Ophthalmology (Eye & Ear Hospital) - Theses

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    Development of a bioengineered corneal surface replacement
    Francis, David Patrick. (University of Melbourne, 2006)
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    Development of a bioengineered corneal surface replacement
    Francis, David Patrick. (University of Melbourne, 2006)
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    Embracing the Future: An Examination of the Potential Role of Artificial Intelligence in Ophthalmology
    Rothschild, Philip Samuel ( 2023-01)
    Background: Substantial developments in artificial intelligence (AI) hold promise for screening and diagnosing ophthalmic diseases. However significant technological advances can be disruptive. Similarly, technology development and adoption do not necessarily occur hand-in-hand. The successful adoption of AI technology in eye health will necessitate education of healthcare professionals as well as appropriate organisational and sector support. Furthermore, it is necessary to make sure that eye health professionals are actively engaged in the implementation of AI applications in the clinical setting, to ensure that they are safe, effective, and used appropriately. Aim: This body of research aims to explore the implementation challenges of AI within ophthalmology and to inform the development of educational frameworks for ophthalmologists and trainees. The aims include: (1) Exploring knowledge and expectations of clinicians in ophthalmology and related medical specialties about AI. (2) Evaluating the impact of AI assistance on the grading performance of eye health professionals engaged in diabetic retinopathy screening. (3) Informing the development of an AI educational curriculum framework for ophthalmology trainees. Methods: A survey of ophthalmologists, dermatologists, radiologists/radiation oncologists and their trainees in Australia and New Zealand was carried out to understand perceptions of AI within these fields of medicine. Furthermore, the impact of a deep learning program as a tool used by optometrists, orthoptists and trainees for grading fundus photographs for diabetic retinopathy (DR) was assessed. Impacts on grading accuracy, confidence, and speed were evaluated. Finally the perspectives of ophthalmology trainees about AI education was explored using focus groups, to help guide the development of a framework educational AI curriculum for ophthalmology trainees. Results: Artificial intelligence was acknowledged by ophthalmologists, dermatologists and radiologists/radiation oncologists to represent a significant advance in healthcare technology that will have a broad-ranging positive influence. Reducing time spent on repetitive tasks and improving access to disease screening were seen as major potential benefits of the use of AI, with education identified as an important factor in the proper preparation of clinicians. In keeping with this, the study of AI assistance in identifying referable DR indicated that AI support was associated with increased accuracy, speed and confidence of optometrists, orthoptists, and their trainees, validating the potential utility of the technology. Furthermore, the focus group study demonstrated that ophthalmology trainees were keen for their College to include instruction on the clinical use of AI in their training curriculum and that trainees were interested in gaining a basic understanding of the technology and its potential implications. Conclusion: Artificial intelligence is perceived by ophthalmologists to likely have a significant and positive effect on their specialty. This perspective was reinforced by ophthalmology trainees who outlined how best to include an approach to AI in their educational curriculum. One AI adjunct was found to assist with DR screening and this may prove to have broader implications for the treatment of eye disease and easing workflow pressures. Preparing for the implementation of AI and understanding how it may affect clinicians plays an important role in underpinning the success of the technology within the field of ophthalmology.
