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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Diabetic retinopathy is a frequent chronic complication of diabetes and may predict nephropathy and cardiovascular events. Development of proliferative lesions and/or macular edema indicates that a sight-threatening stage has been reached which, if left untreated, will almost inevitably evolve to blindness. Prevention of this feared outcome relies upon optimal control of blood glucose and, when hypertension is present, blood pressure. Besides, yearly screening by ophthalmoscopy and/or retinal photography should be carried out in all people with diabetes to identify those who have developed sight-threatening lesions. Though sight-threatening retinopathy is rarely reached during paediatric age, if anything because it takes many years to develop, the retina should be carefully monitored already during childhood and adolescence. "Florid" retinopathy and diabetic papillopathy are possible specific manifestations of retinopathy in diabetic patients during their early post-pubertal years. Pre-pubertal years, though suggested by some as protecting against diabetic retinopathy, may, in fact, contribute to and even be an independent risk factor for the development of proliferative lesions later in life. Apart from controlling glycaemia and blood pressure, ongoing phase 3 trials are evaluating new possible pharmacologic approaches to the prevention and treatment of retinopathy which, to this date, relies upon the hugely effective but destructive application of laser photocoagulation.
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PMID:Diabetic retinopathy and its relevance to paediatric age. An update. 1643 31

Using teleophthalmology for the delivery of routine eye care for patients with diabetes mellitus is becoming an increasingly common practice. Paramount in the consideration of any new diagnostic test is an analysis of its diagnostic accuracy and reliability and how that compares with conventional care. This review summarizes existing data on the diagnostic accuracy and reliability of teleophthalmology and conventional clinic-based eye care for detecting diabetic retinopathy and diabetes mellitus. The sensitivity of ophthalmoscopy for detecting diabetic retinopathy performed by eye care clinicians has varied widely, with point estimates ranging from 0% to 96%. Alternatively, specificity has been universally high. The sensitivity of teleophthalmology for detecting diabetic retinopathy has been shown to be comparable, if not better, than clinic-based examinations. Sensitivity values have ranged from 50% to 93%. The specificity of teleophthalmology, like clinic-based examinations, has been consistently high. High levels of diagnostic reliability, analyzed by both simple agreement and kappa values, have been found between ophthalmoscopy and teleophthalmology for detecting and classifying diabetic retinopathy. Evaluating the accuracy of macular edema detection requires the use of dual gold standards, the clinical examination using slit-lamp biomicroscopy and stereoscopic photography. Teleophthalmology, compared with both gold standards, has, overall, been a highly sensitive and specific test. Reliability studies that compared the two gold standards with one another have found moderate to substantial levels of agreement. Based on existing data, teleophthalmology appears to be an accurate and reliable test for detecting diabetic retinopathy and macular edema.
Diabetes Technol Ther 2006 Feb
PMID:Accuracy and reliability of teleophthalmology for diagnosing diabetic retinopathy and macular edema: a review of the literature. 1647 57

The objective of this study was to establish the baseline retinal hemodynamic characteristics of stratified groups of diabetic patients at increasing risk for the development of diabetic macular edema (DME). Group 1 had 50 control subjects, group 2 had 56 diabetic patients without clinically visible retinopathy, group 3 had 54 diabetic patients with microaneurysms and/or hard exudates within two disc diameters of the fovea in the absence of clinically manifest DME, and group 4 had 40 patients with clinically manifest DME. Retinal hemodynamics (diameter, velocity, maximum-to-minimum velocity ratio, and flow) were assessed. Intraocular pressure, blood pressure, and relevant systemic markers of diabetes control and complications were also undertaken. The maximum-to-minimum velocity ratio was elevated with increasing risk of clinically significant DME (P < 0.0001). No significant differences were found between the groups with respect to diameter, velocity, or flow. The maximum-to-minimum velocity ratio was correlated to age, duration of diabetes, blood pressure, pulse rate, intraocular pressure, and serum potassium levels. In conclusion, the maximum-to-minimum velocity ratio was significantly increased with increasing risk of development of DME. Retinal arteriolar hemodynamics were positively correlated to age, duration of diabetes, and blood pressure. These findings suggest a reduction in the compliance (i.e., an increase of vascular rigidity) of the arteriolar circulation with increasing risk of DME.
Diabetes 2006 Mar
PMID:Retinal hemodynamics in early diabetic macular edema. 1650 48

