Retinal microvascular signs and risk of diabetic kidney disease in asian and white populations.
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ABSTRACT:
SUBMITTER: Nusinovici S
PROVIDER: S-EPMC7921402 | biostudies-literature | 2021 Mar
REPOSITORIES: biostudies-literature
Publications
Retinal microvascular signs and risk of diabetic kidney disease in asian and white populations.
Nusinovici Simon S Sabanayagam Charumathi C Lee Kristine E KE Zhang Liang L Cheung Carol Y CY Tai E Shyong ES Tan Gavin S W GSW Cheng Ching Yu CY Klein Barbara E K BEK Wong Tien Yin TY
Scientific reports 20210301 1
The objective was to examine prospectively the association between retinal microvascular signs and development of diabetic kidney disease (DKD) in Asian and White populations. We analysed two population-based cohorts, composing of 1,221 Asians (SEED) and 703 White (WESDR) adults with diabetes. Retinal microvascular signs at baseline included vascular caliber (arteriolar-CRAE, and venular-CRVE) and diabetic retinopathy (DR). Incident cases of DKD were identified after ~ 6-year. Incident cases wer ...[more]
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Project description:BackgroundRetinal microvascular signs may provide insights into the structure and function of small vessels that are associated with renal disease. We examined the relationship of retinal microvascular signs with both prevalent and incident end-stage renal disease (ESRD) in a multi-ethnic Asian population.MethodsA total of 5763 subjects (aged ≥ 40 years) from two prospective population-based studies (the Singapore Malay Eye Study and the Singapore Prospective Study) were included for the current analysis. Retinopathy was graded using the modified Airlie House classification system. Retinal vascular parameters were measured using computer-assisted programs to quantify the retinal vessel widths (arteriolar and venular caliber) and retinal vascular network (fractal dimension). Data on ESRD was obtained by record linkage with the ESRD cases registered by National Registry of Diseases Office, Singapore. Multi-variable adjusted regression analyses were performed to assess the associations of baseline retinal vascular parameters and prevalent and incident ESRD.ResultsAt baseline, 21(0.36%) persons had prevalent ESRD. During a median follow-up of 4.3 years, 33 (0.57%) subjects developed ESRD. In our analyses, retinopathy was associated with prevalent ESRD (multi-variable adjusted odds ratio [OR], 3.21, 95% confidence interval [CI]: 1.28-8.05) and incident ESRD (multi-variable adjusted hazard ratio [HR], 2.51, 95%CI: 1.14-5.54). This association was largely seen in person with diabetes (HR, 2.60, 95%CI: 1.01-6.66) and not present in persons without diabetes (HR, 1.65, 95%CI: 0.14-18.98). Retinal arteriolar caliber, retinal venular caliber and retinal vascular fractal dimension were not associated with ESRD.ConclusionRetinopathy signs in persons with diabetes are related to an increased risk of ESRD; however, other microvascular changes in the retina are not associated with ESRD.
