The caliber of the retinal vessels has been shown to be associated with stroke events. However, the consistency and magnitude of association, and the changes in predicted risk independent of traditional risk factors, are unclear. To determine the association between retinal vessel caliber and the risk of stroke events, the investigators combined individual data from 20,798 people, who were free of stroke at baseline, in 6 cohort studies identified from a search of the Medline (National Library of Medicine, Bethesda, Maryland) and EMBASE (Elsevier B.V., Amsterdam, the Netherlands) databases. During follow-up of 5–12 years, 945 (4.5%) incident stroke events were recorded. Wider retinal venular caliber predicted stroke (pooled hazard ratio = 1.15, 95% confidence interval: 1.05, 1.25 per 20-μm increase in caliber), but the caliber of retinal arterioles was not associated with stroke (pooled hazard ratio = 1.00, 95% confidence interval: 0.92, 1.08). There was weak evidence of heterogeneity in the hazard ratio for retinal venular caliber, which may be attributable to differences in follow-up strategies across studies. Inclusion of retinal venular caliber in prediction models containing traditional stroke risk factors reassigned 10.1% of people at intermediate risk into different, mostly lower, risk categories.
cohort studies; meta-analysis; retinal vessels; risk; stroke
The efficacy and safety of repeated injections of intravitreal triamcinolone (IVTA) for diabetic macular oedema is unclear, with results of previous reports conflicting.
This is a prospective, observational case series of 27 eyes receiving IVTA for diabetic macular oedema. LogMAR visual acuity (VA) and central macular thickness (CMT) were measured at baseline and in 3 to 6 monthly intervals for up to 24 months, then correlated with the number of IVTA injections given.
One IVTA injection was required in 6 (18%) eyes, 2 in 8 (24%) eyes, 3 in 13 (39%) eyes and 4–5 in 6 (18%) eyes. VA improved in all patients, but neither the final improvement in VA nor the absolute improvement in CMT from baseline to 24 months correlated with the number of injections received (p = 0.44 and 0.84, respectively). Cataract surgery was more frequent in eyes receiving more injections (p = 0.01).
This study suggests that repeated injections of IVTA continue to be as effective as the first over a 2‐year period. The probability of cataract surgery increases with an increasing number of injections.
The prevalence of obesity has reached epidemic proportions in many countries. While its impact on overall health is well documented, less is known about the ocular manifestations of obesity. Amongst different eye diseases, obesity has been linked with age-related cataract, glaucoma, age-related maculopathy, and diabetic retinopathy. Numerous population-based and prospective studies support an association between obesity and risk of age-related cataract. However, the nature and strength of these associations, particularly with the different cataract subtypes, remains to be determined. There is strong evidence that obesity is associated with elevated intraocular pressure, but there is no convincing data to support a more direct association between obesity and glaucomatous optic neuropathy. Studies to date have not found a consistent pattern of association between obesity and risk of age-related maculopathy or diabetic retinopathy. Thus, while obesity may be a risk factor for many ocular conditions, the present literature is inadequate to establish any convincing associations. Furthermore, whether weight loss reduces the risk of eye diseases remains unresolved. Because of the potential public health impact of obesity, there is a greater need to understand its ocular effects.
age-related maculopathy; body mass index; cataract; eye disease; glaucoma; obesity; pseudotumor celebri; retinal artery occlusion; retinal vein occlusion; retinopathy
Prehypertension has been shown to be an early risk factor of cardiovascular disease (CVD). We investigated the prevalence and pattern of cardiometabolic risk factors in prehypertension in three ethnic Asian populations in Singapore.
We examined data from Chinese (n = 1177), Malay (n = 774), and Indian (n = 985) adults aged 40–80 years who participated in three independent population based studies conducted from 2004–2011 in Singapore who were free of diabetes, hypertension and previous CVD. Prehypertension was defined as systolic blood pressure (BP) 120–139 mm Hg or diastolic BP 80–89 mm Hg. Random blood glucose, glycated haemoglobin (HbA1c), body mass index (BMI), triglycerides, low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol were examined as indicators of adverse cardiometabolic profile. The association between metabolic variables and prehypertension was examined using logistic regression models adjusting for potential confounders.
