Visual Processing Speed and Objective Analysis of Ocular Movements in Multiple Sclerosis

Study Overview
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Brief Summary
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This project aims to analyze ocular motility problems, visual processing speed and microperimetry, and their relationship with consolidated retinal structural biomarkers (optical coherence tomography, OCT) in patients with Multiple Sclerosis w/w reading complaints comparing with healthy subjects.

Detailed Description
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Anamnesis, ophthalmological medical history including difficulties in reading with appropriate glasses. The following protocol will be applied: Comprehensive eye examination Stereopsis Primary gaze position Cover test: far and near Vergence and version eye movements Presence of nystagmus Far and near best corrected visual acuity, with updated refraction -.Pupillary light reflex Biomicroscopy of the anterior pole Intraocular pressure Recording of eye movements during two standardized tests: International Reading Speed Texts test (IReST®) and Developmental Eye Movement Test (DEM™) with Tobii™ Pro Nano hardware package eye-tracking system and Tobii™ Pro Lab - full edition software. Visual processing speed Microperimetry Optical coherence tomography Eye fundus Patients with a history of clinical optic neuritis will additionally undergo contrast sensitivity tests, the Farnsworth® test (Farnsworth test 28 Hue x 100) and normal monocular perimetry using the standard Swedish Interactive Thresholding Algorithm (SITA-central 24-2) perimeter test. Humphrey® (Humphrey visual field analyser) and other tests at the discretion of the investigator.

Official Title
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Visual Processing Speed and Objective Analysis of Supranuclear Ocular Movements Control in Multiple Sclerosis Patients and Its Relationship With OCT and Reading Difficulties

Conditions
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Multiple Sclerosis, Clinically Isolated Syndrome, Relapsing Remitting Multiple Sclerosis, Progressive Multiple Sclerosis

Intervention / Treatment
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* Diagnostic Test: Eye tracking
* Diagnostic Test: Microperimetry
* Diagnostic Test: Optical coherence tomography (OCT)
* Diagnostic Test: Visual processing speed test


