Retinal blood flow is increased in type 1 diabetes mellitus patients with advanced stages of retinopathy.

BACKGROUND: Diabetic retinopathy (DRP) is a common microvascular complication seen in patients with type 1 diabetes mellitus (T1DM). The effects of T1DM and concomitant (proliferative) DRP on retinal blood flow are currently unclear. Therefore, we measured retinal vascular blood flow in T1DM patients with and without DRP and non-diabetic controls. We further assessed the acute effects of panretinal photocoagulation on retinal microvascular bloodflow in eight patients with diabetes. METHODS: Thirty-three T1DM patients with proliferative DRP, previously treated with panretinal photocoagulation (pDRP), 11 T1DM patients with untreated non-proliferative retinopathy (npDRP) and 32 T1DM patients without DRP (nDRP) were compared with 44 non-diabetic gender-matched controls. Using scanning laser Doppler flowmetry (HRF, Heidelberg) blood flow in the retinal microvasculature was measured temporal and nasal of the optic disc and averaged into one flow value per eye. The right eye was used as a default for further analyses. Eight patients with novel proliferative retinopathy (4 T1DM and 4 with type 2 diabetes) were measured before and several months after photocoagulation. Between-group differences in retinal blood flow were assessed using ANOVA corrected for multiple comparisons (Bonferroni). RESULTS: Retinal blood flow was higher in the treated pDRP compared with the nDRP group and controls (all P Bonferroni < 0.01). Furthermore, there was a positive linear trend for blood flow with lowest blood flow in the control group and highest in the pDRP group (P-for-trend < 0.01). In the eight patients with novel proliferative retinopathy, blood flow did not significantly change before and after panretinal photocoagulation (P > 0.05). Using regression analysis, no variables were found as predictors of retinal blood flow. CONCLUSIONS: In comparison with controls and nDRP patients, retinal blood flow significantly increased in the pDRP group, which previously underwent photocoagulation treatment, but not in the npDRP patients. These changes may be a consequence of a failing vascular autoregulation in advanced diabetic retinopathy.

Real-world evidence of suboptimal blood pressure control in patients with type 2 diabetes.

AIMS: In order to eventually improve blood pressure (BP) management, the aim of this study was to identify subgroups of type 2 diabetes mellitus (T2DM) patients with distinct trajectories of SBP levels. Identifying subgroups with distinct SBP trajectories helps to better understand the course of SBP levels in T2DM patients and its associated consequences. Subgroup characteristics were determined and the prevalence of complications and mortality rates over time in the different subgroups was investigated. METHODS: Five thousand, seven hundred and eleven T2DM patients with at least two SBP follow-up measurements were selected from a prospective T2DM cohort of 9849 T2DM patients. The mean follow-up period was 5.7 years (range 2-9 years). Latent Class Growth Modeling, as currently the most flexible cluster analysis available, was performed to identify subgroups of patients with distinct SBP trajectories. Subgroup characteristics were determined by multinomial logistic regression analyses. RESULTS: Four subgroups with distinct SBP trajectories were identified. The largest subgroup (85.6%) showed adequate SBP control (at or around 140 mmHg) over time. The second subgroup (5.6%) were hypertensive in the first years, responded slowly to BP management and eventually reached SBP control. The third subgroup (3.4%) showed deteriorating hypertension during the first 4 years, then showed insufficient response to BP management. The fourth subgroup (5.4%) showed deteriorating hypertension over time. Patients within subgroups 2-4 were significantly older, comprised more women, used more antihypertensive medication and had a higher prevalence of retinopathy, microalbuminuria and cardiovascular disease (CVD) mortality. CONCLUSION: More than 85% reached and maintained adequate SBP control. Subgroups with a more unfavourable course of SBP control also showed higher rates of microvascular complications and CVD mortality over time. This study identified important subgroups to target in order to improve BP management in T2DM patients.

Distinct HbA1c trajectories in a type 2 diabetes cohort.