| S-EPMC4320082 | biostudies-literature
Project description:PurposeTo evaluate the relationships between chronic kidney disease (CKD) with retinal nerve fiber layer (RNFL) and ganglion cell-inner plexiform layer (GCIPL) thickness profiles of eyes in Asian and White populations.DesignCross-sectional analysis.ParticipantsA total of 5066 Asian participants (1367 Malays, 1772 Indians, and 1927 Chinese) from the Singapore Epidemiology of Eye Diseases Study (SEED) were included, consisting of 9594 eyes for peripapillary RNFL analysis and 8661 eyes for GCIPL analysis. Additionally, 45 064 White participants (87 649 eyes) from the United Kingdom Biobank (UKBB) were included for both macular RNFL analysis and GCIPL analysis.MethodsNonglaucoma participants aged ≥ 40 years with complete data for estimated glomerular filtration rate (eGFR) were included from both SEED and UKBB. In SEED, peripapillary RNFL and GCIPL thickness were measured by Cirrus HD-OCT 4000. In UKBB, macular RNFL and GCIPL were measured by Topcon 3D-OCT 1000 Mark II. Chronic kidney disease was defined as eGFR < 60 ml/min/1.73 m2 in both data sets. To evaluate the associations between kidney function status with RNFL and GCIPL thickness profiles, multivariable linear regression with generalized estimating equation models were performed in SEED and UKBB data sets separately.Main outcome measuresAverage peripapillary and macular RNFL thickness and macular GCIPL thickness.ResultsIn SEED, after adjusting for age, gender, ethnicity, systolic blood pressure, antihypertensive medication, diabetes, hyperlipidemia, body mass index, smoking status, and intraocular pressure, presence of CKD (β = -1.31; 95% confidence interval [CI], -2.37 to -0.26; P = 0.015) and reduced eGFR (per 10 ml/min/1.73 m2; β = -0.32; 95% CI, -0.50 to -0.13; P = 0.001) were associated with thinner average peripapillary RNFL. Presence of CKD (β = -1.63; 95% CI, -2.42 to -0.84) and reduced eGFR (per 10 ml/min/1.73 m2; β = -0.30; 95% CI, -0.44 to -0.16) were consistently associated with thinner GCIPL in SEED (all P < 0.001). In UKBB, after adjusting for the above-mentioned covariates (except ethnicity), reduced eGFR (per 10 ml/min/1.73 m2; β = -0.06; 95% CI, -0.10 to -0.01; P = 0.008) was associated with thinner macular RNFL and CKD (β = -0.62; 95% CI, -1.16 to -0.08; P = 0.024) was associated with thinner average GCIPL.ConclusionWe consistently observed associations between CKD and thinning of RNFL and GCIPL across Asian and White populations' eyes. These findings further suggest that compromised kidney function is associated with RNFL and GCIPL thinning.Financial disclosuresThe author(s) have no proprietary or commercial interest in any materials discussed in this article.
| S-EPMC10587624 | biostudies-literature
Project description:Diabetic retinal disease (DRD) remains the most common cause of vision loss in adults of working age. Progress on the development of new therapies for DRD has been limited by the complexity of the human eye, which constrains the utility of traditional research techniques, including animal and tissue culture models-a problem shared by those in the field of kidney disease research. By contrast, significant progress in the study of diabetic kidney disease (DKD) has resulted from the successful employment of systems biology approaches. Systems biology is widely used to comprehensively understand complex human diseases through the unbiased integration of genetic, environmental, and phenotypic aspects of the disease with the functional and structural manifestations of the disease. The application of a systems biology approach to DRD may help to clarify the molecular basis of the disease and its progression. Acquiring this type of information might enable the development of personalized treatment approaches, with the goal of discovering new therapies targeted to an individual's specific DRD pathophysiology and phenotype. Furthermore, recent efforts have revealed shared and distinct pathways and molecular targets of DRD and DKD, highlighting the complex pathophysiology of these diseases and raising the possibility of therapeutics beneficial to both organs. The objective of this review is to survey the current understanding of DRD pathophysiology and to demonstrate the investigative approaches currently applied to DKD that could promote a more thorough understanding of the structure, function, and progression of DRD.