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of Multiple Sclerosis Best distant corrected visual acuity equal or greater than 0.7 (decimal scale). Glasses or soft contact lenses users. Best close corrected visual acuity equal to or greater than 20/30 (Snellen scale).Glasses or soft contact lenses users. Exclusion Criteria: Patients with a history of acute optic neuritis (ON) and/or who experienced an episode of ON <6 months prior to the study, to avoid potential interference of papilledema with accurate peripapillary RNFL thickness measurements. Patients with other retinal and optic nerve diseases, advanced cataracts according to the international Lens Opacities Classification System III (LOCS III) (opacities greater than C2N2) Patients with other ophthalmological diseases that could affect central visual acuity Subjects with high refractive error (+ - 6 diopters). Subjects with other demyelinating disorders (neuromyelitis optica or acute disseminated encephalomyelitis).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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 |
| --- | --- |
| Control group<br>Ophthalmologic examination (best-corrected visual acuity, cover and uncover tests, slit-lamp biomicroscopy, funduscopy) Eye movement recording with the Tobii™ Pro Nano hardware package eye-tracking system and Tobii™ Pro Lab - full edition software Visual processing speed Microperimetry Optical coherence tomography | Diagnostic Test: Eye tracking<br>* Eye tracker will be used to evaluate eye movements<br>* Other names: Tobii™ Pro Nano hardware package eye-tracking system and Tobii™ Pro Lab - full edition software;Diagnostic Test: Microperimetry<br>* Perimetric examination with Expert Exam strategy Microperimetry be used for fixation test<br>* Other names: Macular Integrity Assessment (MAIA™, Centervue, Padova, Italy);Diagnostic Test: Optical coherence tomography (OCT)<br>* Macular Cube 512x128 or 200x200 scan. OCT will be used to analysis of retinal nerve fiber layer, ganglion cell complex and ganglion-cell/inner plexiform layer<br>* Other names: Cirrus High definition (HD) - OCT 5000® ,Carl Zeiss Meditec, Dublin,California, USA;Diagnostic Test: Visual processing speed test<br>* Visual processing speed test will be used for assessing subject visual stimulus search and reach times. Thirty-two different everyday visual stimuli divided in four complexity groups that were presented along 8 radial visual field positions at three different eccentricities.<br>|
| Clinically Isolated Syndrome Patients<br>Ophthalmologic examination Eye movement recording with the Tobii™ Pro Nano hardware package eye-tracking system and Tobii™ Pro Lab - full edition software Visual processing speed Microperimetry Optical coherence tomography Patients with a history of optic neuritis will undergo additional tests at the discretion of the researcher (e.g. visual field, FarnsworthTest) | Diagnostic Test: Eye tracking<br>* Eye tracker will be used to evaluate eye movements<br>* Other names: Tobii™ Pro Nano hardware package eye-tracking system and Tobii™ Pro Lab - full edition software;Diagnostic Test: Microperimetry<br>* Perimetric examination with Expert Exam strategy Microperimetry be used for fixation test<br>* Other names: Macular Integrity Assessment (MAIA™, Centervue, Padova, Italy);Diagnostic Test: Optical coherence tomography (OCT)<br>* Macular Cube 512x128 or 200x200 scan. OCT will be used to analysis of retinal nerve fiber layer, ganglion cell complex and ganglion-cell/inner plexiform layer<br>* Other names: Cirrus High definition (HD) - OCT 5000® ,Carl Zeiss Meditec, Dublin,California, USA;Diagnostic Test: Visual processing speed test<br>* Visual processing speed test will be used for assessing subject visual stimulus search and reach times. Thirty-two different everyday visual stimuli divided in four complexity groups that were presented along 8 radial visual field positions at three different eccentricities.<br>|
| Relapsing-remitting Multiple Sclerosis Patients<br>Ophthalmologic examination (best-corrected visual acuity, cover and uncover tests, slit-lamp biomicroscopy, funduscopy) Eye movement recording with the Tobii™ Pro Nano hardware package eye-tracking system and Tobii™ Pro Lab - full edition software Visual processing speed Microperimetry Optical coherence tomography Patients with a history of optic neuritis will undergo additional tests at the discretion of the researcher (e.g. visual field, FarnsworthTest) | Diagnostic Test: Eye tracking<br>* Eye tracker will be used to evaluate eye movements<br>* Other names: Tobii™ Pro Nano hardware package eye-tracking system and Tobii™ Pro Lab - full edition software;Diagnostic Test: Microperimetry<br>* Perimetric examination with Expert Exam strategy Microperimetry be used for fixation test<br>* Other names: Macular Integrity Assessment (MAIA™, Centervue, Padova, Italy);Diagnostic Test: Optical coherence tomography (OCT)<br>* Macular Cube 512x128 or 200x200 scan. OCT will be used to analysis of retinal nerve fiber layer, ganglion cell complex and ganglion-cell/inner plexiform layer<br>* Other names: Cirrus High definition (HD) - OCT 5000® ,Carl Zeiss Meditec, Dublin,California, USA;Diagnostic Test: Visual processing speed test<br>* Visual processing speed test will be used for assessing subject visual stimulus search and reach times. Thirty-two different everyday visual stimuli divided in four complexity groups that were presented along 8 radial visual field positions at three different eccentricities.<br>|
| Primary Progressive Multiple Sclerosis Patients<br>Ophthalmologic examination (best-corrected visual acuity, cover and uncover tests, slit-lamp biomicroscopy, funduscopy) Eye movement recording with the Tobii™ Pro Nano hardware package eye-tracking system and Tobii™ Pro Lab - full edition software Visual processing speed Microperimetry Patients with a history of optic neuritis will undergo additional tests at the discretion of the researcher (e.g. visual field, FarnsworthTest) Optical coherence tomography | Diagnostic Test: Eye tracking<br>* Eye tracker will be used to evaluate eye movements<br>* Other names: Tobii™ Pro Nano hardware package eye-tracking system and Tobii™ Pro Lab - full edition software;Diagnostic Test: Microperimetry<br>* Perimetric examination with Expert Exam strategy Microperimetry be used for fixation test<br>* Other names: Macular Integrity Assessment (MAIA™, Centervue, Padova, Italy);Diagnostic Test: Optical coherence tomography (OCT)<br>* Macular Cube 512x128 or 200x200 scan. OCT will be used to analysis of retinal nerve fiber layer, ganglion cell complex and ganglion-cell/inner plexiform layer<br>* Other names: Cirrus High definition (HD) - OCT 5000® ,Carl Zeiss Meditec, Dublin,California, USA;Diagnostic Test: Visual processing speed test<br>* Visual processing speed test will be used for assessing subject visual stimulus search and reach times. Thirty-two different everyday visual stimuli divided in four complexity groups that were presented along 8 radial visual field positions at three different eccentricities.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Eye Tracking Data | Characteristics of eye movements recorded with the eye tracker system during reading tests | 24 Hours | 
| Values for Visual Processing Speed (VPS) | VPS will be assessing subject visual stimulus search reaction time (S-RT) and reach reaction time (R-RT), measured in seconds. Thirty-two different everyday visual stimuli were divided in four complexity groups that were presented along 8 radial visual field positions at three different eccentricities (10º, 20º y 30º) | 24 Hours | 
| Retinal sensitivity assessed by microperimetry | Sensitivity and fixation analysis with microperimetry | 24 Hours | 
| Values for OCT neuroretinal and peripapillary parameters | OCT assessment will be by spectral domain-optical coherence tomography to assess the retinal nerve fiber layer thickness and macular volume in humans | 24 Hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fixations recorded with the eye tracker system | number of fixations, duration in milliseconds | 24 Hours | 
| Saccades recorded with the eye tracker system | number of saccades, duration in milliseconds | 24 Hours | 
| Fixation assessment with microperimetry | Fixation assessment: P1, P2 fixation points (indexes P1 and P2) | 24 Hours | 
| Bivariate Contour Ellipse Area (BCEA) analysis with microperimetry | BCEA assessment: areas BCEA 63, BCEA 95 | 24 Hours | 
| Preferred Retinal Locus (PRL) analysis with microperimetry | PRL assessment: Low-PRL, PRL High | 24 Hours | 
| Analysis of the macular integrity (MI) with microperimetry | MI assessment: macular integrity index | 24 Hours | 
| Ganglion Cell Layer measurement (GCL: Macular OCT) | Optical Coherence Tomography (OCT) will be used to assess the GCL of patients with multiple sclerosis | 24 Hours | 
| Retinal Nerve Fiber Layer measurement (RNFL: peri-papillary OCT) | Optical Coherence Tomography (OCT) will be used to assess the RNFL of patients with multiple sclerosis | 24 Hours | 
| Macular ganglion cell-inner plexiform layer thickness measurement (GCIPL) | Optical Coherence Tomography (OCT) will be used to assess the GCIPL of patients with multiple sclerosis | 24 Hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ocular motility disorders, eye movement, eye tracking, microperimetry, fixational eye movements, visual processing speed, optical coherence tomography