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.