Retinal Microvascular Parameters Research Articles

Quantitative measurements of enlarged perivascular spaces in the brain are associated with retinal microvascular parameters in older community-dwelling subjects.

Perivascular Spaces (PVS) become increasingly visible with advancing age on brain MRI, yet their relationship to morphological changes in the underlying microvessels remains poorly understood. Retinal and cerebral microvessels share morphological and physiological properties. We compared computationally-derived PVS morphologies with retinal vessel morphologies in older people. We analysed data from community-dwelling individuals who underwent multimodal brain MRI and retinal fundus camera imaging at mean age 72.55 years (SD=0.71). We assessed centrum semiovale PVS computationally to determine PVS total volume and count, and mean per-subject individual PVS length, width and size. We analysed retinal images using the VAMPIRE software suite, obtaining the Central Retinal Artery and Vein Equivalents (CRVE and CRAE), Arteriole-to-Venule ratio (AVR), and fractal dimension (FD) of both eyes. We investigated associations using general linear models, adjusted for age, gender, and major vascular risk factors. In 381 subjects with all measures, increasing total PVS volume and count were associated with decreased CRAE in the left eye (volume β=-0.170, count β=-0.184, p<0.001). No associations of PVS with CRVE were found. The PVS total volume, individual width and size increased with decreasing FD of the arterioles (a) and venules (v) of the left eye (total volume: FDa β=-0.137, FDv β=-0.139, p<0.01; width: FDa β=-0.144, FDv β=-0.158, p<0.01; size: FDa β=-0.157, FDv β=-0.162, p<0.01). Increase in PVS number and size visible on MRI reflect arteriolar narrowing and lower retinal arteriole and venule branching complexity, both markers of impaired microvascular health. Computationally-derived PVS metrics may be an early indicator of failing vascular health and should be tested in longitudinal studies.

Quantitative analysis of retinal and choroidal microvascular parameters using optical coherence tomography angiography in children with nephrotic syndrome: a pilot study.

To study the retinal and choroidal microvascular parameters in children with nephrotic syndrome (NS). This is a cross-sectional study. Optical coherence tomography angiography was used to evaluate the changes of retinal and choroidal microvessels in patients with NS. Thirty NS children and 20 normal controls were included in this study. The macular vessel density (VD) of the superficial capillary plexus (SCP), deep capillary plexus (DCP), choroid capillary plexus (CCP), and foveal avascular zone (FAZ) area of the SCP and DCP was quantitatively calculated. Clinical data including serum protein, blood lipid, uric acid, urea, serum creatinine, urinary protein concentration, urinary creatinine, 24-h urine volume, 24-h urinary total protein, 24-h creatinine clearance rate, and urinary albumin to creatinine ratio were collected. The VDs of the DCP and CCP in children with NS were significantly lower than those in controls (59.35 ± 2.45 vs. 61.15 ± 1.53, p = 0.002, 66.34 ± 1.43 vs. 67.16 ± 1.23, p = 0.042, respectively). The VD of the SCP in children with NS had a tendency to decrease compared with that in controls, but there were no significant differences. There were also no significant differences in FAZ area between the two groups. The VD of the SCP was positively correlated with serum total protein (ρ = 0.446, p = 0.014), serum albumin (ρ = 0.431, p = 0.017), and 24-h urine volume (ρ = 0.389, p = 0.034) but negatively correlated with triglyceride (ρ = - 0.450, p = 0.013), low-density lipoprotein cholesterol (ρ = -0.432, p = 0.017), urinary protein concentration (ρ = - 0.606, p < 0.001), and 24-h urinary total protein (ρ = - 0.517, p = 0.004). The VDs of the SCP, DCP, and CCP were negatively correlated with the urinary albumin to creatinine ratio (ρ = - 0.473, p = 0.008, ρ = - 0.438, p = 0.015, ρ = -0.467, p = 0.009, respectively). Retinal and choroidal VDs were decreased in children with NS and paralleled the severity of kidney disease. Optical coherence tomography angiography can be used as a noninvasive method for evaluating renal injury in patients with NS.

American Heart Association ideal cardiovascular health score and subclinical atherosclerosis in 22-35-year-old adults conceived with and without assisted reproductive technologies.

