Ovens Christopher A, Grigg John R, Fraser Clare L
Save Sight Institute, Faculty of Medicine and Health, The University of Sydney, Sydney Eye Hospital Campus, Sydney, Australia.
Eye Genetics Research Unit, The Children's Hospital at Westmead, Save Sight Institute, Children's Medical Research Institute, The University of Sydney, Sydney, Australia.
Clin Exp Ophthalmol. 2025 Aug;53(6):652-659. doi: 10.1111/ceo.14543. Epub 2025 May 7.
Dominant Optic Atrophy (DOA) causes slowly progressive visual decline usually beginning in childhood. As new therapies come to clinical trial, the choice of biomarkers to be used as clinical trial endpoints has become a critical question to be addressed.
We undertook a systematic review and meta-analysis of studies reporting longitudinal data of any biomarker in DOA patients.
In total, seven studies were included in the systematic review, and four presented paired results compatible with meta-analysis. Visual acuity was the only biomarker found with reported longitudinal data. Of the included studies in the meta-analysis, the rate of yearly visual acuity decline (0.022 LogMAR/year., 95% CI: -0.008 to 0.052) was not significantly different from zero (Z = 1.4, p = 0.155).
Quantifying this slow rate of visual decline has implications for future study design and suggests that further natural history studies examining alternative biomarkers in DOA are warranted.
显性遗传性视神经萎缩（DOA）通常在儿童期开始导致视力缓慢进行性下降。随着新疗法进入临床试验，用作临床试验终点的生物标志物的选择已成为一个亟待解决的关键问题。
我们对报告DOA患者任何生物标志物纵向数据的研究进行了系统评价和荟萃分析。
系统评价共纳入7项研究，4项呈现了与荟萃分析相符的配对结果。视力是唯一有纵向数据报告的生物标志物。在荟萃分析纳入的研究中，年视力下降率（0.022 LogMAR/年，95%CI：-0.008至0.052）与零无显著差异（Z = 1.4，p = 0.155）。
量化这种缓慢的视力下降速度对未来的研究设计具有重要意义，并表明有必要进一步开展自然史研究，以检验DOA中的替代生物标志物。
