[Show abstract][Hide abstract] ABSTRACT: Purpose:
To describe the relationship between peripapillary choroidal thickness and retinal nerve fiber layer (RNFL) thickness in a population-based sample of non-glaucomatous eyes.
Population-based, cross-sectional study.
478 non-glaucomatous subjects aged over 40 years were recruited from the Singapore Malay Eye Study (SiMES-2). All participants underwent a detailed ophthalmic examination, including Cirrus and Spectralis optical coherence tomography (OCT) for the measurements of RNFL thickness and peripapillary choroidal thickness respectively. Associations between peripapillary choroidal thickness and RNFL thickness were assessed using linear regression models with generalized estimating equations.
Of the 424 included subjects (843 non-glaucomatous eyes), 39% were men, and the mean (SD) age was 66.7 (10.5) years. The mean peripapillary choroidal thickness was 135.59 ± 56.74 μm and the mean RNFL thickness was 92.92 ± 11.41 μm. In terms of distribution profile, peripapillary choroid was thickest (150.04 ± 59.72 μm) at superior and thinnest (110.71 ± 51.61 μm) at inferior quadrant, whereas RNFL was thickest (118.60 ± 19.83 μm) at inferior and thinnest (67.36 ± 11.36 μm) at temporal quadrant. We found that thinner peripapillary choroidal thickness was independently associated with thinner RNFL thickness globally (regression coefficient [β] = - 1.334 μm for per SD decrease in PPCT, p = 0.003), and in the inferior (β = - 2.565, p = 0.001) and superior (β = - 2.340, p = 0.001) quadrants even after adjusting for potential confounders.
Thinner peripapillary choroid was independently associated with thinner RNFL globally and in the inferior and superior regions. This structure-structure relationship may need further exploration in glaucomatous eyes to apply in clinical settings.
American Journal of Ophthalmology 09/2015; DOI:10.1016/j.ajo.2015.09.018 · 3.87 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background:
Glaucoma is the leading cause of irreversible blindness in the world. Estimated to affect 60 million people worldwide, this figure is expected to rise to 80 million by 2020. Untreated, glaucoma leads to visual decay and eventually to blindness, and can significantly reduce quality of life. First-line treatment in patients with primary open-angle glaucoma and exfoliative glaucoma is topical medical therapy with ocular hypotensives as eye drops. However, eye drops have several disadvantages including cost, possible local and systemic side effects, and adherence and perseverance issues. Randomised controlled trials have demonstrated that selective laser trabeculoplasty is equally as effective in lowering intraocular pressure as eye drops. However, the impact of these two treatment modalities from the patient and economic perspectives has not been adequately determined. Thus, it remains unclear whether topical medical therapy or selective laser trabeculoplasty should be recommended as first-line treatment for glaucoma.
This protocol describes an international, multi-centre, randomised controlled trial to determine the optimum first-line therapy for people with primary open-angle glaucoma and exfoliative glaucoma. This study will compare the effect of selective laser trabeculoplasty and topical medication with respect to patients' generic and glaucoma-specific quality of life. The trial will also provide a detailed cost-effectiveness analysis and compare the clinical effectiveness with respect to the degree of intraocular pressure lowering and rates of treatment failure. Research coordinators in each centre will identify and recruit previously untreated patients with primary open-angle glaucoma and exfoliative glaucoma. Those who meet the eligibility criteria will be invited to enter a randomised controlled trial with either selective laser trabeculoplasty or topical ocular hypotensive therapy, according to a stepped regimen. Outcome assessment will be measured at 6 weeks and at 6, 12, and 24 months post-treatment. Regular clinic follow-ups will continue as clinically indicated between study outcome visits.
The Glaucoma Initial Treatment Study is the first multi-centred RCT to determine the optimum first-line therapy for people with glaucoma. Our trial will have an unprecedented capacity to meaningfully transform the treatment and management of glaucoma in Australia and overseas.
ACTRN12611000720910 ; Date registered: 11 July 2011.
[Show abstract][Hide abstract] ABSTRACT: Aim:
To explore the association between alcohol consumption and the severity of diabetic retinopathy (DR).
In this cross-sectional study, patients with type 2 diabetes answered questions on consumption of low and full-strength beer, white wine/champagne, red wine, fortified wines, and spirits. Never, moderate and high consumption of each alcoholic beverage, and overall alcoholic beverage consumption, were defined as <1, 1-14 and >14 standard drinks/week, respectively. DR was categorized into none; non vision-threatening DR (VTDR) and VTDR. Multivariable logistic regression determined the associations between alcohol consumption and DR.
Of the 395 participants (mean age±SD [standard deviation] 65.9±10.4years; males=253), 188 (47.6%) consumed alcohol and 235 (59.5%) had any DR. Compared to no alcohol consumption, moderate alcohol consumption (overall) was significantly associated with reduced odds of any DR (OR=0.47, 95% CI [confidence interval] 0.26-0.85). Moderate consumption of white wine/champagne or fortified wine was also associated with reduced odds of any DR (OR=0.48, 95% CI 0.25-0.91, and OR=0.15, 95% CI 0.04-0.62, respectively). Similar results were observed for non-VTDR and VTDR.
