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  • Exploring clinical phenotypes of open-angle glaucoma and their significance in practice
    (2023) Rafla, Daniel
    Thesis
    There are several enduring questions regarding the differentiation of clinical phenotypes of glaucoma which clinicians may derive clinical meaning directed towards patient’s management and prognostication. This thesis seeks to address the following issues relating to distinguishing clinical phenotypes of glaucoma: “Evaluating the impact of changing visual field test density on macular structure-function relationships to identify central-involving glaucoma phenotypes”; and “Identifying quantitative structural and functional clinical parameters that may distinguish between intraocular pressure (IOP) defined glaucoma phenotypes”; Two studies were undertaken to examine clinical phenotypes of glaucoma. The first study utilised systematic approach to assessing the impact of test point density in macular visual field (VF) testing on structure-function concordance for identifying centrally-involving glaucoma phenotypes. The second study used multivariate regression analysis and principal component analysis (PCA) to examine quantitative structural (using optical coherence tomography) and functional (VF) clinical data of newly-diagnosed glucoma patients to determine if there are clinically meaningful distinctions between IOP-defined phenotypes (i.e. low-tension vs high-tension glaucoma). Study 1) Using a systematic approach of test point addition and subtraction, we identified a critical number of test locations (8-14) in macular VF testing where binarised structure-function concordance is maximised, and discordance minimised. This methodology provides a framework for optimising macular VF test patterns for detection of centrally-involving glaucoma phenotypes. Study 2) Despite statistical significance in differences between low- and high-tension glaucoma, PCA applied to quantitative clinical structural and functional parameters returned no groups of clinical parameters that reliably distinguished between patients in IOP-defined glaucoma phenotypes. The present work provides a framework to identify phenotypic groups of glaucoma, the clinical significance of which may vary. We identified the minimum number of test points required to detect central-involving glaucoma in visual field testing. We also demonstrate that IOP-defined phenotypes are not clinically distinguishable at the point of diagnosis, suggesting that these phenotypes form part of a continuum of open-angle glaucoma. These findings have implications for disease staging and preferred treatment modality.