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    Multimodal Retinal Imaging in Alzheimer's Disease
    Ashraf, Gizem ( 2023-02)
    Background There are over 44 million people living with dementia worldwide, and most have Alzheimer's disease (AD). The current diagnostic methods for AD include brain imaging modalities such as magnetic resonance imaging and positron emission tomography which require significant resources, cost, and time. In contrast, retinal imaging modalities are much more widely available, accessible, and are lower in cost. The retina is an extension of the brain and they share a common embryological origin, thus highlighting the potential role for retinal imaging in the diagnosis of AD. Aims The aims of this thesis are: firstly, to perform a systematic review and meta-analysis to understand and evaluate the current evidence regarding retinal imaging in AD. Secondly, to perform a cross-sectional study of retinal imaging in people with biomarker-defined AD compared to healthy controls by exploring the association between these biomarkers and retinal parameters measured by optical coherence tomography (OCT), optical coherence tomography-angiography (OCT-A), and hyperspectral imaging. Thirdly, to explore the role of multimodal imaging in AD by combining findings from various retinal imaging methods to assess the potential of a composite biomarker of AD. Methods A systematic review of PubMed, EMBASE and Scopus was performed in accordance with PRISMA guidelines. Random-effects meta-analyses of standardised mean difference, correlation and diagnostic accuracy were conducted. The findings of this review were used to guide a cross-sectional study, to examine retinal parameters from OCT, OCT-A, and hyperspectral imaging of 35 people with AD and 38 healthy controls. Finally, a literature review on multimodal imaging was performed, and a novel multimodal model was generated using a machine learning approach. Results Meta-analysis of previous studies demonstrated that in people with AD there was a trend towards thinning in most retinal layers on OCT, increased foveal avascular zone area on OCT-A, and reduced arteriole and venule fractal dimension on fundus photography. The cross-sectional study demonstrated that, when compared to healthy controls, AD patients had no significant differences in retinal thickening in most retinal layers on OCT, significantly higher numbers of branching arterioles and venules on OCT infrared en face images, increased foveal avascular zone area and vessel density changes on OCT-A, and increased hyperspectral scores on hyperspectral imaging. The literature review of multimodal imaging outlined current terminology, approaches and challenges in the field. Finally, a novel multimodal model was generated and its clinical utility and limitations were discussed. Conclusion Prior research has identified associations between a number of retinal imaging parameters and AD, however limitations in study design including small sample sizes and non-biological definition of AD cases combined with heterogeneity in imaging methods and reporting make it difficult to determine the utility of these changes as AD biomarkers. Additional retinal imaging biomarkers were found to be associated with AD in our cross-sectional study of a biologically defined AD cohort and the role of combining retinal imaging parameters from multiple imaging modalities in a multimodal approach was explored.
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    The global socioeconomics of vision impairment and cataract surgery
    Yan, William ( 2019)
    The overwhelming majority of the world’s vision impaired reside in low-income settings. Cataract is the leading cause of blindness and the second-leading cause of moderate to severe vision impairment (MSVI). Proxy measures of cataract disease burden and access to cataract surgery services include cataract surgery rate (CSR) and cataract surgery coverage (CSC) rates. The present research aims to evaluate and model associations between the scale of vision loss and burden of cataract disease with socioeconomic indices, drawing comparisons with other countries globally to identify key country policies, practices and initiatives that have resulted in significant improvements to service delivery. A meta-analysis was conducted using CSR data between 2005 and 2014 from published literature and unpublished literature. A systematic review of Rapid Assessment of Avoidable Blindness (RAAB) studies from 1995 to 2015 extracted information on the prevalence and causes of blindness, rate of cataract blindness, cataract surgery coverage (CSC), and visual acuity outcomes of cataract surgery (CSO). HDI and GDP data were collected from the United Nations Development Program (UNDP) and World Bank repositories respectively. Estimates of age-standardised prevalence data of vision impairment and blindness were collected from the 2010 Global Burden of Disease Study (GBD). CSR was found to be closely associated with GDP and GNI using data throughout the study period. HDI levels accounted for the majority of global variance in the prevalence of moderate-severe VI and blindness. Of the three HDI components, education was identified as the most influential factor, accounting for two-thirds of the global variance in MSVI and blindness prevalence. Lower total health expenditure per capita, and as a proportion of total GDP, were associated with a higher prevalence of moderate-severe VI and blindness. A strong association exists between socioeconomic factors as indicated by GDP, GNI and HDI and the quality and quantity of cataract surgery. This suggests there are strong relationships between resource availability and healthcare delivery. Low-cost and innovative services as well as strategic investment in capacity development is important to address cataract surgery needs in low-resource settings.
