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dc.contributor.advisorCampbell, Matthewen
dc.contributor.authorO'Riordan, Matthewen
dc.date.accessioned2024-09-10T18:11:26Z
dc.date.available2024-09-10T18:11:26Z
dc.date.issued2024en
dc.date.submitted2024en
dc.identifier.citationO'Riordan, Matthew, The ophthalmic manifestations of neurological disease, Trinity College Dublin, School of Genetics & Microbiology, Genetics, 2024en
dc.identifier.otherYen
dc.descriptionAPPROVEDen
dc.description.abstractThe retina is responsible for visual processing by converting light signals into nerve impulses. It comprises both the central retina, termed the macula, and the peripheral retina. There are several subtypes of peripheral retinal degenerations. In this thesis, we examine the retinal manifestations of specific neurological disorders. These are mild traumatic brain injury (mTBI), multiple sclerosis (MS) and tuberous sclerosis complex (TSC). Microcystoid degeneration is reported as a common finding in the peripheral retina, and it is thought to relate to the process of aging. It presents as small reddish vesicles with indistinct boundaries in the far-peripheral retina or ora serrata. On OCT, these manifest as saw-tooth patterns of hypo-reflective intraretinal cystoid cavities with broad columns. mTBI is the most common form of TBI, and frequently occurs in many contact and collision sports. It is associated with numerous long-term sequelae including cognitive and memory impairments, epilepsy, visual disturbances, and chronic pain. It leads to acute and chronic disruption of the blood-brain barrier (BBB), which shares structural and functional similarities with the neurovascular unit comprising the inner blood-retina barrier (iBRB). In the mTBI study, we sought to use ultra-widefield (UWF) fundus photography, FFA, and far- peripheral OCTs to assess the peripheral retina in athletes exposed to recurrent mTBIs. We recruited 32 participants, including active and retired athletes of contact and collision sports with a history of multiple mTBIs , non-athletes with prior mTBIs, and control subjects without these injuries. Far-peripheral cystoid degeneration was a common occurrence, with 35 instances detected in 21 participants (65.6 %). The far-temporal quadrant accounted for 74.3 % of all instances of microcystoid degeneration. Individuals with prior mTBIs had a greater proportion of OCT quadrants containing cystoid degeneration, compared to those without prior mTBIs (28.2 % vs. 17.3 %, p = 0.11). The cystoid degeneration in these individuals took up a greater vertical diameter of the retina (202.8 vs. 156 microns, p = 0.1). Additionally, those with prior mTBIs also had significantly thicker far-peripheral retinas as measured on OCT (265.2 vs. 225.2 microns, *p = 0.02). We postulate that mTBIs may contribute to the development or progression of peripheral cystoid degeneration. This could represent a structural biomarker of mTBIs. Recruitment of participants is still ongoing in order to improve the study power . A prospective longitudinal study may also be warranted in athletes exposed to recurrent mTBIs to identify a causal role between trauma and peripheral cystoid degeneration. In the MS study, we assess the feasibility of UWF FFA and OCT in assessing the peripheral retina. Participants with MS and healthy controls underwent bilateral UWF fundus photography, FFA, and mid-peripheral OCTs. Five individuals with relapsing remitting MS were recruited, with a mean age of 36.9 years, mean disease duration of 11 years, and a median expanded disability status score of 0.75. In all MS participants, the disease was not active clinically or radiologically. Using UWF-FFA and OCT, we did not detect clear evidence of peripheral retinal abnormalities, which is consistent with the participants having inactive MS. In this pilot study of UWF-FFA and peripheral OCT to examine the retina in MS, our results suggest that it may be useful to perform a larger prospective longitudinal study to establish its potential as a monitor of disease activity. Future iterations of this research will seek to examine this hypothesis. The retinal manifestations of TSC include retinal astrocytic hamartomas (RAH) and achromatic patches. In the TSC study, we sought to use a multimodal imaging approach including FFA to assess the retinal lesions in TSC and evaluate their correlation with intracranial tuber burden on magnetic resonance imaging (MRI). Nine participants with TSC were recruited, and underwent bilateral dilated multimodal retinal imaging. Participants' most recent MRI brain scans were analysed to determine intracranial tuber load. Seven (78 %) had retinal lesions; 5 (56 %) had retinal astrocytic hamartomas and 2 (22 %) had achromatic patches. OCT identified all RAH lesions, IR identified 75 %, fundus photography identified 63 %, while FFA detected just 57 %. All participants had intracranial tubers with a mean of 9.4 - 5.1 tubers each. There were significant positive correlations between the quantities of intracranial tubers and all TSC-retinal lesions (r = 0.8, **p < 0.01) and all RAH lesions (r = 0.8, *p = 0.01). Here, we concluded that a multimodal imaging based approach with fundal photography, infrared imaging and OCT should be used to assess the retina in TSC as it may indicate the intracranial tuber burden. FFA is useful for larger lesions where there is concern for the integrity of the inner blood-retina barrier and for the identification of active lesions.en
dc.publisherTrinity College Dublin. School of Genetics & Microbiology. Discipline of Geneticsen
dc.rightsYen
dc.subjectblood-retina barrieren
dc.subjectblood-retinal barrieren
dc.subjectiBRBen
dc.subjecttuberous sclerosis complexen
dc.subjectmultiple sclerosisen
dc.subjectmild traumatic brain injuryen
dc.subjectperipheral retinal degenerationen
dc.titleThe ophthalmic manifestations of neurological diseaseen
dc.typeThesisen
dc.type.supercollectionthesis_dissertationsen
dc.type.supercollectionrefereed_publicationsen
dc.type.qualificationlevelMasters (Research)en
dc.identifier.peoplefinderurlhttps://tcdlocalportal.tcd.ie/pls/EnterApex/f?p=800:71:0::::P71_USERNAME:ORIORDM2en
dc.identifier.rssinternalid269317en
dc.rights.ecaccessrightsembargoedAccess
dc.date.ecembargoEndDate2025-08-31
dc.identifier.urihttps://hdl.handle.net/2262/109209


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