力随时间呈线性下降，且GAA重复长度越高下降速率越大。对比敏感度有可能在未来弗里德赖希共济失调研究中作为生物标志物和替代结局。
