REtinal Markers In Neuroinflammatory Diseases ("REMIND")

NCT06369766 | Recruiting

• 1 other identifier: 2023-02144; ko23Papadopoulou4
• Study Type: observational
• Target: 500
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Multiple Sclerosis; Neuroinflammatory Diseases

Keywords

Retinal Markers; OCT; Disease Progression; Progression Independent of Relapse Activity (PIRA)

Outcome Measures

Primary Outcomes (6)

• Occurence of Progression Independent of Relapse Activity (PIRA)

  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).

  5 Years (or for a subgroup up to 10 years) after baseline

• Neuroaxonal loss in the retina (as marker of neurodegeneration in the CNS)

  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).

  Baseline and once every year over up to 5 years

• Neuroinflammation in the retina

  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.

  Baseline and once every year over up to 5 years

• Fixation instability (as marker of global neuronal dysfunction in the CNS)

  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).

  Baseline and once every year over up to 5 years

• Structural changes of the retinal vessels (as marker of systemic microvascular health)

  To determine structural changes of the retinal vessels, the retinal arterior and venular diameters are measured by static retinal vessel analysis.

  Baseline and once every year over up to 5 years

• (For a subgroup of participants) Functional/perfusional changes of the retinal vessels

  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

  Baseline and once every year over up to 5 years

Secondary Outcomes (3)

• 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

• 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

Study Arms (3)

Healthy Controls

Healthy control subjects without neurological diseases

Diagnostic Test: Optical coherence tomography (OCT); Diagnostic Test: Static retinal vessel analyzer; Diagnostic Test: Dynamic retinal vessel analyzer; Diagnostic Test: Laser speckle flowgraphy system; Other: Questionnaire

Patients with Multiple Sclerosis

Diagnostic Test: Optical coherence tomography (OCT); Diagnostic Test: Static retinal vessel analyzer; Diagnostic Test: Dynamic retinal vessel analyzer; Diagnostic Test: Laser speckle flowgraphy system; Other: Questionnaire

Patients with other neuroinflammatory diseases of the CNS

Diagnostic Test: Optical coherence tomography (OCT); Diagnostic Test: Static retinal vessel analyzer; Diagnostic Test: Dynamic retinal vessel analyzer; Diagnostic Test: Laser speckle flowgraphy system; Other: Questionnaire

Interventions

Optical coherence tomography (OCT) DIAGNOSTIC_TEST

OCT is used to measure: * peripapillary retinal nerve fiber layer (mean thickness in μm) * ganglion cell-inner plexiform layer (volume in mm\^3 and mean thickness in μm) * other retinal layers (inner nuclear layer, outer plexiform layer, outer nerve layer; volumes in mm\^3 and mean thickness in μm). The "scanner laser ophthalmoscopy"-function of the OCT device is used to continuously record the exact location of each participant's fixation point in relation to their fovea and thereby allows the assessment of the fixation instability. In a subgroup of participants, the "angiography"-module of the OCT device is used to image the retinal blood flow and thereby allows to measure the vascular area density of the superficial retinal capillary plexus and deep retinal capillary plexus.

Healthy Controls; Patients with Multiple Sclerosis; Patients with other neuroinflammatory diseases of the CNS

Static retinal vessel analyzer DIAGNOSTIC_TEST

Static retinal vessel analyzer is used to determine: * central retinal arteriolar diameter equivalents (in μm) * central retinal venular diameter equivalents (in μm) * arteriolar-to-venular diameter ratio

Healthy Controls; Patients with Multiple Sclerosis; Patients with other neuroinflammatory diseases of the CNS

Dynamic retinal vessel analyzer DIAGNOSTIC_TEST

In a subgroup of participants, the dynamic retinal vessel analyzer is used to determine the arteriolar ficker light-induced dilatation, venular ficker light-induced dilatation, and Arteriolar constriction, measured in % dilatation in comparison to baseline.

Healthy Controls; Patients with Multiple Sclerosis; Patients with other neuroinflammatory diseases of the CNS

Laser speckle flowgraphy system DIAGNOSTIC_TEST

In a subgroup of participants, the laser speckle flowgraphy system is used to measure the relative ocular blood flow as expressed in arbitary units of Mean Blur Rate.

Healthy Controls; Patients with Multiple Sclerosis; Patients with other neuroinflammatory diseases of the CNS

Questionnaire OTHER

All study participants will be asked to fill in a questionnaire with various questions regarding existing eye diseases, other diseases (including vascular diseases/risk factors), and daily physical activity that could influence the results of the retinal examinations. Physical activity will be assessed using an adapted form of the standardized Global Physical Activity Questionnaire.

Healthy Controls; Patients with Multiple Sclerosis; Patients with other neuroinflammatory diseases of the CNS

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Patients with Multiple Sclerosis and the other neuroinflammatory diseases are recruited in the Multiple Sclerosis and Neuroimmunology center of the Department of Neurology at the University Hospital Basel in Basel. These patients with Multiple Sclerosis are participants of the ongoing observational Swiss Multiple Sclerosis Cohort Study. Healthy Controls are recruited from an older healthy control-cohort, which were matched to the Multiple Sclerosis patients and underwent Optical Coherence Tomography in 2016/2017. Further Healthy Controls are recruited bycontacting volunteers that participated in previous studies and agreed to be contacted again for new studies and by public announcements.

You may qualify if:

• 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

You may not qualify if:

• 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.)

Sponsors & Collaborators

• University Hospital, Basel, Switzerland: lead
• University of Basel: collaborator

Study Sites (1)

University Hospital Basel, Department of Neurology

Basel, 4031, Switzerland

RECRUITING

MeSH Terms

Conditions

Multiple Sclerosis; Neuroinflammatory Diseases; Disease Progression

Interventions

Tomography, Optical Coherence; Surveys and Questionnaires

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Disease Attributes

Intervention Hierarchy (Ancestors)

Tomography, Optical; Optical Imaging; Diagnostic Imaging; Diagnostic Techniques and Procedures; Diagnosis; Tomography; Investigative Techniques; Data Collection; Epidemiologic Methods; Health Care Evaluation Mechanisms; Quality of Health Care; Health Care Quality, Access, and Evaluation; Public Health; Environment and Public Health

Study Officials

• Athina Papadopoulou, PD Dr. med.

  University Hospital Basel, Department of Neurology

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Athina Papadopoulou, PD Dr. med.

CONTACT

+41 61 32 85704; Athina.Papadopoulou@usb.ch

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 12, 2024
• First Posted: April 17, 2024
• Study Start: January 31, 2024
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): February 1, 2029
• Last Updated: May 23, 2025

Record last verified: 2025-05

Locations

CH (1)