Retinal Markers in Neuroinflammatory Diseases: a Prospective Observational Study
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 500
- 试验地点
- 1
- 主要终点
- Fixation instability (as marker of global neuronal dysfunction in the CNS)
研究概览
简要总结
The goal of this observational study, including patients with Multiple Sclerosis, patients with other neuroinflammatory diseases and healthy controls, is to determine the predictive value of retinal markers in predicting disease progression. Participants complete a questionnaire and undergo various non-invasive retinal routine clinical examinations.
详细描述
Multiple Sclerosis (MS) is an autoimmune disease of the central nervous system (CNS) and represents one of the most common neurological disorders affecting young adults worldwide and often leads to significant disability over time. While MS typically presents with recurrent neurological symptoms known as relapses, most patients also experience progressive neurological deterioration independent of relapses, referred to as progression independent of relapse activity (PIRA). PIRA is a major contributor to long-term disability and represents a significant challenge in the management of MS. Early identification of patients at high risk to develop PIRA is crucial for therapeutic decisions and testing treatment efficacy, highlighting the urgent need for accurate predictive markers of progression in MS.
The primary objective of this longitudinal, observational, prospective, single center study is to investigate the predictive value of various retinal markers in predicting PIRA in MS patients.
The study assesses several easily obtained, non-invasive retinal measures:
- Neuroaxonal loss in the retina: This serves as a marker of neurodegeneration in the CNS. It will be assessed by measuring the volume of the ganglion cell-inner plexiform layer and the thickness of the peripapillary retinal nerve fiber layer using optical coherence tomography (OCT).
- Neuroinflammation in the retina: This will be assessed by evaluating thickening of other retinal layers in OCT, particularly the inner nuclear layer.
- Fixation instability of the patients: This serves as a marker of global neuronal dysfunction in the CNS. It will be measured using Scanner Laser Ophthalmoscopy-OCT.
- Structural changes of the retinal vessels: Particularly, the arteriolar and venular diameters will be assessed. This serves as a marker of systemic microvascular health and will be measured using static retinal vessel analysis.
- Functional/perfusional changes of the retinal vessels: For a subgroup of patients, this will be evaluated using OCT-angiography, and/or dynamic retinal vessel analysis, and/or laser speckle flowgraphy. These measures provide insights into the functional and perfusional changes of the retinal vessels.
As secondary objectives, this study comprises:
研究设计
- 研究类型
- Observational
- 观察模型
- Case Control
- 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
- •All groups:
- •Age >18 years old
- •Patients with Multiple Sclerosis:
- •Diagnosis of Multiple Sclerosis, according to the last revisions of the McDonald Criteria (2017)
- •Patients with other neuroinflammatory diseases:
- •Diagnosis of Neuromyelitis optica spectrum disorder or Myelin oligodendrocyte glycoprotein antibody disease or other neuroinflammatory disorders other than Multiple Sclerosis
排除标准
- •All groups:
- •Inability to undergo Optical Coherence Tomography (OCT) and/or retinal vessel imaging (e.g. severe nystagmus that prevents eye fixation on both eyes)
- •Presence of any ocular pathology that may interfere with the validity of the OCT/retinal vessel analysis (cataracts, glaucoma, history of refractive defects >6 D etc.).
- •Pregnancy and Lactation
- •Healthy Controls
- •History of other neurological conditions: participants with a history of other significant neurological conditions that might interfere with the assessment or interpretation of the signs and symptoms will be excluded (e.g. confirmed Stroke, Acute disseminated encephalomyelitis, Chronic inflammatory Demyelinating Disease, Polyneuropathy, etc.)
结局指标
主要结局
Fixation instability (as marker of global neuronal dysfunction in the CNS)
时间窗: Baseline and once every year over up to 5 years
To determine the fixation instability, visual fixation measurements are recorded via the "Scanner Laser Ophthalmoscopy"-function of the OCT device (as described by Mallery et al., 2018; PMID: 29340646).
Structural changes of the retinal vessels (as marker of systemic microvascular health)
时间窗: Baseline and once every year over up to 5 years
To determine structural changes of the retinal vessels, the retinal arterior and venular diameters are measured by static retinal vessel analysis.
(For a subgroup of participants) Functional/perfusional changes of the retinal vessels
时间窗: Baseline and once every year over up to 5 years
To determine the functional/perfusional changes of the retinal vessels, a subgroup of participants (patients= 100, Healthy Controls= 50) undergoes additional examinations: * OCT-Angiography: measurement of retinal perfusion * Dynamic Retinal vessel analysis: measurement examining the motility and function of the retinal vessels * Laser Speckle Flowgraphy: measurement of ocular perfusion
Occurence of Progression Independent of Relapse Activity (PIRA)
时间窗: 5 Years (or for a subgroup up to 10 years) after baseline
The group of "Multiple Sclerosis patients" undergo a detailed neurological interview and examination for the calculation of the Expanded Disability Status Scale (EDSS) at each clinical visit every 6 or 12 months. The EDSS worsening is used to define PIRA retrospectively (increase of ≥1.5 points if baseline EDSS was 0 points, increase of ≥1.0 points if baseline EDSS was 1-5.5 points or increase of ≥0.5 point if baseline EDSS was \>5.5 points), with no relapse between the reference- event- and confirmation score visits. Relapse is defined as objectively observed signs typical of an acute CNS inflammatory demyelinating event, with duration of at least 24hours in the absence of fever or infection, separated from the last relapse by ≥30 days. The occurence of PIRA (yes/no) is assessed at the end of the follow-up period of the different retinal markers (5 years or for a subgroup up to 10 years after baseline).
Neuroinflammation in the retina
时间窗: Baseline and once every year over up to 5 years
To determine the neuroinflammation in the retina, the thickening of the outer plexiform layer, outer nerve layer and ,in particular, of the inner nuclear layer are assessed by OCT.
Neuroaxonal loss in the retina (as marker of neurodegeneration in the CNS)
时间窗: Baseline and once every year over up to 5 years
To determine the neuroaxonal loss in the retina, the thickness of the peripapillary retinal nerve fiber layer and the volume of the ganglion cell-inner plexiform layer are assessed by optical coherence tomography (OCT).
次要结局
- Comparison of the examined retinal markers of Multiple Sclerosis patients with Healthy Controls and with patients with other neuroinflammatory diseases of the CNS(Baseline and once every year over up to 5 years)
- The relationship between neuroaxonal loss, functional deficits and vascular changes in Multiple Sclerosis(Baseline and once every year over up to 5 years)
- Relative value of retinal markers for the prediction of PIRA compared to or combined with other biomarkers of neuroaxonal damage(Baseline and once every year over up to 5 years)