Is ART related with the association of American Heart Association (AHA) ideal cardiovascular health score and markers of subclinical atherosclerosis? The associations between AHA score and markers of subclinical atherosclerosis in ART and non-ART groups were similar in magnitude. Long-term consequences of ART on cardiovascular health are unknown. The study cohort for the cross-sectional analyses consisted of 172 ART-conceived and 78 non-ART conceived individuals of same age (range 22-35 years). Cardiovascular risk factor status was evaluated with American Heart Association (AHA) ideal cardiovascular health score consisting of seven factors (body mass index, blood pressure, total cholesterol, glucose, diet and physical activity, non-smoking). Carotid artery intima-media thickness (cIMT), arterial pulse-wave velocity (PWV) and retinal microvascular parameters were evaluated as markers of early atherosclerosis. Group comparisons in continuous variables were performed with t-tests. For categorical variables, comparisons were performed with chi-square tests. The relationships between AHA score and the markers of atherosclerosis were examined with linear regression analyses adjusted for age and sex. There was no difference in AHA ideal health score between the ART and non-ART groups; mean (SD) scores were 4.1(1.4) versus 4.0(1.5), respectively, P= 0.65. No differences were observed between groups for any individual ideal health metric (P always >0.2). AHA score was not associated with cIMT or retinal measures in either group (P always >0.05). An inverse association was observed between AHA score and PWV in the ART group (beta (95% CI) -0.18(-0.26 to -0.10)). A numerically similar relationship was observed in the smaller non-ART group (-0.19(-0.39 to 0.01)). Even though this cohort is among the largest ART studies with extensive cardiovascular data, the sample is still relatively small and the statistical power is limited. As the study population was still in early adulthood, we were not able to evaluate the associations with clinical cardiovascular events, but utilized non-invasive methods to assess early markers of subclinical atherosclerosis. These findings suggest that ART-conceived individuals do not have increased vulnerability for cardiovascular risk factors. This study was funded by a National Health & Medical Research Council Project Grant (APP1099641), The Royal Children's Hospital Research Foundation, Monash IVF Research and Education Foundation, and Reproductive Biology Unit Sperm Fund, Melbourne IVF. The authors have no conflicts of interest relevant to this article to disclose.

Cardiovascular health and retinal microvascular geometry in Australian 11–12 year-olds

Traditional retinal microvascular parameters (smaller arteriolar and greater venular caliber) are associated with cardiovascular risk factors, pre-clinical vascular phenotypes and clinical cardiovascular events in adults. Although novel retinal microvascular geometric parameters showed analogous associations in adults, less is known whether these parameters are associated with cardiovascular health from childhood. In a population-based cross-sectional study in children (n = 1126, mean age 11.4 years, 50.3% girls), we examined associations of cardiovascular risk factors and pre-clinical arterial phenotypes with retinal geometric parameters. Cardiovascular parameters included body mass index (BMI), an inflammatory marker (GlycA), low-density lipoprotein and high-density lipoprotein (HDL) cholesterol, systolic (SBP) and diastolic blood pressure, large artery functional (pulse wave velocity, PWV and carotid arterial elasticity) and structural (carotid intima-media thickness) phenotypes. Retinal geometric parameters (fractal dimension (Df) and tortuosity) were quantified from retinal images. Multivariable regression models were performed and adjusted for potential confounders. Higher values for BMI, SBP and PWV showed weak associations with lower (i.e. worse) arteriolar but not venular Df (standardized mean difference (SMD) ranging from −0.07 to −0.09, 95% CIs −0.15 to −0.01). Higher HDL was associated with greater arteriolar Df (SMD 0.07, 95% CI 0.01 to 0.13). Only higher SBP was associated with higher (i.e. worse) arteriolar but not venular tortuosity (SMD 0.09, 95% CI 0.02 to 0.16). In generally healthy children, some risk factors and pre-clinical arterial phenotypes show small associations with retinal geometric parameters. In childhood, emerging relationships between microvascular parameters and cardiometabolic risk may be better described by retinal vascular caliber than by geometric parameters.