The prevalence of prehypertension was 59.8% (Chinese), 68.9% (Malays) and 57.7% Indians. Higher levels of blood glucose, HbA1c and BMI were significantly associated with prehypertension in all three ethnic groups, odds ratio (95% confidence interval) of prehypertension in Chinese, Malays and Indians were: 1.42 (1.10, 1.83), 1.53 (1.05, 2.24), 1.49 (1.13, 1.98) for high-glucose; 3.50 (1.01, 12.18), 3.72 (1.29, 10.75), 2.79 (1.31, 5.94) for high-HbA1c; 1.86 (1.34, 2.56), 2.96 (2.10, 4.18), 1.68 (1.28, 2.20) for high-BMI. In addition, higher levels of LDL cholesterol in Chinese and higher levels of triglycerides were significantly associated with prehypertension. These associations persisted when metabolic variables were analysed as continuous variables.
Higher levels of blood glucose, HbA1c and BMI were associated with prehypertension in all three ethnic groups in Singapore. Screening for prehypertension and lifestyle modifications could potentially reduce the burden of CVD in otherwise healthy Asian adults living in Singapore.
Prehypertension; Metabolic syndrome; Indian; Cardiometabolic
To describe the relationship of blood pressure (BP), antihypertensive medication use, and other factors to serial measurements of retinal arteriolar diameters over time in the Beaver Dam Eye Study.
Retinal arteriolar diameter was measured by computer-assisted methods and summarized as central retinal arteriolar equivalent (CRAE) in 4573 persons aged 43–99 years at 4 examinations (each five years apart) over a 15-year interval. Associations of CRAE with risk factors measured concurrently and 5 years previously were determined using multivariate analyses.
While adjusting for image quality, refraction, and lens status, age (per 10 years: β estimate −0.73, p<.001), systolic BP (SBP, per 10 mmHg: concurrent exam −2.74, p<.001; previous exam −1.75, p<0.001), smoking status (smoker vs. non-smoker: concurrent exam 4.29, p<.001; previous exam 1.63, p=0.004), body mass index (BMI, per category: concurrent exam −0.51, p=0.04; previous exam −0.22, p=0.44), and heavy drinking (current vs. past/never heavy drinker: concurrent exam −2.54, p=0.03; previous exam −2.42, p=0.02) were associated with CRAE. In the same model, there were significant interactions between concurrent and previous SBP (−0.11, p=0.003) and between concurrent and previous BMI (0.12, p=0.04). Use of calcium channel blockers at both the concurrent and past exam (vs. neither exam 1.59; P=0.01), but not other classes of antihypertensive drugs was associated with CRAE.
These data show retinal arteriolar diameter is independently associated with past and current SBP, calcium channel blocker use, smoking status, BMI, and heavy drinking over 5-year intervals. The relationships with CRAE were stronger for concurrent than for past measures of these variables.
retinal vessels; retinal arteriolar narrowing; hypertension; epidemiology
Serum apolipoprotein (apo)AI and -B have been shown to be associated with diabetic retinopathy, but the underlying mechanisms are unclear. We investigated whether apoAI and apoB levels are associated with measures of systemic and retinal microvascular function in patients with diabetes. We recruited 224 diabetic patients (85 type 1 and 139 type 2) and assessed serum lipids and lipoproteins from fasting blood, skin responses to sodium nitroprusside (endothelium independent) and acetylcholine (ACh) (endothelium dependent) iontophoresis, flicker-light–induced retinal vasodilatation, and retinal vascular tortuosity. After adjustment for age and sex, every SD increase in apoAI level was associated with ACh-induced skin perfusion (mean change 1.27%; P < 0.001 for apoAI) and flicker-light retinal arteriolar vasodilatation (0.33%; P = 0.003) and was associated inversely with arteriolar tortuosity (−2.83 × 10−5; P = 0.044). Each SD increase in apoB was associated with arteriolar tortuosity only (1.75 × 10−5; P = 0.050). These associations, except for apoB, remained in multivariate models. Serum apoAI was associated with increased vasomotor responsiveness to ACh and flickering light and inversely related to retinal vessel tortuosity—a characteristic that has both structural and functional dimensions. These findings provide additional insights into the potential mechanisms of apos in the pathogenesis of diabetic retinopathy and other diabetic microvascular complications.
•Structural parameters of the eye change with increasing chronological age.•Ocular age-related parameters may serve as biomarkers of aging.•Relevant ocular parameters include retinal vessel calibre and lens density.