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    Second eye at risk: predicting the development of advanced age-related macular degeneration
    Goh, Jonathan Kwan Soon ( 2017)
    Hypothesis 1: In people who develop a choroidal neovascular membrane (CNVM) secondary to Age-Related Macular Degeneration (AMD), presenting visual acuity varies. Eyes with worse visual acuities at presentation have worse visual acuity outcomes compared to eyes that present with better visual acuities despite treatment. Aim 1: To determine and compare the visual acuity of first and second eyes diagnosed with CNVM secondary to AMD at presentation and through two years of follow-up to determine the long-term visual consequences of poor presenting visual acuity. Methods 1: Retrospective review of clinical notes of patients presenting with newly diagnosed CNVM secondary to AMD in their first eye from the Royal Victorian Eye and Ear Hospital from January 2012 to April 2014. Visual acuity was recorded up to two years. Visual acuity in the second eye developing CNVM was recorded at diagnosis and for a further two years from the time of diagnosis. Results 1: First eyes presented with a visual acuity of 6/52 and second eyes presented with a visual acuity of 6/21. Although this did not reach statistical significance, first eyes tended to have worse visual acuity during the 2 years of follow up. This suggests that there is room to identify and begin treatment earlier once CNVM has developed. Hypothesis 2: Reduced microperimetric macular sensitivity, or a decrease in microperimetric macular sensitivity over time, is associated with an increased risk of developing CNVM in an eye with large drusen whose fellow eye has CNVM secondary to AMD. Aim 2: To determine if reduced macular function, or a decrease in macular function over time, as determined by microperimetry, can predict the development of CNVM in eyes with large drusen whose fellow eye has CNVM secondary to AMD. Methods 2: Participants with unilateral CNVM secondary to AMD in one eye and large drusen in the other eye (study eye, group 1) were recruited prospectively from the Royal Victorian Eye and Ear Hospital, East Melbourne, Victoria Australia between February and May 2014. All participants underwent microperimetry testing at baseline and 12 months study eye developed CNVM or GA. Results 2: Reduced microperimetric sensitivity is associated with the development of CNVM or GA collectively (P=0.045). All eyes that developed CNVM or GA had a mean macular microperimetric sensitivity less than 25dB at baseline. This confirms our hypothesis, and provides further evidence that macular function, as tested by microperimetry, may be a useful biomarker for predicting disease progression. Hypothesis 3: Microstructural changes, such as drusen, EZ disruption, HF, RPD and nGA, are independently associated with decreased retinal function, which partially explain the reduced microperimetric retinal sensitivity seen in eyes that progress to late AMD from Aim 2. Aim 3: To determine if macular structure-function relationships explain the reduced microperimetric macular sensitivity in fellow eyes with large drusen that ultimately go on to develop late AMD of people with unilateral CNVM secondary to AMD in their other eye. Methods 3: Group 1 from Aim 2 was used in Aim 3. Controls with bilateral intermediate AMD in both eyes (group 2) were recruited as a comparison group. All participants from groups 1 and 2 underwent multimodal imaging, including spectral domain optical coherence tomography, fundus autoflourescence, and fundus infrared reflectance. Results 3: Mean microperimetric macular sensitivity is lower in cases compared to controls (P<0.001) at baseline and is independently associated with the development of CNVM or GA collectively (P=0.039), and GA alone (P=0.005) when taking into account microstructural changes. Conclusion: People with CNVM secondary to AMD are presenting with poor vision in an Australian population, which limits their long-term visual outcome despite treatment. Within our study population, all eyes developing late AMD had a baseline mean microperimetric macular sensitivity less than 25dB. Furthermore, microperimetric macular sensitivity is associated with the development of late AMD whose fellow eye already has established CNVM independent of microstructural changes. This provides substantial evidence that microperimetric macular sensitivity, in conjunction with the quantification of structural changes, may prove to be a useful biomarker that could potentially allow for greater risk stratification of those likely to develop late AMD. As such, macular microperimetry has the potential to become a useful clinical tool with practical implications in terms of monitoring.
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    Investing the laser-induced model of choroidal neovascularisation in Long Evans rats
    Prea, Selwyn ( 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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    The role and benefits of collaborative care through task sharing in eye health service delivery
    Tsonis, Stephanie ( 2015)
    This thesis demonstrated the role of collaborative care in eye health service delivery through task sharing and the anticipated benefits of utilising existing workforces to meet future demands. The research evaluated a model of collaborative care between ophthalmology and optometry and an exploratory study to understand the occasions of service required for the three chronic eye conditions age-related macular degeneration, diabetic retinopathy and glaucoma. It is anticipated the findings and conclusions will potentially inform future models of care and management guidelines in Australia.
