Visual Acuity, Full-field Stimulus Thresholds, and Electroretinography for 4 Years in The Rate of Progression of USH2A-related Retinal Degeneration (RUSH2A) Study

IF 4.6 Q1 OPHTHALMOLOGY Ophthalmology science Pub Date : 2024-11-08 DOI:10.1016/j.xops.2024.100648

David G. Birch PhD , Peiyao Cheng PhD , Maureen G. Maguire PhD , Jacque L. Duncan MD , Allison R. Ayala MS , Janet K. Cheetham PharmD , Nicole R. Doucet MPH , Todd A. Durham PhD , Abigail T. Fahim MD, PhD , Frederick L. Ferris III MD , Rachel M. Huckfeldt MD, PhD , Michele Melia ScM , Michel Michaelides MD (Res) , Mark E. Pennesi MD, PhD , José-Alain Sahel MD , Katarina Stingl MD , Ajoy Vincent MBBS, MS , Christina Y. Weng MD, MBA , Foundation Fighting Blindness Clinical Consortium Investigator Group

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Abstract

Purpose

To describe progression of best-corrected visual acuity (BCVA), full-field stimulus thresholds (FST), and electroretinography (ERG) over 4 years in the USH2A-related Retinal Degeneration study and to assess their suitability as clinical trial endpoints.

Design

Prospective natural history study.

Participants

Participants (n = 105) with biallelic disease-causing sequence variants in USH2A and BCVA letter scores of ≥54 were included.

Methods

BCVA, FST, fundus-guided microperimetry, static perimetry, and spectral domain OCT were performed annually and ERG at baseline and 4 years only. Mixed effects models were used to estimate annual rates of change with 95% confidence intervals. Associations of change from baseline to 4 years between BCVA, FST, ERG, and other metrics were assessed with Spearman correlation coefficients (r_s).

Main Outcome Measures

Best-corrected visual acuity, FST, and ERG.

Results

The annual rate of decline in BCVA was 0.83 (95% confidence interval: 0.65−1.02) letters/year. For FST, the change was 0.09 (0.07−0.11) log cd.s/m²/year for white threshold, 0.10 (0.08−0.12) log cd.s/m²/year for blue threshold, and 0.05 (0.04−0.06) log cd.s/m²/year for red threshold. Changes were 22.6 (17.4−28.2)%/year for white threshold, 26.0 (20.3−32.1)%/year for blue threshold, and 12.3 (8.7−16.0)%/year for red threshold. The high percentage of eyes with undetectable ERGs at baseline limited assessment of change.

Conclusions

Best-corrected visual acuity was not a sensitive measure of progression over 4 years. Full-field stimulus threshold was a more sensitive measure; however, additional information on the clinical relevance of changes in FST is needed before this test can be adopted as an endpoint for clinical trials.

Financial Disclosure(s)

Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

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ush2a相关性视网膜变性（RUSH2A）进展速度研究的4年视力、全视野刺激阈值和视网膜电图

目的：描述 USH2A 相关视网膜变性研究中最佳矫正视力 (BCVA)、全场刺激阈值 (FST) 和视网膜电图 (ERG) 在 4 年内的进展情况，并评估其作为临床试验终点的适宜性：设计：前瞻性自然史研究：方法：BCVA、FST、眼底检查：每年进行一次BCVA、FST、眼底引导显微验光、静态验光和光谱域OCT检查，仅在基线和4年进行ERG检查。混合效应模型用于估算每年的变化率及 95% 的置信区间。用斯皮尔曼相关系数（rs）评估BCVA、FST、ERG和其他指标之间从基线到4年的变化关系：主要结果测量指标：最佳矫正视力、FST和ERG：BCVA 的年下降率为 0.83（95% 置信区间：0.65-1.02）个字母/年。就 FST 而言，白色阈值的变化率为 0.09 (0.07-0.11) log cd.s/m2/年，蓝色阈值的变化率为 0.10 (0.08-0.12) log cd.s/m2/年，红色阈值的变化率为 0.05 (0.04-0.06) log cd.s/m2/年。白色阈值的变化率为 22.6 (17.4-28.2)%/年，蓝色阈值的变化率为 26.0 (20.3-32.1)%/年，红色阈值的变化率为 12.3 (8.7-16.0)%/年。基线时无法检测到ERG的眼睛比例较高，这限制了对变化的评估：结论：最佳矫正视力并不能灵敏地衡量4年的视力进展。全视野刺激阈是一种更灵敏的测量方法；然而，在将全视野刺激阈测试作为临床试验的终点之前，还需要更多关于该测试变化的临床相关性的信息：专利或商业信息披露请参见本文末尾的 "脚注和披露"。

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