Neuroretinal Biomarkers in Neurodegenerative Diseases

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT02047760
Recruitment Status : Completed
First Posted : January 28, 2014
Last Update Posted : May 11, 2016
Information provided by (Responsible Party):
University of Edinburgh

Brief Summary:
There is increasing evidence that examining our eyes can tell us a lot of information about our health, and systemic diseases. We want to study what eyes can reveal about serious neurodegenerative diseases like multiple sclerosis, and motor neurone disease, by analysing the retinal images from a simple non-invasive eye scan, that is already being routinely used to provide immediate clinical information in this group of patients.

Condition or disease
Multiple Sclerosis

Detailed Description:

The identification of reliable biomarkers in multiple sclerosis (MS), and other neurodegenerative diseases, has become increasingly important with the development of disease-modifying treatments.

A range of genetic, metabolic and imaging biomarkers exist, in correlations with diagnosis, phenotypic expression, inflammation, degeneration and prognosis; although there is wide variation in specificity, sensitivity, reproducibility and cost.

In MS specifically, we know that whilst the primary pathological process is demyelination of neurones (which can be accompanied by inflammation, and resolving symptoms), it is the subsequent axonal loss - neurodegeneration - that gives rise to the permanent functional disability.

Magnetic resonance imaging (MRI) brain scans are currently our primary source of objective information in assessing MS disease status, in terms of neurodegeneration and possibly prognosis. Measurements of brain atrophy have shown worsening rates are higher in untreated MS patients compared with healthy controls and also correlate with subsequent disability status eight years later.

However, brain atrophy measures sometimes reveal paradoxical outcomes, particularly of white matter atrophy, where normal or increased volume as a result of pathological processes, such as tissue damage and repair, can impact upon the measures.

The search then for other markers of neurodegenerative disease status and prognosis continues, with renewed interest in the eye.

In MS, early work has suggested certain retinal measures, particularly the width of the layer that consists largely of retinal ganglion cell nerve axons, as candidate biomarkers, under the hypothesis that neuroretinal tissue reflects global central nervous system (CNS) pathology. Conceptually, this would seem reasonable, given the frequency for anterior visual pathway involvement as the primary presentation of MS; and in addition, the unmyelinated ganglion cell axons that form the retinal nerve fibre layer (RNFL) are a direct extension of the brain, and global neurodegeneration would be expected to involve these neurones - particularly in MS, where the disease lesions have a predilection for the periventricular regions, which are in close proximity to the optic radiations.

However, the natural history of neuroretinal tissue integrity is poorly understood, and in vivo measurement is a very new modality, requiring validation and context to any interpretation.

In addition, retinal imaging permits the direct visualisation, and subsequent analysis, of the retinal vasculature - shown in studies of stroke and hypertension to be an accurate representation of brain vasculature, with diagnostic and prognostic potential.

In summary, a combined score of neuroretinal integrity as measured by retinal imaging may yield new insights into sever neurodegenerative disease.

Study Type : Observational
Estimated Enrollment : 80 participants
Observational Model: Case Control
Time Perspective: Prospective
Official Title: Investigation Into the Role of Neuroretinal Biomarkers in the Phenotyping of Neurodegenerative Diseases, and Potential for Tracking Progression and Monitoring Impact of Interventions, Events and Therapies.
Study Start Date : March 2014
Actual Primary Completion Date : February 2016
Actual Study Completion Date : February 2016

Resource links provided by the National Library of Medicine

U.S. FDA Resources

MS patients
All MS sub-types
sex- and age-matched controls

Primary Outcome Measures :
  1. Retinal nerve fibre layer (RNFL) thickness change over time [ Time Frame: 0, 6, 12, 24 months ]
    Monitoring of RNFL thickness over time, as measured by optical coherence tomography (OCT) retinal scanning, particularly in relation to disease events, or interventions.

Secondary Outcome Measures :
  1. Retinal vascular fractal dimension change over time [ Time Frame: 0, 6, 12, 24 months ]
    Monitoring of retinal vessel metrics, of bifurcation optimality and tortuosity; and combination with neuroretinal measures as a combined score.

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population
All MS patients attending the ARRNC research clinic

Inclusion Criteria:

  • willing to participate with informed consent
  • age 18-75
  • male or female
  • confirmed diagnosis of multiple sclerosis

Exclusion Criteria:

  • concurrent eye disease, or media opacity
  • high refractive error (> +6 or -6)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT02047760

United Kingdom
Anne Rowling Regenerative Neurology Clinic
Edinburgh, United Kingdom, EH16 4SB
Sponsors and Collaborators
University of Edinburgh
Principal Investigator: James Cameron, FRCOphth University of Edinburgh

Responsible Party: University of Edinburgh Identifier: NCT02047760     History of Changes
Other Study ID Numbers: 147305
First Posted: January 28, 2014    Key Record Dates
Last Update Posted: May 11, 2016
Last Verified: December 2015

Additional relevant MeSH terms:
Multiple Sclerosis
Neurodegenerative Diseases
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Demyelinating Diseases
Autoimmune Diseases
Immune System Diseases