Evaluation of Relapse Presence in Multiple Sclerosis

Evaluation of Relapse Presence in Multiple Sclerosis Patients by Cross-Sectional In-Vivo Corneal Confocal Microscopy

Purpose: This study aims to investigate the demonstrability of increased inflammation and neurodegeneration in multiple sclerosis (MS) patients in relapse period compared to MS patients in remission by cross-sectional analysis of in-vivo corneal confocal microscopy (IVCM), and to evaluate the alternations with a second IVCM administered at least 6 months after the relapse period.

Methods: This prospective, non-randomized-controlled, cross-sectional study included 58 MS patients which were grouped regarding the presence of relapse (MS-Relapse group [n=27] and MS-Control group [n=31]), and age-sex matched 30 healthy controls (HC). The corneal nerve fiber density (CNFD), the corneal nerve branch density (CNBD), the corneal nerve fiber length (CNFL), and dendritic cell (DC) density were evaluated in all MS patients and HCs by IVCM. If the patients in the MS-relapse group did not have an attack within 6 months, the same parameters were evaluated with the second IVCM. The patients with a history of optic neuritis or trigeminal symptoms were excluded.

Study Overview

• Status: Completed
• Conditions: Multiple Sclerosis, Relapsing-Remitting; Multiple Sclerosis Relapse
• Intervention / Treatment: Diagnostic test: in-vivo Corneal Confocal Microscopy

• Study Type: Observational
• Enrollment (Actual): 87

Contacts and Locations

Study Locations

• Turkey
  • Istanbul, Turkey, 34899
    • Marmara University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Fifty-eight patients with RRMS and 30 HCs were included in the study. The RRMS patients were divided into two subgroups: 1) Thirty-one patients (MS-Control) who were followed up with the diagnosis of RRMS, 2) Twenty-seven patients (MS-Relapse) for whom the administration of intravenous corticosteroids was decided due to the diagnosis of new relapse.

Description

Inclusion Criteria:

• Patients for whom the administration of intravenous corticosteroids was decided due to the diagnosis of new relapse
• Patients who were followed up with the diagnosis of RRMS
• Healthy controls

Exclusion Criteria:

• Being younger than 18 years old
• Having any other neurological or metabolic diseases
• Ophthalmological diseases
• A history of optic neuritis and trigeminal symptoms
• Ocular trauma or surgery
• Contact lens use
• The patients who had a relapse attack 6 months prior to the study

