Narrower Retinal Arteriolar Diameters Research Articles

Retinal Microvascular Diameters are Associated with Diabetic Kidney Disease in Patients with Type 2 Diabetes Mellitus.

To investigate the association between retinal microvascular diameters and diabetic kidney disease (DKD) in patients with type 2 diabetes mellitus (T2DM). A total of 690 patients with T2DM were included in this retrospective study. Patients were divided into DKD and non-DKD groups according to urine microalbumin/creatinine ratio and estimated glomerular filtration rate. Retinal microvascular diameters were measured by the automated retinal image analysis system. Multivariate logistic regression analysis and restricted cubic splines were used to assess the relationships between the retinal microvascular diameters and DKD in patients with T2DM. Multivariate logistic regression showed that widened diameters of retinal venules and narrowed diameters of retinal arterioles were associated with DKD after adjusting for potential confounding variables. There was a significant linear trend between the diameters of superior temporal retinal venula (P for trend < 0.001, P for non-linearity = 0.080), inferior temporal retinal venula (P for trend < 0.001, P for non-linearity = 0.111) and central retinal venular equivalent (CRVE) (P for trend < 0.001, P for non-linearity = 0.392) and risk of DKD in patients with T2DM. The restricted cubic splines showed that narrowed retinal arteriolar diameters, superior and inferior nasal retinal venulas were associated with the risk of DKD in a non-linear fashion (all P for non-linearity < 0.001). Wider retinal venular diameters and narrower retinal arteriolar diameters were associated with an increased risk of DKD in patients with T2DM. Widened retinal venular diameters, especially CRVE, superior and inferior temporal retinal venula, were positively associated with an increased risk of DKD in a linear fashion. In contrast, narrowed retinal arteriolar diameters were associated with the risk of DKD in a non-linear fashion.

Retinal vessel caliber and tortuosity and prediction of 5-year incidence of hypertension.

With arterial hypertension as a global risk factor for cerebrovascular and cardiovascular diseases, we examined whether retinal blood vessel caliber and tortuosity assessed by a vessel-constraint network model can predict the incidence of hypertension. The community-based prospective study included 9230 individuals who were followed for 5 years. Ocular fundus photographs taken at baseline were analyzed by a vessel-constraint network model. Within the 5-year follow-up, 1279 (18.8%) and 474 (7.0%) participants out of 6813 individuals free of hypertension at baseline developed hypertension and severe hypertension, respectively. In multivariable analysis, a higher incidence of hypertension was related to a narrower retinal arteriolar diameter ( P < 0.001), wider venular diameter ( P = 0.005), and a smaller arteriole-to-venule diameter ratio ( P < 0.001) at baseline. Individuals with the 5% narrowest arteriole or the 5% widest venule diameter had a 17.1-fold [95% confidence interval (CI):7.9, 37.2] or 2.3-fold (95% CI: 1.4, 3.7) increased risk for developing hypertension, as compared with those with the 5% widest arteriole or the 5% narrowest venule. The area under the receiver operator characteristic curve for predicting the 5-year incidence of hypertension and severe hypertension was 0.791 (95% CI: 0.778, 0.804) and 0.839 (95% CI: 0.821, 0.856), respectively. Although the venular tortuosity was positively associated with the presence of hypertension at baseline ( P = 0.01), neither arteriolar tortuosity nor venular tortuosity was associated with incident hypertension (both P ≥ 0.10). Narrower retinal arterioles and wider venules indicate an increased risk for incident hypertension within 5 years, while tortuous retinal venules are associated with the presence rather than the incidence of hypertension. The automatic assessment of retinal vessel features performed well in identifying individuals at risk of developing hypertension.

Association between retinal arterial narrowing and left ventricular diastolic dysfunction in masked hypertensives.

