Optometry and Vision Sciences - Theses
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ItemIntegration of auditory and visual temporal rate in aging( 2017)This thesis investigated how aging affects the integration of visual flicker (the temporal modulation of luminance) with auditory flutter (the temporal modulation of sound amplitude) to produce a unified audiovisual percept of temporal modulation rate. A group of younger and older adults judged the temporal rate of an auditory and/or visual stimulus oscillating at 10 Hz. Whichever sensory modality discriminates temporal rate more precisely, contributes more to the audiovisual percept. Consequently, the first experiment explored how aging affected the precision of auditory temporal rate discrimination relative to vision. Auditory temporal rate discrimination in older adults was degraded by an age-related impairment in sensitivity to auditory amplitude modulation. In subsequent audiovisual experiments, auditory modulation depth was individually tailored to equate flutter and flicker temporal rate discrimination thresholds to normalise for this age-related sensory loss. When auditory and visual rates were conflicting, partial integration distorted perceived rate such that the auditory or visual rate subjectively equivalent to a reference was nonveridical. Distortions in perceived rate were unaffected by older age, indicating that the ability to integrate conflicting auditory and visual rates is preserved in aging. However, younger adults’ heightened sensitivity to auditory amplitude modulation was sufficient to increase the influence of audition on perceived rate when the modulation depth of auditory flutter was the same as the average older adult. Therefore, the age-related impairment in auditory rate discriminability is expected to increase visual influence on audiovisual rate perception in older adults. When auditory and visual rates are identical, temporal rate discrimination thresholds improved in line with statistically optimal integration in younger but not older adults. This indicates an age-related impairment in integration, which will be further compounded by the age-related decline in auditory temporal rate discriminability under natural conditions. These findings indicate that older adults will perceive audiovisual temporal rate differently to younger adults. These age-related changes in audiovisual rate perception will be the complex product of the age-related interaction between rate congruence and integration ability, and the age-related decline in auditory temporal rate discrimination.
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ItemThe role of oral long chain omega-3 supplements for treating dry eye disease( 2017)Dry eye disease (DED) is a highly prevalent multifactorial eye condition. While traditional therapies, such as ocular lubricants, provide symptomatic relief for dry eye sufferers, they do not treat the inflammatory overlay found in DED. Omega-3 (ω-3) essential fatty acid (EFA) supplements show promise as a potential treatment for DED. The major aim of this thesis was to compare the efficacy of two forms of long chain ω-3 EFAs, stored primarily as either triacylglycerides (fish oil) or as phospholipids (krill oil), for treating DED. In this regard, a randomised, placebo-controlled, double-masked, three-arm, parallel- group clinical trial was conducted. Sixty participants with clinically significant DED-related symptoms were enrolled for a three-month study. In addition this thesis aimed to determine the effects of elevated tear osmolarity on central corneal thickness (CCT) and corneal reflectivity. In a cross-sectional study involving 38 participants with hyperosmolar tears and 10 age-similar controls with normo-osmolar tears, anterior-segment optical coherence tomography (OCT) was used to detect subtle corneal microstructural changes that occur in association with tear hyperosmolarity. This study aimed to examine the effects of elevated tear osmolarity on central corneal thickness (CCT); and to measure the effects of elevated tear osmolarity and corneal reflectivity. Central corneal thickness (CCT) of participants with severely hyperosmolar tears (defined as eyes in the upper quartile for tear hyperosmolarity, 539.1 ± 7.4 µm) was found to be less than those with mildly hyperosmolar tears (defined as hyperosmolar eyes in the lower quartile for tear hyperosmolarity, 622.7±5.8 µm, p<0.0001) and control eyes (583.1 ± 15.0 µm, p = 0.02). Central corneal reflectivity (45.1 ± 0.3 versus 48.1 ± 0.6 greyscale units, p = 0.02) was relatively lower and peak tear film reflectivity higher (by 4.8% ± 3.5%, p = 0.04) in eyes with hyperosmolar tears than eyes having normo-osmolar tears. In order to test the relative efficacy of two forms of long-chain ω-3 EFA supplements over a three