Certain anatomic and functional parameters of the eye change with increasing chronological age. They may, therefore, serve as potential biomarkers of ageing. We investigated associations between four such ocular parameters (lens density, retinal vessel calibre, corneal endothelial cells and retinal nerve fibre layer thickness) and two ‘cellular’ biomarkers of ageing (leukocyte telomere length and CDKN2A expression), with frailty (a clinical correlate of biological ageing) in a population of South African adults. All ocular parameters revealed an association with either telomere length or CDKN2A expression. However, lens density was most strongly correlated with age, increased CDKN2A expression, and with frailty (p = 0.05 and 0.03, respectively). Narrow retinal arteriolar diameter, associated with increased chronological age, was also associated with increased CDK2NA expression (0.42 vs. 0.31, p = 0.02) but not with frailty. Ocular parameters may aid in determining biological age, warranting investigation in longitudinal studies.
Telomeres; CDKN2A; Lens density; Retinal vessel calibre; Corneal endothelium; Retinal nerve fibre layer; Frailty
Background and Purpose
We examined the relationship of age-related macular degeneration (AMD) with incident stroke, including stroke subtypes of cerebral infarction and intracerebral haemorrhage (ICH).
We included 12,216 participants with retinal photographs taken at the third examination visit (1993–1995) from the Atherosclerosis Risk in Communities Study (ARIC), a population-based cohort study in middle-aged persons. Images were evaluated for AMD signs according to a standardized protocol. Incident events of stroke and its subtypes were identified and validated via case record review over time.
AMD was diagnosed in 591 participants, of whom 576 had early and 15 late AMD. After a mean follow-up of 13.0 years (standard deviation: 3.3), 619 persons developed an incident stroke, including 548 cerebral infarction and 57 ICH. Participants with any AMD were at an increased risk of stroke (multi-variable adjusted hazard ratio [HR]: 1.51; 95% confidence interval [CI]: 1.11–2.06), with a stronger association for ICH (HR: 2.64; 95% CI: 1.18–5.87) than cerebral infarction (HR: 1.42; 95% CI: 1.01–1.99).
Persons with AMD are at an increased risk of both cerebral infarction and ICH. These data provide further insights into common pathophysiological processes between AMD and stroke subtypes.
retinal imaging; age-related macular degeneration; cerebral infarction; intra-cerebral hemorrhage
To determine whether age-related macular degeneration (AMD) is a risk indicator for coronary heart disease (CHD) and cardiovascular disease (CVD) events independent of other known risk factors in a multi-ethnic cohort.
Population-based prospective cohort study.
A diverse population sample of 6233 men and women aged 45–84 without known CVD from the Multi-Ethnic Study of Atherosclerosis (MESA).
Participants in the MESA had retinal photographs taken between 2002 and 2003. Photographs were evaluated for AMD. Incident CHD/CVD events were ascertained during clinical follow-up visits for up to 8 years after the retinal images were taken.
Main Outcome Measures
Incident CHD/CVD events.
Of the 6814 persons at risk of CHD, there were 893 participants with early AMD (13.1%) and 27 (0.5%) at baseline. Over a mean follow-up period of 5.4 years, there was no statistically significant difference in incident CHD or CVD between the AMD and non-AMD groups (5.0%vs. 3.9%, p=0.13 for CHD and 6.6 vs. 5.5%, p=0.19 for CVD, respectively). In Cox regression models adjusting for CVD risk factors, there was no significant relationship between presence of any AMD and any CHD/CVD events (HR=0.99, 95% CI 0.74–1.33, p=0.97). No significant association was found between subgroups of early AMD or late AMD and incident CHD/CVD events.
In persons without a history of cardiovascular disease, AMD was not associated with an increased risk of CHD or CVD.
Retinal vessels may provide a readily accessible surrogate approach to study vascular disease in brain small vessels. Previous epidemiologic studies of retinal microvascular abnormalities and cognition have not included large numbers of Latinos who have a high prevalence of diabetes and hypertension.
We used data from 809 elderly Latino participants in the Los Angeles Latino Eye Study (LALES) to assess whether retinal vessel caliber and microvascular abnormalities are cross-sectionally associated with lower cognitive function. Cognitive screening was conducted with the Cognitive Abilities Screening Instrument-Short form (CASI-S) and in-depth testing with the Spanish English Neuropsychological Assessment Scales (SENAS). Retinal photographs were used to identify retinopathy signs and measure retinal vessel caliber.
A total of 65.8% had high blood pressure, 34.5% had diabetes; self-reported diagnoses of heart attack, heart failure, angina and stroke were rare. Retinal calibers and any retinopathy were not associated with the CASI-S, total SENAS or any SENAS cognitive factors assessed as continuous variables. The odds of a low CASI-S score were two times higher in subjects with generalized arteriolar narrowing (OR = 2.04, 95% CI = 1.14, 3.66), and one and half times as high in those with both generalized arteriolar narrowing and retinopathy signs (OR = 1.49, 95% CI = 0.47, 4.75) though this result was based on only four cases with both risk factors and confidence limits were wide and included the null.
