Identification of Retinal Perivascular Inflammation in Patients With Multiple Sclerosis Using Adaptive Optics (RETIMUS) (RETIMUS)

Identification of Retinal Perivascular Inflammation in Patients With Multiple Sclerosis Using Adaptive Optics

Using a technique called adaptive optics imaging applied on retina, investigators aim to gain access to vascular changes that could occur early in the course of Multiple Sclerosis (MS) and which could reflect vascular changes occurring along the optic nerve of the brain parenchyma. Indeed, our team has been able to develop a quantitative method to measure the perivascular infiltrate in the retina of patients with various inflammatory retinal disease. It has been observed in MS patients that this perivascular infiltrate can also be detected in the retina. However, its distribution across MS phenotypes (relapsing or progressive MS, with and without optic neuritis) is still unknown.

Study Overview

• Status: Completed
• Conditions: Nervous System Diseases; Progressive Multiple Sclerosis; Multiple Sclerosis; Eye Diseases; Optic Neuritis; Optic Nerve Diseases; Relapsing Remitting Multiple Sclerosis
• Intervention / Treatment: Other: Adaptive Optics Ophthalmoscopy (AOO)

Detailed Description

This is a monocentric pathophysiological, interventional, prospective, open label, non-randomized pilot study which aims to identify in patients with MS at different stages if the presence of retinal perivascular inflammation can be detected and quantified using adaptive optics, which is a non-invasive examination.

Investigators will recruit MS patients in 3 subgroups, depending on their phenotype (Relapsing Remitting Multiple Sclerosis (RRMS) without optic neuritis, RRMS with optic neuritis, progressive MS), with 15 patients in each group.

15 healthy volunteers (HV) will also be enrolled.

The comparison of these groups is necessary to determine if there are significant differences, allowing us to highlight biomarkers in MS patients in order to enable highly efficient and robust trials designs in the future.

To test the hypothesis, the study has 3 visits over 6 months (M0, M3 and M6). Neurological evaluation, blood sample, imaging, ophthalmologic evaluation and Adaptive optics ophthalmoscopy assessments will be performed.

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Paris, France
    • Institut du Cerveau et de la Moelle epiniere - Hopital Pitie Salpetriere

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

Group 1:

• Age between 18 and 60 years old.
• Relapsing remitting MS (criteria of McDonald 2017)
• Less than 10 years of disease duration
• Subject who has never presented a clinical episode of optic neuritis
• Affiliation to a social security scheme or beneficiary of such a scheme

Group 2:

• Age between 18 and 60 years old
• Relapsing remitting MS (criteria of McDonald 2017)
• Less than 10 years of disease duration
• Subject presenting an acute episode of retrobulbar optic neuritis within 3 months from onset
• After optimal treatment for the retrobulbar optic neuritis
• Affiliation to a social security scheme or beneficiary of such a scheme

Group 3:

• Age between 18 and 60 years old
• Primary or Secondary progressive multiple sclerosis within 10 years of progressive phase;
• Affiliation to a social security scheme or beneficiary of such a scheme

Group 4 (Healthy Subjects):

• Age between 18 and 60 years old
• Affiliation to a social security scheme or beneficiary of such a scheme

Exclusion Criteria:

For all patients (Group 1; 2; 3):

• Corticosteroid treatment within one month from inclusion
• Other neurological, ophthalmologic or systemic disease;
• Severe symptoms of uncontrolled chronic disease (renal, hepatic, hematologic, gastro-intestinal, pulmonary or cardiac or any intercurrent uncontrolled disease at inclusion)
• Severe renal dysfunction (glomerular filtration rate < 30mL/min). This non-inclusion criteria will be verified by serum creatinine test within six months from inclusion;
• Contraindication for MRI;
• Pregnancy or breast-feeding;
• Unwillingness to be informed in case of abnormal MRI (with a significant medical anomaly)
• Incapacity to understand or sign the consent form;
• Adults legally protected (under judicial protection, guardianship, or supervision), persons deprived of their liberty.