AIMS: The aim of this study was to identify subgroups of type 2 diabetes mellitus patients with distinct hemoglobin A1c (HbA1c) trajectories. Subgroup characteristics were determined and the prevalence of microvascular complications over time was investigated. STUDY DESIGN AND SETTING: Data from a cohort of 5,423 type 2 diabetes patients from a managed primary care system were used [mean follow-up 5.7 years (range 2-9 years)]. Latent class growth modeling was used to identify subgroups of patients with distinct HbA1c trajectories. Multinomial logistic regression analyses were conducted to determine which characteristics were associated with different classes. RESULTS: Four subgroups were identified. The first and largest subgroup (83 %) maintained good glycemic control over time (HbA1c ≤53 mmol/mol), the second subgroup (8 %) initially showed severe hyperglycemia, but reached the recommended HbA1c target within 2 years. Patients within this subgroup had significantly higher baseline HbA1c levels but were otherwise similar to the good glycemic control group. The third subgroup (5 %) showed hyperglycemia and a delayed response without reaching the recommended HbA1c target. The fourth subgroup (3.0 %) showed deteriorating hyperglycemia over time. Patients within the last two subgroups were significantly younger, had higher HbA1c levels and a longer diabetes duration at baseline. These subgroups also showed a higher prevalence of retinopathy and microalbuminuria. CONCLUSION: Four subgroups with distinct HbA1c trajectories were identified. More than 90 % reached and maintained good glycemic control (subgroup one and two). Patients within the two subgroups that showed a more unfavorable course of glycemic control were younger, had higher HbA1c levels and a longer diabetes duration at baseline.

Low-grade inflammation and endothelial dysfunction explain the association between retinopathy and left ventricular ejection fraction in men: an 8-year follow-up of the Hoorn Study.

PURPOSE: The aim of this study was to prospectively investigate the association of retinopathy with changes in left ventricular (LV) function. METHODS: Within the Hoorn Study, a population-based cohort study of diabetes in The Netherlands, retinal photography and echocardiography were performed in the year 2000 (baseline) and 2008 (follow-up). Retinopathy was graded according to the Eurodiab classification and further defined as absent or present retinopathy. LV systolic and diastolic functions were assessed by LV ejection fraction (%), LV mass (g/m(2.7)) and left atrial (LA) volume indices and the ratio of LV inflow (E) and early diastolic lengthening (e') velocities. Linear regression analyses stratified for sex were completed to investigate associations of retinopathy with changes in LV function in participants with impaired glucose metabolism and type 2 diabetes. RESULTS: One hundred forty-seven participants (58% men, mean age 66) were included in the study, of whom 13.6% were present with retinopathy at baseline. LV ejection fraction was similar among participants with and without retinopathy (60.2% versus 60.7%) at baseline. Eight years later, retinopathy was significantly associated with a lower LV ejection fraction (ß -8.0 95% CI -15.37 to -0.68) in men, independent of risk factors. Microvascular endothelial dysfunction ([ED] ß -4.87 95% CI -13.40 to 3.67) and low-grade inflammation ([LGI] ß -5.30 95% CI -13.72 to 3.12) both diminished the association. No significant associations between retinopathy and other LV function parameters were observed. CONCLUSION: Retinopathy was significantly associated with a lower LV ejection fraction in men but not in women. LGI and ED might explain the observed association.

Validation of a model to estimate personalised screening frequency to monitor diabetic retinopathy.

AIMS/HYPOTHESIS: Our study aimed to validate a model to determine a personalised screening frequency for diabetic retinopathy. METHODS: A model calculating a personalised screening interval for monitoring retinopathy based on patients' risk profile was validated using the data of 3,319 type 2 diabetic patients in the Diabetes Care System West-Friesland, the Netherlands. Two-field fundus photographs were graded according to the EURODIAB coding system. Sight-threatening retinopathy (STR) was considered to be grades 3-5. Validity of the model was assessed using calibration and discrimination measures. We compared model-based time of screening with time of STR diagnosis and calculated the differences in the number of fundus photographs using the model compared with those in annual or biennial screening. RESULTS: During a mean of 53 months of follow-up, 76 patients (2.3%) developed STR. Using the model, the mean screening interval was 31 months, leading to a reduced screening frequency of 61% compared with annual screening and 23% compared with biennial screening. STR incidence occurred after a mean of 26 months after the model-based time of screening in 67 patients (88.2%). In nine patients (11.8%), STR had developed before the model-based time of screening. The discriminatory ability of the model was good (C-statistic 0.83; 95% CI 0.74, 0.92). Calibration showed that the model overestimated STR risk. CONCLUSIONS/INTERPRETATION: A large reduction in retinopathy screening was achieved using the model in this population of patients with a very low incidence of retinopathy. Considering the number of potentially missed cases of STR, there is room for improvement in the model. Use of the model for personalised screening may eventually help to reduce healthcare use and costs of diabetes care.

Objectives of teaching direct ophthalmoscopy to medical students.

