Vincent Ajoy, Liang Wendi, Maguire Maureen G, Duncan Jacque L, Ayala Allison R, Bernstein Paul S, Carroll Joseph, Cheetham Janet K, Durham Todd A, Farsiu Sina, Hoyng Carel B, Huckfeldt Rachel M, Jaffe Glenn J, Loo Jessica, Pennesi Mark E, Sahel José-Alain, Singh Mandeep S, Zemborain Zane Z, Birch David G, Lad Eleonora M
From the Departments of Ophthalmology and Vision Sciences (A.V.), The Hospital for Sick Children, The University of Toronto, Toronto, Ontario, Canada.
Jaeb Center for Health Research (W.L., M.G.M., A.R.A.), Tampa, Florida, USA.
Am J Ophthalmol. 2025 Aug;276:336-349. doi: 10.1016/j.ajo.2025.04.034. Epub 2025 May 3.
To describe the natural history of optical coherence tomography (OCT) and mesopic microperimetry (MP) parameters in the Rate of Progression of USH2A-related Retinal Degeneration (RUSH2A) study.
Multicenter, international, prospective, longitudinal natural history study.
Study Population: 105 participants with biallelic disease-causing variants in USH2A with a clinical diagnosis of Usher Syndrome or autosomal recessive retinitis pigmentosa who underwent annual testing over 4 years.
MAIN OUTCOME MEASURE(S): Ellipsoid zone (EZ) area and central sub-field thickness (CST) on OCT. Mean sensitivity (MS) and mean pointwise sensitivity at predefined functional transition points (MS) on MP.
A total of 101 and 94 participants met criteria for OCT and MP analysis, respectively. The average EZ area was 3.9 ± 5.3 mm at baseline which decreased to 3.3 ± 4.1 mm at 4 years (rate of change [ROC] [-0.18 mm/year]). The average CST decreased from 249.7 ± 35.6 to 244.1 ± 39.3 microns over 4 years (-2.14 microns/year). The average MP MS declined from 6.0 ± 5.1 dB (baseline) to 4.5 ± 4.2 (4 years) (-0.39 dB/year). The MS significantly decreased over time (17.9 dB [baseline] to 10.8 dB [4 years]). Notably, at 4 years, there was a meaningful decrease (≥ 7dB) in MS in 46% of study eyes.
This study establishes the natural history of key structural and functional parameters in USH2A-retinopathy. The MS is a novel, robust parameter that showed clinically meaningful change over time and is a promising tool to monitor treatment efficacy in clinical trials.
描述在USH2A相关视网膜变性进展速率（RUSH2A）研究中光学相干断层扫描（OCT）和中视微视野计（MP）参数的自然病程。
多中心、国际性、前瞻性、纵向自然病程研究。
研究人群：105名携带USH2A双等位基因致病变异且临床诊断为Usher综合征或常染色体隐性视网膜色素变性的参与者，他们在4年中每年接受检测。
OCT上的椭圆体带（EZ）面积和中心子野厚度（CST）。MP上在预定义功能转换点的平均敏感度（MS）和平均逐点敏感度。
分别有101名和94名参与者符合OCT和MP分析标准。基线时平均EZ面积为3.9±5.3平方毫米，4年后降至3.3±4.1平方毫米（变化率[ROC][-0.18平方毫米/年]）。4年中平均CST从249.7±35.6微米降至244.1±39.3微米（-2.14微米/年）。平均MP MS从6.±5.1分贝（基线）降至4.5±4.2（4年）（-0.39分贝/年）。MS随时间显著下降（从基线时的17.9分贝降至4年时的10.8分贝）。值得注意的是，在4年时，46%的研究眼MS有显著下降（≥7分贝）。
本研究确立了USH2A视网膜病变关键结构和功能参数的自然病程。MS是一个新的、可靠的参数，显示出随时间有临床意义的变化，是监测临床试验中治疗效果的有前景的工具。
