Evaluation of Relapse Presence in Multiple Sclerosis

Study Overview
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Brief Summary
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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.

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

Conditions
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Multiple Sclerosis, Relapsing-Remitting, Multiple Sclerosis Relapse

Intervention / Treatment
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* Diagnostic Test: in-vivo Corneal Confocal Microscopy


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| MS-Relapse<br>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<br>* 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.<br>|
| MS-Control<br>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<br>* 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.<br>|
| Healthy Controls<br>Thirty healthy age and gender similar population These subjects underwent Corneal Confocal Microscopy (IVCM). | Diagnostic Test: in-vivo Corneal Confocal Microscopy<br>* 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.<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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multiple sclerosis, in-vivo corneal confocal microscopy, relapse, inflammation, neurodegeneration, neuroregeneration