| S-EPMC8003049 | biostudies-literature
Project description:BACKGROUND AND PURPOSE:Small-vessel disease contributes to the pathophysiology of stroke, and retinal microvascular signs have been linked to the risk of stroke. We examined the relationship of retinal signs with incident stroke in a multiethnic cohort. METHODS:The Multi-Ethnic Study of Atherosclerosis (MESA) is a prospective cohort study that enrolled participants without clinical cardiovascular diseases from 6 US communities between 2000 and 2002. Of the participants, 4849 (71.2%) had fundus photography performed in 2002 to 2004. Retinopathy and retinal vessel caliber were assessed from retinal images. Stroke risk factors including high-sensitivity C-reactive protein, carotid artery intima-media thickness, and coronary artery calcium were measured using standardized protocols. Incident stroke was confirmed from medical record review and death certificates. RESULTS:After 6 years of follow-up, there were 62 incident strokes. Narrower retinal arteriolar caliber was associated with increased risk of stroke after adjusting for conventional cardiovascular risk factors (adjusted incidence rate ratio, 2.83; 95% CI, 1.34-5.95; P=0.006; adjusted hazard ratio, 3.01; 95% CI, 1.29-6.99; P=0.011). Retinopathy in persons without diabetes was associated with increased risk of stroke (adjusted adjusted incidence rate ratio, 2.96; 95% CI, 1.50-5.84; P=0.002; adjusted hazard ratio, 3.07; 95% CI, 1.17-8.09; P=0.023). These associations remained significant after adjusting for high-sensitivity C-reactive protein, carotid intima-media thickness, or coronary artery calcium. CONCLUSIONS:Narrower retinal arteriolar caliber and retinopathy in nondiabetic persons were associated with increased risk of stroke in this relatively healthy multiethnic cohort independent of traditional risk factors and measures of atherosclerosis. The association between narrower retinal arteriolar caliber and stroke warrants further investigation.
| S-EPMC3508325 | biostudies-literature
Project description:ObjectivesTo determine the risk factors for retinal microvascular impairment on optical coherence tomography angiography (OCT-A) in type 2 diabetic patients without clinical diabetic retinopathy (DR).MethodsThis retrospective and cross-sectional study enrolled 74 diabetic patients without clinically evident DR for the study group and 34 healthy subjects for the control group. OCT-A parameters were measured to determine vascular density (VD) and the foveal avascular zone (FAZ) size in the superficial and deep capillary plexuses (SCP/DCP) of the retina. Clinical data were collected on sex, age, diabetes duration, hemoglobin A1c (HbA1c), hypertension, dyslipidemia, low-density lipoprotein cholesterol (LDL-C), estimated glomerular filtration rate (eGFR) and smoking status. Multiple linear regression analyses were performed to represent the associated clinical variables with OCT-A parameters in diabetic patients.ResultsIn comparison between the study and control groups, the VD in the SCP and DCP were significantly lower in diabetic patients compared to the controls (P = 0.022 and 0.003, respectively). The FAZ size in the SCP and DCP were significantly greater in diabetic patients compared to the controls (P = 0.035 and <0.001, respectively). In age- and sex-adjusted multiple regression analyses for the diabetic patients, dyslipidemia and hypertension were negatively associated with SCP-VD (β = -0.357, P = 0.002; β = -0.239, P = 0.039, respectively). Current smoking was correlated with lower DCP-VD (β = -0.255, P = 0.043). Greater SCP-FAZ size was associated with dyslipidemia and greater LDL-C (β = 0.254, P = 0.013; β = 0.232, P = 0.029, respectively), and greater DCP-FAZ size, with lower eGFR and greater LDL-C (β = -0.355, P = 0.004; β = 0.235, P = 0.037, respectively).ConclusionsDiabetic patients without clinical DR showed lower VD and greater FAZ size in the SCP and DCP compared to healthy controls. In diabetic patients without clinical DR, dyslipidemia and/or high LDL-C were important risk factors for retinal microvascular impairment. Hypertension, current smoking and lower eGFR also contributed to microvascular impairment.