For healthy subjects (Group 4):

• Neurological, ophthalmologic or systemic disease;
• Severe symptoms of uncontrolled chronic disease (renal, hepatic, hematologic, gastro-intestinal, pulmonary or cardiac or any intercurrent uncontrolled disease at inclusion);
• Contraindication for MRI;
• Pregnancy or breast-feeding;
• Unwillingness to be informed in case of abnormal MRI (with a significant medical anomaly)
• Incapacity to understand or sign the consent form;
• Adults legally protected (under judicial protection, guardianship, or supervision), persons deprived of their liberty.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: MS patients; RRMS Patients with optic neuritis, RRMS patients without optic neuritis or Progressive MS patients	Other: Adaptive Optics Ophthalmoscopy (AOO); AOO will permit to detect and quantify retinal perivascular inflammation in patients with MS in comparison to Healthy volunteers (control group)
Other: Control group; Healthy volunteers	Other: Adaptive Optics Ophthalmoscopy (AOO); AOO will permit to detect and quantify retinal perivascular inflammation in patients with MS in comparison to Healthy volunteers (control group)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Quantification of retinal perivascular cuff width across MS phenotypes	The primary endpoint is to quantify retinal perivascular cuff width across MS phenotypes, compared among a group of control at baseline.	Baseline

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Variation of size of perivascular sheathing	Variation of size of perivascular sheathing along retinal vessels in the posterior pole during follow up (at month 3 and month 6) in patients with MS and a group of control	month 3 and month 6
Clinical disability measure with EDSS	Evolution of Clinical disability: Expanded Disability Status Scale (EDSS: 0: normal neurological exam; 10 : death of the patient) at month 3 for MS patients with optic neuritis and at month 6 for all MS patients	month 3 and month 6
Clinical disability measured with MSFC	Evolution of Clinical disability: Multiple Sclerosis Functional Composite (MSFC) at month 3 for MS patients with optic neuritis and at month 6 for all MS patients	month 3 and month 6
Number of relapses	Evolution of Clinical disability: number of relapses at month 3 for MS patients with optic neuritis and at month 6 for all MS patients	month 3 and month 6
Presence of disc oedema measured at Optical Coherence Tomography (OCT) measurements	Evolution of OCT measurements (presence of disc oedema) at month 3 for MS patients with optic neuritis and at month 6 for all MS patients	month 3 and month 6
RNLF thickness measured at Optical Coherence Tomography (OCT) measurements	Evolution of OCT measurements : retinal nerve fiber layer thickness (RNFL, µm) at month 3 for MS patients with optic neuritis and at month 6 for all MS patients	month 3 and month 6
parenchymal T2 lesion volume at MRI	Evolution of MRI metrics: parenchymal T2 lesion volume	Baseline
gadolinium enhanced T1 lesion at MRI	Evolution of MRI metrics: gadolinium enhanced T1 lesion	Baseline
optic nerve cross-sectional area at MRI	Evolution of MRI metrics: optic nerve cross-sectional area	Baseline
Hyperintensity on the optic nerve at MRI	Evolution of MRI metrics: Hyperintensity on the optic nerve	Baseline

Collaborators and Investigators

• Sponsor: Institut National de la Santé Et de la Recherche Médicale, France
• Collaborators: Biogen
• Investigators: Principal Investigator: Celine Louapre, MD, PHD, Institut du Cerveau et de la Moelle Epinière

Publications and helpful links

General Publications

• Gofas-Salas E, Mossad M, Beigneux Y, Norberg N, Castro Farias D, Vignal C, Paques M, Louapre C, Grieve K. In vivo characterization of a retinal cellular biomarker of inflammation in multiple sclerosis. Brain Commun. 2025 Nov 28;8(1):fcaf471. doi: 10.1093/braincomms/fcaf471. eCollection 2026.

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2020
• Primary Completion (Actual): June 26, 2024
• Study Completion (Actual): July 17, 2024

Study Registration Dates

• First Submitted: February 25, 2020
• First Submitted That Met QC Criteria: February 26, 2020
• First Posted (Actual): February 28, 2020

Study Record Updates

• Last Update Posted (Actual): April 27, 2026
• Last Update Submitted That Met QC Criteria: April 22, 2026
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Keywords: Optic neuritis; multiple sclerosis; relapsing remitting Multiple sclerosis; Progressive Multiple Sclerosis; adaptive optics; eye disease; peripheral nervous system disease
• Additional Relevant MeSH Terms: Pathologic Processes; Neuromuscular Diseases; Chronic Disease; Disease Attributes; Autoimmune Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Cranial Nerve Diseases; Pathological Conditions, Signs and Symptoms; Multiple Sclerosis; Peripheral Nervous System Diseases; Eye Diseases; Nervous System Diseases; Multiple Sclerosis, Relapsing-Remitting; Multiple Sclerosis, Chronic Progressive; Optic Nerve Diseases; Optic Neuritis
• Other Study ID Numbers: C19-25

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No