Nicholas Witt

Abnormalities of Retinal Microvascular Structure and Risk of Mortality From Ischemic Heart Disease and Stroke

Abnormalities of the retinal microcirculation are found in hypertension and diabetes and predict cardiovascular mortality. This study examined the relationship between abnormalities of the retinal microvasculature and death from ischemic heart disease (IHD) and stroke. A population-based, nested case-control study was undertaken within the Beaver Dam Eye Study. Subjects (43 to 74 years) who died of IHD (n=126) or stroke (n=28) over a 10-year period were age and gender matched with controls subjects (n=528; case:control matching, ≈1:4). Retinal photographs of cases and controls were digitized and analyzed using a computer-based technique. Increased risk of IHD death was associated with a suboptimal relationship of arteriolar diameters at bifurcation (P=0.02 unadjusted) and decreased retinal arteriolar tortuosity (P=0.011 unadjusted). These associations remained significant after adjustment for age, sex, past history of cardiovascular disease, and other known cardiovascular risk factors. Increased arteriolar length:diameter ratio, a measure of generalized arteriolar narrowing, was associated with increased stroke mortality (P=0.02 unadjusted). This association was independent of age and gender but was attenuated by adjustment for systolic blood pressure (P=0.15). Other quantitative measures of the retinal microvascular network (eg, venular tortuosity and arteriolar and venular bifurcation angle) were not associated with death from IHD or stroke. Retinal microvascular abnormalities are predictive of death from IHD and stroke. A detailed assessment of the retinal microvascular network from digitized photographs may be useful in the noninvasive assessment of target organ damage and cardiovascular risk.

Computer algorithms for the automated measurement of retinal arteriolar diameters.

AIMS Quantification of retinal vascular change is difficult and manual measurements of vascular features are slow and subject to observer bias. These problems may be overcome using computer algorithms. Three automated methods and a manual method for measurement of arteriolar diameters from digitised red-free retinal photographs were compared. METHODS 60 diameters (in pixels) measured by manual identification of vessel edges in red-free retinal images were compared with diameters measured by (1) fitting vessel intensity profiles to a double Gaussian function by non-linear regression, (2) a standard edge detection algorithm (Sobel), and (3) determination of points of maximum intensity variation by a sliding linear regression filter (SLRF). Method agreement was analysed using Bland–Altman plots and the repeatability of each method was assessed. RESULTS Diameter estimations obtained using the SLRF method were the least scattered although diameters obtained were approximately 3 pixels greater than those measured manually. The SLRF method was the most repeatable and the Gaussian method less so. The Sobel method was the least consistent owing to frequent misinterpretation of the light reflex as the vessel edge. CONCLUSION Of the three automated methods compared, the SLRF method was the most consistent (defined as the method producing diameter estimations with the least scatter) and the most repeatable in measurements of retinal arteriolar diameter. Application of automated methods of retinal vascular analysis may be useful in the assessment of cardiovascular and other diseases.

Impact of Size at Birth on the Microvasculature: The Avon Longitudinal Study of Parents and Children

BACKGROUND. The impact of early life factors on the microvasculature is relatively unknown. OBJECTIVES. We hypothesized that small birth size may be associated with structural variations in the retinal vasculature in children. METHODS. The Avon Longitudinal Study of Parents and Children followed a cohort of children born in 1991–1992 from birth. The current study included the first 263 children who were systematically screened in the year-12 follow-up. Complete data were available for 166 children with a gestation of ≥37 weeks. Retinal circulatory measures were evaluated, including retinal microvascular tortuosity and bifurcation optimality deviance, an indicator of abnormal endothelial function. RESULTS. Optimality deviance and retinal tortuosity were higher among those with lower birth weight. Linear regression modeling was used to assess the association of retinal microvascular measures with birth weight. The standardized β coefficient between optimality deviance and birth weight was −.182 adjusted for gender and age in weeks; additional adjustment for systolic blood pressure and heart rate had little impact on the β coefficient. A similar association was observed for retinal tortuosity. CONCLUSION. The findings of this study suggest that early life factors may have an important impact on retinal vascular structure, possibly through an adverse effect on endothelial function.

Determinants of retinal microvascular architecture in normal subjects.

Background: Recent studies have shown that changes in the retinal microvasculature predict cardiovascular disease (CVD); however, little is known regarding influences on the retinal microvasculature in healthy people without overt cardiovascular or metabolic disease.