PURPOSE: To propose the objectives of undergraduate training in direct ophthalmoscopy (DO). METHOD: Narrative review of the literature on (i) opinions about the expected proficiency from students in DO, and (ii) estimates of its diagnostic value. RESULTS: (i) Authorities disagree on the proficiency in DO that they expect from students. Textbooks of physical diagnosis differ in their coverage of DO. Surveys have indicated that US physicians expect students to be able to detect optic nerve head abnormalities. The Association of American Medical Colleges expects students to perform ophthalmoscopic examination and describe observations. The International Council of Ophthalmology expects students to recognize also diabetic and hypertensive retinopathies. The Association of University Professors in Ophthalmology requires that students recognize papilloedema, cholesterol emboli, glaucomatous cupping and macular degeneration. (ii) There is evidence that DO, even by ophthalmologists, is inadequate for screening for glaucoma, diabetic and hypertensive retinopathies. Two studies have suggested a limited value of DO in detecting clinical emergencies. CONCLUSIONS: The evidence that DO, even by ophthalmologists, is sub-optimal in detecting common abnormalities challenges existing the notions of training medical students. On pending the results of additional studies of the value of DO in detecting emergencies, we suggest that undergraduate teaching of DO should impart the following: (i) an ability to identify the red fundus reflex and optic disc; (ii) an ability to recognize signs of clinical emergencies in patients, mannequins or fundus photographs; and (iii) knowledge about, but not an ability to detect, other retinopathies.

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, HbA(1c), 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.

[Visual loss as a sign of hypertension]. / Visusklachten als uiting van verhoogde bloeddruk.

A 26-year-old male patient had been suffering from a decreased visual acuity in both eyes for 3 weeks. This appeared to be due to malignant hypertension. The hypertension went unnoticed until papillary and macular oedema were detected during fundoscopy. Hypertension can develop at all ages and may give rise to visual complaints or even to loss of vision. Insufficient clinical awareness of the atypical manifestations of severe hypertension and of the differential diagnosis of loss of vision may lead to irreversible damage of organs, in this patient the left eye. Fundoscopy is sometimes indicated in patients with severe hypertension to assess damage to the eye and to decide whether the patient must be hospitalised.

Reliability of screening methods for diabetic retinopathy.

AIM: To review studies of the reliability (reproducibility) of the commonly used methods (ophthalmoscopy and inspection of retinal images) of screening for diabetic retinopathy (DR). RESEARCH DESIGN AND METHODS: Literature search. RESULTS: We found six studies of the intra-examiner agreement after examining the same retinal images. Three of these found an almost perfect agreement (k > 0.8) after inspecting colour slides and digital images; three other studies reported 'significant differences' in microaneurysm counts and only 39-85% agreement rates between two assessments by the same examiner. The inter-examiner agreement was reported in 24 studies. Using stereoscopic photographs, one study found almost perfect agreement after examining seven fields; another study found a substantial to moderate (k = 0.4-0.8) agreement after examining five fields and a third study found a fair agreement (k = 0.2-0.4) after examining a single field. Studies using single- or two-field monoscopic photographs also have reported agreement rates that have varied between almost perfect, substantial and moderate. In four other studies using biomicroscopy, agreement levels varied between perfect and moderate. CONCLUSIONS: Relative to the large number of studies on the validity of the various methods for screening for DR, there are only few studies of their reliability, with a marked variability in their findings. We suggest that future studies of the effectiveness of the various methods for screening for DR should also include data on their reliability.

Measuring the refractive properties of the diabetic eye during blurred vision and hyperglycaemia using aberrometry and Scheimpflug imaging.

PURPOSE: This study aimed to measure the refraction and geometry in the diabetic eye during the presence and absence of hyperglycaemia and blurred vision, using aberrometry and Scheimpflug imaging. METHODS: Aberrometry and Scheimpflug imaging were used to examine ocular refraction and higher-order aberrations, as well as the shape of the cornea and the lens, in 25 patients with diabetes mellitus. From these parameters, the equivalent refractive index of the lens was calculated. Using paired t-tests, comparisons were made between a first series of measurements (Visit 1) taken in the presence of blurred vision and hyperglycaemia (> 10.0 micromol/l), and a second series of measurements (Visit 2) taken under normal conditions. RESULTS: The mean difference in blood glucose between Visits 1 and 2 was 5.9 mmol/l (standard deviation [SD] 3.1) (p < 0.0001). Both small hyperopic and myopic shifts of equivalent refractive error (ERE) were found in nine patients (mean absolute difference ERE: 0.38 D [SD 0.12]; p = 0.02). Furthermore, higher-order aberrations (root mean square [RMS] error) were slightly increased in four patients (mean difference RMS error: 0.07 microm [SD 0.02]; p = 0.04) at Visit 1, compared to Visit 2. No significant changes were observed in the shape of the cornea or lens in any of the patients. No significant correlations were found between changes in blood glucose levels and the measured parameters in diabetic eyes. CONCLUSIONS: The present study suggests that subjective symptoms of blurred vision during hyperglycaemia are not necessarily caused by changes in the refractive properties of the diabetic eye.

