Incidence of sight-threatening diabetic retinopathy in people with Type 2 diabetes mellitus and numbers needed to screen: a systematic review.

AIM: To investigate the incidence of sight-threatening diabetic retinopathy in Type 2 diabetes mellitus. BACKGROUND: In most countries, yearly or biennial screening intervals for diabetic retinopathy in people with Type 2 diabetes are recommended. Fewer screening sessions reduce the effort required of people with Type 2 diabetes and reduce healthcare costs. METHODS: We conducted a search of PubMed, Embase, Web of Science and the COCHRANE Library for studies published betweeen 1 January 2000 and 1 January 2017. Eligible studies were those that included general populations of >100 people with Type 2 diabetes mellitus. Additional study population criteria were absence of moderate diabetic retinopathy or more severe diabetic retinopathy at last screening session and at least two gradable retinal screening sessions. Outcomes of interest in the included studies were moderate and severe non-proliferative diabetic retinopathy (R2), proliferative diabetic retinopathy (R3) or maculopathy (M1), collectively known as sight-threatening or referable diabetic retinopathy. RESULTS: A total of 17 studies were included. In people with Type 2 diabetes without or with only mild diabetic retinopathy at baseline, the average incidence rates of sight-threatening diabetic retinopathy were ~1 per 100 person-years and ~8 per 100 person-years, respectively. The average numbers needed to screen to detect one case of sight-threatening diabetic retinopathy were 175 and 19 in people without and with mild retinopathy at last screening, respectively. CONCLUSION: In people with Type 2 diabetes without retinopathy at last screening, the incidence of severe sight-threatening retinopathy at the subsequent screening session was low. In people with mild retinopathy, progression to sight-threatening diabetic retinopathy was nearly 10-fold higher. This review supports lengthening of the screening interval of patients with Type 2 diabetes without retinopathy at last screening session.

Fasting proinsulin levels are significantly associated with 20 year cancer mortality rates. The Hoorn Study.

AIMS/HYPOTHESIS: Proinsulin is possibly associated with cancer through activation of insulin receptor isoform A. We sought to investigate the associations between proinsulin and 20 year cancer mortality rates. METHODS: The study was performed within the Hoorn Study, a population-based study of glucose metabolism in individuals aged 50-75 years in the Dutch population. Fasting proinsulin levels were measured twice by a double-antibody radioimmunoassay. Participants were continuously followed to register mortality; causes of death were derived from medical records. Cox survival analyses were performed to assess the 20 year risk of death from cancer in relation to proinsulin. All analyses were adjusted for age and sex, with additional adjustments for traditional risk factors. The effect modification of glucose metabolism and sex was tested. RESULTS: Proinsulin levels were measured in 438 individuals (41% normal glucose tolerance, 35.7% impaired glucose metabolism, 23.3% type 2 diabetes). Of these participants, 53 died from cancer. After adjustment for age and sex, proinsulin >16.5 pmol/l (the upper tertile) was significantly associated with a twofold risk of cancer mortality (HR 2.01, 95% CI 1.16, 3.46) compared with individuals with lower proinsulin levels. Additional adjustment for glucose metabolism, BMI and smoking did not substantially change the results (HR 1.91, 95% CI 1.04, 3.52). No interaction with glucose metabolism or sex was observed. CONCLUSIONS/INTERPRETATION: Individuals with fasting proinsulin levels >16.5 pmol/l have a twofold risk of cancer mortality over a 20 year time span. These findings provide population-based evidence for the independent association between high proinsulin levels and cancer mortality rates.

Diabetic retinopathy screening in patients with diabetes mellitus in primary care: Incentives and barriers to screening attendance.

AIM: Although diabetic retinopathy (DR) screening is a basic component of diabetes care, uptake of screening programs is less than optimal. Because attendance rates and reasons for non-attendance in an unselected diabetes population are unknown, this study examines incentives and barriers to attend DR-screening. METHOD: Four focus groups provided patient-related themes concerning individual decision-making regarding attendance at DR-screening. A questionnaire measuring attendance rates and the influence of several factors was sent to 3236 diabetes patients (>18 years) in 20 Dutch general practices, of which 2363 (73%) responded. RESULTS: In the past 3 years, 81% of the patients had attended DR-screening. Patients not attending had lower levels of education, a more recent diagnosis of diabetes, and less frequently used insulin. There was no difference in DM types 1 and 2 patients regarding attendance. Patients attending more often visited health-care providers. Patients reported 'knowledge of detrimental effects of DR on visual acuity', 'sense of duty' and 'fear of impaired vision' as main incentives. The main barrier was the absence of a recommendation by the health-care provider. CONCLUSION: Knowledge about detrimental effects of DR on visual acuity and recommendation by health-care providers are important, possibly modifiable, factors in the attendance to DR screening.

[Revised guideline 'Diabetic retinopathy: screening, diagnosis and treatment']. / Richtlijn 'diabetische retinopathie: screening, diagnostiek en behandeling' (herziening).

The revised evidence-based guideline 'Diabetic retinopathy: screening, diagnosis and treatment' contains important recommendations concerning screening, diagnosis and treatment of diabetic retinopathy. Regular screening and the treatment of risk factors, such as hyperglycemia, hypertension, adipositas and dyslipidemia, can prevent retinopathy and slow down its development. Fundus photography is recommended as a screening method. If necessary, diagnosis by biomicroscopy and a treatment consisting of photocoagulation and/or vitrectomy should be performed by the ophthalmologist. The reassessment of responsibilities is a vital component of the implementation of the guideline bearing in mind that the screening in particular, can be performed by personnel other than ophthalmologists.

