ORCID Profile
0000-0002-8800-7834
Current Organisations
Centre for Eye Research Australia
,
University of Melbourne
Does something not look right? The information on this page has been harvested from data sources that may not be up to date. We continue to work with information providers to improve coverage and quality. To report an issue, use the Feedback Form.
Publisher: Cold Spring Harbor Laboratory
Date: 29-01-2021
DOI: 10.1101/2021.01.29.428701
Abstract: Retinal neovascularization, or pathological angiogenesis in the retina, is a leading cause of blindness in developed countries. Transforming growth factor-β-activated kinase 1 (TAK1) is a mitogen-activated protein kinase kinase kinase (MAPKKK) activated by TGF-β1 and other pro-inflammatory cytokines. TAK1 is also a key mediator of inflammation, innate immune responses, apoptosis and tissue homeostasis and plays an important role in physiological angiogenesis. Its role in pathological angiogenesis, particularly in retinal neovascularization, remains unclear. We investigated the regulatory role of TAK1 in pathological angiogenesis in the retina. Transcriptome analysis of human retina featuring retinal neovascularization revealed enrichment of known TAK1-mediated signaling pathways. Selective inhibition of TAK1 activation by 5Z-7-oxozeaenol attenuated aberrant retinal angiogenesis in rats following oxygen-induced retinopathy. Transcriptome profiling revealed that TAK1 activation in human microvascular endothelial cells under TNFα stimulation led to increase the gene expression related to cytokines and leukocyte-endothelial interaction, mainly through nuclear factor kappa B (NFκB) signaling pathways. These results reveal that inhibition of TAK1 signaling may have therapeutic value for the treatment of pathological angiogenesis in the retina.
Publisher: Elsevier BV
Date: 2012
Publisher: Wiley
Date: 29-06-2017
DOI: 10.1111/AOS.13386
Publisher: Wiley
Date: 04-2023
DOI: 10.1002/DAD2.12421
Abstract: We performed a systematic review and meta‐analysis of the association between retinal imaging parameters and Alzheimer's disease (AD). PubMed, EMBASE, and Scopus were systematically searched for prospective and observational studies. Included studies had AD case definition based on brain amyloid beta (Aβ) status. Study quality assessment was performed. Random‐effects meta‐analyses of standardized mean difference, correlation, and diagnostic accuracy were conducted. Thirty‐eight studies were included. There was weak evidence of peripapillary retinal nerve fiber layer thinning on optical coherence tomography (OCT) ( p = 0.14, 11 studies, n = 828), increased foveal avascular zone area on OCT‐angiography ( p = 0.18, four studies, n = 207), and reduced arteriole and venule vessel fractal dimension on fundus photography ( p 0.001 and p = 0.08, respectively, three studies, n = 297) among AD cases. Retinal imaging parameters appear to be associated with AD. Small study sizes and heterogeneity in imaging methods and reporting make it difficult to determine utility of these changes as AD biomarkers. We performed a systematic review on retinal imaging and Alzheimer's disease (AD). We only included studies in which cases were based on brain amyloid beta status. Several retinal biomarkers were associated with AD but clinical utility is uncertain. Studies should focus on biomarker‐defined AD and use standardized imaging methods.
Publisher: Public Library of Science (PLoS)
Date: 04-04-2017
Publisher: Wiley
Date: 09-2018
DOI: 10.1111/CEO.13377
Publisher: Informa UK Limited
Date: 14-11-2018
Publisher: Informa UK Limited
Date: 27-03-2017
DOI: 10.1080/09286586.2017.1296166
Abstract: To present the recruitment and testing methodology of the National Eye Health Survey (NEHS), a population-based study that aimed to determine the prevalence and causes of vision impairment and blindness in Australia. Non-Indigenous Australians aged 50 years and older and Indigenous Australians aged 40 years and older were recruited using a door-to-door approach from 30 randomly selected geographical areas, stratified by remoteness. Participants underwent a vision examination, anterior segment assessment, intraocular pressure testing, perimetry, and fundus photography. In total, recruiters approached 23,235 residences, and 11,883 residents were successfully contacted (51.1%). Of these, 6760 (56.9%) were deemed eligible and 5764 agreed to participate (positive response rate = 85.3%). Of those who agreed, 4836 residents attended the examination (4836/6760 = 71.5%). This included 1738 Indigenous Australians (41.1% male) aged 40-92 years (mean ± standard deviation = 55.0 ± 10.0 years) and 3098 non-Indigenous Australians (46.4% male), aged 50-98 years (mean ± standard deviation = 66.6 ± 9.7 years). The NEHS achieved an excellent positive response rate, and the data collected from 4836 Australians will provide the first population-based national estimate of the prevalence of vision impairment and blindness. This data will guide future economic analysis, policy formulation, and eye health service delivery in Australia.
Publisher: Elsevier BV
Date: 04-2022
DOI: 10.1016/J.ORET.2021.11.004
Abstract: To examine the association between hyporeflective cores within drusen (HCD) and disease progression in age-related macular degeneration (AMD) and with visual function. Longitudinal observational study. Two hundred and eighty eyes from 140 participants with bilateral large drusen, without late AMD. Multimodal imaging and microperimetry were performed at baseline and subsequently every 6 months for up to 3 years. Baseline OCT scans were graded for the presence of HCD and used to calculate drusen volume. The total area of the drusenoid lesions containing hyporeflective cores (HCD extent) on color fundus photographs (CFPs) was calculated. CFPs were also graded for the presence of pigmentary abnormalities. The association between HCD extent with progression to late AMD (including OCT signs of atrophy) and visual sensitivity measured using microperimetry at baseline and its rate of change over time was evaluated with and without adjustment for confounders of drusen volume, pigmentary abnormalities, and age. Time to develop late AMD and visual sensitivity. Twenty (7%) eyes from 12 (9%) in iduals were found to have HCD at baseline, which was associated with a nonsignificantly increased rate of progression to late AMD (unadjusted P = 0.050). HCD extent was significantly associated with an increased rate of progression to late AMD (unadjusted P = 0.034) and lower visual sensitivity at baseline (unadjusted P < 0.001). However, these associations were no longer significant (P ≥ 0.264 for both) after adjusting for known risk factors for AMD progression. HCD extent was also not associated with a faster rate of visual sensitivity decline before the development of late AMD, with or without adjustment (P ≥ 0.674 for both). Increasing age and larger drusen volume were associated with HCD extent (P ≤ 0.041). In a cohort with bilateral large drusen, HCD presence and extent were not independently associated with an increased rate of progression to late AMD over 3 years, nor with lower visual sensitivity or an increased rate of visual sensitivity decline before the development of late AMD, after adjusting for known risk factors for disease progression.