Morphological change in retinal vessel diameters has been reported to be associated with negative cardiovascular outcomes, but its association with left ventricular diastolic dysfunction (LVDD) is not clear. This study aimed to examine the association between echocardiographic markers of LVDD and retinal vascular diameters, in untreated masked hypertension (MH). In this observational study, 105 MH patients without other cardiovascular risks were included (mean age 48.4±5.7, female 72.4%). All individuals underwent extensive clinical and laboratory investigations, including echocardiography, ambulatory blood pressure monitoring, and retinal vascular diameters measured by optical coherence tomography. In the group, LVDD was diagnosed in 36 participants evaluated by left ventricular volume index, E/A and E/e' ratio. Compared to non-LVDD, LVDD subjects displayed narrower retinal arteriolar diameter (139.1±33.8 vs 165.1±29.1; adjusted P=.007) and wider retinal venular diameter (237.9±42.2 vs 214.9±44.8; adjusted P=.045). Significant and independent associations were demonstrated for retinal arteriolar narrowing and E/A ratio (adjusted β=0.744, P=.031) and for retinal arteriolar diameter and E/e' ratio (adjusted β=-0.158, P=.001) after controlling for age, gender, body mass index, ambulatory systolic blood pressure, low-density lipoprotein cholesterol, and retinal venular diameter. In untreated MH subjects, retinal arteriolar diameter, a marker of microvascular damage, was independently associated with echocardiographic markers of diastolic dysfunction. These findings might underscore the hypothesis that microvascular disease could contribute to cardiac remodeling.

Retinal vascular changes and right ventricular structure and function: the MESA-Right Ventricle and MESA-Eye studies.

Retinal vessel diameters have been associated with left ventricular morphology and function but their relationship with the right ventricle (RV) has not been studied. We hypothesized that wider retinal venules and narrower retinal arterioles are associated with RV morphology and function. RV end-diastolic mass (RVEDM), end-diastolic volume (RVEDV), end-systolic volume (RVESV), stroke volume (RVSV), and ejection fraction (RVEF) were assessed using cardiac magnetic resonance imaging (MRI) scans of 4204 participants without clinical cardiovascular disease at the baseline examination; retinal photography was obtained at the second examination. Mean diameters of retinal arterioles and venules were measured and summarized as central retinal vein and artery equivalents (“veins” and “arteries,” respectively). After adjusting for covariates, wider veins were associated with greater RVEDM and RVEDV in women (P = 0.04 and P = 0.02, respectively), whereas there was an inverse association with RVEDV in men (P = 0.02). In both sexes, narrower arteries were associated with lower RVEDM (P < 0.001 in women and P = 0.002 in men) and smaller RVEDV (P < 0.001 in women and P = 0.04 in men) in adjusted models. Narrower arteries were also associated with lower RVEF in men but this was of borderline significance after adjusting for the LVEF (P = 0.08). Wider retinal venular diameter was associated with sex-specific changes in RVEDM and RVEDV in adults without clinical cardiovascular disease. Narrower retinal arteriolar diameter was associated with significantly lower RVEDM and smaller RVEDV in both sexes.

Serum lipid profiles and dyslipidaemia are associated with retinal microvascular changes in children and adolescents

The present study aims to assess the relationship between serum lipid parameters and retinal microvascular calibres in children and adolescents. A total of 950 participants aged 7 to 19 years were recruited. Central retinal arteriolar equivalent (CRAE) and central retinal venular equivalent (CRVE) were measured from digital retinal images. Serological testing was performed to obtain lipid profiles. Dyslipidaemia was defined according to the US national expert panel guideline. After adjusted for age, sex, mean arterial blood pressure, axial length, body mass index and the fellow retinal vascular calibre, no significant association was found between retinal vascular diameters and any lipid parameters (all P > 0.05) in children younger than 12 years. Among the adolescents 12 years and older, increased triglycerides, total cholesterol, low-density lipoprotein cholesterol, and apoB were associated with decrease in CRAE (β = −1.33, −1.83, −1.92 and −7.18, P = 0.031, 0.003, 0.006, and 0.009, respectively). Compared with normolipidemic counterparts, adolescents with dyslipidaemia had significantly narrower retinal arteriolar diameters. No significant relationship between lipid subclass levels and CRVE was revealed in adolescents. The present findings suggest that the elevation of atherogenic lipids in adolescents is closely related to the adverse changes of retinal arterioles. Dyslipidaemia may affect systemic microvasculature from childhood on.

Chronic kidney disease and the severity of coronary artery disease and retinal microvasculature changes: a cross-sectional study.

