Neuroretinal Biomarkers in Neurodegenerative Diseases
Condition: Multiple Sclerosis
MeSH terms: Multiple Sclerosis; Neurodegenerative Diseases
Study type: Observational

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.
    

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.
    

Observational model: Case-Control
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        All MS patients attending the ARRNC research clinic