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oai:figshare.com:article/32826329 2026-10-01T16:08:51Z portal_1172 item_type_8 month_year_10_2026

Structural, functional and molecular changes at the human peripheral retina Jamie William Mitchell (24304556) PUREID: 687776195 Retina neurodegeneration multimodality Down Syndrome Multiple sclerosis Alzheimer’s disease The retina shares embryological origins and physiological similarities with the brain, offering a non-invasive, high-resolution window into the Central Nervous System (CNS). Historically, retinal studies have focused mainly on the macula and structural layer thickness. This thesis, however, examines the peripheral retinal changes alongside central microvascular and molecular alterations as potential early indicators of neurodegenerative conditions. Specifically, it investigates eye-related changes linked to Alzheimer’s disease (AD), using Down syndrome (DS) as a genetically predetermined model of disease, as well as Multiple Sclerosis (MS). In adults with DS, retinal imaging shows supernumerary retinal vessels, wider vessel calibres with rapid thinning, and a reduced choroidal vascularity index (CVI). Further, microaneurysms and haemorrhages were found exclusively in the far-peripheral retina, potentially reflecting early AD-related amyloid angiopathy. In MS, patients showed narrower central retinal venules and reduced venular complexity. Peripheral retinal vascular attenuation correlated with faster clinical disability progression. The thesis also identifies a novel "ring-like" spatial redistribution of macular pigment in MS eyes, offering a new potential molecular sign of smouldering neurovascular degeneration. Finally, the thesis introduces the REVEAL study, which is underway and aims to temporally track and correlate retinal changes with molecular biofluid markers (blood, tears, and saliva) across DS, mild cognitive impairment, and healthy cohorts. This research shows us that accessible retinal markers hold significant clinical utility for the early detection and monitoring of neurodegenerative diseases, especially in cohorts with cognitive disabilities. This research demonstrates that utilising non-invasive retinal assessments, specifically those that include the peripheral retina, microvascular networks, and spatial molecular profiles, offers a powerful modality for marker identification. These accessible markers could hold significant clinical utility, assisting gold standard neurological exams for the early detection, prognosis, and longitudinal monitoring of CNS neurodegenerative diseases. Thesis is embargoed unitl 31 July 2027. 2026-10-01T16:08:51Z Text Thesis 10.17034/32826329.v1 https://figshare.com/articles/thesis/Structural_functional_and_molecular_changes_at_the_human_peripheral_retina/32826329 All Rights Reserved Open Access after 2027-07-31