[Therapeutic possibilities for diabetic macular oedema]. / Behandelingsmogelijkheden voor diabetisch macula-oedeem.

The number of patients with diabetes mellitus will increase over the coming years, so that there will also be more patients with diabetic macular oedema. Diabetic macular oedema and diabetic retinopathy are the most important causes of legal blindness in adults. The current therapy of diabetic macular oedema consists of the prevention, detection and treatment of risk factors (e.g., hypertension, hyperglycaemia, dyslipidaemia, proteinuria and obesity), complemented if necessary by photocoagulation therapy. Photocoagulation therapy may prevent or reduce vision loss in many patients, but usually does not improve visual acuity. New treatment strategies include intravitreal corticosteroids or vascular endothelial growth factor (VEGF) inhibitors, and oral protein kinase C inhibitors, angiotensin converting enzyme (ACE) inhibitors, acetylsalicylic acid or statins. The long-term positive effect of these strategies is controversial and the side effects can be serious.

Inflammation and endothelial dysfunction are associated with retinopathy: the Hoorn Study.

AIMS/HYPOTHESIS: The 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. METHODS: As 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 degrees 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. RESULTS: The 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/INTERPRETATION: In this study, inflammatory activity and endothelial dysfunction were associated with retinopathy, which suggests their involvement in the pathogenesis of retinopathy.

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.

Visual field and electrophysiological abnormalities due to vigabatrin.

The purpose of this study was to determine the electrophysiological changes in patients using the anti epileptic drug vigabatrin and to correlate these findings with the previously reported risk for visual field loss in these patients. In 1998 the neurologists of both involved hospitals referred all patients on vigabatrin medication for ophthalmological examination to the outpatients clinics. Of the 33 patients whom were referred to our outpatient clinics, four had to be dropped from the study because of disability to perform the examinations the remaining 29 patients were included in the study. Standard ophthalmological investigations were carried out, and contrast sensitivity, visual field (Humphrey 30-2 and Esterman or Octopus 32), colour vision (panel D15), ERG and EOG according to ISCEV standards were tested. 18 patients continued the medication and 11 stopped taking the drug during the study. Nine of the patients who stopped the drug were followed during at least half a year afterwards, this group will be described in the combined article 'Electro ophthalmic recovery after withdrawal from vigabatrin' (Graniewski and Van der Torren, this issue). The electro-ophthalmological findings in the group of 29 patients were correlated with the visual fields and the daily and cumulative dosages of vigabatrin. Of the patients, 32% showed no visual field constriction at all; from these patients 64% had EOG and/or ERG changes. Of the patients with slight to marked visual field constriction, 90% presented EOG and/or ERG changes. Significant correlation between daily dosages of vigabatrin and visual field defects was shown as well as between visual field defects and rod and cone b wave amplitude reductions. Cumulative vigabatrin dosages presented a significant correlation with EOG ratio and ERG rod b-wave amplitude. Conclusively EOG and ERG testing were found to be even an more accurate way to monitor the direct vigabatrin effect on the outer retina and is possible different from the visual field testing.

Angiotensin converting enzyme inhibiting therapy is associated with lower vitreous vascular endothelial growth factor concentrations in patients with proliferative diabetic retinopathy.

AIMS/HYPOTHESIS: Vascular endothelial growth factor (VEGF) is thought to be instrumental in the progression of diabetic retinopathy. Indications exist that the renin-angiotensin system is involved in VEGF overexpression. We assessed the vitreous VEGF concentrations in patients and related them to anti-hypertensive treatment, with special interest in the use of ACE-inhibitors. METHODS: Samples of vitreous fluid (10-80 microl) were obtained from 39 patients both with Type I (insulin-dependent) and Type II (non-insulin-dependent) diabetes mellitus and 11 non-diabetic patients undergoing intra-ocular surgery. The VEGF-A concentrations were assessed by immunoassay. RESULTS: Control patients and patients without proliferative diabetic retinopathy ( n = 8) had low and comparable VEGF concentrations (medians < 50 pg/ml). In contrast, patients with proliferative diabetic retinopathy ( n = 31) had high vitreous VEGF concentrations (median 1134 pg/ml), which showed a negative correlation with the use of ACE inhibiting medication (Spearman rank-R = - 0.54; p = 0.002, n = 13). Diastolic and systolic blood pressure did not differ significantly between the two subgroups with proliferative diabetic retinopathy, i. e. those patients receiving ACE-inhibition (medians 88/160 mm Hg, respectively) and the others (90/160). For the mostly used ACE-inhibitor in the proliferative diabetic retinopathy group, i. e. enalapril ( n = 8), a linear dose-effect relation was observed (-20 +/- 4 pg x ml(-1) x mg(-1) x day(-1); p = 0.024; coefficient +/- SEM). CONCLUSION/INTERPRETATION: Treatment with ACE-inhibitors attenuates retinal overexpression of VEGF-A in patients with proliferative diabetic retinopathy, probably by interference with a local effect of angiotensin II.