Retinal microvasculature imaging may provide insights into small blood vessel influences on cognition in Latino populations. Additional studies in diverse populations and prospective settings are needed.
Epidemiology; Cognition; Retina; Latinos; Microvasculature
To prospectively examine the association of retinal microvascular signs with incident diabetes and impaired fasting glucose (IFG) in a multi-ethnic population-based cohort.
The multi-ethnic study of atherosclerosis comprised Caucasians, African-Americans, Hispanics and Chinese aged 45–84 years. Retinal vascular calibre and retinopathy were quantified from baseline retinal photographs. Incident diabetes and IFG were ascertained prospectively.
After a median follow-up of 3 years, 243 (4.9%) people developed diabetes and 565 (15.0%) developed IFG. After adjusting for known risk factors, participants with wider retinal arteriolar calibre had a higher risk of developing diabetes [HR: 1.60; 95% CI: 1.12–2.29, p = 0.011 comparing highest with lowest arteriolar calibre tertile]. In ethnic subgroup analysis, the association between wider retinal arteriolar calibre and incident diabetes was stronger and statistically significant only in Caucasians [HR: 2.78; 95% CI: 1.37–5.62, p = 0.005]. Retinal venular calibre and retinopathy signs were not related to risk of diabetes or IFG.
Wider retinal arteriolar calibre is independently associated with an increased risk of diabetes, supporting a possible role for early arteriolar changes in diabetes development. This effect was largely seen in Caucasians, and not in other ethnic groups, and may reflect ethnic differences in susceptibility to diabetes from microvascular pathways.
Retinal microvascular calibre; Retinopathy; Diabetes; Impaired fasting glucose
Whether the increase in vascular disease prevalence and mortality in OA populations is a result of co-occurrence of cardiovascular disease and OA, which are both common in the older population, is due to OA treatments or to the common association with reduced physical activity and/or obesity is unclear. One way to explore this non-invasively is to examine the cross-sectional relationship between changes in retinal microvasculature, which have been shown to be markers of generalized vascular pathology, and knee structural changes in an asymptomatic community-based population.
A community sample of 289 (61% women) aged 50–79 years with no knee symptoms underwent magnetic resonance imaging (MRI) of their dominant knee in 2003. Cartilage volume and bone marrow lesions (BMLs) were determined. All subjects also had retinal photographs taken from which retinal arteriolar and venular diameters were determined and summarized as the central retinal arteriolar equivalent (CRAE) and the central retinal venular equivalent (CRVE).
Retinal venular diameter was significantly wider in subjects with a BML compared with subjects without a BML (mean (SD) 214.2 (2.8) μm versus 207.5 (1.1) μm respectively independent of age, gender and BMI. A trend for decreased medial tibial cartilage with increasing CRAE was also observed (regression coefficient −2.70 μl, 95%CI-5.74, 0.5, p=0.08).
These findings suggest that vascular pathology, indicative of inflammatory processes, is associated with early structural knee changes. The role of micro-vascular changes in the pathogenesis of OA warrants further investigation.
To describe the prevalence of choroidal nevi in four racial/ethnic groups (white, black, Hispanic, and Chinese) in the United States (US).
Participants of the second examination of the Multi-Ethnic Study of Atherosclerosis (MESA), involving 6176 persons aged 45–85 years without clinical cardiovascular disease at baseline selected from 6 US communities.
Fundus images were taken using a 45° digital camera through dark-adapted pupils and were graded for choroidal nevi using the modified Wisconsin Age-Related Maculopathy Grading System and the Blue Mountains Eye Study protocol.
Main Outcome Measure
The overall prevalence of choroidal nevi in the whole cohort was 2.1%, with prevalences higher in whites (4.1%) than blacks (0.7%), Hispanics (1.2%) and Chinese (0.4%, P < 0.001 for any differences among groups). The lowest prevalence of choroidal nevi occurred in those 75–84 years old. The nevi were subfoveal in 4% of eyes with nevi and were not associated with a decrease in visual acuity. Characteristics of the nevi (size, shape, location, color, drusen on surface) did not differ among racial/ethnic groups. With the exception of associations with higher C-reactive protein levels (odds ratio [OR] per mg/dL on the logarithmic scale 1.23; 95% confidence interval [CI] 1.06–1.43; P = 0.01) and lower systolic blood pressure (OR per 10 mmHg 0.90; 95% CI 0.82–0.99; P = 0.04), choroidal nevi were not associated with other potential risk factors (e.g., sex, smoking status, alcohol consumption, lipid levels, coagulation factors or kidney disease).