Publisher: Wiley
Date: 28-07-2020
DOI: 10.1111/CEO.13818
Publisher: Wiley
Date: 17-08-2020
DOI: 10.1111/CEO.13819
Publisher: American Medical Association (AMA)
Date: 23-03-2005
Publisher: Elsevier BV
Date: 12-2017
DOI: 10.1016/J.OPHTHA.2017.06.001
Abstract: To conduct a nationwide survey on the prevalence and causes of vision loss in Indigenous and non-Indigenous Australians. Nationwide, cross-sectional, population-based survey. Indigenous Australians aged 40 years or older and non-Indigenous Australians aged 50 years and older. Multistage random-cluster s ling was used to select 3098 non-Indigenous Australians and 1738 Indigenous Australians from 30 sites across 5 remoteness strata (response rate of 71.5%). Sociodemographic and health data were collected using an interviewer-administered questionnaire. Trained examiners conducted standardized eye examinations, including visual acuity, perimetry, slit-l examination, intraocular pressure, and fundus photography. The prevalence and main causes of bilateral presenting vision loss (visual acuity <6/12 in the better eye) were determined, and risk factors were identified. Prevalence and main causes of vision loss. The overall prevalence of vision loss in Australia was 6.6% (95% confidence interval [CI], 5.4-7.8). The prevalence of vision loss was 11.2% (95% CI, 9.5-13.1) in Indigenous Australians and 6.5% (95% CI, 5.3-7.9) in non-Indigenous Australians. Vision loss was 2.8 times more prevalent in Indigenous Australians than in non-Indigenous Australians after age and gender adjustment (17.7%, 95% CI, 14.5-21.0 vs. 6.4%, 95% CI, 5.2-7.6, P < 0.001). In non-Indigenous Australians, the leading causes of vision loss were uncorrected refractive error (61.3%), cataract (13.2%), and age-related macular degeneration (10.3%). In Indigenous Australians, the leading causes of vision loss were uncorrected refractive error (60.8%), cataract (20.1%), and diabetic retinopathy (5.2%). In non-Indigenous Australians, increasing age (odds ratio [OR], 1.72 per decade) and having not had an eye examination within the past year (OR, 1.61) were risk factors for vision loss. Risk factors in Indigenous Australians included older age (OR, 1.61 per decade), remoteness (OR, 2.02), gender (OR, 0.60 for men), and diabetes in combination with never having had an eye examination (OR, 14.47). Vision loss is more prevalent in Indigenous Australians than in non-Indigenous Australians, highlighting that improvements in eye healthcare in Indigenous communities are required. The leading causes of vision loss were uncorrected refractive error and cataract, which are readily treatable. Other countries with Indigenous communities may benefit from conducting similar surveys of Indigenous and non-Indigenous populations.
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 04-2007
DOI: 10.1167/IOVS.06-0531
Abstract: To investigate the inheritance of susceptibility to oxygen-induced retinopathy in the rat with the use of formal backcross analysis. Neonatal offspring of inbred albino Fischer 344 (F344) and pigmented Dark Agouti (DA) crosses and F1xF344 and F1xDA backcrosses were exposed to alternating 24-hour cycles of hyperoxia (80% oxygen in air) and normoxia (21% oxygen in air) for 14 days. Retinal avascular area was analyzed by staining with Griffonia simplicifolia isolectin B4, a marker of vascular endothelial cells. Expression of erythropoietin (EPO) mRNA in retinas was quantified by real-time reverse-transcription polymerase chain reaction. Oxygen-exposed offspring of two F344xDA F1 crosses showed retinal avascular areas and ocular and coat pigmentation that were similar to those of the DA strain. Mean retinal avascular area was 73%. Offspring of two DAxF1 backcrosses were similar to F344xDA F1 pups, with pigmented eyes and coats and a mean retinal avascular area of 76%. In contrast, offspring of two F344xF1 backcrosses exhibited a range of eye and coat pigmentation. Mean retinal avascular area of pigmented offspring of the F344xF1 backcrosses was 71% (P 0.05 compared with F344 rats). The normalized expression of EPO mRNA was 3.01 +/- 1.00 in retinas from pigmented F344xF1 backcross offspring compared with 1.31 +/- 0.69 for albino offspring (P < 0.001). Segregation of the susceptibility trait to oxygen-induced retinopathy in the DA and F344 rat strains is associated with pigmentation and erythropoietin expression and can be modeled using an autosomal dominant pattern of inheritance.
