Ophthalmology (Eye & Ear Hospital) - Research Publications
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ItemFlicker Light-Induced Retinal Vasodilation in Diabetes and Diabetic Retinopathy(AMER DIABETES ASSOC, 2009-11)OBJECTIVE: Flicker light-induced retinal vasodilation may reflect endothelial function in the retinal circulation. We investigated flicker light-induced vasodilation in individuals with diabetes and diabetic retinopathy. RESEARCH DESIGN AND METHODS: Participants consisted of 224 individuals with diabetes and 103 nondiabetic control subjects. Flicker light-induced retinal vasodilation (percentage increase over baseline diameter) was measured using the Dynamic Vessel Analyzer. Diabetic retinopathy was graded from retinal photographs. RESULTS: Mean +/- SD age was 56.5 +/- 11.8 years for those with diabetes and 48.0 +/- 16.3 years for control subjects. Mean arteriolar and venular dilation after flicker light stimulation were reduced in participants with diabetes compared with those in control subjects (1.43 +/- 2.10 vs. 3.46 +/- 2.36%, P < 0.001 for arteriolar and 2.83 +/- 2.10 vs. 3.98 +/- 1.84%, P < 0.001 for venular dilation). After adjustment for age, sex, diabetes duration, fasting glucose, cholesterol and triglyceride levels, current smoking status, systolic blood pressure, and use of antihypertensive and lipid-lowering medications, participants with reduced flicker light-induced vasodilation were more likely to have diabetes (odds ratio 19.7 [95% CI 6.5-59.1], P < 0.001 and 8.14 [3.1-21.4], P < 0.001, comparing lowest vs. highest tertile of arteriolar and venular dilation, respectively). Diabetic participants with reduced flicker light-induced vasodilation were more likely to have diabetic retinopathy (2.2 [1.2-4.0], P = 0.01 for arteriolar dilation and 2.5 [1.3-4.5], P = 0.004 for venular dilation). CONCLUSIONS: Reduced retinal vasodilation after flicker light stimulation is independently associated with diabetes status and, in individuals with diabetes, with diabetic retinopathy. Our findings may therefore support endothelial dysfunction as a pathophysiological mechanism underlying diabetes and its microvascular manifestations.
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ItemRetinal Vascular Fractal Dimension and Risk of Early Diabetic Retinopathy A prospective study of children and adolescents with type 1 diabetes(AMER DIABETES ASSOC, 2009-11)OBJECTIVE: To examine the prospective association of retinal vascular fractal dimension with diabetic retinopathy risk in young people with type 1 diabetes. RESEARCH DESIGN AND METHODS: This was a hospital-based prospective study of 590 patients aged 12-20 years with type 1 diabetes free of retinopathy at baseline. All patients had seven-field retinal photographs taken of both eyes. Incident retinopathy was ascertained from retinal photographs taken at follow-up visits. Fractal dimension was measured from baseline photographs using a computer-based program following a standardized protocol. RESULTS: Over a mean +/- SD follow-up period of 2.9 +/- 2.0 years, 262 participants developed mild nonproliferative diabetic retinopathy (15.0 per 100 person-years). After adjusting for age, sex, diabetes duration, A1C, and other risk factors, we found no association between retinal vascular fractal dimension and incident retinopathy. CONCLUSIONS: Retinal vascular fractal dimension was not associated with incident early diabetic retinopathy in this sample of children and adolescents with type 1 diabetes.
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ItemQuantitative Assessment of Early Diabetic Retinopathy Using Fractal Analysis(AMER DIABETES ASSOC, 2009-01)OBJECTIVE: Fractal analysis can quantify the geometric complexity of the retinal vascular branching pattern and may therefore offer a new method to quantify early diabetic microvascular damage. In this study, we examined the relationship between retinal fractal dimension and retinopathy in young individuals with type 1 diabetes. RESEARCH DESIGN AND METHODS: We conducted a cross-sectional study of 729 patients with type 1 diabetes (aged 12-20 years) who had seven-field stereoscopic retinal photographs taken of both eyes. From these photographs, retinopathy was graded according to the modified Airlie House classification, and fractal dimension was quantified using a computer-based program following a standardized protocol. RESULTS: In this study, 137 patients (18.8%) had diabetic retinopathy signs; of these, 105 had mild retinopathy. Median (interquartile range) retinal fractal dimension was 1.46214 (1.45023-1.47217). After adjustment for age, sex, diabetes duration, A1C, blood pressure, and total cholesterol, increasing retinal vascular fractal dimension was significantly associated with increasing odds of retinopathy (odds ratio 3.92 [95% CI 2.02-7.61] for fourth versus first quartile of fractal dimension). In multivariate analysis, each 0.01 increase in retinal vascular fractal dimension was associated with a nearly 40% increased odds of retinopathy (1.37 [1.21-1.56]). This association remained after additional adjustment for retinal vascular caliber. CONCLUSIONS: Greater retinal fractal dimension, representing increased geometric complexity of the retinal vasculature, is independently associated with early diabetic retinopathy signs in type 1 diabetes. Fractal analysis of fundus photographs may allow quantitative measurement of early diabetic microvascular damage.