Prior studies have suggested the association between incidence of coronary artery disease (CAD) with chronic kidney disease (CKD) and poor glomerular filtration function. However to the best of our knowledge, few studies have specifically assessed this relationship based on the severity of CAD as quantified using Extent and Gensini scores. Between June 2009 and January 2012, data were collected from 1,680 participants as part of the Australian Heart Eye Study (AHES) cohort. Coronary angiograms were scored according to Gensini (severity) and Extent scores. Retinal vessel calibres were measured using validated semi-automated software. Potential confounders were adjusted for using multivariate analysis. There were no significant associations found between CKD status with Extent and Gensini scores for CAD severity, both unadjusted and when adjusted for confounding factors. In unadjusted analyses, a significant association between CKD and narrower retinal arteriolar diameter was observed (P=0.0072). After multivariate adjustment, the association between CKD and retinal arteriolar diameter was attenuated and was no longer significant (P=0.1466). No associations were observed between retinal venular calibre and prevalent CKD. The present study demonstrated no independent associations between CKD and CAD severity. These results warrant validation by future large, prospective longitudinal studies.

The Relationship of Retinal Vessel Caliber With Erectile Dysfunction in Patients With Type 2 Diabetes

To investigate the relationship of retinal vessel caliber with erectile dysfunction (ED) in males with type 2 diabetes. A hospital-based cross-sectional study. Male patients with type 2 diabetes were recruited from the Diabetic Management Project. All underwent a complete eye examination, a comprehensive interview, and blood and urine tests. Retinal vessel diameter was measured from retinal photographs by trained graders using semiautomated software. ED was defined as problems achieving or maintaining an erection and was assessed using a self-reported questionnaire. A total of 289 male patients with a mean (±SD) age of 65.3 years (±11.2) were assessed. After adjusting for age, diastolic blood pressure, duration of diabetes, HbA1c, total cholesterol, presence of diabetic retinopathy, and any diabetic complication, narrower retinal arteriolar diameter (odds ratio [OR] 1.66; 95% confidence interval [CI] 1.09-2.54; P = 0.019) and wider venular diameter (OR 1.58; 95% CI 1.03-2.44; P = 0.038) were associated with ED. Narrower retinal arteriolar and wider venular diameter are independently associated with an increased risk of self-reported ED. These results suggest a microvascular component in the pathogenesis of this condition.

Prevalence and Risk Factors of Epiretinal Membrane in Asian Indians

To describe the prevalence of epiretinal membrane (ERM) and its risk factors in an Indian population and compare the findings with other populations. The Singapore Indian Eye Study is a population-based survey of 3400 Asian Indians aged between 40 and 80 years. A comprehensive ophthalmic examination, standardized interviews, and laboratory blood tests were performed. Digital retinal fundus photographs were assessed for the presence of ERM following the definitions used in the Blue Mountains Eye Study (BMES). ERM was classified into a less severe form termed "cellophane macular reflex" (CMR) and a more severe form termed "preretinal macular fibrosis" (PMF) and also as primary and secondary (if it was associated with retinal pathology or cataract surgery). A total of 3328 persons (mean age 57.8 ± [SD] 10.1 years, and 50.2% male) provided data in this study. The age-standardized prevalence of ERM was 7.6% (95% confidence interval [CI], 6.8-8.6), CMR 4.1% (95% CI, 3.5-4.9), and PMF 3.5% (95% CI, 2.9-4.2). Older age (odds ratio [OR], 1.09; 95% CI, 1.07-1.11, per year increase), increasing myopic refraction (OR, 1.14; 95% CI, 1.07-1.22, per diopter decrease), and narrower retinal arteriolar diameter (OR, 1.02; 95% CI, 1.00-1.03, per μm decrease) were significantly associated with primary ERM. The age-standardized prevalence of ERM in the Indian population in Singapore was 7.6%. This is similar to Malays in Singapore (8.0%) and higher than the prevalence in whites in Australia (4.7%). Significant factors associated with primary ERM were older age, myopia, and narrower retinal arteriolar diameter.

