Neuroretinal Biomarkers in Neurodegenerative Diseases

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2014 by University of Edinburgh
Sponsor:
Information provided by (Responsible Party):
University of Edinburgh
ClinicalTrials.gov Identifier:
NCT02047760
First received: January 22, 2014
Last updated: June 23, 2014
Last verified: January 2014
  Purpose

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
Multiple Sclerosis

Study Type: Observational
Study Design: 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.

Resource links provided by NLM:


Further study details as provided by University of Edinburgh:

Primary Outcome Measures:
  • Retinal nerve fibre layer (RNFL) thickness change over time [ Time Frame: 0, 6, 12, 24 months ] [ Designated as safety issue: No ]
    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:
  • Retinal vascular fractal dimension change over time [ Time Frame: 0, 6, 12, 24 months ] [ Designated as safety issue: No ]
    Monitoring of retinal vessel metrics, of bifurcation optimality and tortuosity; and combination with neuroretinal measures as a combined score.


Estimated Enrollment: 80
Study Start Date: March 2014
Estimated Study Completion Date: February 2016
Estimated Primary Completion Date: February 2016 (Final data collection date for primary outcome measure)
Groups/Cohorts
MS patients
All MS sub-types
Controls
sex- and age-matched controls

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.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population

All MS patients attending the ARRNC research clinic

Criteria

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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02047760

Contacts
Contact: James Cameron, FRCOphth 01314659514 james.cameron@ed.ac.uk

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

No publications provided

Responsible Party: University of Edinburgh
ClinicalTrials.gov Identifier: NCT02047760     History of Changes
Other Study ID Numbers: 147305
Study First Received: January 22, 2014
Last Updated: June 23, 2014
Health Authority: United Kingdom: Research Ethics Committee

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

ClinicalTrials.gov processed this record on August 20, 2014