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ItemA health policy for hearing impairment in older Australians: what should it include?(Springer Science and Business Media LLC, 2005-12-13)BACKGROUND: As in all western countries, Australia's older population experiences high levels of hearing impairment coupled with relatively low levels of hearing device usage. Poor hearing diminishes the quality of life of affected individuals and their families. This paper discusses how to improve Australian hearing health policies in order to better combat this impairment amongst older Australians. METHOD: We searched the databases Medline, Meditext and Web of Science to find articles that discussed strategies and innovations to assist the hearing health of older people, and related this material to observations made during the Blue Mountains Hearing Study in NSW between 1997 and 2003. RESULTS AND DISCUSSION: The literature search identified five areas for inclusion in a comprehensive hearing health policy in Australia. These are: early intervention; addressing of hearing aid expense; the use of assisted listening devices; hearing rehabilitation, and; screening and education. Further research in Australia is critical if we are to develop a strong approach to the increasing prevalence of age-related hearing loss. CONCLUSION: Australia needs to act now to address hearing impairment as it is a major cause of disability in those aged 55 and over. Federal and State governments should collaborate to construct a comprehensive hearing health policy that tackles poor levels of hearing health through early intervention, addressing hearing aid expense, encouraging the use of assisted listening devices, rehabilitation, screening and education. A good start would be to declare age related hearing impairment as a National Health Priority Area.
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ItemNo Preview AvailableMitochondrial DNA variants of respiratory complex I that uniquely characterize haplogroup T2 are associated with increased risk of age-related macular degeneration.(Public Library of Science (PLoS), 2009)BACKGROUND: Age-related macular degeneration (AMD), a chronic neurodegenerative and neovascular retinal disease, is the leading cause of blindness in elderly people of western European origin. While structural and functional alterations in mitochondria (mt) and their metabolites have been implicated in the pathogenesis of chronic neurodegenerative and vascular diseases, the relationship of inherited variants in the mitochondrial genome and mt haplogroup subtypes with advanced AMD has not been reported in large prospective cohorts. METHODOLOGY/PRINICIPAL FINDINGS: We examined the relationship of inherited mtDNA variants with advanced AMD in 1168 people using a three-stage design on samples from 12-year and 10-year prospective studies on the natural history of age-related eye disease. In Stage I we resequenced the entire genome in 99 elderly AMD-free controls and 215 people with advanced AMD from the 12-year study. A consistent association with AMD in 14 of 17 SNPs characterizing the mtDNA T haplogroup emerged. Further analysis revealed these associations were driven entirely by the T2 haplogroup, and characterized by two variants in Complex I genes (A11812G of MT-ND4 and A14233G of MT-ND6). We genotyped T haplogroups in an independent sample of 490 cases and 61 controls from the same study (Stage II) and in 56 cases and 246 controls from the 10-year study (Stage III). People in the T2 haplogroup were approximately 2.5 times more likely to have advanced AMD than their peers (odds ratio [OR] = 2.54, 95%CI 1.36-4.80, P
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ItemAngiotensin-converting enzyme gene and retinal arteriolar narrowing: The Funagata Study(NATURE PUBLISHING GROUP, 2009-12)The purpose of this study is to determine whether the angiotensin-converting enzyme (ACE) gene polymorphism is associated with retinal arteriolar narrowing, a subclinical marker of chronic hypertension. The Funagata Study examined a population-based sample of Japanese aged 35+ years; 368 participants had both retinal vessel diameter measurements and ACE insertion/deletion (ACE I/D) polymorphism analyses performed. Assessment of retinal vessel diameter and retinal vessel wall signs followed the protocols used in the Blue Mountains Eye Study. ACE gene polymorphisms D/D, I/D and I/I were present in 34 (9.2%), 170 (46.2%) and 164 (44.5%) participants, respectively, distributed in Hardy-Weinberg equilibrium. After multivariable adjustment, retinal arteriolar diameter was significantly narrower in subjects with the D/D genotype compared to subjects with I/D and I/I genotypes (mean difference -6.49 microm, 95% confidence interval (CI): -12.86 microm, -0.11 microm). Our study suggests that the ACE I/D polymorphism may be associated with subclinical structural arteriolar changes related to chronic hypertension.