The amount and type of alcohol are associated with risk of DR in patients with type 2 diabetes. A longitudinal study is needed to assess the protective effect of alcohol consumption and DR.
Journal of diabetes and its complications 09/2015; DOI:10.1016/j.jdiacomp.2015.09.001 · 3.01 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To determine the prevalence and risk factors of pre-diabetes, diagnosed and undiagnosed diabetes mellitus in rural Bangladesh.
Using a population-based cluster random sampling strategy, 3104 adults aged 30 years or older were recruited. Fasting capillary blood glucose, blood pressure (BP), height, weight, waist circumference, and Knowledge, Attitudes and Practice (KAP) related to diabetes were recorded. Diabetes Mellitus (DM) was defined as fasting glucose ≥7.0 mmol/L or self-reported diagnosed diabetes and impaired fasting glucose as fasting glucose (IFG) ≥6.1 and <7.0 mmol/L.
The overall crude prevalence of DM was 7.2% (95% confidence interval (CI) 6.3-8.1%; n=222) of which 55% (n=123) was previously undiagnosed (UDM). The prevalence of IFG was 5.3% (95% CI 4.5-6.1%; n=163). Age standardized prevalence of DM was 6.6% and of IFG 5.0%. UDM was higher in people with lower socio-economic status (59% versus 31%; p<0.001). Of those with known DM 56% had poor glycaemic control (fasting glucose ≥7.0 mmol/L) and 37% were not on medication. Overall knowledge of DM was poor. For example, only 16.3% with UDM, 17.8% with IFG, and 13.4% with normal fasting glucose knew that diabetes causes eye disease compared to 55.6% people with KDM (p<0.001 for trend).
In this rural Bangladeshi community, the percentage of UDM was high and lower socioeconomic status was associated with a higher risk of UDM. Overall knowledge of DM was poor. Public health programmes should target those of low socioeconomic status and aim at increasing knowledge of DM in rural Bangladesh.
This article is protected by copyright. All rights reserved.
Journal of Diabetes 08/2015; DOI:10.1111/1753-0407.12294 · 1.93 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Diabetic retinopathy is a serious complication of diabetes mellitus and can lead to blindness. A genetic component, in addition to traditional risk factors, has been well described although strong genetic factors have not yet been identified. Here, we aimed to identify novel genetic risk factors for sight-threatening diabetic retinopathy using a genome-wide association study.
Retinopathy was assessed in white Australians with type 2 diabetes mellitus. Genome-wide association analysis was conducted for comparison of cases of sight-threatening diabetic retinopathy (n = 336) with diabetic controls with no retinopathy (n = 508). Top ranking single nucleotide polymorphisms were typed in a type 2 diabetes replication cohort, a type 1 diabetes cohort and an Indian type 2 cohort. A mouse model of proliferative retinopathy was used to assess differential expression of the nearby candidate gene GRB2 by immunohistochemistry and quantitative western blot.
The top ranked variant was rs3805931 with p = 2.66 × 10(-7), but no association was found in the replication cohort. Only rs9896052 (p = 6.55 × 10(-5)) was associated with sight-threatening diabetic retinopathy in both the type 2 (p = 0.035) and the type 1 (p = 0.041) replication cohorts, as well as in the Indian cohort (p = 0.016). The study-wide meta-analysis reached genome-wide significance (p = 4.15 × 10(-8)). The GRB2 gene is located downstream of this variant and a mouse model of retinopathy showed increased GRB2 expression in the retina.
Genetic variation near GRB2 on chromosome 17q25.1 is associated with sight-threatening diabetic retinopathy. Several genes in this region are promising candidates and in particular GRB2 is upregulated during retinal stress and neovascularisation.
[Show abstract][Hide abstract] ABSTRACT: Albuminuria, a marker of diabetic kidney disease, is closely associated with diabetic retinopathy (DR) and diabetic macular edema (DME). However, the relationship between estimated glomerular filtration rate (eGFR) with DR and DME remains unclear, particularly in type 2 diabetes. We investigated the association of eGFR with DR and DME in a sample of patients with type 2 diabetes.
We included 263 Caucasian patients with type 2 diabetes aged ≥18 years who participated in a clinic-based cross-sectional study in Melbourne, Australia. Diabetic retinopathy (n = 140) and DME (n = 61) were assessed from retinal photographs graded using the modified Airlie House classification and further confirmed with optical coherence tomography. Estimated glomerular filtration rate, assessed using the CKD-EPI formula, was analyzed continuously (per SD change) and categorically (normal renal function ≥ 90; impaired renal function, 60-89, and chronic kidney disease [CKD] < 60 mL/min/1.73 m2).
When eGFR was analyzed categorically, impaired renal function and CKD were associated with the presence of DR when compared to normal renal function in multivariable models (odds ratio [OR] with 95% confidence interval [CI] of 2.97 [1.12-7.87] and 3.77 [1.28-11.10]), respectively. In DR severity analyses, CKD showed significant associations with moderate (5.83 [1.44-23.5], P-trend = 0.02) and severe DR (4.91 [1.26-19.0], P-trend = 0.04). These associations persisted when eGFR was analyzed continuously (P = 0.04). No significant associations were found between eGFR and DME.
