■定义中心体蛋白290(CEP290)相关遗传性视网膜变性(IRD)的临床特征,并确定哪些评估可以在未来的介入试验中提供可靠的终点。
■这项自然史研究的参与者被纳入2个最佳矫正视力(BCVA)队列:光感知到>1.0对数的最小分辨率角(logMAR)和1.0logMAR到0.4logMAR。每个包括4个年龄组(3-5、6-11、12-17和≥18岁)。
■由内含子26c.2991+1655A>G突变和BCVA引起的CEP290相关IRD患者,范围从光感知到0.4logMAR。
■最佳矫正视力,全场刺激阈值(FST)灵敏度,Ora-视觉导航挑战(Ora-VNC)综合得分,和OCT-外核层(OCT-ONL)的平均厚度在筛选时进行评估,基线,3个月,6个月,和12个月。
■最佳矫正视力,FST灵敏度,Ora-VNC综合评分,和OCT-ONL平均厚度。
■本分析包括26名参与者。十九个是女性。所有参与者均为白人,4名报告为西班牙裔。在筛选时,16名成年人中的13名和10名儿科参与者中的9名的BCVA>1.0logMAR。基线BCVA是可变的(中位数[range]=2.0[0.5,3.9]logMAR),与年龄无关,VNC综合评分也是如此,FST灵敏度,和OCT-ONL平均厚度。BCVA(n=25)的平均(95%置信区间[CI])重测变异性为-0.04(-0.09,0.01)logMAR;VNC综合评分(n=18)为0.6(-0.1,1.3);和0.10(-0.07,0.27)logcd。s/m2为红色FST(n=14)。大于预期的重测变异性(5[0,10]μm,观察到OCT-ONL平均厚度n=14),因为眼球震颤影响了在相同视网膜位置重复测量的能力。功能评估在12个月内是稳定的。BCVA(n=23)与基线相比的平均(95%CI)变化为0.06(-0.17,0.29)logMAR;VNC综合评分(n=21)为-0.1(-1.2,1.0);-0.15(-0.43,0.14)logcd。s/m2为红色FST(n=16)。
■视力在12个月内保持稳定。最佳矫正视力,FST,和VNC综合评分是CEP290相关IRD未来研究的潜在可行终点。OCT测量的可重复性对量化该人群的解剖学变化提出了挑战。
■专有或商业披露可在本文末尾的脚注和披露中找到。
UNASSIGNED: To define the clinical characteristics of centrosomal protein 290 (CEP290)-associated inherited retinal degeneration (IRD) and determine which assessments may provide reliable endpoints in future interventional trials.
UNASSIGNED: Participants in this natural history
study were enrolled into 2 best-corrected visual acuity (BCVA) cohorts: light perception to > 1.0 logarithm of the minimum angle of resolution (logMAR) and 1.0 logMAR to 0.4 logMAR. Each comprised 4 age cohorts (3-5, 6-11, 12-17, and ≥ 18 years).
UNASSIGNED: Patients with CEP290-associated IRD caused by the intron 26 c.2991+1655A>G mutation and BCVA ranging from light perception to 0.4 logMAR.
UNASSIGNED: Best-corrected visual acuity, full-field stimulus threshold (FST) sensitivity, Ora-Visual Navigation Challenge (Ora-VNC) composite score, and OCT-outer nuclear layer (OCT-ONL) average thickness were assessed at screening, baseline, 3 months, 6 months, and 12 months.
UNASSIGNED: Best-corrected visual acuity, FST sensitivity, Ora-VNC composite score, and OCT-ONL average thickness.
UNASSIGNED: Twenty-six participants were included in this analysis. Nineteen were female. All participants were White and 4 reported Hispanic ethnicity. At screening, 13 of 16 adult and 9 of 10 pediatric participants had BCVA > 1.0 logMAR. Baseline BCVA was variable (median [range] = 2.0 [0.5, 3.9] logMAR) and was uncorrelated with age, as were VNC composite score, FST sensitivity, and OCT-ONL average thickness. Mean (95% confidence interval [CI]) test-retest variability was -0.04 (-0.09, 0.01) logMAR for BCVA (n = 25); 0.6 (-0.1, 1.3) for VNC composite score (n = 18); and 0.10 (-0.07, 0.27) log cd.s/m2 for red FST (n = 14). A greater than expected test-retest variability (5 [0, 10] μm, n = 14) was observed for OCT-ONL average thickness as nystagmus impacted ability to repeat measures at the same retinal location. Functional assessments were stable over 12 months. Mean (95% CI) change from baseline was 0.06 (-0.17, 0.29) logMAR for BCVA (n = 23); -0.1 (-1.2, 1.0) for VNC composite score (n = 21); and -0.15 (-0.43, 0.14) log cd.s/m2 for red FST (n = 16).
UNASSIGNED: Vision was stable over 12 months. Best-corrected visual acuity, FST, and VNC composite score are potentially viable endpoints for future studies in CEP290-associated IRD. Repeatability of OCT measures poses challenges for quantifying anatomical changes in this population.
UNASSIGNED: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.