COARSE AND TRAFFIC-RELATED PARTICULATE MATTER AND THE HUMAN MICROVASCULATURE IN VIVO ASSESSED VIA RETINAL IMAGING: THE MULTI-ETHNIC STUDY OF ATHEROSCLEROSIS

Background and Aims: Airborne particulate matter may affect cardiovascular health via underlying vascular disease. While recent evidence links fine particles (PM2.5) to microvasculature changes, associations with larger coarse particles (PM10-2.5) and traffic-related particles remain unknown. Methods: Associations between retinal arteriolar diameters, a microvasculature measure, and chronic residential concentrations of PM10-2.5 mass, PM10-2.5 copper (an indicator of motor vehicle brake wear), and residential proximity to major roadways were examined among Chicago-based Multi-Ethnic Study of Atherosclerosis participants. Subjects aged 46 to 87 years and without clinical cardiovascular disease at enrollment (2000-2002) underwent retinal photography between 2002-2003. Participant-specific concentrations were estimated using speciated PM10-2.5 data and a universal kriging spatial prediction model. A binary nearness to major roadways variable was also calculated. All associations were examined using linear regression models adjusted for age, sex, race/ethnicity, education, income, smoking status, alcohol use, physical activity, body mass index, family history of cardiovascular disease, diabetes, serum cholesterol, glucose, blood pressure, emphysema, C-reactive protein, and medication use. Secondary analyses included control for long-term concentrations of PM2.5. Results: Among 779 participants with complete data, retinal arteriolar diameters were not associated with PM10-2.5 concentrations but were associated with traffic-related exposures. Narrower arterioles were found among persons residing near roadways (-3.0 μm, 95% CI: -5.1 to -0.8) and among persons living in areas of higher PM10-2.5 copper concentrations (-1.2 μm per 4 ng/m3, 95% CI: -2.7 to 0.2). Control for PM2.5 strengthened the associations with PM10-2.5 copper (-2.4 μm per 4 ng/m3, 95% CI: -4.7 to -0.1), whereas associations with residential proximity to roadways were unaffected. Conclusions: Higher exposures to traffic as assessed by residential proximity and PM10-2.5 copper concentrations, but not PM10-2.5 mass, were associated with narrower retinal arteriolar diameters in older individuals. This suggests that the retinal microvasculature is sensitive to traffic pollution but not coarse particulate mass.

Air Pollution and the Microvasculature: A Cross-Sectional Assessment of In Vivo Retinal Images in the Population-Based Multi-Ethnic Study of Atherosclerosis (MESA)

Long- and short-term exposures to air pollution, especially fine particulate matter (PM(2.5)), have been linked to cardiovascular morbidity and mortality. One hypothesized mechanism for these associations involves microvascular effects. Retinal photography provides a novel, in vivo approach to examine the association of air pollution with changes in the human microvasculature. Chronic and acute associations between residential air pollution concentrations and retinal vessel diameters, expressed as central retinal arteriolar equivalents (CRAE) and central retinal venular equivalents (CRVE), were examined using digital retinal images taken in Multi-Ethnic Study of Atherosclerosis (MESA) participants between 2002 and 2003. Study participants (46 to 87 years of age) were without clinical cardiovascular disease at the baseline examination (2000-2002). Long-term outdoor concentrations of PM(2.5) were estimated at each participant's home for the 2 years preceding the clinical exam using a spatio-temporal model. Short-term concentrations were assigned using outdoor measurements on the day preceding the clinical exam. Residential proximity to roadways was also used as an indicator of long-term traffic exposures. All associations were examined using linear regression models adjusted for subject-specific age, sex, race/ethnicity, education, income, smoking status, alcohol use, physical activity, body mass index, family history of cardiovascular disease, diabetes status, serum cholesterol, glucose, blood pressure, emphysema, C-reactive protein, medication use, and fellow vessel diameter. Short-term associations were further controlled for weather and seasonality. Among the 4,607 participants with complete data, CRAE were found to be narrower among persons residing in regions with increased long- and short-term levels of PM(2.5). These relationships were observed in a joint exposure model with -0.8 µm (95% confidence interval [CI] -1.1 to -0.5) and -0.4 µm (95% CI -0.8 to 0.1) decreases in CRAE per interquartile increases in long- (3 µg/m(3)) and short-term (9 µg/m(3)) PM(2.5) levels, respectively. These reductions in CRAE are equivalent to 7- and 3-year increases in age in the same cohort. Similarly, living near a major road was also associated with a -0.7 µm decrease (95% CI -1.4 to 0.1) in CRAE. Although the chronic association with CRAE was largely influenced by differences in exposure between cities, this relationship was generally robust to control for city-level covariates and no significant differences were observed between cities. Wider CRVE were associated with living in areas of higher PM(2.5) concentrations, but these findings were less robust and not supported by the presence of consistent acute associations with PM(2.5). Residing in regions with higher air pollution concentrations and experiencing daily increases in air pollution were each associated with narrower retinal arteriolar diameters in older individuals. These findings support the hypothesis that important vascular phenomena are associated with small increases in short-term or long-term air pollution exposures, even at current exposure levels, and further corroborate reported associations between air pollution and the development and exacerbation of clinical cardiovascular disease. Please see later in the article for the Editors' Summary.