Association between Coronary Artery Measurements and Retinal Microvasculature in Children with New Onset of Kawasaki Disease

About a quarter of children with new onset of Kawasaki disease (KD) encounter coronary arterial involvement. While KD is known to cause vasculitis of medium-sized vessels, few studies have been done to study the involvement of the microcirculation. We aimed to investigate the association between coronary arterial dilatation and retinal microvasculature in a pilot setting, in order to further study the pathophysiological mechanism of KD from the perspective of small vessels changes. We performed a cross-sectional, observational, hospital-based study on 11 children aged 2 years and above with new-onset KD. Cardiac imaging technicians performed the echocardiographic examinations and recorded right coronary artery (RCA), left coronary artery (LCA) and left anterior descending artery (LAD). Qualified retinal graders reviewed and graded standardised retinal photographs to assess retinal microvascular parameters. Among 11 participants, there were 7 boys and 4 girls. Median and interquartile range of participants’ age were 5.92 (3.08) years. After adjusting for age and sex, each unit increase in LAD (mm) was significantly associated with increment of retinal arteriolar tortuosity (4.25 × 10−5 units, 95% Confidence Interval: 1.19, 7.32). Retinal arteriolar geometric changes were associated with LAD dilatation in 11 children with new onset of KD. Our pilot provided proof-of-concept that retinal imaging might be useful for detecting coronary arterial involvement in young children with KD and it needs further investigation.

Correlation of OCTA and Volumetric MRI in Mild Cognitive Impairment and Alzheimer's Disease.

To evaluate the relationship between retinal microvascular parameters on optical coherence tomography angiography (OCTA) and neurodegenerative changes assessed by measurement of brain volume on volumetric magnetic resonance imaging (MRI) in Alzheimer's disease (AD) and mild cognitive impairment (MCI). Sixteen subjects with AD and MCI underwent OCTA imaging (3 mm × 3 mm and 6 mm × 6 mm scans) and volumetric brain MRI imaging with automated volumetric segmentation and quantification. Spearman's correlation (ρ) was performed between forebrain parenchyma, cortical gray matter, inferolateral ventricle (ILV), lateral ventricle (LV), and hippocampus (HP) MRI volumes and vessel density (VD), along with perfusion density (PD) for the 6-mm circle, 6-mm ring, 3-mm circle, and 3-mm ring Early Treatment Diabetic Retinopathy Study regions of the superficial capillary plexus. Thirty eyes of 16 patients (seven MCI and nine AD) with good-quality OCTA images were analyzed. ILV volume inversely correlated with the VD in the 6-mm circle (ρ = -0 .565, P = .028) and 3-mm ring (ρ = -0.569, P = .027) and PD in the 3-mm ring (ρ = -0.605, P = .0169). Forebrain, cortical gray matter, LV, and HP volumes did not significantly correlate with either VD or PD (P > .05). In this pilot investigation, the authors found a significant correlation between reduction in the superficial capillary plexus VD and PD on OCTA and expansion of the ILV in MCI and AD. This relationship between the retinal microvasculature and cerebral volumetric changes deserves further investigation. [Ophthalmic Surg Lasers Imaging Retina. 2019;50:709-718.].

Retinal microvascular findings and risk of incident peripheral artery disease: An analysis from the Atherosclerosis Risk in Communities (ARIC) Study

Background and aimsLower-extremity peripheral artery disease (PAD) is usually considered large artery disease. Interestingly, retinal microvascular findings were shown to predict PAD progression in diabetes. However, it is unknown whether retinal microvascular parameters are associated with incident PAD and its severe form, critical limb ischemia (CLI), in a community-based cohort. MethodsAmong 9371 ARIC participants (aged 49–72 years) free of a history of PAD, we quantified the associations of several retinal measures by retinal photography during the period 1993–1995 with PAD risk using Cox models. Incident PAD was defined as the first hospitalization with PAD diagnosis or leg revascularization (considered CLI if an additional diagnosis of ulcer, gangrene, or amputation). ResultsDuring a median follow-up of 18.8 years, 303 participants developed PAD (including 91 CLI cases). Although generalized retinal arteriolar narrowing was not associated with PAD, most measures of retinopathy demonstrated strong associations with PAD beyond potential confounders including diabetes, with adjusted hazard ratios (HR) of 3.26 (95% CI 2.18–4.90) for blot-shaped hemorrhages, 3.11 (1.83–5.29) for hard exudates, and 2.18 (1.62–2.95) for any retinopathy. Adjusted HRs were significantly greater for CLI (ranging from 3.2 to 5.9) than for PAD (all p-values <0.05). Retinopathy measures showed particularly strong associations in participants with diabetes (p-value for interaction [vs. those without diabetes] <0.001). ConclusionsSeveral retinopathy measures were strongly associated with PAD, especially with CLI and in diabetes. Our results support the contribution of microvascular abnormalities to the development and progression of PAD and would have implications on its preventive and therapeutic approaches.