Publisher: Elsevier BV
Date: 05-2016
DOI: 10.1016/J.EXER.2016.03.001
Abstract: It has been established that beyond middle age, mice are slower to recover inner retinal function following an acute intraocular pressure (IOP) injury. While 3 month old animals exhibit near-complete recovery 1 week following injury, 12 and 18 month old animals demonstrate prolonged inner retinal dysfunction. In this study we aim to determine whether age-related differences in functional recovery of the inner retina are due to differences in retinal ganglion cell (RGC) axonal transport. C57BL/6J mice at 3 (n = 8) and 18 months (n = 8) of age were used. At day 0, right eyes were cannulated and the IOP was maintained at 50 mmHg for 30 min. At day 5, mice received bilateral intravitreal injections of choleratoxin subunit B (CTB) conjugated to Alexafluor 488. At day 7, mice were euthanized and tissue was collected. Axonal transport of CTB was quantified in retinas and superior colliculi (SC) using fluorescent microscopy. In response to IOP elevation, the overall degree of axonal transport was comparable between young and old mice. Furthermore, no differences in axonal transport were detected between control eyes and injured in mice at any age. In conclusion, impaired recovery of inner retinal function 1 week following acute IOP injury in old mice is not associated with changes in active axonal transport in RGCs at this time.
Publisher: Springer Science and Business Media LLC
Date: 21-07-2013
DOI: 10.1038/NN.3469
Publisher: Informa UK Limited
Date: 09-2008
DOI: 10.1111/J.1444-0938.2008.00305.X
Abstract: We review the fundamental changes that are now occurring to the management of neovascular (wet) age-related macular degeneration (AMD). An improved understanding of the role of vascular endothelial growth factor (VEGF) in the genesis of choroidal neovascular membranes has led to the creation and use of intravitreous anti-VEGF antibodies (bevacizumab and ranubizumab) and an aptamer (pegaptanib) in the treatment of these lesions. These new intravitreous injections for AMD have supplanted previous treatments in both efficacy and safety and are now the standard of care for neovascular AMD. We discuss the biochemistry of the anti-VEGF pathway. While there is substantial evidence for the use of ranubizumab and pegaptanib, the intravitreous administration of bevacizumab has not been tested in randomised controlled clinical trials. We review the evidence base for all three agents and the patho-physiological basis for adverse reactions to intravitreous VEGF blockade.
Publisher: Informa UK Limited
Date: 02-06-2022
Publisher: Asia Pacific Academy of Ophthalmology
Date: 2017
DOI: 10.22608/APO.2016187
Publisher: Elsevier BV
Date: 2021
Publisher: Wiley
Date: 30-01-2017
DOI: 10.1111/CEO.12892
Abstract: This paper presents the s ling methodology of the National Eye Health Survey that aimed to determine the prevalence of vision impairment and blindness in Australia. The National Eye Health Survey is a cross-sectional population-based survey. Indigenous Australians aged 40 years and older and non-Indigenous Australians aged 50 years and older residing in all levels of geographic remoteness in Australia. Using multistage, random-cluster s ling, 30 geographic areas were selected to provide s les of 3000 non-Indigenous Australians and 1400 Indigenous Australians. S ling involved (i) selecting Statistical Area- Level 2 sites, stratified by remoteness (ii) selecting Statistical Area- Level 1 sites within Statistical Area- Level 2 sites to provide targeted s les and (iii) grouping of contiguous Statistical Area- Level 1 sites or replacing Statistical Area- Level 1 sites to provide sufficient s les. The main outcome measures involved Sites sites selected and participants s led in the survey. Thirty sites were generated, including 12 Major City sites, 6 Inner Regional sites, 6 Outer Regional sites, 4 Remote sites and 2 Very Remote sites. Three thousand ninety-eight non-Indigenous participants and 1738 Indigenous participants were recruited. Selection of Statistical Area- Level 1 site overestimated the number of eligible residents in all sites. About 20% (6/30) of Statistical Area- Level 1 sites were situated in non-residential bushland, and 26.67% (8/30) of Statistical Area- Level 1 populations had low eligibility or accessibility, requiring replacement. Representative s les of Indigenous and non-Indigenous Australians were selected, recruited and tested, providing the first national data on the prevalence of vision impairment and blindness in Australia.
Publisher: Springer Science and Business Media LLC
Date: 06-01-2017
DOI: 10.1038/EYE.2016.281
Publisher: Elsevier BV
Date: 05-2017
DOI: 10.1016/J.PHARMTHERA.2017.01.003
Abstract: Diabetic retinopathy (DR), a chronic and progressive complication of diabetes mellitus, is a sight-threatening disease characterized in the early stages by neuronal and vascular dysfunction in the retina, and later by neovascularization that further damages vision. A major contributor to the pathology is excess production of vascular endothelial growth factor (VEGF), a growth factor that induces formation of new blood vessels and increases permeability of existing vessels. Despite the recent availability of effective treatments for the disease, including laser photocoagulation and therapeutic VEGF antibodies, DR remains a significant cause of vision loss worldwide. Existing anti-VEGF agents, though generally effective, are limited by their short therapeutic half-lives, necessitating frequent intravitreal injections and the risk of attendant adverse events. Management of DR with gene therapies has been proposed for several years, and pre-clinical studies have yielded enticing findings. Gene therapy holds several advantages over conventional treatments for DR, such as a longer duration of therapeutic effect, simpler administration, the ability to intervene at an earlier stage of the disease, and potentially fewer side-effects. In this review, we summarize the current understanding of the pathophysiology of DR and provide an overview of research into DR gene therapies. We also examine current barriers to the clinical application of gene therapy for DR and evaluate future prospects for this approach.
Publisher: Rockefeller University Press
Date: 07-12-2015
Abstract: The mechanisms regulating differentiation of oligodendrocyte (OLG) progenitor cells (OPCs) into mature OLGs are key to understanding myelination and remyelination. Signaling via the retinoid X receptor γ (RXR-γ) has been shown to be a positive regulator of OPC differentiation. However, the nuclear receptor (NR) binding partner of RXR-γ has not been established. In this study we show that RXR-γ binds to several NRs in OPCs and OLGs, one of which is vitamin D receptor (VDR). Using pharmacological and knockdown approaches we show that RXR–VDR signaling induces OPC differentiation and that VDR agonist vitamin D enhances OPC differentiation. We also show expression of VDR in OLG lineage cells in multiple sclerosis. Our data reveal a role for vitamin D in the regenerative component of demyelinating disease and identify a new target for remyelination medicines.