Low prevalences of choroidal nevi were found in the four groups participating in MESA cohort, with whites having higher prevalence than the other racial/ethnic groups. The higher prevalence in whites than in other groups was not explained by any of the factors studied. When choroidal nevi were present, their characteristics did not differ among racial/ethnic groups.
Background. Changes in retinal microvascular caliber, which occur prior to onset of retinopathy, may indicate presence of kidney damage.
Methods. This study examined the association between retinal arteriolar [central retinal artery equivalent (CRAE)] and venular caliber [central retinal venule equivalent (CRVE)] and presence of albuminuria (micro- or macroalbuminuria) among participants of the Multi-Ethnic Study of Atherosclerosis (MESA), a cohort of adults aged 45–84 years without baseline clinical cardiovascular disease. During the second MESA exam, digital fundus photography was completed in 5897 participants who provided spot urine specimens. Albuminuria was defined by spot urine albumin/creatinine ratios ≥30 mg/g. Multivariable adjusted odds of albuminuria by quintiles of CRAE and CRVE were determined using logistic regression. Analyses were repeated after stratifying by presence of type 2 diabetes.
Results. Albuminuria was noted in 11.5% (n = 675) and included 584 subjects with microalbuminuria and 91 with macroalbuminuria. A significant U-shaped pattern was seen with higher prevalence of albuminuria across quintile extremes in CRAE (15.7, 8.8 and 10.6% in CRAE Quintiles 1, 3 and 5, respectively; P <0.0001). After adjustment for covariates, both narrower CRAE [odds ratios (OR) 1.55; 95% confidence interval (CI) 1.17–2.04, Quintile 1 versus 3) and wider CRAE (OR 1.44; 95% CI 1.07–1.93, Quintile 5 versus 3) were significantly associated with albuminuria. Associations appeared substantially stronger in adults with than without type 2 diabetes but the interaction term for diabetes and CRAE on presence of albuminuria did not meet statistical significance (P = 0.3). No association was noted between CRVE quintiles and albuminuria.
Conclusions. Albuminuria is associated with narrower and wider arteriolar caliber. Future studies should determine whether variation in arteriolar caliber predicts incident albuminuria and whether associations are mediated by hypertension and diabetes. Such information could further clarify early microvascular processes in the pathogenesis of kidney disease.
albuminuria; diabetic retinopathy; MESA (Multi-Ethnic Study of Atherosclerosis); retinal arteriolar; retinal venular
There are limited data on the natural history and longitudinal changes of retinal microvascular lesions. We examined 10-year changes in retinal microvascular lesions, focusing on those related to hypertension and shown to predict development of cardiovascular disease.
1,120 middle-aged participants without diabetes of the Atherosclerosis Risk in Communities (ARIC) Study in 1993–5 and again 10 years later in 2003–5.
. Retinal microvascular lesions were graded from retinal photographs using the same protocol at both examinations, with changes (incidence or disappearance) adjudicated by a side-by-side comparison of photographs. The study sample was stratified by carotid intima-media thickness (IMT) and ARIC field center; thus all analyses were weighted by these factors. Persons with diabetes were excluded because the frequency and pathophysiology of diabetic retinal lesions is different.
Main Outcome Measures
Incidence and disappearance rates of lesions.
. The 10 year incidence of focal arteriolar narrowing, arteriovenous (AV) nicking, and retinopathy in persons without diabetes was 3.4% (95% confidence intervals 2.3–4.9), 2.5% (1.6–3.9), and 2.2% (1.3–3.5) respectively. Over the 10 year period, of 32, 219, and 24 eyes with focal arteriolar narrowing, AV nicking and retinopathy at baseline, 50.3% (28.6–71.9), 40.7% (32.7–49.4) and 65.9% (42.4–83.5), respectively, disappeared. Higher baseline plasma fibrinogen and white cell count were associated with incident focal arteriolar narrowing; antihypertensive medication use associated with incident AV nicking; and higher diastolic blood pressure, carotid IMT and white cell count associated with incident retinopathy. Higher fasting serum glucose was not significantly associated with incident retinopathy, though this may be related to the small number of lesions.(Odds ratio 5.88, 95% confidence interval 0.74–46.64 per standard deviation difference)
In this sample of middle-aged adults, new retinal microvascular lesions appeared at a rate between 2–4% over 10 years. A high percentage of lesions (40% or more) disappeared over the same period, suggesting considerable remodeling in the retinal microvasculature.