month intervention period, a randomised, placebo-controlled, double-masked, three-arm, parallel-group clinical trial was conducted. Sixty participants with clinically significant DED-related symptoms (Ocular Surface Disease Index Score (OSDI) score of 18-64) and tear hyperosmolarity (≥ 316 mOsmol/L) were randomly allocated (1:1:1) to one of three groups: triacylglyceride ω-3 EFAs (1000 mg/day eicosapentaenoic acid, EPA + 500 mg/day docosahexaenoic acid, DHA), phospholipid ω-3 EFAs (945 mg/day EPA, + 510 mg/day DHA) or placebo (1500 mg/day of olive oil). Primary outcome measures were: mean change in tear osmolarity and OSDI score from baseline (Day 1) to Day 90. Secondary outcomes included: mean change in key clinical signs of DED (ocular surface staining, ocular redness, meibomian gland integrity, anterior blepharitis, tear stability, tear production and tear volume). Fifty-four participants completed the study. Tear osmolarity was significantly reduced from baseline in both the triacylglyceride (fish oil) [n = 19, -19.8 ± 4.5 mOsmol/L, p < 0.001] and phospholipid (krill oil) [n = 18, -18.6 ± 4 mOsmol/L, p < 0.001] groups at Day 90. Only the krill oil group showed a significant reduction in OSDI symptom score [-61.4% ± 5.2%, p = 0.009] relative to the placebo group [n = 17, -32.4% ± 9.6%] at Day 90. Secondary outcome measures of ocular redness, meibomian gland capping, tear stability and corneal staining, were all significantly improved with long-chain ω-3 EFA treatment at Day 90 compared to baseline. There were no significant inter-group difference in tear production, tear volume, corneal thickness, corneal transparency, peak tear film reflectivity or Symptom Assessment in Dry Eye (SANDE) questionnaire scores relative to baseline. These two studies give insight into both the corneal micro-structural changes that occur in association with tear hyperosmolarity and provide evidence that moderate daily doses of long-chain ω-3 EFA supplements, in either predominantly triacylglyceride or phospholipid form, significantly reduce key clinical signs and symptoms of DED, compared to placebo over a three-month treatment period.
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ItemThe effect of chronic hypertension on retinal susceptibility to chronic intraocular pressure elevation( 2016)Higher blood pressure and thus better blood flow should protect the eye against glaucoma, but epidemiological studies suggest the opposite. This thesis provides direct experimental evidence in a rodent model of glaucoma that chronic hypertension impairs the capacity of the ocular blood vessels to cope with changes in blood pressure. This negates any benefit gained from having higher blood perfusion into the eye. These data provide an explanation for why chronic hypertension is a risk factor for glaucoma.
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ItemVascular autoregulation: retina as a non-invasive biomarker for the brain( 2016)The retinal vasculature maybe a useful surrogate for the brain blood vascular network. There has yet to be a direct comparison of the capacity of vessels in the eye and brain to respond to changes in blood pressure or blood gas concentration. We showed that arteries in the rat’s eye and brain demonstrated qualitatively similar vascular autoregulatory capacity in response to a wide range of blood pressure and different blood gas concentrations.
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ItemInvesting the laser-induced model of choroidal neovascularisation in Long Evans rats( 2016)Laser-induced choroidal neovascularisation (LI CNV) involves delivering laser energy to the retina to produce a breach in Bruch’s membrane (BM). Elevation of pro-angiogenic and inflammatory cytokines in addition to extracellular matrix remodelling promotes the ingrowth of CNV following breach. A review of CNV, the effect of laser on the retina, and LI CNV is given in Chapter 2. Calibration of laser and all experimental methods are dealt with in Chapter 3. The dose-response of laser energy for BM breach is investigated in experimental Chapter 4 along with non-invasive measures of BM rupture. The minimum laser energy required for successful breach of BM on 95% of occasions was determined. The change in pro-angiogenic and inflammatory markers following laser rupture of BM was investigated in Chapter 5 using a laser energy flux of 5.10 J/mm2. The rate at which laser lesions converted to experimental CNV using this laser energy was investigated. We show that the presence of bubble at the time of laser application is an accurate predictor of BM breach at 28 days as established by IHC. SD-OCT is also an accurate predictor of breach that has advantages in allowing longitudinal (non-invasive) study of the animal. This could enhance the development of therapeutic interventions.