Effect of obesity on retinal vascular structure in pre-adolescent children

OBJECTIVES. In adults, obesity is linked to changes in the retinal microvasculature. Limited research has been conducted into this association in children. We examined in a cohort of pre-adolescents the relationship between body mass index (BMI) and retinal vascular structure, including retinal vessel diameter and retinal vessel fractals, a measure of geometric patterns reflecting vessel density. A population-based study among school children (2 353/3 144 [75.3%], median age, 12.7 years) recruited from a random cluster sample of 21 schools was conducted during 2004-5. Retinal images were taken and vessel diameter and fractal dimension were quantified using computer-based programs following standardized protocols. Anthropometric measures (weight, height, waist circumference, and BMI) were obtained and defined using standardized protocols. Children with the highest quartile of BMI had narrower retinal arteriolar diameter (2.8 μm narrower, p<0.0001) and wider venular caliber (4.2 μm wider, p=0.001) than those with BMI in the lowest quartile, after adjusting for age, sex, ethnicity, mean arterial blood pressure, iris color, axial length, birth weight and fellow retinal vessel caliber. Obese children had narrower retinal arteriolar diameter (2.8 μm narrower, p=0.01) and wider venular diameter (4.5 μm wider, p=0.01) than in non-overweight/obese children. Retinal fractal dimension was not significantly associated with BMI. Increasing quartiles of waist circumference were also associated with retinal vessel diameter. Our data provide evidence of adverse retinal microvascular caliber changes in obese pre-adolescent children, well before the onset of metabolic and cardiovascular disease in adulthood, and support an early, generalized adverse effect of adiposity on microvascular structure.

Retinal vessel diameters and risk of hypertension: the Multiethnic Study of Atherosclerosis

To describe the prospective relationship of retinal vessel diameters with risk of hypertension in a multiethnic population-based cohort. The Multi-Ethnic Study of Atherosclerosis is a population-based study of subclinical cardiovascular disease among white, African-American, Hispanic, and Chinese American adults aged 45-84 years. Retinal vessel diameters were measured using a standardized imaging software at the second examination (considered baseline in this analysis) and summarized as the central retinal artery/vein equivalent. Presence of retinopathy and retinal focal arteriolar narrowing and arteriovenous nicking was assessed by trained graders. Incidence of hypertension was defined among participants at risk as systolic blood pressure at least 140 mmHg, diastolic blood pressure at least 90 mmHg, or use of an antihypertensive medication. Of the initial 6237 participants at baseline, 2583 were at risk of hypertension. After 3.2 +/- 0.5 years of follow-up, 448 (17.3%) participants developed hypertension. After adjusting for age, sex, race/ethnicity, the average of mean arterial blood pressure in the first and second examination, and other vascular risk factors, persons with narrower retinal arteriolar diameter and wider venular diameter at baseline were more likely to develop hypertension [odds ratio per SD decrease in central retinal artery equivalent 1.20, 95% confidence intervals 1.02, 1.42; and odds ratio per SD increase in central retinal vein equivalent 1.18, 95% confidence interval 1.02, 1.37]. Persons with focal arteriolar narrowing were also more likely to develop hypertension (odds ratio 1.80, 95% confidence interval 1.09, 2.97). Findings from this multiethnic population confirm that narrower retinal arteriolar diameter and wider venular diameter are associated with the development of hypertension independent of traditional risk factors.