Publisher: Wiley
Date: 09-09-2016
DOI: 10.1111/ACEL.12512
Publisher: Elsevier BV
Date: 09-2017
DOI: 10.1016/J.EXER.2017.07.015
Abstract: The aim of the current work was to test whether increased intake of dietary fat and sucrose in mice modifies the response of retinal ganglion cells (RGCs) of the optic nerve to injury, and whether any effects of diet are influenced by physical activity levels. C57BL/6J mice were given a high-fat high-sucrose (HFS) diet for 7 weeks, with or without exposure to regular exercise by swimming (60 min/day, 5 days/week). Injury to RGCs was subsequently induced by acute elevation of intraocular pressure (IOP) and retinas were assessed for function and structure. We report that mice on a HFS diet had similar body mass and blood glucose levels compared to mice on a control diet but suffered a 30% greater loss of RGC function following injury, as measured in vivo with the electroretinogram. RGC dysfunction in retinas from mice on the HFS diet was accompanied by activation of retinal macroglia but was not associated with neuronal cell loss. Exercising mice by swimming did not prevent HFS-induced RGC dysfunction in response to injury. This study shows for the first time that a short term increase in dietary fat and sucrose enhances the vulnerability of RGCs to dysfunction and cell stress after an acute injury, and that this is independent of obesity or hyperglycemia. Furthermore, our results suggest that detrimental effects of diet predominate over protective effects of exercise.
Publisher: Portland Press Ltd.
Date: 18-03-2016
DOI: 10.1042/CS20150103
Abstract: Corneal neovascularization, the growth of new blood vessels in the cornea, is a leading cause of vision impairment after corneal injury. Neovascularization typically occurs in response to corneal injury such as that caused by infection, physical trauma, chemical burns or in the setting of corneal transplant rejection. The NADPH oxidase enzyme complex is involved in cell signalling for wound-healing angiogenesis, but its role in corneal neovascularization has not been studied. We have now analysed the role of the Nox2 isoform of NADPH oxidase in corneal neovascularization in mice following chemical injury. C57BL/6 mice aged 8–14 weeks were cauterized with an applicator coated with 75% silver nitrate and 25% potassium nitrate for 8 s. Neovascularization extending radially from limbal vessels was observed in corneal whole-mounts from cauterized wild type mice and CD31+ vessels were identified in cauterized corneal sections at day 7. In contrast, in Nox2 knockout (Nox2 KO) mice vascular endothelial growth factor-A (Vegf-A), Flt1 mRNA expression, and the extent of corneal neovascularization were all markedly reduced compared with their wild type controls. The accumulation of Iba-1+ microglia and macrophages in the cornea was significantly less in Nox2 KO than in wild type mice. In conclusion, we have demonstrated that Nox2 is implicated in the inflammatory and neovascular response to corneal chemical injury in mice and clearly VEGF is a mediator of this effect. This work raises the possibility that therapies targeting Nox2 may have potential for suppressing corneal neovascularization and inflammation in humans.
Publisher: Wiley
Date: 18-06-2021
DOI: 10.1111/DME.14611
Abstract: To examine psychosocial and behavioural impacts of the novel coronavirus disease 2019 (COVID‐19) pandemic and lockdown restrictions among adults with type 2 diabetes. Participants enrolled in the PRogrEssion of DIabetic ComplicaTions (PREDICT) cohort study in Melbourne, Australia ( n = 489 with a baseline assessment pre‐2020) were invited to complete a phone/online follow‐up assessment in mid‐2020 (i.e., amidst COVID‐19 lockdown restrictions). Repeated assessments that were compared with pre‐COVID‐19 baseline levels included anxiety symptoms (7‐item Generalised Anxiety Disorder scale [GAD‐7]), depressive symptoms (8‐item Patient Health Questionnaire [PHQ‐8]), diabetes distress (Problem Areas in Diabetes scale [PAID]), physical activity/sedentary behaviour, alcohol consumption and diabetes self‐management behaviours. Additional once‐off measures at follow‐up included COVID‐19‐specific worry, quality of life (QoL), and healthcare appointment changes (telehealth engagement and appointment cancellations/avoidance). Among 470 respondents (96% aged 66 ± 9 years, 69% men), at least ‘moderate’ worry about COVID‐19 infection was reported by 31%, and 29%–73% reported negative impacts on QoL dimensions (greatest for: leisure activities, feelings about the future, emotional well‐being). Younger participants reported more negative impacts ( p 0.05). Overall, anxiety/depressive symptoms were similar at follow‐up compared with pre‐COVID‐19, but diabetes distress reduced ( p 0.001). Worse trajectories of anxiety/depressive symptoms were observed among those who reported COVID‐19‐specific worry or negative QoL impacts ( p 0.05). Physical activity trended lower (~10%), but sitting time, alcohol consumption and glucose‐monitoring frequency remained unchanged. 73% of participants used telehealth, but 43% cancelled a healthcare appointment and 39% avoided new appointments despite perceived need. COVID‐19 lockdown restrictions negatively impacted QoL, some behavioural risk factors and healthcare utilisation in adults with type 2 diabetes. However, generalised anxiety and depressive symptoms remained relatively stable.
