Eye as a window to the brain: investigating the clinical utility of retinal imaging derived biomarkers in the phenotyping of neurodegenerative disease.
Item statusRestricted Access
Embargo end date30/06/2019
Cameron, James R.
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.