Changes in the internal structure of the human crystalline lens with diabetes mellitus type 1 and type 2.

PURPOSE: To investigate the effect of diabetes mellitus (DM) type 1 and type 2 on the internal structure of the lens. DESIGN: Observational cross-sectional study. PARTICIPANTS AND CONTROLS: One hundred seven patients with DM type 1, 106 patients with DM type 2, and 75 healthy control subjects. METHODS: Scheimpflug photography was used to image the lens of the right eye of 213 patients with DM and 75 healthy control subjects. The densitogram of the Scheimpflug image was used to indicate the nucleus and the different layers of the cortex of the lens. Lenses with cataract were excluded. MAIN OUTCOME MEASURES: The size of the nucleus and the different layers of the cortex of the lens. RESULTS: The nucleus and the different cortical layers of the DM type 1 lenses were significantly thicker compared with those of the control group (P<0.001). A significant association was found between the duration of DM type 1 and both the anterior and posterior cortex, its different layers, and the nucleus (P<0.001). The increase in the anterior and posterior cortex with the duration of DM was comparable with that of the nucleus. No important differences in the internal structure of the lens were found between the patients with DM type 2 and the control group. CONCLUSIONS: Diabetes mellitus type 1 has a significant effect on the internal structure of the lens. The difference in effect of DM type 1 and type 2 on internal lens structure suggests an essential difference in pathogenesis. Furthermore, the results of the present study may indicate that the increase in the size of the lens with DM type 1 is the result of a generalized swelling of the lens, affecting all its different parts.

Precision and reliability of retinal thickness measurements in foveal and extrafoveal areas of healthy and diabetic eyes.

PURPOSE: To determine the precision and reliability of retinal thickness measurements with an optical coherence tomograph (Stratus OCT 3; Carl Zeiss Meditec, Dublin, CA) and a retinal thickness analyzer (RTA; Talia Technology Ltd., Neve-Ilan, Israel) in foveal, parafoveal, and perifoveal areas. METHODS: Three measurements of all areas were performed within 1 hour on the same day with each instrument in the eyes of healthy volunteers and diabetic patients. The latter group was divided into eyes with and without macular edema. RESULTS: Measurement precision, expressed as the 95% limits of agreement (LA 95%), was significantly higher (i.e., a lower LA 95%, P < 0.01) for the OCT in comparison to the RTA in virtually all areas of the retina. Moreover, measurement reliability, expressed as the intraclass correlation coefficient, was high with the OCT (>0.90) and moderate to low with the RTA (0.26-0.89). A direct influence of macular edema itself on measurement precision of para- and perifoveal areas was found in the OCT measurements. CONCLUSIONS: The high measurement precision and reliability of the OCT suggests that this instrument is currently the most suitable technique for detection and follow-up of diabetic macular edema. When macular edema is present, the OCT can reliably detect changes of at least 36 microm at the fovea, 55 microm in parafoveal areas below a thickness of 744 microm, and 42 microm in perifoveal areas below a thickness of 1011 microm.

The influence of diabetes mellitus type 1 and 2 on the thickness, shape, and equivalent refractive index of the human crystalline lens.

