Eye as a window to the brain: investigating the clinical utility of retinal imaging derived biomarkers in the phenotyping of neurodegenerative disease.
Background
Neurodegenerative diseases, like multiple sclerosis, dementia and motor neurone
disease, represent one of the major public health threats of our time. There is a clear
persistent need for novel, affordable, and patient‐acceptable biomarkers of these
diseases, to assist with diagnosis, prognosis and impact of interventions. And these
biomarkers need to be sensitive, specific and precise.
The retina is an attractive site for exploring this potential, as it is easily accessible to
non‐invasive imaging. Remarkable technology revolutions in retinal imaging are
enabling us to see the retina in microscopic level detail, and measure neuronal and
vascular integrity.
Aims and objectives
I therefore propose that retinal imaging could provide reliable and accurate markers of
these neurological diseases.
In this project, I aimed to explore the clinical utility of retinal imaging derived measures
of retinal neuronal and vessel size and morphology, and determine their candidacy for
being reliable biomarkers in these diseases.
I also aimed to detail the methods of retinal imaging acquisition, and processing, and
the principles underlying all these stages, in relation to understanding of retinal
structure and function. This provides an essential foundation to the application of
retinal imaging analysis, highlighting both the strengths and potential weaknesses of
retinal biomarkers and how they are interpreted.
Methods
After performing detailed systematic reviews and meta‐analyses of the existing work
on retinal biomarkers of neurodegenerative disease, I carried out a prospective,
controlled, cross‐sectional study of retinal image analysis, in patients with MS,
dementia, and ALS. This involved developing new software for vessel analysis, to add
value and maximise the data available from patient imaging episodes.
Results
From the systematic reviews, I identified key unanswered questions relating to the
detailed analysis and utility of neuroretinal markers, and diseases with no studies yet
performed of retinal biomarkers, such as non‐AD dementias.
I recruited and imaged 961 participants over a two‐year period, and found clear
patterns of significance in the phenotyping of MS, dementia and ALS.
Detailed analysis has provided new insights into how the retina may yield important
disease information for the individual patient, and also generate new hypotheses with
relation to the disease pathophysiology itself.
Conclusions
Overall, the results show that retinal imaging derived biomarkers have an important
and specific role in the phenotyping of neurodegenerative diseases, and support the
hypothesis that the eye is an important window to neurological brain disease