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ItemThe relationship between ocular blood flow, oxygen saturation and visual function during IOP elevation( 2013)PURPOSE: This thesis explores the intra- and inter-session repeatability of retinal vessel oxygen saturation measured using the Oxymap retinal oximeter (Chapter 3). Moreover, it considers the effect of moderate intraocular pressure (IOP) perturbation on retinal oxygen saturation, blood flow and the pattern electroretinogram (PERG) in young, healthy participants (Chapter 4). METHODS: Ten fundus oximetry images were acquired from 18 healthy participants (age 22 -38) using the Oxymap retinal oximeter T1, with a further ten images obtained one to two weeks later. All pixels returned from the vessel detection algorithm were analysed by plotting frequency histograms of oxygen saturation, which were then modelled using Gaussian functions to return peak oxygen saturation for arteries and veins of various diameters. Intra- and inter-session variability was quantified by evaluating the coefficient of variation and establishing the 95% confidence limits on this coefficient using Bland and Altman analysis. In a further study, 23 young (22-38 years), healthy participants had PERG, retinal oximetry and flowmetry images recorded before, during and after IOP elevation. Using a probe placed on the lower eyelid, IOP was increased by ~30 mmHg to lower ocular perfusion pressure (OPP) by ~30%. Steady-state PERG waveforms (8.3 Hz) were recorded bilaterally (200 sweeps) to return the second harmonic amplitude (16.7 reversals/sec). Peak oxygen saturation for arteries and veins of various diameters on oximetry (Oxymap retinal oximeter) was assessed by fitting Gaussian functions to frequency histograms of all pixels. Blood flow, volume and velocity (Heidelberg retinal flowmeter) were averaged within a 10x10 pixel window at the temporal retina. RESULTS: Bland and Altman analysis showed that there was no bias within and between recording sessions, with variable intra- and inter-session confidence limits depending on the analysis technique and number of images analysed (Chapter 3). In Chapter 4, PERG amplitude was significantly reduced (F(2,44) = 24.24, p < 0.01) and phase significantly delayed (F(2,44) = 17.00, p < 0.01) during IOP perturbation. Contralateral eyes were unchanged. Arterial oxygen saturation remained the same (F(1.43,30.08) = 3.69, p = 0.05), whereas venous saturations reduced (F(1.39,29.15) = 38.64, p < 0.01). Blood flow was shown to change across the 3 conditions (F(2,36) = 5.37, p < 0.01). Poor correlation was found between OPP reduction and either PERG amplitude, PERG phase or venous oxygen saturation. CONCLUSIONS: Oxymap retinal oxygen saturation measurements of arteries and veins are variable, both within and between clinical sessions. Like PERG amplitude, retinal oxygen saturation is sensitive to an acute, moderate IOP perturbation in young participants. The implications of the above outcomes and future directions are discussed in Chapter 5.
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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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ItemThe effects of ageing and visual field loss on visuomotor control( 2012)Aspects of visual localisation, such as foveal hyperacuity, decline with age. However, the effect of ageing on the visual localisation judgements required for goal-directed reaching movements has not been studied. It is also unknown whether pointing precision to such visual stimuli are altered with ageing. Further, the effects of visual impairment on these tasks are not understood. This thesis aimed to investigate the effects of ageing and compromised peripheral visual function on visual localisation and pointing precision. The first part of this thesis aimed to investigate the effects of ageing on visual localisation and pointing precision (Chapter 4). Experiment 1 consisted of a cohort of younger and older observers performing visual localisation and pointing tasks. The results suggest that both the visual localisation and pointing systems remain largely intact with ageing. However, the visual localisation precision of older adults was more affected by the removal of visual references than younger observers. These findings are encouraging for older adults; especially with the increasingly active part they play in the workforce, and society at large. In order to further probe the state of the older visuomotor system, the second part of this thesis investigated the pointing and visual localisation precision of older observers with compromised visual status (Chapter 5). Older adults with glaucoma, a chronic eye disease that results in reduced visual field sensitivity, were used as the model for compromised visual status in Experiment 2. Results suggest that patients with glaucoma show a reduced ability to locate objects both visually and manually. However, perimetry – a clinical measure of visual field sensitivity – provides only a small indication of the degree of this difficulty. Observers with glaucoma also showed a reduced benefit of binocularity compared with their older controls for visual localisation tasks, suggesting that reduced visual field sensitivity may inhibit aspects of binocular processing.