PURPOSE: To study the influence of diabetes mellitus (DM) types 1 and 2 on the thickness, radius of curvature, equivalent refractive index, and power of the lens. DESIGN: Observational cross-sectional study. PARTICIPANTS AND CONTROLS: One hundred fourteen patients with DM type 1, 112 patients with DM type 2, and 75 control subjects. METHODS: Lens thickness and the anterior and posterior radius of the lens were measured by means of corrected Scheimpflug imaging. Ocular refraction was determined with Hartmann-Shack aberrometry. The equivalent refractive index and the power of the lens were calculated from these parameters. Several systemic parameters (e.g., duration of DM, glycated hemoglobin, and type of medication) and ocular comorbidity (e.g., level of diabetic retinopathy) were recorded. MAIN OUTCOME MEASURES: The thickness, anterior and posterior radii, equivalent refractive index, and power of the lens. RESULTS: The lenses of the patients with DM type 1 were significantly thicker and more convex, compared with those of the control group (P<0.001). Furthermore, there was a significant decrease in the equivalent refractive index of their lenses compared with the control group. No difference in lens parameters was found between the patients with DM type 2 and the control group. In the DM type 1 group, the duration of DM was an important determinant of lens biometry; the independent effects of the duration of DM per year on lens thickness, anterior radius, posterior radius, and equivalent refractive index were respectively 95%, 88%, 207%, and 45% of the effect of age per year. Lens power and ocular refraction were not affected by DM types 1 or 2. CONCLUSIONS: The results of the present study show that DM type 1 has a major impact on lens biometry. Furthermore, the difference in effect of DM types 1 and 2 on lens biometry may indicate a fundamental difference in pathogenesis. The decrease in equivalent refractive index of the lens seemed to compensate for the profound increase in lens convexity in patients with DM type 1, resulting in no significant change in lens power or ocular refraction with the duration of DM.

Refractive properties of the healthy human eye during acute hyperglycemia.

PURPOSE: To measure the refractive properties of the healthy human eye during acute hyperglycemia by means of Scheimpflug imaging and Hartmann-Shack aberrometry. METHODS: Acute hyperglycemia was induced in five healthy subjects (two males, three females, mean age +/-SD 24.8 years +/- 4.6) by means of an oral glucose tolerance test (OGTT) after subcutaneous somatostatin injection. Before and every 30 minutes after the OGTT, measurements with Scheimpflug imaging and Hartmann-Shack aberrometry were performed. The main outcome measures were the thickness and shape of the lens, and the ocular refractive error and higher order aberrations. The equivalent refractive index of the lens was calculated from these parameters. Measurements at baseline and during hyperglycemia were analyzed by means of Wilcoxon signed rank sum tests. RESULTS: During hyperglycemia (mean blood glucose level at baseline: 4.0 mmol/l; mean maximal blood glucose level: 18.4 mmol/l) no changes could be found in the refractive properties within the group. In one subject, a hyperopic shift (0.4 D) was observed, together with a more convex shape of the anterior lens surface and a decrease in the equivalent refractive index of the lens. CONCLUSIONS: This study shows that hyperglycemia generally does not cause changes in the refractive properties of the healthy eye. Nevertheless, in one subject a hyperopic shift accompanied by a change in shape and refractive index of the lens was measured. This finding could provide an explanation for the mechanism underlying the refractive changes that are often observed during hyperglycemia.

The effect of acute hyperglycemia on retinal thickness and ocular refraction in healthy subjects.

PURPOSE: To quantify the retinal thickness and the refractive error of the healthy human eye during hyperglycemia by means of optical coherence tomography (OCT) and Hartmann-Shack aberrometry. METHODS: Hyperglycemia was induced in five healthy subjects who were given a standard oral glucose tolerance test (OGTT) after a subcutaneous injection of somatostatin. Main outcome parameters were the central, pericentral and peripheral thickness of the fovea, measured by means of optical coherence tomography (OCT3). Ocular refractive error was determined with Hartmann-Shack aberrometry. Measurements at baseline and during maximal hyperglycemia were analyzed, and a change was considered clinically significant if the difference between the measurements exceeded the threshold of 50 microm for retinal thickness and 0.2 D for refractive error. RESULTS: During hyperglycemia (mean blood glucose level at baseline: 4.0 mmol/l; mean maximal blood glucose level: 18.4 mmol/l) no significant changes could be found in the central, pericentral, or peripheral foveal thickness in any of the five subjects. One of the subjects had a hyperopic shift of 0.4 D, but no significant change in refractive error was found in any of the other subjects. CONCLUSIONS: The present study shows that in healthy subjects induced hyperglycemia does not affect retinal thickness, but it can cause a small hyperopic shift of refraction.

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.

The influence of chronic diabetes mellitus on the thickness and the shape of the anterior and posterior surface of the cornea.