Publisher: Wiley
Date: 11-07-2012
DOI: 10.1111/J.1442-9071.2012.02820.X
Abstract: The aim of this study is to examine the relationship between sociodemographic factors and utilization of eye care services in patients presenting in acute angle-closure (AAC). A hospital-based retrospective, case-control study. Fifty-five patients consecutively presenting to the emergency department of the Royal Victorian Eye and Ear Hospital with AAC (cases), and 43 patients consecutively referred to the outpatient department for prophylactic laser peripheral iridotomy (controls) over a 3-year period. Standardized telephone questionnaires. Comparisons were made for sociodemographic factors, utilization of eye care services and provision of information on glaucoma and premonitory symptoms of AAC. No significant differences across a range of socioeconomic and demographic factors were found. Fewer cases reported having attended an eye care professional ever (P = 0.02), or in the 12 months preceding their acute hospital attendance (P = 0.002), and had less awareness of angle closure glaucoma (P = 0.001). Logistic regression modelling demonstrated premonitory symptoms of AAC (odds ratio 3.96, [95% confidence interval 1.52-10.32], P < 0.001) and a period of greater than 12 months since the last eye examination (odds ratio 3.89, [95% confidence interval 1.64-9.21]) were significantly associated with the risk of AAC. No significant differences in socioeconomic or demographic parameters between cases and controls were identified. Control subjects had a history of more frequent and recent access to eye care services than cases. The finding that more than one-third of patients presenting with AAC had consulted an eye care provider in the preceding year suggests that a significant proportion of in iduals at risk of AAC remain undetected.
Publisher: Wiley
Date: 2016
DOI: 10.1111/CEO.12697
Publisher: Springer Science and Business Media LLC
Date: 30-01-2018
DOI: 10.1007/S00347-018-0649-5
Abstract: Visual recovery is an established but poorly studied phenomenon in glaucoma. To provide insights into functional recovery of retinal ganglion cells (RGCs) with a view to providing information on the development of forms of treatment that improve RGC function after injury. A model of recoverable RGC function in the mouse eye, induced by short-term elevation of intraocular pressure (IOP). The RGCs manifest near complete functional recovery after a prolonged period of dysfunction following acute IOP elevation. Increasing age and a high fat diet were subsequently found to impair recovery, whereas exercise substantially improved recovery such that older mice recovered in a similar way to young mice. Injured RGCs have the capacity to restore function after periods of functional impairment. Therapies that specifically target injured RGCs and enhance their capacity to recover function may provide a new approach for treating glaucoma.
Publisher: BMJ
Date: 16-11-2007
Publisher: Elsevier BV
Date: 09-2023
Publisher: Springer Science and Business Media LLC
Date: 18-08-2017
DOI: 10.1038/S41598-017-09421-9
Abstract: We assessed the validity and reliability of self-report of eye disease in participants with unilateral vision loss (presenting visual acuity worse than 6/12 in the worse eye and equal to or better than 6/12 in the better eye) or bilateral vision loss (presenting visual acuity worse than 6/12 in the better eye) in Australia’s National Eye Health Survey. In total, 1738 Indigenous Australians and 3098 non-Indigenous Australians were s led from 30 sites. Participants underwent a questionnaire and self-reported their eye disease histories. A clinical examination identified whether participants had cataract, age-related macular degeneration, diabetic retinopathy and glaucoma. For those identified as having unilateral or bilateral vision loss (438 Indigenous Australians and 709 non-Indigenous Australians), self-reports were compared with examination results using validity and reliability measures. Reliability was poor for all four diseases (Kappa 0.06 to 0.37). Measures of validity of self-report were variable, with generally high specificities (93.7% to 99.2%) in all diseases except for cataract (63.9 to 73.1%) and low sensitivities for all diseases (7.6% in Indigenous Australians with diabetic retinopathy to 44.1% of non-Indigenous Australians with cataract). This study suggests that self-report is an unreliable population-based research tool for identifying eye disease in those with vision loss.
Publisher: MDPI AG
Date: 31-10-2023
Publisher: American Medical Association (AMA)
Date: 11-2017
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 29-10-2013
Abstract: The proliferation of new blood vessels in the retina is a leading cause of vision impairment. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (Nox) is involved in cell signaling for ischemia-induced angiogenesis, but its role in retinal neovascularization is unclear. We have analyzed the dependence of retinal neovascularization on the Nox2 isoform in oxygen-induced retinopathy (OIR) in mice. Neonatal C57BL/6 mice aged 7 days (P7) were placed in a hyperoxic chamber (75% O2) for 5 days, followed by 5 days of exposure to room air. Eyes were harvested on P8 and P17 for the quantification of retinal vaso-obliteration and neovascularization, respectively. The retinal expression of Nox2 and VEGF-A were measured by RT-PCR, while superoxide generation was detected by in situ dihydroethidium (DHE) staining of fresh frozen sections. In wild type (WT) mice, OIR was characterized by central retinal vaso-obliteration at P8 and neovascularization at P17, which was associated with increases in Nox2 and VEGF-A gene expression, superoxide generation, and accumulation of Iba-1 positive cells in the inner retina. In contrast, Nox2 knockout mice exhibited markedly less retinal neovascularization and VEGF-A mRNA expression at P17, despite showing comparable vaso-obliteration at P8. These changes were accompanied by reductions in DHE fluorescence and Iba-1-positive cell accumulation in the hypoxic retina. The Nox2-generated reactive oxygen species (ROS) facilitate the retinal expression of VEGF-A and neovascularization in this mouse model of OIR. Therapies targeting Nox2 could be of value to reduce aberrant retinal neovascularization in retinopathy of prematurity, diabetes, and other disease processes driven by VEGF.
Publisher: The Company of Biologists
Date: 15-06-2013
DOI: 10.1242/DEV.092262
Abstract: The growing burden of the rapidly ageing global population has reinvigorated interest in the science of ageing and rejuvenation. Among organ systems, rejuvenation of the central nervous system (CNS) is arguably the most complex and challenging of tasks owing, among other things, to its startling structural and functional complexity and its restricted capacity for repair. Thus, the prospect of meaningful rejuvenation of the CNS has seemed an impossible goal however, advances in stem cell science are beginning to challenge this assumption. This Review outlines these advances with a focus on ageing and rejuvenation of key endogenous stem and progenitor cell compartments in the CNS. Insights gleaned from studies of model organisms, chiefly rodents, will be considered in parallel with human studies.