microvascular signs; hypertension; microcirculation; retina; ARIC
Diabetic retinopathy (DR) is the most common microvascular complication of diabetes and one of the major causes of blindness worldwide. The pathogenesis of DR has been investigated using several animal models of diabetes. These models have been generated by pharmacological induction, feeding a galactose diet, and spontaneously by selective inbreeding or genetic modification. Among the available animal models, rodents have been studied most extensively owing to their short generation time and the inherited hyperglycemia and/or obesity that affect certain strains. In particular, mice have proven useful for studying DR and evaluating novel therapies because of their amenability to genetic manipulation. Mouse models suitable for replicating the early, non-proliferative stages of the retinopathy have been characterized, but no animal model has yet been found to demonstrate all of the vascular and neural complications that are associated with the advanced, proliferative stages of DR that occur in humans. In this review, we summarize commonly used animal models of DR, and briefly outline the in vivo imaging techniques used for characterization of DR in these models. Through highlighting the ocular pathological findings, clinical implications, advantages and disadvantages of these models, we provide essential information for planning experimental studies of DR that will lead to new strategies for its prevention and treatment.
The main objective of this study was to investigate whether plasma pentosidine levels were associated with cataract and low estimated glomerular filtration rate (eGFR) in nonproteinuric type 2 diabetic patients.
We characterized 888 nonproteinuric type 2 diabetic patients residing in Singapore according to their eGFR values. Proteinuria was excluded on the basis of multiple urinalyses. Patients with low renal function (cases, n = 125) and controls (n = 763) were defined as having eGFR < and ≥60 mL/min/1.73 m2, respectively. Pentosidine levels were measured by enzyme-linked immunosorbent assay. Multinomial logistic regression was used to test the association between plasma pentosidine levels and the joint phenotype of cataract and low eGFR.
Cases had higher triacylglycerol values, higher systolic blood pressure, and were more likely to be treated with two or more antihypertensive medications. In univariate analysis, cases were potentially more than twice as likely to have had a history of cataract compared with controls. This association persisted in multivariate analyses after adjusting for the significant covariates, hypertension and triacylglycerol, but was attenuated when age was included in the model. Plasma pentosidine levels were significantly higher in cases with low eGFR who also had a history of cataract. This association persisted in multivariate analyses that included the covariates, glycosylated hemoglobin, hypertension, and diabetic retinopathy, as well as age.
Carbonyl stress, as reflected by pentosidine levels, is present in a subset of nonproteinuric diabetic patients. Clinically, this stress was associated with the joint presence of cataract and low eGFR.
advanced glycation endproducts; Chinese; normoalbuminuria; renal function
Endothelial dysfunction has been hypothesized as a possible pathogenic factor in the development of diabetic retinopathy (DR). We examined the relationship of DR to endothelium-dependent and endothelium-independent responses in skin microvascular flow.
RESEARCH DESIGN AND METHODS
Participants consisted of 224 individuals with diabetes: 85 with type 1 diabetes and 139 with type 2 diabetes. Sodium nitroprusside (SNP) and acetylcholine (ACh) were delivered across the skin by iontophoresis. Laser Doppler flowmetry was used to assess the skin microcirculation response to SNP (endothelium-independent response) and ACh (endothelium-dependent response). The presence and severity of DR were graded from retinal photographs using a standard protocol.
Of 224 participants, 64.3% had DR. After multivariable adjustment, participants with reduced responses to SNP or ACh were more likely to have DR, with an odds ratio (OR) of 2.33 (95% CI 1.09–5.01) for SNP and 2.20 (1.05–4.61) for ACh, comparing participants with responses below and above the median values. Participants with reduced responses (below the median) to both SNP and ACh were nearly four times more likely to have DR (OR 3.86 [1.45–10.3]) than those with SNP and ACh both above the median values.
The presence of DR was associated with a reduction in skin microcirculation responses to iontophoresis of both SNP and ACh, suggesting that vascular processes associated with both endothelial dysfunction and endothelial function-independent mechanisms may be pathogenically related to DR.
Persons with diabetic retinopathy (DR) have an increased risk of clinical cardiovascular events. Our study aimed to determine whether DR is associated with a range of measures of subclinical cardiovascular disease (CVD) in persons without clinical CVD.
Population-based, cross-sectional epidemiologic study
Nine hundred and twenty seven persons with diabetes without clinical CVD in the Multi-Ethnic Study of Atherosclerosis.