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Prospective

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
MS-Relapse; Twenty-seven patients (MS-Relapse) for whom the administration of intravenous corticosteroids was decided due to the diagnosis of new relapse. The diagnosis of RRMS and the new relapse was confirmed and decided by a senior neurologist (K.A) of Marmara University Department of Neurology, according to the revised McDonald criteria, based on clinical and radiological findings These subjects underwent Corneal Confocal Microscopy (IVCM).	Diagnostic test: in-vivo Corneal Confocal Microscopy; All study subjects underwent IVCM (Rostock Cornea Module, Heidelberg Retinal Tomograph III; Heidelberg Engineering, Germany). Before the examination, two drops of topical anesthetic with proparacaine hydrochloride (Alcaine 0.5%, Alcon-Couvreur, Belgium) were applied to both eyes. A carbomer-based gel (Viscotears 0.2%; Dr. Gerhard Mann, Chem.- Pharm. Fabrik, Germany) was used as the coupling agent between the cornea and the applanating cap of IVCM. For correctly positioning the central cornea, all subjects were asked to fixate a determined fixation point and controlled with the device camera. All scans were performed in approximately 5 minutes for each eye by a single experienced ophthalmologist, masked from the subject's disease status.
MS-Control; Thirty-one patients (MS-Control) who were followed up with the diagnosis of RRMS The diagnosis of RRMS and the new relapse was confirmed and decided by a senior neurologist (K.A) of Marmara University Department of Neurology, according to the revised McDonald criteria, based on clinical and radiological findings. These subjects underwent Corneal Confocal Microscopy (IVCM).	Diagnostic test: in-vivo Corneal Confocal Microscopy; All study subjects underwent IVCM (Rostock Cornea Module, Heidelberg Retinal Tomograph III; Heidelberg Engineering, Germany). Before the examination, two drops of topical anesthetic with proparacaine hydrochloride (Alcaine 0.5%, Alcon-Couvreur, Belgium) were applied to both eyes. A carbomer-based gel (Viscotears 0.2%; Dr. Gerhard Mann, Chem.- Pharm. Fabrik, Germany) was used as the coupling agent between the cornea and the applanating cap of IVCM. For correctly positioning the central cornea, all subjects were asked to fixate a determined fixation point and controlled with the device camera. All scans were performed in approximately 5 minutes for each eye by a single experienced ophthalmologist, masked from the subject's disease status.
Healthy Controls; Thirty healthy age and gender similar population These subjects underwent Corneal Confocal Microscopy (IVCM).	Diagnostic test: in-vivo Corneal Confocal Microscopy; All study subjects underwent IVCM (Rostock Cornea Module, Heidelberg Retinal Tomograph III; Heidelberg Engineering, Germany). Before the examination, two drops of topical anesthetic with proparacaine hydrochloride (Alcaine 0.5%, Alcon-Couvreur, Belgium) were applied to both eyes. A carbomer-based gel (Viscotears 0.2%; Dr. Gerhard Mann, Chem.- Pharm. Fabrik, Germany) was used as the coupling agent between the cornea and the applanating cap of IVCM. For correctly positioning the central cornea, all subjects were asked to fixate a determined fixation point and controlled with the device camera. All scans were performed in approximately 5 minutes for each eye by a single experienced ophthalmologist, masked from the subject's disease status.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Corneal nerve fiber density (CNFD)	Automated tracing of nerve fibers program - CCMetrics (CCMetrics; M. A. Dabbah, ISBE, University of Manchester, Manchester, UK) was used to analyze CNFD.	Baseline
Corneal nerve fiber density (CNFD)	Automated tracing of nerve fibers program - CCMetrics (CCMetrics; M. A. Dabbah, ISBE, University of Manchester, Manchester, UK) was used to analyze CNFD.	6 Month
Corneal nerve branch density (CNBD)	Automated tracing of nerve fibers program - CCMetrics (CCMetrics; M. A. Dabbah, ISBE, University of Manchester, Manchester, UK) was used to analyze CNBD.	Baseline
Corneal nerve branch density (CNBD)	Automated tracing of nerve fibers program - CCMetrics (CCMetrics; M. A. Dabbah, ISBE, University of Manchester, Manchester, UK) was used to analyze CNBD.	6 Month
Corneal nerve fiber length (CNFL)	Automated tracing of nerve fibers program - CCMetrics (CCMetrics; M. A. Dabbah, ISBE, University of Manchester, Manchester, UK) was used to analyze CNFL.	Baseline
Corneal nerve fiber length (CNFL)	Automated tracing of nerve fibers program - CCMetrics (CCMetrics; M. A. Dabbah, ISBE, University of Manchester, Manchester, UK) was used to analyze CNFL.	6 Months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dendritic Cells	the number of DCs counted by ImageJ's Cell Counter plug-in	Baseline
Dendritic Cells	the number of DCs counted by ImageJ's Cell Counter plug-in	6 Months

Collaborators and Investigators

• Sponsor: Marmara University

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2021
• Primary Completion (Actual): October 1, 2021
• Study Completion (Actual): January 1, 2022

Study Registration Dates

• First Submitted: January 20, 2022
• First Submitted That Met QC Criteria: January 20, 2022
• First Posted (Actual): February 1, 2022

Study Record Updates

• Last Update Posted (Actual): February 1, 2022
• Last Update Submitted That Met QC Criteria: January 20, 2022
• Last Verified: January 1, 2022

More Information

Terms related to this study

• Keywords: multiple sclerosis, in-vivo corneal confocal microscopy, relapse, inflammation, neurodegeneration, neuroregeneration
• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Disease Attributes; Multiple Sclerosis; Sclerosis; Multiple Sclerosis, Relapsing-Remitting; Recurrence
• Other Study ID Numbers: 09.2021.240

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No