Intereye and intraeye asymmetry analysis of retinal microvascular and neural structure parameters for diagnosis of primary open-angle glaucoma.

To investigate the diagnostic values of intereye or intraeye asymmetry of retinal perfused vessel density and neural structure parameters for detection of glaucoma. In total, 152 healthy subjects and 72 bilateral primary open-angle glaucoma (POAG) patients were enrolled. Total POAG group contains all glaucoma patients. Early to moderate POAG group contains patients whose binocular mean defect values were larger than -12 dB. The retinal perfused vessel densities were acquired using optic coherence tomography angiography. The neural structure parameters include RNFL, GCC thickness and its derivative indices like focal loss volume percentage (FLV%) and global loss volume percentage (GLV%). Intereye asymmetry equaled to the absolute difference of parameters between paired eyes. Intraeye asymmetry was defined as absolute difference between the inferior and superior hemisphere values from one random selected eye. The areas under the receiver operating characteristic curves (AUROCs) were calculated to evaluate diagnostic ability. From pairwise comparison analysis of ROC curves, the intereye asymmetric parameters with the largest diagnostic accuracy were FLV and GLV% (AUROC = 0.944), which were significantly superior to the intereye asymmetry of perfused vessel density in peripapillary area and parafoveal area (P < 0.05). Particularly, the intereye asymmetry of FLV% (AUROC = 0.926) and GLV% (AUROC = 0.950) showed excellent diagnostic precision for detecting early to moderate glaucoma patients. However, the intraeye asymmetry of microvascular parameters and neural structure parameters showed fair diagnostic ability for identifying POAG patients. The intereye asymmetry of neural structure parameters, particularly the FLV% and GLV%, outperformed the microvascular parameters for identifying POAG patients.

Macro- and Microvascular Parameters After Toxic Shock Syndrome.

Whether individuals who had toxic shock syndrome in childhood have differences in macro- and retinal microvascular parameters indicative of increased cardiovascular risk is unknown. We found no evidence of adverse macrovascular changes in 22 toxic shock syndrome participants compared with 60 control participants. Microvascular comparisons showed a reduction in retinal total fractal dimension, which has been associated with cardiovascular risk factors in children.

Retinal microvascular parameters are not associated with reduced renal function in a study of individuals with type 2 diabetes

The eye provides an opportunistic “window” to view the microcirculation. There is published evidence of an association between retinal microvascular calibre and renal function measured by estimated glomerular filtration rate (eGFR) in individuals with diabetes mellitus. Beyond vascular calibre, few studies have considered other microvascular geometrical features. Here we report novel null findings for measures of vascular spread (vessel fractal dimension), tortuosity, and branching patterns and their relationship with renal function in type 2 diabetes over a mean of 3 years. We performed a nested case-control comparison of multiple retinal vascular parameters between individuals with type 2 diabetes and stable (non-progressors) versus declining (progressors) eGFR across two time points within a subset of 1072 participants from the GoDARTS study cohort. Retinal microvascular were measured using VAMPIRE 3.1 software. In unadjusted analyses and following adjustment for age, gender, systolic blood pressure, HbA1C, and diabetic retinopathy, no associations between baseline retinal vascular parameters and risk of eGFR progression were observed. Cross-sectional analysis of follow-up data showed a significant association between retinal arteriolar diameter and eGFR, but this was not maintained following adjustment. These findings are consistent with a lack of predictive capacity for progressive loss of renal function in type 2 diabetes.

Review of the association between retinal microvascular characteristics and eye disease.

Computerized retinal imaging technologies enable the static and dynamic measurement of a range of retinal microvascular parameters. Large population-based studies have reported associations between these microvascular indices and various ophthalmic diseases including diabetes, age-related macular degeneration, retinal artery embolism, retinal vein occlusion, glaucoma and non-glaucomatous optic neuropathies. Increasingly, sophisticated imaging and analysis techniques have the potential to provide relevant clinical information regarding disease risk and progression; however, further studies are required to verify associations and strengthen the predictive power of these techniques. We summarize the current state of knowledge regarding retinal microvascular characteristics and eye disease.

Regional Patterns of Retinal Oxygen Saturation and Microvascular Hemodynamic Parameters Preceding Retinopathy in Patients With Type II Diabetes.

