Investigating the role of optical coherence tomography and angiography as a disease biomarker in Multiple Sclerosis

This thesis explores the roles of Optical coherence tomography (OCT) and OCT angiography (OCTA) as a biomarker in Multiple Sclerosis (MS) within an evolving field that increasingly prioritises a pathobiological disease definition. There remains a pressing need for convenient, cost-effective biomarkers with clinical relevance. Whilst magnetic resonance imaging (MRI) is widely regarded as the gold standard, it is costly, and volumetric data is not easily reproducible in routine clinical practice. I initially investigated the utility of OCT and visual biomarkers in predicting long-term disease progression in patients 15 years after a first demyelinating event. I found that colour vision was more impaired in non-optic neuritis eyes of patients who progressed to MS, compared to those who remained clinically isolated, and this impairment correlated with thinner peripapillary retinal nerve fibre layer (pRNFL) and macular ganglion cell inner plexiform layer (mGCIPL) on OCT and a higher lesion burden on MRI. Then I explored the existing evidence for OCTA as a surrogate for brain hypoperfusion in MS and its role as an evolving biomarker. This involved validating the methodology through quality control standards (OSCAR-MP) and assessing test–retest repeatability and reliability. I then conducted a cross-sectional analysis within a prospective cohort of adult and paediatric MS patients (POINT-MS cohort) to explore mechanisms of brain damage using OCTA. This revealed distinct associations between OCTA metrics and regional brain volume loss, which differ from those observed with OCT. In adults, OCTA measures were also associated with visual function and Expanded disability status scale (EDSS) scores, with stronger correlations seen in early disease. In paediatric patients, neuroplasticity may contribute to a structural–functional mismatch, resulting in weaker associations between OCT/OCTA measures and both visual outcomes and EDSS. However, correlations persisted between OCTA metrics and higher-order visual association MRI volumes. These findings highlight OCTA’s complementary role to OCT in revealing links between neurodegeneration, central nervous system hypoperfusion, and inflammation across ages.