Chandran, Siddharthan

Dhillon, Baljean

Cameron, James R.

2018-07-19T12:52:17Z

2018-07-19T12:52:17Z

2018-06-30

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.

http://hdl.handle.net/1842/31379

en

The University of Edinburgh

Lateral thinking ‐ symmetry and asymmetry in neurovascular patterning, in health and disease. JR Cameron, RD Megaw, AJ Tatham, S McGrory, TJ MacGillivray, F Doubal, JM Wardlaw, E Trucco, S Chandran, B Dhillon Progress in Retinal and Eye Research 2017; 59: 131‐157

Retinal imaging in early Alzheimer’s disease. TJ MacGillivray, S McGrory, T Pearson, JR Cameron Book chapter in ‘Biomarkers for Preclinical Alzheimer’s Disease’: NeuroMethods Vol. 137, Robert Perneczky (Ed.), Humana Press. (2018)

The application of retinal fundus imaging in dementia: a systematic review. S McGrory, JR Cameron, C Warren, F Doubal, IJ Deary, B Dhillon, J Wardlaw, E Trucco, TJ MacGillivray Alzheimer’s & Dementia (Amst) 2017; 6(1): 91‐107

OCT update: Beyond the nerve fibre layer. JR Cameron View on Glaucoma 2017; 12(1): 9‐13

Chorioretinal thinning in chronic kidney disease links to inflammation & endothelial dysfunction. C Balmforth, J van Bragt, T Ruijs, JR Cameron, R Kimmitt, R Moorhouse, A Czopek, M Hu, P Gallacher, J Dear, S Borooah, I MacIntyre, T Pearson, L Willox, D Talwar, M Tafflet, C Roubeix, F Sennlaub, S Chandran, B Dhillon, D Webb, N Dhaun JCI Insight 2016; 1(20): e89173

Modulation of retinal image vasculature analysis to extend utility and provide secondary value from optical coherence tomography imaging. JR Cameron, L Ballerini, C Langan, C Warren, N Denholm, K Smart, TJ MacGillivray Journal of Medical Imaging 2016 May; 3(2): 020501

A Window to Beyond the Orbit: the value of optical coherence tomography in non‐ocular disease. JR Cameron, AJ Tatham Acta Ophthalmologica 2016; 94: 533‐539

The APOSTEL recommendations for reporting quantitative optical coherence studies. JR Cameron Neurology 2016; 87(18): 1960

Suitability of UK Biobank retinal images for automatic analysis of morphometric properties of the vasculature. TJ MacGillivray, JR Cameron, Q Zhang, AYM El‐Medany, C Mulholland, Z Sheng, B Dhillon, FN Doubal, PJ Foster, E Trucco, C Sudlow for the UK Biobank Eye and Vision Consortium PLoS ONE 2015; 10(5): e0127914

Systematic review & meta‐analysis of optical coherence tomography in dementia. KL Thomson, JM Yeo, B Waddell, JR Cameron, S Pal Alzheimer’s & Dementia (Amst) 2015; 1(2): 136‐143

Retinal imaging as a source of biomarkers for diagnosis, characterisation and prognosis of chronic illness or long‐term conditions. TJ MacGillivray, E Trucco, JR Cameron, B Dhillon, JG Houston, EJR van Beek British Journal of Radiology 2014; 87: 20130832

retinal diseases

neurological conditions

biomarkers

Eye as a window to the brain: investigating the clinical utility of retinal imaging derived biomarkers in the phenotyping of neurodegenerative disease

Thesis or Dissertation

Doctoral

PhD Doctor of Philosophy