| S-EPMC6084984 | biostudies-literature
Project description:ObjectiveTo develop a deep learning algorithm (DLA) to detect diabetic kideny disease (DKD) from retinal photographs of patients with diabetes, and evaluate performance in multiethnic populations.Materials and methodsWe trained 3 models: (1) image-only; (2) risk factor (RF)-only multivariable logistic regression (LR) model adjusted for age, sex, ethnicity, diabetes duration, HbA1c, systolic blood pressure; (3) hybrid multivariable LR model combining RF data and standardized z-scores from image-only model. Data from Singapore Integrated Diabetic Retinopathy Program (SiDRP) were used to develop (6066 participants with diabetes, primary-care-based) and internally validate (5-fold cross-validation) the models. External testing on 2 independent datasets: (1) Singapore Epidemiology of Eye Diseases (SEED) study (1885 participants with diabetes, population-based); (2) Singapore Macroangiopathy and Microvascular Reactivity in Type 2 Diabetes (SMART2D) (439 participants with diabetes, cross-sectional) in Singapore. Supplementary external testing on 2 Caucasian cohorts: (3) Australian Eye and Heart Study (AHES) (460 participants with diabetes, cross-sectional) and (4) Northern Ireland Cohort for the Longitudinal Study of Ageing (NICOLA) (265 participants with diabetes, cross-sectional).ResultsIn SiDRP validation, area under the curve (AUC) was 0.826(95% CI 0.818-0.833) for image-only, 0.847(0.840-0.854) for RF-only, and 0.866(0.859-0.872) for hybrid. Estimates with SEED were 0.764(0.743-0.785) for image-only, 0.802(0.783-0.822) for RF-only, and 0.828(0.810-0.846) for hybrid. In SMART2D, AUC was 0.726(0.686-0.765) for image-only, 0.701(0.660-0.741) in RF-only, 0.761(0.724-0.797) for hybrid.Discussion and conclusionThere is potential for DLA using retinal images as a screening adjunct for DKD among individuals with diabetes. This can value-add to existing DLA systems which diagnose diabetic retinopathy from retinal images, facilitating primary screening for DKD.
| S-EPMC10654858 | biostudies-literature
Project description:BackgroundTo explore the characteristics of retina microvascular changes in patients with diabetic nephropathy (DN) and its risk factors.MethodsRetrospective, observational study. 145 patients with type 2 diabetic mellitus (DM) and DN were included in the study. Demographic and clinical parameters were obtained from medical records. Presence of diabetic retinopathy (DR), hard exudates (HEs) and diabetic macular edema (DME) were evaluated according to the color fundus images, optical coherence tomography (OCT) and fluorescence angiography (FFA).ResultsDR accounted for 61.4% in type 2 DM patients with DN, of which proliferative diabetic retinopathy (PDR) accounted for 23.6% and sight threatening DR accounted for 35.7%. DR group had significantly higher levels of low-density lipoprotein cholesterol (LDL-C) (p = 0.004), HbA1c (P = 0.037), Urine albumin creatine ratio (ACR) (p < 0.001) and lower level of estimated glomerular filtration rate (eGFR) (P = 0.013). Logistic regression analysis showed DR was significantly associated with ACR stage (p = 0.011). Subjects with ACR stage3 had higher incidence of DR compared with subjects with ACR stage1 (OR = 24.15, 95%CI: 2.06-282.95). 138 eyes of 138 patients were analyzed for HEs and DME, of which 23.2% had HEs in posterior pole and 9.4% had DME. Visual acuity was worse in HEs group than in non-HEs group. There was significant difference in the LDL-C cholesterol level, total cholesterol (CHOL) level and ACR between HEs group and non-HEs group.ConclusionsA relatively higher prevalence of DR was found in type 2 DM patients with DN. ACR stage could be recognized as a risk factor for DR in DN patients. Patients with DN needs ophthalmic examination more timely and more frequently.
| S-EPMC10161482 | biostudies-literature
Project description:Diabetic retinopathy (DR) has been considered a microvascular disease, but it has become evident that neurodegeneration also plays a key role in this complex pathology. Indeed, this complexity is reflected in its progression which occurs at different rates in different type 2 diabetic (T2D) individuals. Based on this concept, our group has identified three DR progression phenotypes that might reflect the interindividual differences: phenotype A, characterized by low microaneurysm turnover (MAT <6), phenotype B, low MAT (<6) and increased central retinal thickness (CRT); and phenotype C, with high MAT (≥6). In this study, we evaluated the progression of DR neurodegeneration, considering ganglion cell+inner plexiform layers (GCL+IPL) thinning, in 170 T2D individuals followed for a period of 5 years, to explore associations with disease progression or risk phenotypes. Ophthalmological examinations were performed at baseline, first 6 months, and annually. GCL+IPL average thickness was evaluated by optical coherence tomography (OCT). Microaneurysm turnover (MAT) was evaluated using the RetMarkerDR. ETDRS level and severity progression were assessed in seven-field color fundus photography. In the overall population there was a significant loss in GCL+IPL (-0.147 μm/year), independently of glycated hemoglobin, age, sex, and duration of diabetes. Interestingly, this progressive thinning in GCL + IPL reached higher values in phenotypes B and C (-0.249 and -0.238 μm/year, respectively), whereas phenotype A remained relatively stable. The presence of neurodegeneration in all phenotypes suggests that it is the retinal vascular response to the early neurodegenerative changes that determines the course of the retinopathy in each individual. Therefore, classification of different DR phenotypes appears to offer relevant clarification of DR disease progression and an opportunity for improved management of each T2D individual with DR, thus playing a valuable role for the implementation of personalized medicine in DR.