Differential Effects of Antihypertensive Treatment on the Retinal Microcirculation. An Anglo-Scandinavian Cardiac Outcomes Trial Substudy

Changes in the retinal microcirculation are associated with hypertension and predict cardiovascular mortality. There are few data describing the impact of antihypertensive therapy on retinal vascular changes. This substudy of the Anglo-Scandinavian Cardiac Outcomes Trial compared the effects of an amlodipine-based regimen (373 patients) with an atenolol-based regimen (347 patients) on retinal microvascular measurements made from fundus photographs. The retinal photographs were taken at a stage in the trial when treatments were stable and blood pressure was well controlled. Amlodipine-based treatment was associated with a smaller arteriolar length:diameter ratio than atenolol-based treatment (13.32 [10.75 to 16.04] versus 14.12 [11.27 to 17.81], median [interquartile range]; P<0.01). The association remained significant after adjustment for age, sex, cholesterol, systolic and diastolic blood pressures, body mass index, smoking, and statin treatment. This effect appeared to be largely attributable to shorter retinal arteriolar segment lengths in the amlodipine-treated group and is best explained by the vasodilator effects of amlodipine causing the visible emergence of branching side vessels. Photographic assessment of the retinal vascular network may be a useful approach to evaluating microvascular structural responses in clinical trials of antihypertensive therapy.

Retinal arterioles have impaired reactivity to hyperoxia in type 1 diabetes

Purpose:  Diabetes has adverse effects on the retinal microvasculature. The purpose of this study was to compare the effects of inhalation of hypoxic, hyperoxic and normoxic–hypercapnic gas mixtures on retinal vessel diameter in people with and without diabetes.

Serum Amyloid A, C-Reactive Protein, and Retinal Microvascular Changes in Hypertensive Diabetic and Nondiabetic Individuals An Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT) substudy

OBJECTIVE To study the association of the inflammatory markers serum amyloid A (SAA) and C-reactive protein (CRP) with retinal microvascular parameters in hypertensive individuals with and without type 2 diabetes. RESEARCH DESIGN AND METHODS This cross-sectional analysis was a substudy in 711 patients (159 with and 552 without diabetes) of the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT) based on digital 30-degree images of superior and inferior temporal retinal fields. RESULTS SAA was associated with arteriolar length-to-diameter ratio positively in nondiabetic patients (Ptrend= 0.028) but negatively in diabetic patients (Ptrend= 0.005). The difference was unlikely to be a chance finding (P = 0.007 for interaction). Similar results were found for the association of SAA with arteriolar tortuosity (P = 0.05 for interaction). Associations were less pronounced for CRP and retinal parameters. CONCLUSIONS Inflammatory processes are differentially involved in retinal microvascular disease in diabetic compared with nondiabetic hypertensive individuals.

Serum Amyloid A, C-reactive Protein and Retinal Microvascular Changes in Hypertensive Diabetic and Non-diabetic Individuals: An ASCOT Substudy

OBJECTIVE To study the association of the inflammatory markers serum amyloid A (SAA) and C-reactive protein (CRP) with retinal microvascular parameters in hypertensive individuals with and without type 2 diabetes. RESEARCH DESIGN AND METHODS This cross-sectional analysis was a substudy in 711 patients (159 with and 552 without diabetes) of the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT) based on digital 30-degree images of superior and inferior temporal retinal fields. RESULTS SAA was associated with arteriolar length-to-diameter ratio positively in nondiabetic patients (Ptrend= 0.028) but negatively in diabetic patients (Ptrend= 0.005). The difference was unlikely to be a chance finding (P = 0.007 for interaction). Similar results were found for the association of SAA with arteriolar tortuosity (P = 0.05 for interaction). Associations were less pronounced for CRP and retinal parameters. CONCLUSIONS Inflammatory processes are differentially involved in retinal microvascular disease in diabetic compared with nondiabetic hypertensive individuals.

Differential effects of adiposity and childhood growth trajectories on retinal microvascular architecture.

We hypothesized that trajectories of adiposity across childhood would be associated with retinal microcirculatory diameters at age 12 years, independent of BP.

Impact of fetal growth and preterm birth on the retinal microvasculature in mid-adulthood.

We hypothesized that preterm birth and being born SGA would be associated with changes in retinal microvascular architecture and that these changes would be more marked among those born preterm. We further hypothesized that these microvascular changes would correlate with early markers of CVD in mid‐adulthood.