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Phenotypic Heterogeneity and its influence on visual and morphological outcomes in age-related macular degeneration

Chandra, Shruti; (2024) Phenotypic Heterogeneity and its influence on visual and morphological outcomes in age-related macular degeneration. Doctoral thesis (Ph.D), UCL (University College London). Green open access

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Abstract

Age related macular degeneration (AMD) is a complex condition with significant heterogeneity in presentation, rate of progression and outcomes. The overarching aim of the studies in this thesis was to characterize the heterogeneity by conducting in-depth imaging and visual function tests to inform future clinical trial design in non-neovascular AMD, neovascular AMD (nAMD) and geographic atrophy (GA). In a prospective structure-function correlation study on 254 participants with normal fundus and varying severity of non-neovascular AMD, subretinal drusenoid deposits (SDD), hyperreflective foci and nascent GA were found to be imaging characteristics that are associated with visual function losses. In addition, quantitative fundus autofluorescence decreased with increasing AMD severity suggesting that decreasing lipofuscin load is of questionable therapeutic benefit in AMD. In a cohort study on 2,128 patients with new-onset nAMD that completed the loading phase of aflibercept injections, structure-function correlation identified non-white ethnicity, male and eyes with increased CST or those presenting with SRF only as determinants of residual fluid post-loading. Restricting early-phase interventional clinical trials to patients with these characteristics is more likely to provide an indication of benefit over aflibercept, the current comparator of clinical trials in nAMD. In a study on 50 patients with GA, multifocality, SDD, and junctional hyperautofluorescence were identified as features of fast progression and so targeting interventional trials to this GA group would likely yield more reliable results in a shorter period. Using a computer-aided tool on OCT scans on 13 GA patients also revealed that photoreceptor loss precedes GA growth and could be used as an early clinical endpoint for GA trials. In conclusion, various phenotypes were identified within each AMD stage that largely explains differences in visual function, treatment responses and disease progression. These findings could be used to design more efficient and effective clinical trials in AMD.

Type: Thesis (Doctoral)
Qualification: Ph.D
Title: Phenotypic Heterogeneity and its influence on visual and morphological outcomes in age-related macular degeneration
Open access status: An open access version is available from UCL Discovery
Language: English
Additional information: Copyright © The Author 2024. Original content in this thesis is licensed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0) Licence (https://creativecommons.org/licenses/by-nc/4.0/). Any third-party copyright material present remains the property of its respective owner(s) and is licensed under its existing terms. Access may initially be restricted at the author’s request.
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Institute of Ophthalmology
URI: https://discovery.ucl.ac.uk/id/eprint/10187396
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