Racial difference in the prevalence of epiretinal membrane between Caucasians and Asians

Background/aims:To describe the prevalence and risk factors of epiretinal membranes (ERM) in Asian Malays and to compare this with a white population.Methods:The Singapore Malay Eye Study examined 3280 persons (78.7%...

Retinal Arteriolar Narrowing, Hypertension, and Subsequent Risk of Diabetes Mellitus

Microvascular disease and hypertension have been linked with risk of diabetes mellitus. We examined the association of retinal arteriolar narrowing, a marker of chronic hypertension, with incident diabetes. Prospective cohort study of 3251 nondiabetic persons aged 43 to 86 years living in Wisconsin. The diameters of retinal vessels were measured from baseline retinal photographs of participants. Retinal measurements were summarized as the retinal arteriole-to-venule ratio, with smaller ratios indicating narrower arteriolar diameters. Incident diabetes cases were ascertained at the 5-year and 10-year follow-up examinations. There were 249 incident diabetes cases. Participants with narrower retinal arteriolar diameters had a higher incidence of diabetes (cumulative incidences of 5.1%, 7.0%, 9.2%, and 11.7%, comparing decreasing quartiles of arteriole-to-venule ratio). After controlling for baseline casual blood glucose level, glycosylated hemoglobin level, body mass index, and other risk factors, retinal arteriolar narrowing was significantly associated with risk of incident diabetes (multivariable-adjusted relative risk, 1.53; 95% confidence interval, 1.03-2.27; comparing smallest to largest arteriole-to-venule ratio quartiles). Participants with both hypertension and retinal arteriolar narrowing had a 3-fold higher risk of incident diabetes (multivariable-adjusted relative risk, 3.41; 95% confidence interval, 1.66-6.98) than normotensive participants without arteriolar narrowing. Retinal arteriolar narrowing is related to risk of incident diabetes. These data suggest a possible link between systemic arteriolar narrowing associated with hypertension and diabetes development.

Retinal vessel diameter and open-angle glaucoma: The Blue Mountains Eye Study

To examine the relationship between open-angle glaucoma (OAG) and retinal vessel diameter among baseline participants in the Blue Mountains Eye Study. Population-based cross-sectional study. The study included 3654 persons older than 49 years, representing 82.4% of permanent residents living in an area west of Sydney. Participants had a detailed eye examination, including automated perimetry and stereo optic disc photography. A computer-assisted program measured retinal vessel diameters from digitized photographs of right eyes. Open-angle glaucoma was diagnosed from matching visual field defects and optic disc cupping, without reference to intraocular pressure (IOP) level. Ocular hypertension was defined as IOP of >21 mmHg in either eye, without matching glaucomatous optic disc and field changes. Average retinal vessel diameters, measured from right eyes, were summarized as arteriolar and venular equivalents. The lowest quintile of the arteriolar equivalent or arteriole-to-venule ratio was used to define generalized retinal arteriolar narrowing. The study included 3314 participants, after excluding those with incomplete data or nonglaucomatous optic nerve disease. Of persons included, 59 (1.8%) had evidence of glaucomatous damage affecting the right eye, 3065 (92.5%) had no damage to either eye, and 163 (4.9%) had ocular hypertension. Right eyes with glaucomatous damage had significantly narrower retinal arteriolar diameters (183+/-2.6 microm) than eyes without glaucoma (194+/-0.4 microm, P = 0.0001) or eyes with ocular hypertension (195+/-1.6 microm, P = 0.0002), after adjusting for age, mean arterial blood pressure, and other confounding variables, including refraction. Right eyes with glaucomatous damage were at least 2 times more likely to have generalized retinal arteriolar narrowing than eyes without glaucoma (odds ratio, 2.7; 95% confidence interval, 1.5-4.8). These population-based data suggest that generalized retinal arteriolar narrowing, an indicator of localized vascular change, is significantly associated with optic nerve damage caused by OAG. It is not clear whether such a retinal arteriolar change reflects an ischemic process leading to optic nerve damage or results from loss of retinal neurons secondary to glaucoma.