DR was ascertained from retinal photographs according to modification of the Airlie House Classification system. Vision threatening DR (VTDR) was defined as severe non-proliferative DR, proliferative DR or clinically significant macular edema. Subclinical CVD measures were assessed and defined as follows: high coronary artery calcium (CAC) score, defined as CAC score≥400; low ankle-brachial index (ABI), defined as ABI<0.9; high ABI, defined as ABI≥1.4; high carotid intima-media thickness (IMT), defined as highest 25% of IMT; and carotid stenosis, defined as >25% stenosis or presence of carotid plaque.
MAIN OUTCOME MEASURES
Associations between DR and subclinical CVD measures.
The prevalence of DR and VTDR in this sample was 30.0% and 7.2%, respectively. VTDR was associated with a high CAC score (odds ratio [OR] 2.33, 95% condifence interval [CI] 1.15–4.73), low ABI (OR 2.54; 95%CI, 1.08–5.99) and high ABI (OR 12.6, 95% CI, 1.14, 140.6), after adjusting for risk factors including hemoglobin A1c level and duration of diabetes. The association between VTDR and high CAC score remained significant after further adjustment for hypoglycemic, anti-hypertensive and cholesterol-lowering medications. DR was not significantly associated with measures of carotid artery disease.
In persons with diabetes without a history of clinical CVD, the presence of advanced stage of DR is associated with subclinical coronary artery disease. These findings emphasize the need to be careful about the use of anti-vascular endothelial growth factor for the treatment of DR.
Physical activities and sedentary behaviors are 2 broad classes of behavior that may be clearly distinguished from each other and have different patterns of determinants. The authors examined the associations of physical activity and television viewing time with retinal vascular caliber among US adults (n = 5,893) from 4 racial/ethnic groups in the Multi-Ethnic Study of Atherosclerosis (2002–2004) that included non-Hispanic whites, blacks, Hispanics, and Chinese. Physical activity and television viewing time were assessed by using a questionnaire, and vascular calibers (arteriolar and venular) were measured from digital retinal photographs. Those in the lowest quartile of physical activity had wider retinal venular caliber compared with those in the highest quartile in multivariate models adjusted for demographic, cardiovascular, behavioral, and inflammatory risk factors. This was noted in non-Hispanic whites and Hispanics but not in blacks or Chinese. For television viewing time, non-Hispanic whites (but not the other racial/ethnic groups) who were in the highest quartile of television viewing time had wider retinal venular caliber compared with those in the lowest quartile. No associations were noted with arteriolar caliber. Lower levels of physical activity (among non-Hispanic whites and Hispanics) and higher levels of television viewing time (among whites) are associated with wider retinal venules.
arterioles; microvessels; motor activity; retina; sedentary lifestyle; venules
This paper describes the rationale and design of the ENVIS-ion Study, which aims to determine whether low-dose aspirin reduces the development of white matter hyper-intense (WMH) lesions and silent brain infarction (SBI). Additional aims include determining whether a) changes in retinal vascular imaging (RVI) parameters parallel changes in brain magnetic resonance imaging (MRI); b) changes in RVI parameters are observed with aspirin therapy; c) baseline cognitive function correlates with MRI and RVI parameters; d) changes in cognitive function correlate with changes in brain MRI and RVI and e) whether factors such as age, gender or blood pressure influence the above associations.
Double-blind, placebo-controlled trial of three years duration set in two Australian academic medical centre outpatient clinics. This study will enrol 600 adults aged 70 years and over with normal cognitive function and without overt cardiovascular disease. Subjects will undergo cognitive testing, brain MRI and RVI at baseline and after 3 years of study treatment. All subjects will be recruited from a 19,000-patient clinical outcome trial conducted in Australia and the United States that will evaluate the effects of aspirin in maintaining disability-free longevity over 5 years. The intervention will be aspirin 100 mg daily versus matching placebo, randomized on a 1:1 basis.
This study will improve understanding of the mechanisms at the level of brain and vascular structure that underlie the effects of aspirin on cognitive function. Given the limited access and high cost of MRI, RVI may prove useful as a tool for the identification of individuals at high risk for the development of cerebrovascular disease and cognitive decline.
clinicaltrials.gov Identifier: NCT01038583
To describe and compare the associations of serum lipoproteins and apolipoproteins with diabetic retinopathy.