PURPOSE: To determine the influence of diabetes mellitus (DM) type 1 and type 2 on the thickness, radius of curvature, power, and asphericity of the cornea. METHODS: In this observational cross-sectional study, 102 patients with DM type 1, 101 patients with DM type 2, and 69 healthy subjects were measured by means of Scheimpflug imaging to determine central corneal thickness and the radius and asphericity of the anterior and posterior corneal surfaces. Corneal power was calculated from these parameters. Several systemic parameters (eg, duration of diabetes, glycated hemoglobin, blood glucose levels, and type of medication) and ocular comorbidity (eg, stage of retinopathy) were recorded. RESULTS: Patients with DM type 1 and 2 had significantly smaller posterior corneal radii (P < 0.05) than those of healthy subjects (men: 6.49/6.48/6.64 mm; women: 6.36/6.30/6.49 mm). As a result, the optical power of the posterior corneal surface of the patients with diabetes differed from that of the healthy subjects (P < 0.01; men: DM, -6.2 D; healthy, -6.0 D; women: DM, -6.3 D; healthy, -6.2 D). However, corneal thickness, anterior radius and asphericity, and overall corneal power did not differ significantly between the groups. Furthermore, none of the systemic factors or ocular comorbidity had any influence on the corneal thickness or shape. CONCLUSIONS: DM affects the posterior corneal radius, resulting in a small change in posterior corneal power. However, chronic DM does not seem to significantly influence the overall corneal power.

Are retinal microvascular abnormalities associated with large artery endothelial dysfunction and intima-media thickness? The Hoorn Study.

It has been hypothesized that microvascular dysfunction affects endothelial dysfunction of the large arteries, which may explain the relationship of microvascular disease with macrovascular disease. The aim of the present study was to investigate the relationship of retinal microvascular disorders with endothelium-dependent FMD (flow-mediated vasodilatation) and carotid IMT (intima-media thickness). A total of 256 participants, aged 60-85 years, 70 with normal glucose metabolism, 69 with impaired glucose metabolism and 109 with Type II diabetes, were included in this study. All participants were ophthalmologically examined, including funduscopy and two field 45 degrees fundus photography, and were graded for retinal sclerotic vessel abnormalities and retinopathy. Retinal arteriolar and venular diameters were measured with a computer-assisted method. Brachial artery, endothelium-dependent FMD and carotid IMT were assessed ultrasonically as measurements of endothelial function and early atherosclerosis respectively. After adjustment for age, sex and glucose tolerance status, retinal vessel diameters, retinal sclerotic vessel abnormalities and retinopathy were not significantly associated with FMD. In contrast with other retinal microvascular abnormalities, retinal venular dilatation was associated with increased IMT [standardized beta value (95% confidence interval), 0.14 (0.005-0.25)]. This association was attenuated and lost statistical significance after adjustment for cardiovascular risk factors, in particular after correction for fasting insulin. In the present study, retinal microvascular disorders are not independently associated with impaired FMD. In addition, retinal venular dilatation is associated with increased IMT, although non-significantly after multivariable adjustment for cardiovascular risk factors. Therefore our data provide evidence that retinal microvascular disease is of limited value in risk stratification for future cardiovascular events.

Diabetic retinopathy is associated with mortality and cardiovascular disease incidence: the EURODIAB prospective complications study.

OBJECTIVE: To study the relationship of nonproliferative and proliferative retinopathy with all-cause mortality and cardiovascular disease (CVD) incidence in type 1 diabetic patients and, additionally, the role of cardiovascular risk factors in these associations. RESEARCH DESIGN AND METHODS: This prospective study included 2,237 type 1 diabetic patients from 31 centers in 16 European countries at baseline, aged 15-60 years, who were examined for retinopathy by taking two-field 45 degrees fundus photographs, which were centrally graded. Mortality and cardiovascular morbidity follow-up was assessed 6-8 years after baseline examination according to a standardized protocol. RESULTS: After 7.9 years of follow-up, 64 patients had died and 128 patients had incident CVD. The age- and sex-adjusted hazard ratios (HRs) of all-cause mortality were 1.45 (95% CI 0.71-2.96) and 4.16 (1.96-8.84) in patients with nonproliferative and proliferative retinopathy at baseline, respectively. Adjustments for cardiovascular risk factors completely obliterated the association with nonproliferative retinopathy, whereas the association with proliferative retinopathy remained twofold increased, although nonsignificant. The age- and sex-adjusted HRs of incident CVD were 1.73 (1.15-2.60) and 2.05 (1.22-3.45) in patients with nonproliferative and proliferative retinopathy, respectively. After adjustments for cardiovascular risk factors, both associations were attenuated and lost statistical significance. CONCLUSIONS: This study shows that type 1 diabetic patients with nonproliferative or proliferative retinopathy have an increased risk for all-cause mortality and incident CVD. The presence of cardiovascular risk factors explained the associations to a large extent, except for the associations with proliferative retinopathy, which suggests that other shared mechanisms may be involved.