Publisher: AMPCo
Date: 05-2017
DOI: 10.5694/MJA16.00989
Abstract: To determine adherence to NHMRC eye examination guidelines for Indigenous and non-Indigenous Australian people with diabetes. Cross-sectional survey using multistage, random cluster s ling. Thirty randomly selected geographic sites in the five mainland Australian states and the Northern Territory, stratified by remoteness. 1738 Indigenous Australians aged 40-92 years and 3098 non-Indigenous Australians aged 50-98 years were recruited and examined between March 2015 and April 2016 according to a standardised protocol that included a questionnaire (administered by an interviewer) and a series of standard eye tests. Adherence rates to NHMRC eye examination guidelines factors influencing adherence. Adherence to screening recommendations was significantly greater among non-Indigenous Australians (biennial screening 77.5%) than Indigenous Australians (annual screening 52.7% P < 0.001). Greater adherence by non-Indigenous Australians was associated with longer duration of diabetes (adjusted odds ratio [aOR], 1.19 per 5 years P = 0.018), while increasing age was associated with poorer adherence in non-Indigenous Australians (aOR, 0.70 per decade P = 0.011). For Indigenous Australians, residing in inner regional areas (aOR, 1.66 P = 0.007) and being male (aOR, 1.46 P = 0.018) were significant factors positively associated with adherence. More than three-quarters of non-Indigenous Australians with diabetes and more than half of Indigenous Australians with diabetes adhere to the NHMRC eye examination guidelines. The discrepancy between the adherence rates may point to gaps in the provision or uptake of screening services in Indigenous communities, or a lack of awareness of the guidelines. A carefully integrated diabetic retinopathy screening service is needed, particularly in remote areas, to improve adherence rates.
Publisher: Wiley
Date: 19-11-2018
DOI: 10.1111/CEO.13393
Abstract: The prevalence of diabetes and diabetic retinopathy is increasing around the world. Glycaemic control is important in reducing the long-term risk of complications of diabetes, however intensive glycaemic control, particularly in patients with longstanding and poorly controlled diabetes, is associated with the risk of early worsening of diabetic retinopathy and vision loss. We present two clinical cases to illustrate the presentation of early worsening and to highlight a role for intravitreal anti-vascular endothelial growth factor therapies in ameliorating this phenomenon, as well as a review of the current understanding of this phenomenon. We emphasise the importance of identifying in iduals at risk of early worsening of diabetic retinopathy and recommend regular ophthalmological review during the period of intensive glycaemic control to ensure optimal visual outcomes.
Publisher: Wiley
Date: 25-08-2017
DOI: 10.1111/CEO.13031
Abstract: In Australia, knowledge of the epidemiology of retinal vein occlusion remains scarce because of a paucity of recent population-based data. The National Eye Health Survey (2015-2016) provides an up-to-date estimate of the prevalence of retinal vein occlusion in non-Indigenous and Indigenous Australian adults. To determine the prevalence and associations of retinal vein occlusion in a national s le of Indigenous and non-Indigenous Australian adults. Population-based cross-sectional study. A total of 3098 non-Indigenous Australians (aged 50-98 years) and 1738 Indigenous Australians (aged 40-92 years) living in 30 randomly selected sites, stratified by remoteness. Retinal vein occlusions were graded from retinal photographs using standardized protocols and recorded as central retinal vein occlusion or branch retinal vein occlusion. Prevalence of retinal vein occlusion. In the non-Indigenous population, the s ling weight adjusted prevalence of any retinal vein occlusion was 0.96% (95% confidence interval: 0.59, 1.6), with branch retinal vein occlusion observed in 0.72% (95% confidence interval: 0.41, 1.2) and central retinal vein occlusion in 0.24% (95% confidence interval: 0.13, 0.47). Any retinal vein occlusion was found in 0.91% (95% confidence interval: 0.47, 1.7) of Indigenous Australians aged 40 years and over, with branch retinal vein occlusion observed in 0.83% (95% confidence interval: 0.40, 1.7) and central retinal vein occlusion in 0.07% (95% confidence interval: 0.02, 0.32). Older age (odds ratio = 1.64 per 10 years, P = 0.006) and the presence of self-reported diabetes (odds ratio = 3.24, P = 0.006) were associated with any retinal vein occlusion after multivariable adjustments. Retinal vein occlusion was attributed as the cause of monocular vision loss (<6/12) in seven (0.25%) non-Indigenous and six (0.36%) Indigenous participants. These data suggest that retinal vein occlusion is relatively uncommon in the non-Indigenous Australians aged 50 years and over and Indigenous Australians aged 40 years and over. Similar to previous Australian and international reports, the prevalence of retinal vein occlusion rose sharply with age.
Publisher: Elsevier BV
Date: 10-2007
DOI: 10.1016/J.EXER.2007.07.001
Abstract: Recent evidence suggests that retinopathy of prematurity, a potentially blinding condition of premature human neonates, has a genetically-determined component. Different inbred strains of rat exhibit differential susceptibility to oxygen-induced retinopathy (OIR), a well-established experimental model of retinopathy of prematurity. To explore the basis for this differential susceptibility, we quantified the retinal expression of 8 angiogenesis-related genes during early post-natal retinal development in rats with OIR. Inbred Fischer 344 (F344), Dark Agouti (DA) and Sprague Dawley (SPD) rat neonates were exposed to alternating cycles of 80% oxygen in air and normoxia for up to 14 days. After 14 days of cyclic hyperoxic exposure, some rats were exposed to normoxia for a further 4 days. Retinal mRNA for vascular endothelial growth factor (VEGF), VEGF receptor 2 (VEGFR2), pigment epithelium-derived factor (PEDF), angiopoietin-2 (Ang2), Tie2, cyclooxygenase-2 (COX2), insulin-like growth factor-1 (IGF1) and erythropoietin (EPO) were quantified by real-time reverse-transcriptase polymerase chain reaction at different time-points. Time-course analysis showed that expression of mRNA for VEGF, VEGFR2 and Ang2 was significantly greater in OIR-resistant (F344) retinae than in OIR-susceptible (DA) retinae during the first 9 days of cyclic hyperoxia. However, at post-natal days 14 and 18, retinal mRNAs for VEGF, EPO, VEGFR2, Ang2, IGF1, COX2 and PEDF were expressed to a significantly greater extent in OIR-susceptible (DA, SPD) than OIR-resistant (F344) retinae. The VEGF/PEDF ratio was greater in the F344 compared with the DA strain up to day 9, but was higher in the DA than the F344 strain at days 14 and 18. Thus, we found that retinal expression of angiogenesis-related genes was significantly higher in OIR-resistant rats than in OIR-susceptible rats during early retinal development, but the pattern reversed during the proliferative phase of OIR. We conclude that susceptibility to OIR correlates with differential gene expression very early in retinal microvascular development, during periods of cyclic hyperoxic exposure rather than during subsequent sustained hypoxia.
