Bettine C. P. Polak

Inflammation and endothelial dysfunction are associated with retinopathy: the Hoorn study

Aims/hypothesisThe exact pathogenesis of retinopathy in diabetic and non-diabetic individuals is incompletely understood, but may involve chronic low-grade inflammation and dysfunction of the vascular endothelium. The aim of this study was to investigate the association of inflammation and endothelial dysfunction with prevalent retinopathy in individuals with and without type 2 diabetes.MethodsAs part of a population-based cohort study, 625 individuals aged 50–74 years, stratified according to age, sex and glucose tolerance status, underwent an extensive physical examination. Retinopathy was assessed by an ophthalmological examination, including funduscopy and two-field 45° fundus photography with mydriasis in both eyes. Levels of C-reactive protein (CRP), soluble intercellular adhesion molecule-1 (sICAM-1), von Willebrand factor, and soluble vascular adhesion molecule-1 (sVCAM-1) were assessed, together with the urinary albumin : creatinine ratio, and the results were combined to obtain summarising z scores for inflammation and endothelial dysfunction.ResultsThe prevalence of retinopathy was positively associated with tertiles of CRP and sICAM-1. When compared with the lowest tertile, the highest tertile of the inflammatory z score was associated with retinopathy in all subjects (odds ratio [OR]=2.2, 95% CI 1.2–4.1, adjusted for age, sex and glucose tolerance status). The highest tertile of the endothelial dysfunction z score was associated with retinopathy among diabetic individuals (OR=4.4, 95% CI 1.2–15.9, adjusted for age and sex) but not in non-diabetic individuals. Additional adjustment for other risk factors, such as systolic and diastolic blood pressure, BMI, total cholesterol and triglycerides, or mutual adjustment of the inflammatory and endothelial dysfunction z scores did not change the results.Conclusions/interpretationIn this study, inflammatory activity and endothelial dysfunction were associated with retinopathy, which suggests their involvement in the pathogenesis of retinopathy.

Retinal blood flow changes in diabetic retinopathy measured with the Heidelberg scanning laser Doppler flowmeter.

Abstract Background: Investigation of retinal blood flow in patients with and without diabetic retinopathy (DR). Retinal blood flow is measured with the non-invasive Heidelberg Retinal Flowmeter (HRF). The clinical suitability of the HRF in patients with diabetes mellitus is investigated, and measured blood flow is compared with blood flow in a group of non- diabetic persons. Methods: Cross- sectional study of retinal capillary perfusion in eighty diabetic patients and forty-nine control persons, non-invasively measured with the Heidelberg scanning laser Doppler flowmeter. Results: In the control group, HRF measurements could be performed in all subjects. In the diabetes group some patients had media opacities or were not able to maintain stable fixation. Therefore HRF measurement was only possible in 79%, 75% and 60% of the subjects for the nasal, papillo-macular and foveal areas respectively. Retinal blood flow as measured in the perifoveal and nasal areas was associated with the level of diabetic retinopathy. In patients with proliferative DR (levels 4 and 5) the blood flow was reduced, in comparison with that of the patients with exudative or non-proliferative DR (levels 1 and 2) and preproliferative DR (level 3). Blood flow was not correlated with age, systemic blood pressure, intra-ocular pressure and perfusion pressure in either group. A significant negative correlation with the actual blood glucose level was found in the perifoveal area (R=–0.585, P=0.0001). Conclusions: The HRF offers an interesting non-invasive method for measurement of retinal blood flow. In this cross-sectional study variations in retinal blood flow could be detected in various stages of DR in relation to clinically visible funduscopic changes.

Progression and Regression: Distinct Developmental Patterns of Diabetic Retinopathy in Patients With Type 2 Diabetes Treated in the Diabetes Care System West-Friesland, the Netherlands

OBJECTIVE To identify distinct developmental patterns of diabetic retinopathy (DR) and assess the risk factor levels of patients in these clusters. RESEARCH DESIGN AND METHODS A cohort of 3,343 patients with type 2 diabetes mellitus (T2DM) monitored and treated in the Diabetes Care System West-Friesland, the Netherlands, was followed from 2 to 6 years. Risk factors were measured, and two-field fundus photographs were taken annually and graded according to the EURODIAB study group. Latent class growth modeling was used to identify distinct developmental patterns of DR over time. RESULTS Five clusters of patients with distinct developmental patterns of DR were identified: A, patients without any signs of DR (88.9%); B, patients with a slow regression from minimal background to no DR (4.9%); C, patients with a slow progression from minimal background to moderate nonproliferative DR (4.0%); D, patients with a fast progression from minimal or moderate nonproliferative to (pre)proliferative or treated DR (1.4%); and E, patients with persistent proliferative DR (0.8%). Patients in clusters A and B were characterized by lower risk factor levels, such as diabetes duration, HbA1c, and systolic blood pressure compared with patients in progressive clusters (C–E). CONCLUSIONS Clusters of patients with T2DM with markedly different patterns of DR development were identified, including a cluster with regression of DR. These clusters enable a more detailed examination of the influence of various risk factors on DR.

