Optometry and Vision Sciences - Theses
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ItemAge-related changes in structure, function and response to stress in the rat retina( 2016)Ageing is a key risk factor for ocular diseases, though age-related changes in the eye have not been fully characterised. This study investigated age-related changes in retinal function, structure and their response to acute and chronic stress in Long Evans rats. With age, both retinal structure and function decline and the retina loses its ability to cope with acute stress. When exposed to mild chronic stress, older eyes suffered greater functional damage than younger eyes.
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ItemUsing structural information to improve perimetry test procedures( 2015)Existing literature on perimetry suggests that current perimetric test procedures suffer from two major limitations; 1) test-retest variability and 2) sampling density. In this thesis, I aimed to improve perimetric testing by leveraging information about an individual’s retinal structure. Current perimetric test procedures are designed to be applicable for a widespread population and are not based on individual information about a given patient. Optical Coherence Tomography (OCT) provides us with some ready information about an individual’s RNFL thickness which might be useful for perimetric testing. This thesis explores ways to incorporate information gained from OCT into perimetric test procedures. In Experiment 1, an individual’s RNFL thickness information is used to bias the prior of a Bayesian perimetric test procedure. Experiment 2 studies the limitations of the relationship between Retinal Nerve Fiber Layer (RNFL) thickness, as measured by OCT data, and perimetric thresholds. In Experiment 3, an individual’s RNFL thickness information is used to customise visual field test locations. The results of this thesis suggest that an individual’s RNFL thickness information can be used to improve the accuracy, precision and test duration of perimetric testing (Experiment 1). The strength of the structure-function relationship in glaucoma can be better revealed improve by relating both measures using customised optic nerve head sectors rather than choosing fixed optic nerve head sector boundaries (Experiment 2). This thesis also shows that customising visual field locations based on the individual’s RNFL thickness improves the chances of detecting abnormal visual field locations (Experiment 3).
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ItemCustomized, automated stimulus location choice to improve visual field procedures( 2014)It is well accepted in the literature that test-retest variability is a key limitation in current automated perimetric procedures, especially with moderate to advanced visual field loss. This obfuscates the ability to discriminate between true progression of the visual field and measurement noise. Studies have shown that sampling the visual field at a greater spatial resolution not only reduces global measures of test-retest variability, but can also describe the spatial extent of scotomata with more accuracy and detect scotomata otherwise missed in conventional perimetry. However, to date there has been no automated application of these principles, and previous approaches which have employed high resolution sampling have sacrificed test duration in order to measure more locations than standard stimulus distribution patterns. The primary objective of this thesis was to address each of these problems by developing a novel, automated, perimetric approach which customises test location choice based on spatial information and observer response during the examination. It was not only important that new procedures did not increase test times compared to current procedures, but also are computationally feasible to implement. The experimentation reported in this thesis concentrated on computer simulation (Experiments 1 to 3) in order to develop and tune these new procedures before testing their performance on human observers (Experiment 4). The outcome measures were precision of threshold estimates (test-retest variability), accuracy (absolute error) and efficiency (number of presentations). It was discovered that one of the developed approaches, Gradient-Oriented Automated Natural Neighbour Approach (GOANNA), improved accuracy and precision in areas surrounding scotoma borders without increasing test duration compared to current procedures (Chapter 3, Experiment 2). This led to further exploration of GOANNA, whereby it was demonstrated (through computer simulation) that the improvement in scotoma characterisation seen in Experiment 2 gave rise to earlier and more accurate detection of glaucomatous progression. It was assumed that the assumptions made in the simulation studies hold true for real data. This thesis lends support to previous findings that implementing high resolution grids is beneficial in glaucomatous progression detection, and that the conventional 6° rectangular grid of fixed locations may not be the most suitable stimulus arrangement for characterising and monitoring all visual field defects. It also reports on initial approaches that didn’t work, which may be useful for future investigators in this field of research. Most importantly, it provides a novel, principled, automated approach of locally increasing sampling spatial resolution without having to sacrifice efficiency.