Publisher: Public Library of Science (PLoS)
Date: 03-01-2017
Publisher: Wiley
Date: 09-04-2014
DOI: 10.1111/CEO.12306
Abstract: Physical inactivity and sedentary behaviour have been identified as modifiable risk factors for diabetes. However, little is known of the associations between physical activity, sedentary behaviour and diabetic retinopathy. The development of diabetic retinopathy is associated with longer duration of diabetes, elevated blood pressure and poor glycaemic control. However these factors only explain a proportion of the risk of retinopathy in in iduals with diabetes. Several studies have suggested a protective role for physical activity in diabetic retinopathy. Other work has shown that the time spent watching television is independently associated with abnormal retinal vascular signs. Limitations of the existing studies, such as the absence of objective measures of physical activity, a lack of sedentary behaviour measures, the inclusion of only those with type 1 diabetes and a lack of longitudinal data, make it difficult to draw firm conclusions about the strength of these associations.
Publisher: Wiley
Date: 28-11-2018
DOI: 10.1111/CEO.13435
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 04-2005
DOI: 10.1167/IOVS.04-0708
Abstract: To examine the susceptibilities of different rat strains to oxygen-induced retinopathy, a model of human retinopathy of prematurity. Litters of newborn rats of five inbred strains (Fischer 344 [F344], Dark Agouti [DA], Sprague-Dawley [SD], Wistar-Furth [WF], Lewis [LEW]) and one outbred strain (Hooded Wistar [HW]) were maintained in room air or were exposed to alternating 24-hour cycles of hyperoxia (80% oxygen in air) and normoxia (21% oxygen in air) for 14 days and were killed for analysis, either immediately (postnatal day 14, [P14]) or after 4 days in room air (P18). The fluorophore-conjugated isolectin GS-IB4 was used to label the endothelial cells of wholemounted retinas, and digital images were analyzed for avascular area and for morphologic abnormalities. Exposure to cyclic hyperoxia inhibited retinal vascularization in all strains relative to age-matched room air control animals. Total retinal avascular area at P14 after cyclic hyperoxia varied significantly among strains (P < 0.001). Avascular areas were smallest for the albino F344, WF, and LEW strains larger for the albino SD strain and largest for the pigmented DA and HW strains. Susceptibility to hyperoxic vascular attenuation was associated with ocular pigmentation, but neither with body mass nor with natural variation in litter size. Room air exposure for 4 days after cyclic hyperoxia was also associated with strain-related differences in retinal vascularization and with abnormalities in vascular morphology (P < 0.05). For all strains, the size of the avascular retinal area at P14 was predictive of the severity of morphologic abnormality at P18. Marked and consistent variations in the response of different inbred rat strains to cyclic hyperoxia were observed, suggestive of a genetic component to oxygen-induced retinopathy.
Publisher: Wiley
Date: 18-12-2019
DOI: 10.1111/BPH.14554
Publisher: Informa UK Limited
Date: 13-02-2022
Publisher: Springer Science and Business Media LLC
Date: 19-09-2009
DOI: 10.1007/S10633-009-9196-3
Abstract: Rodent models of oxygen-induced retinopathy (OIR) provide important insights into the pathogenesis of human retinopathy of prematurity. Herein, we present an overview of our work with rat OIR to date. We have identified marked and consistent variations in susceptibility to OIR amongst different inbred rat strains and provide strong evidence for a genetic determinant of susceptibility to OIR. Furthermore, we have characterised differences in retinal angiogenic factor gene expression amongst different inbred rat strains exposed to cyclic hyperoxia. A key determinant of susceptibility to OIR appears to be the extent to which pro-angiogenic factor genes, such as vascular endothelial growth factor and erythropoietin, are expressed during the period of hyperoxic exposure. Those strains in which expression is relatively well maintained are less susceptible to retinopathy than are those in which expression is reduced. In addition, we identify an association between ocular pigmentation and OIR susceptibility.
Publisher: AMPCo
Date: 09-2017
DOI: 10.5694/MJA17.00057
Abstract: To determine cataract surgery coverage rates for Indigenous and non-Indigenous Australians. National cross-sectional population-based survey. Thirty randomly selected Australian geographic sites, stratified by remoteness. 3098 non-Indigenous Australians aged 50 years or more and 1738 Indigenous Australians aged 40 years or more, recruited and examined in the National Eye Health Survey (NEHS) between March 2015 and April 2016. Participants underwent an interviewer-administered questionnaire that collected socio-demographic information and past ocular care history, including cataract surgery. For those with visual acuity worse than 6/12, anterior segment photography and slit l examinations were conducted. Cataract surgery coverage rates according to WHO and NEHS definitions associated risk factors. Cataract surgery coverage rates calculated with the NEHS definition 1 of vision impairment (visual acuity worse than 6/12) were lower for Indigenous than non-Indigenous participants (58.5% v 88.0% odds ratio [OR], 0.32 P < 0.001). According to the World Health Organization definition (eligibility criterion: best-corrected visual acuity worse than 6/18), coverage rates were 92.5% and 98.9% for Indigenous and non-Indigenous Australians respectively. Greater age was significantly associated with higher cataract surgery coverage in Indigenous (OR, 1.41 per 10 years P = 0.048) and non-Indigenous Australians (OR, 1.58 per 10 years P = 0.004). The cataract surgery coverage rate was higher for non-Indigenous than Indigenous Australians, indicating the need to improve cataract surgery services for Indigenous Australians. The WHO definition of the coverage rate may overestimate the cataract surgery coverage rate in developed nations and should be applied with caution.