Homocysteine, S-adenosylmethionine and S-adenosylhomocysteine are associated with retinal microvascular abnormalities: the Hoorn Study.

The aim of the present study was to investigate the relationship between homocysteine and homocysteine metabolism components and retinal microvascular disorders in subjects with and without Type 2 diabetes. In this population-based study of 256 participants, aged 60-85 years, we determined total plasma homocysteine, SAM (S-adenosylmethionine) and SAH (S-adenosylhomocysteine) in plasma and erythrocytes, total folate in serum and erythrocytes, 5-MTHF (5-methyltetrahydrofolate), and vitamins B12 and B6. Participants were examined ophthalmologically by means of indirect funduscopy and two-field 45 degrees fundus photography, and were graded for retinopathy and retinal sclerotic vessel abnormalities. A computer-assisted method was used to measure retinal vessel diameters. Total plasma homocysteine was inversely associated with retinal arteriolar diameters {standardized beta, -0.20 [95% CI (confidence interval), -0.33 to -0.07]} or a decrease of 3.78 microm CRAEs (central retinal arteriolar equivalents) per 1 S.D. increase in homocysteine level (=4.6 micromol/l). In addition, the SAM/SAH ratio in plasma was inversely associated with retinal sclerotic vessel abnormalities and retinopathy [odds ratios, 0.61 (95% CI, 0.39-0.96) and 0.50 (95% CI, 0.30-0.83) per 1 S.D. respectively]. The associations were independent of age, sex, glucose tolerance status, other homocysteine metabolism components and cardiovascular risk factors. In conclusion, the results of the present study support the concept that total plasma homocysteine and a low SAM/SAH ratio in plasma, which may reflect reduced transmethylation reactions, may contribute to the pathogenesis of (retinal) microangiopathy.

Cost-effectiveness of glycemic control and ophthalmological care in diabetic retinopathy

AIMS Glycemic control and ophthalmological care are known to significantly diminish the risk of visual impairment and blindness by diabetic retinopathy (DRP). The (cost-)effectiveness of both strategies was studied to highlight their benefits for patients and care providers. METHODS A computer analysis was developed, following the progression of DRP and the effectiveness of metabolic control and ophthalmological care continuously and individually in cohorts of type I and type II DM patients with divergent degrees of compliance. Costs relate to present medical charges in the Netherlands. RESULTS Intensive glycemic control shortens the duration of blindness in a type I DM patient by 0.76 years, intensive ophthalmological care by 0.53 years. One year sight gain may cost 1126 euros by providing ophthalmological care and 50479 euros by glycemic control. The duration of blindness drops in a type II DM patient by 0.48 and 0.13 years, respectively, whereas the effectiveness decreases as the age of onset of DM rises. CONCLUSIONS The vast majority of diabetic patients benefits from both intensive glycemic control and intensive ophthalmological care, but these cost-effective interventions which are not only complementary, but also substitute each other, require lasting, full compliance by all parties concerned.

Risk Factors for Incident Retinopathy in a Diabetic and Nondiabetic Population

Methods: The incidence of retinopathy was determined in 233 individuals, aged 50 to 74 years, by ophthalmoscopy and fundus photography at baseline and after an average follow-up of 9.4 years. Relative risks for retinopathy, estimated by odds ratios, were calculated for tertiles of cardiovascular risk factors at baseline. Logistic regression analysis was used, without and with adjustment for age, sex, hypertension, and glucose metabolism. metabolism were 7.3%, 13.6%, and 17.5%, respectively. Adjustedoddsratiosforretinopathywere2.36(95%confidence interval, 1.02-5.49) for hypertension and 3.29 (95%confidenceinterval,1.11-9.72)and8.67(95%confidenceinterval,1.85-40.60)forthehighesttertilesofglycosylated hemoglobin level and waist-hip ratio, respectively.Noconsistentorstatisticallysignificantassociations with retinopathy were present for age, sex, body mass index,smoking,andserumlevelsoftriglyceridesandtotal, high-densitylipoprotein,andnon–high-densitylipoprotein cholesterol (P.05 for all). Conclusion: Glycemia, hypertension, and abdominal obesity are determinants for retinopathy in a general population.