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ItemEPHA2 Is Associated with Age-Related Cortical Cataract in Mice and Humans(PUBLIC LIBRARY SCIENCE, 2009-07)Age-related cataract is a major cause of blindness worldwide, and cortical cataract is the second most prevalent type of age-related cataract. Although a significant fraction of age-related cataract is heritable, the genetic basis remains to be elucidated. We report that homozygous deletion of Epha2 in two independent strains of mice developed progressive cortical cataract. Retroillumination revealed development of cortical vacuoles at one month of age; visible cataract appeared around three months, which progressed to mature cataract by six months. EPHA2 protein expression in the lens is spatially and temporally regulated. It is low in anterior epithelial cells, upregulated as the cells enter differentiation at the equator, strongly expressed in the cortical fiber cells, but absent in the nuclei. Deletion of Epha2 caused a significant increase in the expression of HSP25 (murine homologue of human HSP27) before the onset of cataract. The overexpressed HSP25 was in an underphosphorylated form, indicating excessive cellular stress and protein misfolding. The orthologous human EPHA2 gene on chromosome 1p36 was tested in three independent worldwide Caucasian populations for allelic association with cortical cataract. Common variants in EPHA2 were found that showed significant association with cortical cataract, and rs6678616 was the most significant in meta-analyses. In addition, we sequenced exons of EPHA2 in linked families and identified a new missense mutation, Arg721Gln, in the protein kinase domain that significantly alters EPHA2 functions in cellular and biochemical assays. Thus, converging evidence from humans and mice suggests that EPHA2 is important in maintaining lens clarity with age.
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ItemComparison of age-specific cataract prevalence in two population-based surveys 6 years apart.(Springer Science and Business Media LLC, 2006-04-20)BACKGROUND: In this study, we aimed to compare age-specific cortical, nuclear and posterior subcapsular (PSC) cataract prevalence in two surveys 6 years apart. METHODS: The Blue Mountains Eye Study examined 3654 participants (82.4% of those eligible) in cross-section I (1992-4) and 3509 participants (75.1% of survivors and 85.2% of newly eligible) in cross-section II (1997-2000, 66.5% overlap with cross-section I). Cataract was assessed from lens photographs following the Wisconsin Cataract Grading System. Cortical cataract was defined if cortical opacity comprised > or = 5% of lens area. Nuclear cataract was defined if nuclear opacity > or = Wisconsin standard 4. PSC was defined if any present. Any cataract was defined to include persons who had previous cataract surgery. Weighted kappa for inter-grader reliability was 0.82, 0.55 and 0.82 for cortical, nuclear and PSC cataract, respectively. We assessed age-specific prevalence using an interval of 5 years, so that participants within each age group were independent between the two surveys. RESULTS: Age and gender distributions were similar between the two populations. The age-specific prevalence of cortical (23.8% in 1st, 23.7% in 2nd) and PSC cataract (6.3%, 6.0%) was similar. The prevalence of nuclear cataract increased slightly from 18.7% to 23.9%. After age standardization, the similar prevalence of cortical (23.8%, 23.5%) and PSC cataract (6.3%, 5.9%), and the increased prevalence of nuclear cataract (18.7%, 24.2%) remained. CONCLUSION: In two surveys of two population-based samples with similar age and gender distributions, we found a relatively stable cortical and PSC cataract prevalence over a 6-year period. The increased prevalence of nuclear cataract deserves further study.
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ItemOcular associations of diabetes other than diabetic retinopathy(AMER DIABETES ASSOC, 2008-09)
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ItemRisk factors for age-related maculopathy: the Visual Impairment Project(American Medical Association, 2001-10)Objective: To describe the risk factors and associated population attributable risk for age-related maculopathy (ARM) and age-related macular degeneration (AMD) in Australians aged 40 years and older. Methods: Residents were recruited from 9 randomly selected urban clusters and 4 randomly selected rural clusters in Victoria, Australia. At locally established test sites, the following information was collected: visual acuity, medical and health history, lifetime sunlight exposure, dietary intake, and fundus photographs. Age-related maculopathy and AMD were graded from the fundus photographs using an international classification and grading system. Backwards logistic regression was used to identify the independent risk factors for ARM and AMD. Results: The participation rate was 83% (n=3271) among the urban residents and 92% (n=1473) among the rural residents. Gradable fundus photographs of either eye were available for 4345 (92%) of the 4744 participants. There were 656 cases of ARM, giving a weighted prevalence of 15.1% (95% confidence limit [ CL] , 13.8, 16.4 ); and there were 30 cases of AMD, giving a weighted prevalence of 0.69% (95% CL, 0.33, 1.03). In multiple logistic regression, the risk factors for AMD were as follows: age (odds ratio [OR], 1.23; 95% CL, 1.17, 1.29), smoked cigarettes for longer than 40 years (OR, 2.39; 95% CL, 1.02, 5.57), and ever taken angiotensin-convening enzyme inhibitors (OR, 3.26; 95% CL, 1.33,8.01 ). The magnitude of all of these risk factors was slightly less for ARM, and having ever taken blood cholesterol-lowering medications was also significant (OR, 1.67; 95% CL, 1.12, 2.47; P=.001). Conclusion: Smoking is the only modifiable risk factor for ARM and AMD, among the many environmental and systemic factors that were assessed.