Retinal Abnormalities as Biomarker of Disease Progression and Early Diagnosis of Parkinson Disease
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 166
- 试验地点
- 1
- 主要终点
- Retinal ganglion cell layer (GCL) thickness
研究概览
简要总结
- To determine whether retinal abnormalities, as measured by high definition optical coherence tomography (HD-OCT) and visual electrophysiology techniques can be used as a clinical biomarker to monitor disease progression overtime in patients with Parkinson disease.
- To establish whether these measures can be used to identify patients with PD in the premotor phase.
- To define the rate of progression of retinal abnormalities in PD (both in the motor and premotor stages) for potential use as a clinical outcome measure
详细描述
The retina is actually brain tissue and is considered part of the central nervous system (CNS). It is the only part of the CNS that can be visualized directly and non-invasively. There is already a body of evidence that retinal neurons accumulate alpha-synuclein and degenerate in Parkinson disease (PD). Whether retinal imaging could be useful as an objective biomarker to track disease progression and response to disease-modifying treatments in patients with PD is not known.
While there are a variety of imaging techniques available (e.g., PET, SPECT, MRI), none of them has emerged as a fully reliable method to accurately measure clinical progression in PD.
The structure of the retina can be studied easily in vivo using spectral domain high definition optical coherence tomography (OCT), a non-invasive imaging technique with a resolution of ~1 microns (0.001 mm). OCT quantifies the thickness of the different retinal layers. The primary aim of this proposal is to determine whether OCT is a reliable clinical measure that can objectively measure clinical progression in PD.
Our group has shown recently that OCT can be used as a means to measure progressive neuronal loss in the retina in patients with a synucleinopathy closely related to PD (multiple system atrophy, MSA). In MSA, retinal degeneration was closely associated with disease severity and progressively worsened overtime in a predictable fashion, sufficient for biostatistical modeling. We now want to find out if this is also true in PD.
There is a panel of non-motor clinical features that increase the risk of developing PD. We propose to measure retinal nerve fiber density in these patients considering them as "pre-motor" PD and follow their clinical evolution overtime. If OCT proves useful as a means to identify pre-motor PD, such a result would present an important therapeutic window to intervene with disease modifying drugs and to prevent the development of CNS deficits.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Subjects with PD, MSA and DLB that fulfill current diagnostic criteria.
- •Subjects with RBD that have polysomnography-confirmed diagnosis showing evidence of lack of muscle atonia and dream enacting behaviors during REM sleep.
- •Subjects with isolated autonomic failure (i.e., no motor deficits) that have evidence of neurogenic orthostatic hypotension and other features of autonomic failure without clinical evidence of cognitive impairment.
- •Control subjects with no history of neurological or ophthalmological disorders.
排除标准
- •Subjects with glaucoma, retinopathy, or significant media opacification (e.g., cataracts).
- •Subjects with a history of eye surgery or eye trauma
- •Inability to comply with the requirements of the study
结局指标
主要结局
Retinal ganglion cell layer (GCL) thickness
时间窗: Every 6 months from baseline to 3 years
The results of the GCL thickness will be expressed in microns in different zones around the fovea region: temporal- superior, superior, nasal-superior, nasal inferior, inferior, temporal inferior and global.
Retinal nerve fiber layer (RNFL) thickness
时间窗: Every 6 months from baseline to 3 years
The results of the RNFL thickness will be expressed in microns in different zones around the optic nerve: temporal, superior, nasal, inferior and global.
次要结局
- • Visual Acuity(Every 6 months from baseline to 3 years)
- • Color Discrimination(Every 6 months from baseline to 3 years)
- • Pupillometry(Every 6 months from baseline to 3 years)
- • Videonystagmography(Every 6 months from baseline to 3 years)