Alterations in retinal oxygen metabolism and retinal microcirculation are signs of impending diabetic retinopathy (DR). However, if specific retinal regions are primarily affected is so far unknown. The purpose of this study was to investigate if retinal oxygen saturation (SO2) and microvascular hemodynamic parameters follow a distinct regional pattern in patients with diabetes but no DR. Patients with type II diabetes without clinically apparent DR were imaged as follows: SO2 in peripapillary vessels was assessed with dual-wavelength oximetry. Optical coherence tomography angiography (OCTA) scans were acquired with a prototype system using a swept-source laser with an effective 400 kHz A-scan rate and 16° field of view. Regional flow indices termed "flux" were calculated for the peripapillary microvasculature. Parafoveal capillary density was evaluated with the commercially available AngioVue OCTA. Twenty-nine eyes of 16 consecutive patients (59 ± 10 years, 6 females) were included in this study. SO2 differed significantly between quadrants (P < 0.001), with a decreasing pattern from the upper nasal through the lower nasal, the upper temporal and the lower temporal quadrant in arterioles and venules. In contrast, peripapillary flux followed an increasing trend from nasally to temporally. Peripapillary and parafoveal microvascular hemodynamic parameters demonstrated no significant regional variability as observed for retinal oxygenation. Metabolic imaging identified regional differences in retinal SO2 without an associated topographic variance in microvascular hemodynamics in type II diabetes without DR. Future studies should focus on the mechanisms causing this heterogeneity in metabolic demand.

Retinal Vascular Imaging Markers and Incident Chronic Kidney Disease: A Prospective Cohort Study

Retinal microvascular changes indicating microvascular dysfunction have been shown to be associated with chronic kidney disease (CKD) in cross-sectional studies, but findings were mixed in prospective studies. We aimed to evaluate the relationship between retinal microvascular parameters and incident CKD in an Asian population. We examined 1256 Malay adults aged 40–80 years from the Singapore Malay Eye Study, who attended both the baseline (2004–07) and the follow-up (2011–13) examinations and were free of prevalent CKD. We measured quantitative retinal vascular parameters (arteriolar and venular calibre, tortuosity, fractal dimension and branching angle) using a computer-assisted program (Singapore I Vessel Assessment, SIVA) and retinopathy (qualitative parameter) using the modified Airlie house classification system from baseline retinal photographs. Incident CKD was defined as an estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2 + 25% decrease in eGFR during follow-up. Over a median follow-up period of 6 years, 78 (6.21%) developed CKD (70.5% had diabetes). In multivariable models, smaller retinal arterioles (hazards ratio [95% confidence interval] = 1.34 [1.00–1.78]), larger retinal venules (2.35 [1.12–5.94] and presence of retinopathy (2.54 [1.48–4.36]) were associated with incident CKD. Our findings suggest that retinal microvascular abnormalities may reflect subclinical renal microvascular abnormalities involved in the development of CKD.

Retinopathy Signs Improved Prediction and Reclassification of Cardiovascular Disease Risk in Diabetes: A prospective cohort study

CVD risk prediction in diabetics is imperfect, as risk models are derived mainly from the general population. We investigate whether the addition of retinopathy and retinal vascular caliber improve CVD prediction beyond established risk factors in persons with diabetes. We recruited participants from the Singapore Malay Eye Study (SiMES, 2004–2006) and Singapore Prospective Study Program (SP2, 2004–2007), diagnosed with diabetes but no known history of CVD at baseline. Retinopathy and retinal vascular (arteriolar and venular) caliber measurements were added to risk prediction models derived from Cox regression model that included established CVD risk factors and serum biomarkers in SiMES, and validated this internally and externally in SP2. We found that the addition of retinal parameters improved discrimination compared to the addition of biochemical markers of estimated glomerular filtration rate (eGFR) and high-sensitivity C-reactive protein (hsCRP). This was even better when the retinal parameters and biomarkers were used in combination (C statistic 0.721 to 0.774, p = 0.013), showing improved discrimination, and overall reclassification (NRI = 17.0%, p = 0.004). External validation was consistent (C-statistics from 0.763 to 0.813, p = 0.045; NRI = 19.11%, p = 0.036). Our findings show that in persons with diabetes, retinopathy and retinal microvascular parameters add significant incremental value in reclassifying CVD risk, beyond established risk factors.

