MacGillivray, Thomas

Muniz Terrera, Graciela

Dhillon, Baljean

Trucco, Manuel

Megaw, Roly

Gibbon, Samuel

Biotechnology and Biological Sciences Research Council (BBSRC)

EASTBIO BBSRC Doctoral Training Partnership

Alzheimer’s Research UK

2025-08-14T12:34:26Z

2025-08-14T12:34:26Z

2025-08-14

BACKGROUND: There is a growing need for accurate and cost-effective biomarkers for neurological disorders. Brain imaging is not suited to mass screening, owing to its cost and complexity of operation. The retina offers a promising and accessible alternative as it is directly connected to the brain via the optic nerve and shares its blood supply, embryological origins, and structural features. Changes in the brain are often reflected in the retina. One such change observed in multiple neurological disorders is thinning of the retinal nerve fibre layer (RNFL), which is measured using Optical Coherence Tomography (OCT), reflecting loss of nerve tissue in the brain. However, OCT is not universally accessible and may be challenging to use with certain populations, such as frail individuals or those with movement disorders. An alternative approach still utilising the retina involves assessing the paleness of the optic disc in colour fundus photographs, based on the premise that a pale disc indicates RNFL degeneration or loss. Fundus photographs are the most widely available retinal imaging modality and routinely captured during high-street eye examinations and other standard clinical settings. OBJECTIVE: In this thesis I aim to develop a method for quantifying optic disc pallor in fundus images, and to investigate optic disc pallor and in conditions affecting the health of the brain. METHODS: I developed software to measure optic disc pallor using a combination of image processing techniques and deep learning segmentation networks. Validation was performed by comparing pallor measurements to peripapillary RNFL thickness from the same eyes and by assessing how pallor values aligned with clinically diagnosed pallor in an external dataset. I applied the software to three clinical datasets using linear, logistic, and linear mixed-effects models to investigate associations between pallor measurements and clinical features, including MRI-detected lesions, cerebral small vessel disease (cSVD) ratings, stroke type, and Parkinson’s disease (PD) status and duration. I also manually reviewed 1,485 images from an aggregated dataset and used these labels to create two methods for automated quality control. RESULTS: The resulting software can process an image in under one second. In clinical research, I found that disc pallor was associated with MRI-visible enlarged perivascular spaces (indicative of underlying cSVD), lacunar stroke, cSVD ratings, and PD status and disease duration. CONCLUSION: Optic disc pallor, measured in colour fundus photographs, reveals insights into neurological dysfunction. Future investigation is warranted to see if pallor could be an imaged-derived biomarker of disease or whether it holds predictive value in addition to conventional risk factors used clinically.

https://hdl.handle.net/1842/43812

http://dx.doi.org/10.7488/era/6343

en

The University of Edinburgh

Gibbon, S., Muniz-Terrera, G., Yii, F.S., Hamid, C., Cox, S., Maccormick, I.J., Tatham, A.J., Ritchie, C., Trucco, E., Dhillon, B. and MacGillivray, T.J., 2024. PallorMetrics: Software for Automatically Quantifying Optic Disc Pallor in Fundus Photographs, and Associations With Peripapillary RNFL Thickness. Translational Vision Science & Technology, 13(5), pp.20-20.

Gibbon, S., Low, A., Hamid, C., Reid‐Schachter, M., Muniz‐Terrera, G., Ritchie, C.W., Trucco, E., Dhillon, B., O'Brien, J.T. and MacGillivray, T.J., 2024. Association of optic disc pallor and RNFL thickness with cerebral small vessel disease in the PREVENT‐ Dementia study. Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring, 16(3), p.e12633.

Gibbon, S., Doubal, F., Chappell, F., Wardlaw, J.M., Dhillon, B. and MacGillivray, T., 2024. Association between optic disc pallor and lacunar stroke. BMJ Neurology Open, 6(2), p.e000789.

Gibbon, S., Breen, D.P., MacGillivray, T.J. and UK Biobank Eye & Vision Consortium, 2025. Optic Disc Pallor in Parkinson's Disease: A UK Biobank Study. Movement Disorders

Yii F, Gibbon S, MacGillivray T. Sectoral changes in neuroretinal rim pallor across refractive error. Ophthalmol Sci. Published online January 7, 2025:100705. doi:10.1016/j.xops.2025.100705

Gibbon S, Muniz-Terrera G, Yii FS, et al. A method for quantifying sectoral optic disc pallor in fundus photographs and its association with peripapillary RNFL thickness. Published online November 13, 2023. doi:10.48550/arXiv.2311.07213

retinal biomarker

retinal nerve fibre layer

optic disc pallor

neurological disease detection

automated quality control

Optic disc pallor and brain health

Thesis or Dissertation

Doctoral

PhD Doctor of Philosophy