| S-EPMC9231566 | biostudies-literature
Project description:BACKGROUND AND PURPOSE:We hypothesized that retinal microvascular signs are associated with executive dysfunction, slow gait, and depressive mood, which are characteristic features of microvascular disease affecting frontal subcortical regions of the brain. METHODS:In the Cardiovascular Health Study, 1744 participants (mean age, 78) free of stroke had retinal photographs and carotid ultrasound during the 1997 to 1998 visit. We examined the cross-sectional association of retinal signs with the digit-symbol substitution test (DSST) score, gait speed, the Center for Epidemiologic Studies-Depression score, and depressive mood, defined as Center for Epidemiologic Studies-Depression score >9 or antidepressant use. RESULTS:After adjusting for potential confounders, retinal signs were associated with lower DSST score (generalized arteriolar narrowing and arteriovenous nicking), slower gait (retinopathy), and depressive mood (generalized arteriolar narrowing). A higher number of retinal signs was associated with lower DSST score (-0.76 and -2.79 points for 1 sign and ?2 signs versus none; P<0.001) and slower gait (-0.009 and -0.083 m/s; P=0.047), but not with the square root of Center for Epidemiologic Studies-Depression score (0.079 and -0.208; P=0.072). In addition, coexistence of retinal signs (generalized arteriolar narrowing and arteriovenous nicking) and carotid atherosclerosis was associated with lower DSST score compared with either process alone (P for interaction <0.01). Notably, further adjustment for ventricular size, white matter disease, and infarcts on MRI did not attenuate the association. CONCLUSIONS:Retinal signs are associated with executive dysfunction and slow gait, and possibly with depressive mood, suggesting a common process involving small vessels.
| S-EPMC3127407 | biostudies-literature
Project description:Diabetic retinopathy is a severe microvascular problem in diabetes mellitus. Silymarin is a flavonoid compound, and according to previous studies, it is a bioactive compound with potent antioxidant and anti-inflammatory properties. This investigation aims to peruse the impact of silymarin against diabetic retinopathy in streptozotocin (STZ)-provoked rats. Thirty-two adult male Wistar rats were randomly allocated into the control group, STZ group, STZ + silymarin (50 mg/kg), and STZ + silymarin (100 mg/kg). STZ rats received silymarin every day until 2 months after diabetes induction. The serum and retinal tissues were collected 2 months after silymarin treatment to determine biochemical and molecular analyses. Silymarin markedly lowered the serum glucose concentration in diabetic rats. Silymarin reduced the increased levels of advanced glycosylated end products (AGEs), the receptors for AGEs (RAGE), and reactive oxygen species (ROS) in diabetic rats. Silymarin also attenuated the phosphorylation of p38 MAP kinase and nuclear factor (NF)-κB p65 and diminished diabetes-induced overexpression of inflammatory cytokines, vascular endothelial growth factor (VEGF), adhesion molecules, and extracellular matrix proteins in STZ rats. Our data suggested that silymarin has protective effects against diabetic retinopathy, which might be related to the inhibition of the AGEs/RAGE axis and its antioxidant and anti-inflammatory activities.
| S-EPMC9508129 | biostudies-literature