Neuroretinal Biomarkers in Neurodegenerative Diseases
|ClinicalTrials.gov Identifier: NCT02047760|
Recruitment Status : Completed
First Posted : January 28, 2014
Last Update Posted : May 11, 2016
|Condition or disease|
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|
|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|
All MS sub-types
sex- and age-matched controls
- 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.
- 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.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02047760
|Anne Rowling Regenerative Neurology Clinic|
|Edinburgh, United Kingdom, EH16 4SB|
|Principal Investigator:||James Cameron, FRCOphth||University of Edinburgh|