目的:Zellweger谱系障碍(ZSD)患者表现出广泛的临床表型,但几乎所有人都有视网膜变性导致失明。发作时,视网膜发现的范围和进展尚未得到很好的描述.现在至关重要的是了解ZSD视力丧失的自然史,为潜在的即将进行的介入试验确定可靠的终点。这里,我们描述了迄今为止数量最多的ZSD患者的眼科发现.
方法:回顾性回顾来自医学图表的纵向数据和来自文献的横断面数据。
方法:66例ZSD患者的回顾性队列和119例文献报道,根据基因型或临床严重程度分为四种疾病表型。
方法:我们回顾了从我们的回顾性队列(Clinicaltrials.govIdentifier:NCT01668186)收集的眼科记录,并对ZSD患者的眼科发现文献进行了范围回顾。我们提取了可用的眼科数据,并根据年龄和疾病严重程度进行了分析。
方法:视敏度(VA),后段和前段描述,眼球震颤,折射,视网膜电图(ERG),视觉诱发电位(VEP)和光学相干断层扫描(OCT)的结果和图像。
结果:对于所分析的所有78名受试者,与年龄较大的中度轻度疾病患者相比,年龄较小的患者的VA更差。最小分辨率角(LogMAR)的中值为0.93对数(20/320Snellen当量)。纵向VA数据显示,随着时间的推移,损失缓慢,平均年龄为7.8岁,合法失明。胃镜检查显示视网膜色素沉着,黄斑异常,在轻度严重程度较轻的人群中,小或苍白的视盘和减弱的血管患病率较高,并没有随着年龄的增长而改变。91%的患者的ERG示踪减少,其中46%熄灭,不随年龄变化。年龄较轻患者的OCT显示18/23个体(年龄1.8-30岁)的Schitic变化,伴有演变或稳定的黄斑水肿。
结论:在ZSD中,VA缓慢恶化,并与疾病严重程度相关,串行ERG对于记录视力丧失进展没有用,和卷内收缩的变化可能是常见的。为了准确评估ZSD中的视觉功能,需要系统地报告多种措施,包括功能视力测量。
OBJECTIVE: Individuals with Zellweger spectrum disorder (ZSD) manifest a spectrum of clinical phenotypes but almost all have retinal degeneration leading to blindness. The onset, extent, and progression of retinal findings have not been well described. It is crucial to understand the natural history of vision loss in ZSD to define reliable endpoints for future interventional trials. Herein, we describe ophthalmic findings in the largest number of ZSD patients to date.
METHODS: Retrospective review of longitudinal data from medical charts and review of cross-sectional data from the literature.
METHODS: Sixty-six patients with ZSD in the retrospective cohort and 119 patients reported in the literature, divided into 4 disease phenotypes based on genotype or clinical severity.
METHODS: We reviewed ophthalmology records collected from the retrospective cohort (Clinicaltrials.gov NCT01668186) and performed a scoping review of the literature for ophthalmic findings in patients with ZSD. We extracted available ophthalmic data and analyzed by age and disease severity.
METHODS: Visual acuity (VA), posterior and anterior segment descriptions, nystagmus, refraction, electroretinography findings, visual evoked potentials, and OCT results and images.
RESULTS: Visual acuity was worse at younger ages in those with severe disease compared with older patients with intermediate to mild disease for all 78 participants analyzed, with a median VA of 0.93 logarithm of the minimum angle of resolution (Snellen 20/320). Longitudinal VA data revealed slow loss over time and legal blindness onset at an average age of 7.8 years. Funduscopy showed retinal pigmentation, macular abnormalities, small or pale optic discs, and attenuated vessels with higher prevalence in milder severity groups and did not change with age. Electroretinography waveforms were diminished in 91% of patients, 46% of which were extinguished and did not change with age. OCT in milder patients revealed schitic changes in 18 of 23 individuals (age range 1.8 to 30 years), with evolution or stable macular edema.
CONCLUSIONS: In ZSD, VA slowly deteriorates and is associated with disease severity, serial electroretinography is not useful for documenting vision loss progression, and intraretinal schitic changes may be common. Multiple systematic measures are required to assess retinal dystrophy accurately in ZSD, including functional vision measures.
BACKGROUND: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.