Publisher: Elsevier BV
Date: 09-2017
Publisher: Informa UK Limited
Date: 20-04-2023
Publisher: Wiley
Date: 11-09-2020
DOI: 10.1111/CEO.13844
Publisher: Wiley
Date: 09-08-2017
DOI: 10.1111/CEO.13003
Abstract: Australia is the only developed country to still have pockets of endemic trachoma. The research provides up-to-date, population-based prevalence data of later complications of trachoma amongst a national s le of Indigenous adults. To report the prevalence of trachomatous trichiasis (TT) in Indigenous Australians aged 40 years and older. Population-based cross-sectional study. A total of 1738 (41% male) Indigenous Australians aged 40 years or older, living amongst 30 randomly selected Australian sites, stratified by remoteness. Anterior segment examination was performed and trachoma grading for the presence of TT and corneal opacification (CO) was conducted using the WHO (WHO) simplified grading system. Prevalence of TT. A total of three (0.17%) participants had TT, and there were no confirmed cases of trachomatous CO in the NEHS. All three participants with TT were female and aged 40 years or older. Although they had likely spent their childhoods in more remote areas, two of the three confirmed cases resided in an urban and outer regional area at the time of their examinations. Our data are in line with ongoing national trachoma surveillance reports that suggest the prevalence of late sequences of trachoma appear to be decreasing in Australia.
Publisher: Elsevier BV
Date: 07-2018
DOI: 10.1016/J.PRETEYERES.2018.04.001
Abstract: Retinal ganglion cell (RGC) degeneration causes vision loss in patients with glaucoma, and this has been generally considered to be irreversible due to RGC death. We question this assertion and summarise accumulating evidence that points to visual function improving in glaucoma patients with treatment, particularly in the early stages of disease. We propose that prior to death, RGCs enter periods of dysfunction but can recover with relief of RGC stress. We first summarise the clinical evidence for vision improvement in glaucoma and then detail our experimental work that points to the underlying processes that underpin clinical improvement. We show that functional recovery can occur following a prolonged course of RGC dysfunction and demonstrate how the capacity for recovery can be modified. Detecting RGC dysfunction and augmenting recovery of such 'comatosed' RGCs holds clinical potential to improve early detection of glaucoma and improve visual function.
Publisher: Wiley
Date: 19-12-2016
DOI: 10.1111/CEO.12872
Abstract: Interest in reliable biomarkers of Alzheimer disease, the leading cause of dementia, has been fuelled by challenges in diagnosing the disease and monitoring disease progression as well as the response to therapy. A range of ocular manifestations of Alzheimer disease, including retinal and lens amyloid-beta accumulation, retinal nerve fiber layer loss, and retinal vascular changes, have been proposed as potential biomarkers of the disease. Herein, we examine the evidence regarding the potential value of these ocular biomarkers of Alzheimer disease.
Publisher: Elsevier BV
Date: 07-2017
DOI: 10.1016/J.OPHTHA.2017.02.004
Abstract: To determine the prevalence of and factors associated with diabetic retinopathy (DR) among non-Indigenous and Indigenous Australian adults with self-reported diabetes. Population-based cross-sectional study. Non-Indigenous Australians (50-98 years of age) and Indigenous Australians (40-92 years of age) with known diabetes. Diabetes was determined based on self-report of previous diagnosis of the disease. Nonmydriatic fundus photographs were obtained of each eye and graded according to the modified Airlie House classification system. Any DR, vision-threatening DR (VTDR), treatment coverage rates (proportion of participants with proliferative DR [PDR], clinically significant macular edema [CSME], or both who had evidence of retinal scatter and focal laser treatment). Four hundred thirty-one non-Indigenous Australians (13.9%) and 645 Indigenous Australians (37.1%) self-reported diabetes, of whom 93% (1004/1076) had retinal images that were gradable for DR. The s ling weight-adjusted prevalence of any DR and VTDR among non-Indigenous adults with self-reported diabetes was 28.5% (95% confidence interval [CI], 22.6-35.3) and 4.5% (95% CI, 2.6-7.9), respectively. Among adults 40 years of age and older, the s ling weight-adjusted prevalence of any DR and VTDR was 39.4% (95% CI, 33.1-46.1) and 9.5% (95% CI, 6.8-13.1), respectively. Longer diabetes duration was associated significantly with VTDR in the Indigenous Australian population (odds ratio [OR], 1.08 per 1-year increase P = 0.005) and non-Indigenous Australian population (OR, 1.05 per 1-year increase P = 0.03). The treatment coverage of PDR and CSME was 75% (56/75) in Indigenous Australians and 79% (15/19) in non-Indigenous Australians. Diabetic retinopathy was attributed as the main cause of vision loss (<6/12 in the better eye) in 9% and 19% of non-Indigenous and Indigenous Australian adults with known diabetes, respectively. Three quarters of non-Indigenous and Indigenous Australian adults with PDR or CSME have received laser treatment. The prevalence of VTDR in Indigenous and non-Indigenous Australians in the present study was lower than that found in previous population-based reports, nevertheless, approximately 1 in 10 Indigenous adults with known diabetes experience VTDR. This highlights that intensified prevention strategies are required to delay or prevent avoidable vision loss resulting from DR in Indigenous Australian communities.
Publisher: Elsevier BV
Date: 09-2020
No related grants have been discovered for Peter van Wijngaarden.