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ItemContrast processing in ageing and early glaucoma( 2014)A natural visual experience commonly requires an ability to differentiate objects of supra-threshold contrast (contrast discrimination) and to adjust to changes in contrast (contrast adaptation). While the loss of contrast sensitivity with glaucoma has been well documented in the literature, the effect of glaucoma on supra-threshold contrast processing is less studied. This thesis investigated the effects of early glaucoma on contrast discrimination and rapid contrast adaptation. Additionally, alterations in retinal and cortical responses to supra-threshold contrast stimuli with glaucoma were investigated using electrophysiology techniques. As age is a risk factor for glaucoma, this thesis also considered the effects of normal ageing on contrast processing. The results of this thesis suggest that glaucoma can result in supra-threshold contrast deficits, with patients having early glaucoma demonstrating a reduction in rapid contrast adaptation and poorer contrast discrimination. As ageing did not alter rapid contrast adaptation, the assessment of contrast adaptation might be a useful functional tool in early glaucoma, although further studies are required to develop this. Further studies are also required to consider the implications of supra-threshold contrast deficits with glaucoma on natural vision. The smaller cortical deficits relative to retinal deficits revealed with electrophysiological recordings suggest that post-retinal abnormalities are minimal in patients with early glaucoma. Hence, there is a possibility that the supra-threshold contrast deficits seen in early glaucoma in this thesis may mainly arise from retinal abnormalities. There is also the possibility that post-retinal compensation resulted in minimal cortical deficits in patients with early glaucoma. Further experiments involving patients with more advanced glaucoma may help to elucidate post-retinal contrast processing mechanisms with glaucoma. In older adults, elevated cortical responses in the presence of reduced retinal responses suggest the possibility of age-related reduction in cortical inhibition. Altogether, the results of this thesis provide further understanding of the mechanisms underlying supra-threshold contrast deficits in early glaucoma and ageing.
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ItemPsychophysical explorations of the illusion underpinning frequency doubling perimetry in glaucoma( 2006-01)The spatial frequency doubling illusion (FDI) occurs when the contrast of a low spatial frequency sinusoidal grating is modulated at high temporal frequencies – its apparent spatial frequency increases. Earlier suggestions were that the FDI is generated by a specific class of retinal ganglion cells, which are preferentially lost in the early stages of glaucoma. Based on this linking theory, frequency doubling perimetry (FDP) was developed and several clinical reports confirmed its high efficiency in diagnosing early glaucomatous vision loss. However, this linking theory is not universally accepted and newer suggestions posit that the illusion arises because of temporal frequency related difficulties in temporal phase encoding ability. This thesis psychophysically examines the spatiotemporal characteristics of both the FDI and temporal phase encoding ability with achromatic and equi-luminant (both red-green (RG) and blue-yellow (BY)) gratings at a range of spatiotemporal parameters including those eliciting the FDI. (For complete abstract open document)
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ItemAgeing effects on ocular blood flow, oxygen tension and function during IOP elevation( 2012)This is the first study to simultaneously measure electroretinography, ocular blood flow, and oxygen tension during intraocular pressure elevation. By doing so it shows that changes in oxygen tension are more closely related to function than blood flow. Moreover, by comparing these parameters in young and older eyes this study shows that older eyes have less oxygen availability with higher intraocular pressure despite having similar function. This argues that older eyes use more oxygen to sustain normal function.
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ItemTime course of retinal changes in models of chronic IOP elevation( 2010)Glaucoma is an increasingly common sight threatening disease. Our understanding of the pathogenesis requires good models for disease risk factors. This thesis refines models of chronic intraocular pressure elevation in rats. Non-invasive assessment showed evidence of widespread retinal dysfunction. It is clear that dysfunction was not solely determined by intraocular pressure, but is associated with either ocular trauma or agent toxicity. Clear methodological recommendations are provided to minimise widespread damage and thus provide improved models for understanding glaucoma.
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ItemExploring the mechanisms of Rarebit perimetry( 2009)Visual field testing, or perimetry, measures peripheral visual loss in eye diseases such as glaucoma. Rarebit Perimetry (RBP) is a new and novel perimetric method, introduced in 2002 by Lars Frisén (2002), with the aim of detecting low degrees of neural damage within the retina. RBP is unlike conventional perimetric methods that measure levels of retinal sensitivity, but instead uses very bright (i.e. suprathreshold) and very small targets to detect tiny areas of absolute blindness within otherwise normal areas of vision. RBP thus claims to locate miniscule gaps in the receptive field matrix of neurons in the retina, with the assumption that dead neurons leave gaps in this matrix. The most useful application of this idea is to detect progressive eye disease in the earliest stages (Frisén, 2002). Current research shows that RBP correlates with other standard visual field tests (Brusini, Salvetat, et al., 2005; Frisén, 2003; Gedik, Akman, et al., 2007; Martin & Wanger, 2004), but may afford greater sensitivity by detecting very mild visual losses missed by other tests (Martin, Ley, et al., 2004; Martin & Nilsson, 2007; Nilsson, Wendt, et al., 2007). To date, there are no studies that definitively test the theoretical basis of RBP, so in this thesis I aim to explore the proposed underlying mechanisms and assumptions of this test. In particular, the proposed mechanism of RBP leads to specific predictions as to how responses will alter when the luminances of the RBP targets are systematically decreased. I therefore compared RBP responses of mean hit rate as a function of target luminance and found results to be inconsistent with the proposed RBP mechanism. Mathematical simulations were performed to explore reasons for the differences between the two groups (Chapter Seven).