Evidence of Microvascular Changes in the Retina following Kawasaki Disease

It is unclear whether all children with Kawasaki disease (KD) have increased later cardiovascular risk. The retinal microvasculature reflects changes in the microcirculation and is associated with traditional cardiovascular risk factors and events. The aim of this study was to investigate retinal microvascular parameters in two populations of patients with previous KD and control participants. We performed case-control studies of 116 (57 patients and 59 control participants) Australian and 156 (78 patients and 78 control participants) Singaporean individuals, at least two years since their acute illness. Standardised retinal photographs were graded by trained technicians using a semi-automated software, which quantifies the retinal microvasculature (calibre, branching angle, fractal dimensions, and tortuosity). Retinal venules of Singaporean KD patients were 9.67 μm (95% CI 4.87 to 14.51, p < 0.001) larger than control participants following correction for traditional cardiovascular risk factors. An incremental increase in the size of retinal venules in those with coronary artery abnormalities was observed. There was limited evidence that retinal venules were larger in Australian KD patients with coronary artery abnormalities compared to control participants (7.34 μm, 95% CI 1.30 to 15.99, p = 0.10). Differences in retinal microvasculature were particularly evident in Singaporean KD patients. Larger retinal venules may reflect chronic inflammation and endothelial dysfunction, and are associated with coronary artery disease in adults.

A prospective case-control study to investigate retinal microvascular changes in acute dengue infection

Dengue infection can affect the microcirculation by direct viral infection or activation of inflammation. We aimed to determine whether measured retinal vascular parameters were associated with acute dengue infection. Patients with acute dengue were recruited from Communicable Diseases Center, Singapore and age-gender-ethnicity matched healthy controls were selected from a population-based study. Retinal photographs were taken on recruitment and convalescence. A spectrum of quantitative retinal microvascular parameters (retinal vascular caliber, fractal dimension, tortuosity and branching angle) was measured using a semi-automated computer-based program. (Singapore I Vessel Assessment, version 3.0). We included 62 dengue patients and 127 controls. Dengue cases were more likely to have wider retinal arteriolar and venular calibers (158.3 μm vs 144.3 μm, p < 0.001; 227.7 μm vs 212.8 μm, p < 0.001; respectively), higher arteriolar and venular fractal dimensions (1.271 vs 1.249, p = 0.002; 1.268 vs. 1.230, p < 0.001, respectively), higher arteriolar and venular tortuosity (0.730 vs 0.546 [x104], p < 0.001; 0.849 vs 0.658 [x104], p < 0.001; respectively), compared to controls. Resolution of acute dengue coincided with decrease in retinal vascular calibers and venular fractal dimension. Dengue patients have altered microvascular network in the retina; these changes may reflect pathophysiological processes in the immune system.

Retinal microvascular network attenuation in Alzheimer's disease

IntroductionCerebral small-vessel disease has been implicated in the development of Alzheimer's disease (AD). The retinal microvasculature enables the noninvasive visualization and evaluation of the systemic microcirculation. We evaluated retinal microvascular parameters in a case-control study of AD patients and cognitively normal controls. MethodsRetinal images were computationally analyzed and quantitative retinal parameters (caliber, fractal dimension, tortuosity, and bifurcation) measured. Regression models were used to compute odds ratios (OR) and confidence intervals (CI) for AD with adjustment for confounders. ResultsRetinal images were available in 213 AD participants and 294 cognitively normal controls. Persons with lower venular fractal dimension (OR per standard deviation [SD] increase, 0.77 [CI: 0.62–0.97]) and lower arteriolar tortuosity (OR per SD increase, 0.78 [CI: 0.63–0.97]) were more likely to have AD after appropriate adjustment. DiscussionPatients with AD have a sparser retinal microvascular network and retinal microvascular variation may represent similar pathophysiological events within the cerebral microvasculature of patients with AD.

Microvascular network alterations in the retina of patients with Alzheimer's disease