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    Association of serum lipids with diabetic retinopathy, macular edema and macular thickness in adults with diabetes: the Diabetes Management Project (DMP)
    Benarous, Rehab ( 2011)
    PURPOSE: To assess the association of serum lipids with diabetic retinopathy (DR), diabetic macular edema (DME), and macular thickness in adults with diabetes. RESEARCH DESIGN AND METHODS: Diabetic patients aged 18 years or older were prospectively recruited from eye clinics at the Royal Victorian Eye and Ear Hospital, Melbourne, Australia. Fasting total-C [cholesterol], HDL-C, non-HDL-C, triglyceride and LDL-C were assessed. DR was graded from fundus photographs (dilated) as mild, moderate and severe non-proliferative and proliferative; and separately graded for presence of DME, including clinically significant macular edema (CSME). Macular thickness was assessed using optical coherence tomography (OCT). RESULTS: A total of 500 participants (median age = 65 years) were examined. DR, DME and CSME were present in 321 (66.2%), 149 (33.0%), and 68 (15.0%) patients, respectively. In multivariate models adjusting for traditional risk factors and lipid medications, persons with higher total-, LDL-, and non-HDL-C were more likely to have CSME (odds ratio of 1.54, 1.49, and 1.63 per 1 SD increase, respectively; all P<0.05). Serum lipid levels were not related to DR, DME or macular thickness. CONCLUSION: Serum lipids are independently associated with the CSME, but not with DR, mild or moderate DME or macular thickness. These data reflect the impact of hyperlipidaemia in the pathogenesis of severe macular edema and suggest that differential dyslipidemia therapies targeting DR and CSME may be needed.
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    Temporal processing in auditory and visual systems: evidence of wider central nervous system involvement in glaucoma
    O'HARE, FLEUR ( 2011)
    Background: Open Angle Glaucoma (OAG) is a condition that is characterised by a loss of retinal ganglion cells; which in turn inhibits visual signals, through a reduction in the levels of information being sent to the brain for processing. The degree and rate at which this inhibition occurs can vary greatly between individuals and therefore may be a consequence of innate differences in sensory nerve susceptibility to injury. In the event of an underlying neuronal susceptibility, signs of auditory processing dysfunction may be observed in individuals with OAG. Aims: The purpose of this study was to examine whether individuals with OAG display signs of central auditory processing dysfunction. Concurrent investigation of specific visual processing functions was conducted to assess if any similarities in neural processing dysfunction were evident across both visual and auditory systems within the same individuals. Methods: Experiment 1: A comprehensive range of peripheral and central auditory processing tests were conducted in 42 OAG individuals and matched controls. Central auditory function tests included evoked potential measures, tests for auditory temporal processing and speech perception. Experiment 2: Based on the findings of Experiment 1, specific auditory temporal processing tasks were performed in conjunction with hierarchical visual temporal processing tasks. Results: Experiment 1: Compared to age equivalent controls, OAG participants displayed significantly poorer amplitude modulation detection and speech perception under high levels of background noise. Amplitude modulation detection moderately correlated with speech perception and ABR performance within both groups. Collectively, signs indicated evidence of impaired auditory neural temporal processing in a significant proportion of the OAG cohort. Experiment 2: OAG Individuals showed a tendency toward poorer performance on both auditory and visual discriminatory tasks that require a high degree of temporal resolution. Specifically, poorer speech perception under competing noise as well as impaired visual speed discrimination for slow velocities were identified in a significant proportion of OAG individuals (39.13% and 47.82% respectively, were below the 90th percentile of control performance). Overall, performance on auditory processing tasks did not correlate with performance on visual processing tasks for either group. Conclusions: A subgroup of OAG individuals display evidence of central auditory neural processing dysfunction which implies that glaucoma may be associated with other non-visual sensory neural deficits. As such, the results indicate increased neuronal susceptibility in these individuals. Clinical Significance: This is the first study to explore auditory function in OAG individuals beyond assessing sound detection or the integrity of the middle and inner ear. A proportion of OAG individuals have shown signs of central auditory processing dysfunction with subsequent difficulty in perceiving speech in noisy environments. It is therefore suggested that individuals with OAG, who report hearing difficultly, be subsequently assessed to explore the impact and extent of this difficulty in relation to challenging auditory environments. This process will ensure a more comprehensive assessment is undertaken which will lead to more direct and appropriate treatment options offered. In regard to the visual findings, OAG individuals with impaired speed and motion discrimination may require interventional strategies to improve driving/pedestrian safety and navigation, an area for future research. Overall, further research to explore other specialised auditory functions in glaucoma patients would be warranted along with an investigation into how having both auditory and visual impairment impacts upon communication and quality of life.