RESEARCH DESIGN AND METHODS
This was a cross-sectional study of 224 diabetic patients (85 type 1 and 139 type 2) from a diabetes clinic. Diabetic retinopathy was graded from fundus photographs according to the Airlie House Classification system and categorized into mild, moderate, and vision-threatening diabetic retinopathy (VTDR). Serum traditional lipids (total, LDL, non–HDL, and HDL cholesterol and triglycerides) and apolipoprotein AI (apoAI), apolipoprotein B (apoB), and the apoB-to-apoAI ratio were assessed.
Diabetic retinopathy was present in 133 (59.4%) individuals. After adjustment for age, sex, diabetes duration, A1C, systolic blood pressure, and diabetes medications, the HDL cholesterol level was inversely associated with diabetic retinopathy (odds ratio 0.39 [95% CI 0.16–0.94], highest versus lowest quartile; Ptrend = 0.017). The ApoAI level was inversely associated with diabetic retinopathy (per SD increase, 0.76 [95% CI 0.59–0.98]), whereas apoB (per SD increase, 1.31 [1.02–1.68]) and the apoB-to-apoAI ratio (per SD increase, 1.48 [1.13–1.95]) were positively associated with diabetic retinopathy. Results were similar for mild to moderate diabetic retinopathy and VTDR. Traditional lipid levels improved the area under the receiver operating curve by 1.8%, whereas apolipoproteins improved the area by 8.2%.
ApoAI and apoB and the apoB-to-apoAI ratio were significantly and independently associated with diabetic retinopathy and diabetic retinopathy severity and improved the ability to discriminate diabetic retinopathy by 8%. Serum apolipoprotein levels may therefore be stronger biomarkers of diabetic retinopathy than traditional lipid measures.
To describe the relationship of lung disease and function with early age-related macular degeneration (AMD) in a population-based study.
A population-based, cross-sectional study of 12,596 middle-aged participants from the Atherosclerosis Risk in Communities Study.
Lung function was assessed by spirometry. Physician diagnosis of asthma and lung disease was ascertained from a standardized questionnaire. AMD signs were graded from fundus photographs according to the Wisconsin grading protocol.
Of our study population, 587 (4.7%) had early AMD, 638 (5.1%) had asthma and 581 (4.6%) had lung disease. After adjusting for age, gender, smoking and hypertension, each litre increase in predicted forced expiratory volume in one second (FEV1) (odds ratio [OR]: 1.27; 95% confidence interval [CI]: 0.89, 1.80), forced vital capacity (FVC) (OR 1.18; 95% CI: 0.93, 1.51) and peak expiratory flow rate (OR 1.12; 95% CI: 0.95, 1.33) were not significantly associated with early AMD. FEV1/FVC ratio (second quartile OR 1.61; 95%CI 0.88–2.93, third quartile OR 1.65; CI 0.90–3.03, fourth quartile OR 1.28; 95%CI 0.68–2.40) was not significantly associated with early AMD. Similarly, asthma (OR 1.06; 95% CI: 0.86, 1.27) and other lung diseases (OR 1.08; 95% CI: 0.90, 1.29) were not associated with early AMD.
Our data do not support a cross-sectional association between lung disease and risk of early AMD.
To re-evaluate the relationship between glycemia and diabetic retinopathy.
RESEARCH DESIGN AND METHODS
We conducted a data-pooling analysis of nine studies from five countries with 44,623 participants aged 20–79 years with gradable retinal photographs. The relationship between diabetes-specific retinopathy (defined as moderate or more severe retinopathy) and three glycemic measures (fasting plasma glucose [FPG; n = 41,411], 2-h post oral glucose load plasma glucose [2-h PG; n = 21,334], and A1C [n = 28,010]) was examined.
When diabetes-specific retinopathy was plotted against continuous glycemic measures, a curvilinear relationship was observed for FPG and A1C. Diabetes-specific retinopathy prevalence was low for FPG <6.0 mmol/l and A1C <6.0% but increased above these levels. Based on vigintile (20 groups with equal numbers) distributions, glycemic thresholds for diabetes-specific retinopathy were observed over the range of 6.4–6.8 mmol/l for FPG, 9.8–10.6 mmol/l for 2-h PG, and 6.3–6.7% for A1C. Thresholds for diabetes-specific retinopathy from receiver-operating characteristic curve analyses were 6.6 mmol/l for FPG, 13.0 mmol/l for 2-h PG, and 6.4% for A1C.
This study broadens the evidence based on diabetes diagnostic criteria. A narrow threshold range for diabetes-specific retinopathy was identified for FPG and A1C but not for 2-h PG. The combined analyses suggest that the current diabetes diagnostic level for FPG could be lowered to 6.5 mmol/l and that an A1C of 6.5% is a suitable alternative diagnostic criterion.