BackgroundAlthough cerebral small-vessel disease has been implicated in the development of Alzheimer's disease (AD), the cerebral microcirculation is difficult to visualize directly in vivo. Because the retina provides a noninvasive window to assess the microcirculation, we determined whether quantitatively measured retinal microvascular parameters are associated with AD. MethodsWe conducted a case-control study (case:control matching ≈ 1:2). Retinal photographs were analyzed using a computer program, and a spectrum of quantitative retinal microvascular parameters (caliber, fractal dimension, tortuosity, and bifurcation) were measured. Logistic regression models were used to compute the odds ratio (OR) and 95% confidence interval for AD adjusting for age, gender, ethnicity, smoking, hypertension, diabetes, hypercholesterolemia, and history of myocardial infarction. ResultsWe included 136 demented patients with AD and 290 age-gender-race-matched controls. Persons with narrower venular caliber (OR per standard deviation [SD] decrease, 2.01 [1.27–3.19]), decreased arteriolar and venular fractal dimension (OR per SD decrease 1.35 [1.08–1.68], 1.47 [1.17–1.84], respectively) and increased arteriolar and venular tortuosity (OR per SD increase, 1.84 [1.40–2.31], 1.94 [1.48–2.53], respectively) were more likely to have AD. These associations still persisted when only AD cases without a history of cerebrovascular disease were included. ConclusionsPatients with AD have altered microvascular network in the retina (narrower retinal venules and a sparser and more tortuous retinal vessels) compared with matched nondemented controls. These changes in retinal microvasculature may reflect similar pathophysiological processes in cerebral microvasculature in the brains of patients with AD.

Retinal Microvascular Changes and Risk of Stroke

To examine the relationship between retinal microvascular measures and incident stroke in an Asian Malay population. We conducted a prospective, population-based cohort study of Asian Malay persons 40 to 80 years at baseline. Retinal microvascular signs were assessed from baseline retinal photographs including quantitative retinal microvascular parameters (caliber, branching angle, tortuosity, and fractal dimension) and qualitative retinopathy signs. Incident stroke cases were identified during the follow-up period. Cox proportional-hazards regression and incremental usefulness analysis (calibration, discrimination, and reclassification) were performed. A total of 3189 participants were free of prevalent stroke at baseline. During the follow-up (median, 4.41 years), 51 (1.93%) participants had an incident stroke event. In Cox proportional-hazards models adjusting for established stroke predictors (age, sex, systolic blood pressure, total cholesterol, low-density lipoprotein cholesterol, smoking, glycosylated hemoglobin, and antihypertensive medication), retinopathy (hazard ratio, 1.94; 95% confidence interval, 1.01-3.72) and larger retinal venular caliber (hazard ratio, 3.28; 95% confidence interval, 1.30-8.26, comparing fourth versus first quartiles) were associated with risk of stroke. Compared with the model with only established risk factors, the addition of retinal measures improved the prediction of stroke (C-Statistic 0.826 versus 0.792; P=0.017) and correctly reclassified 5.9% of participants with incident stroke and 3.4% of participants with no incident stroke. Retinal microvascular changes are related to an increased risk of stroke in Asian Malay, consistent with data from white populations. Retinal imaging improves the discrimination and stratification of stroke risk beyond that of established risk factors by a significant but small margin.

403 RETINAL MICROVASCULAR GEOMETRIC PARAMETERS AND COGNITIVE IMPAIRMENT

Background: Although midlife hypertension may be related to the development of dementia in late life, there are conflicting findings about the role of late-life hypertension. Novel retinal imaging allows non-invasive assessment of retinal microvascular geometry that may reflect small vessel damage from hypertension. We examined these geometric parameters in relation to cognitive impairment. Methods: This study is part of the Singapore Chinese Eye Study (40–80 years). Subjects aged 60 years and over were invited to undergo clinical assessments, neuropsychological testing and brain magnetic resonance imaging. Novel retinal microvascular geometry parameters include both focal (tortuosity, branching angle, and caliber) and global (fractal dimension) features. Cognitive function was categorized into no cognitive impairment (NCI), mild cognitive impairment no dementia (mild-CIND), moderate-CIND and dementia (moderate-CIND and dementia combined into one group for analysis) using previously validated criteria. Logistic regression models were used adjusting for age and gender, and additionally for education level, hypertension, diabetes mellitus and hyperlipidemia. Results: We included 216 participants (mean age: 70.5 years); 74 persons had CIND-mild, 55 CIND-moderate and 6 dementia. Smaller retinal arteriolar and venular fractal dimension was associated with both mild-CIND (odds ratio (OR) per standard deviation decrease: 1.50; 95% CI: 1.02–2.09) and moderate-CIND/dementia (OR: 1.71; 95% CI: 1.15–2.54). Other retinal microvascular geometry parameters were not related to cognitive impairment. Adjustments for other factors did not alter these results. Conclusions: Persons with smaller retinal fractal dimension were more likely to have cognitive impairment. This association may reflect sparser cerebral vascular network in persons with cognitive impairment.