Our results suggest that lower levels of eGFR were associated with the presence and severity of DR, but not with DME.
[Show abstract][Hide abstract] ABSTRACT: Purpose/Aim: To investigate the association between retinal vascular tortuosity and traditional- and vascular-related risk factors in persons with diabetes.
We recruited 224 diabetic patients. Retinal vascular tortuosity was measured from fundus photographs. Association of tortuosity with the following factors was assessed after adjusting for significant co-factors: diabetes duration, HbA1c, systolic blood pressure (SBP), cholesterol and body mass index (BMI), flicker-light induced retinal vasodilatation, and markers of endothelial function and inflammation (skin microvacular responses to acetylcholine iontophoresis, soluble e-selectin, inter-cellular adhesion molecule-1, vascular cell adhesion molecule-1, endothelin-1, total nitrite, C-reactive protein).
Adjusting for age and gender, longer diabetes duration was associated with more tortuous retinal arterioles (mean difference in arteriolar tortuosity 5.85 × 10(-5), 95% Confidence Interval 1.44-10.3 × 10(-5); p = 0.016; ≤10 versus >10 years duration). Reduced flicker-light induced retinal vasodilatation was associated with tortuous arterioles and venules (mean difference in arteriolar tortuosity 5.62 × 10(-5), 4.50-6.72 × 10(-5); p < 0.001 and in venules 5.94 × 10(-5), 3.33-8.55 × 10(-5); p < 0.001; comparing highest versus lowest tertile of flicker-light vasodilatation). These associations remained after adjusting for co-factors. Diabetes duration explained about 36% and flicker-light vasodilatation 25% of the variation in retinal arteriolar tortuosity. No associations were found between retinal arteriolar or venular tortuosity and HBA1c, SBP, cholesterol, BMI and serum markers of endothelial function.
Increased retinal arteriolar tortuosity was related to longer diabetes duration and reduced flicker-light induced vasodilatory response, suggesting that retinal vascular tortuosity in adults with diabetes may be influenced by multiple diabetes-related physio-pathological changes.
Current eye research 06/2015; DOI:10.3109/02713683.2015.1034371 · 1.64 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To determine the prevalence and risk factors of undiagnosed diabetic retinopathy (DR), in particular vision-threatening DR (VTDR) in a multiethnic Asian cohort.
A population-based survey of 3353 Chinese, 3280 Malays and 3400 Indians (73.6% response) aged 40-80 years residing in Singapore. Diabetes mellitus (DM) was defined as random glucose ≥11.1 mmol/L, use of diabetic medication or a previous physician diagnosis. DR severity was graded from retinal photographs following the modified Airlie House classification. VTDR was defined as the presence of severe non-proliferative DR (NPDR), proliferative DR (PDR) or clinically significant macular oedema (CSMO), using the Eye Diseases Prevalence Research Group definition. Participants were deemed 'undiagnosed' if they reported no prior physician diagnosis in structured interviews, in those with the condition.
Of 10 033 participants, 2376 had DM (23.7%), of which 805 (33.9%) had DR. Among 2376 with DM, 11.1% (n=263) were undiagnosed. Among 805 with DR, 671 (83.3%) were undiagnosed. Among 212 with VTDR, 59 (27.3%) were undiagnosed. In multivariate models, factors associated with undiagnosed VTDR were higher low-density lipoprotein (LDL) cholesterol (OR=1.53, 95% CI 0.99 to 2.35, p=0.05) and absence of visual impairment or blindness in any eye in terms of best-corrected vision OR=3.00, 95% CI 1.47 to 6.11, p=0.003).
In this community, a quarter with VTDR is undiagnosed, and 8 in 10 with any DR are undiagnosed, compared with only 1 in 10 with DM undiagnosed. These findings suggest that screening for diabetes is successful, while screening for DR is currently inadequate in our population. Public health strategies to aid early diagnosis of DR in Singapore are urgently warranted to reduce blindness due to diabetes.
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The British journal of ophthalmology 05/2015; DOI:10.1136/bjophthalmol-2014-306492 · 2.98 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Blood flow in the retina is intrinsically regulated to meet the metabolic demands of its constituent cells. Flickering light or stationary contrast reversals induce an increase in blood flow within seconds of the stimulus onset. This phenomenon is thought to compensate for an increase in ganglion cell activity and energy consumption. Ganglion cell activity is in turn dependent on signals from photoreceptors, bipolar cells, horizontal cells and amacrine cells. The physiological properties of these neurons determine how each type is affected by a particular light characteristic. Neuronal activity then triggers the release of signalling molecules that dilate local blood vessels and increase blood flow. Nitric oxide has been implicated as an important mediator, but metabolites of arachidonic acid may also be involved. Detailed elucidation of these mechanisms, together with advances in imaging technology, may facilitate the use of neurovascular tests to improve the detection of retinal damage in pathological conditions.
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Clinical and Experimental Ophthalmology 03/2015; DOI:10.1111/ceo.12530 · 2.35 Impact Factor