Diabetic retinopathy is characterized by both functional and morphological changes in the retinal microvessels that can lead to macular edema, neovascularization, and vision loss. Hypertension has been identified as a major risk factor for diabetic retinopathy and randomized clinical trials have shown that reduction of blood pressure using angiotensin converting enzyme (ACE) inhibitors reduces the progression of diabetic retinopathy. The major components of the renin-angiotensin system have been identified in ocular tissues. Activation of angiotensin II type 1 (AT1) receptors expressed on retinal endothelial cells and pericytes has been implicated in contributing to the microvascular abnormalities in diabetic retinopathy. We have examined the experimental and clinical evidence for the role of the renin-angiotensin system in the pathogenesis of diabetic retinopathy, including the effects of ACE inhibition and AT1-receptor antagonism on diabetes-induced abnormalities in retinal hemodynamics, vascular permeability, and leukostasis; retinal neovascularization in rodent models of oxygen-induced retinopathy; and results from randomized clinical trials that have investigated the effects of ACE inhibitors on the progression of diabetic retinopathy in diabetic patients in the absence or presence of hypertension. The effects of AT1-receptor antagonism on the retina have been attributed to decreases in systemic blood pressure and the concomitant reduction in mechanical vascular stretch, in addition to the intraocular effects blocking AT1-receptor stimulation of retinal endothelial cells and pericytes. Results from the current DIabetic REtinopathy Candesartan Trials program will evaluate the potential of the AT1-receptor as a therapeutic target for diabetic retinopathy.
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PMID:Role of the angiotensin II type 1 receptor in the pathogenesis of diabetic retinopathy: effects of blood pressure control and beyond. 1660 77

Cardiovascular complications are the leading cause of morbidity and mortality in patients with diabetes mellitus; up to 80% of deaths in patients with diabetes are closely associated with vascular disease. The ability of the organism to form a collateral network of blood vessels constitutes an important response to vascular occlusive disease and determines to a large part the clinical consequences and severity of tissue ischemia. The development of new vessels is significantly reduced in diabetic patients with coronary or peripheral artery disease. This probably contributes to the severe course of limb ischemia in diabetic patients, in which peripheral artery disease often results in foot ulceration and lower extremity amputation. Diabetic retinopathy remains one of the major causes of acquired blindness in developed nations. This is true despite the development of laser treatment, which can prevent blindness in the majority of those who develop macular edema or proliferative diabetic retinopathy. The hallmark of diabetic retinopathy is the lack of microvessels in the macula, leading to hypoxia, associated with peripheral retinal neovascularization that may ultimately cause severe vitreous cavity bleeding and/or retinal detachment. The factors that stimulate retinal blood vessel growth have not been fully defined, but there is accumulating evidence that the renin-angiotensin-bradykinin system may be involved in a number of retinal vascular disorders, including retinopathy of prematurity and proliferative diabetic retinopathy. Only a few studies have specifically evaluated the effect of diabetes on angiogenesis in ischemic vascular disease and in the retina. Moreover, the mechanisms by which diabetes could both limit the formation of new blood vessels in most organs and simultaneously induce proliferative diabetic retinopathy remain largely undefined. In the present review, we aimed to briefly describe the main molecular mechanisms involved in the ischemia-induced angiogenesis, and their alterations in diabetes. Possible therapeutic strategies to restore angiogenesis in diabetic patients are also listed.
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PMID:[Diabetes and peripheral arterial occlusive disease: therapeutic potential and pro-angiogenic strategies]. 1670 93

Diabetes mellitus is the systemic disease that most often leads to blindness. Since the diminishment of visual acuity is a late symptom of the disease, screening examinations are of particular importance, as only in this way can the optimal time point for treatment be determined. Stage-oriented laser therapy prevents blindness due to macular edema or proliferative diabetic retinopathy. For a number of years, vitreoretinal surgery has enabled the treatment of late ocular manifestations such as bleeding into the vitreous body and traction retinal detachment. With appropriate stage-oriented treatment, hopeless cases of diabetic retinopathy ending in blindness should become the exception. The only useful and confirmed effective medical treatment capable of delaying this late complication continues to be careful blood glucose and blood pressure control.
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PMID:[Diagnostic and therapeutic options in diabetic retinopathy]. 1679 86

The prevalence of diabetes has been accelerating at an alarming rate in the last decade; some describe it as an epidemic. Diabetic eye complications are the leading cause of blindness in adults aged 25-74 in the United States. Early diagnosis and development of effective preventatives and treatments of diabetic retinopathy are essential to save sight. We describe efforts to establish functional indicators of retinal health and predictors of diabetic retinopathy. These indicators and predictors will be needed as markers of the efficacy of new therapies. Clinical trials aimed at either prevention or early treatments will rely heavily on the discovery of sensitive methods to identify patients and retinal locations at risk, as well as to evaluate treatment effects. We report on recent success in revealing local functional changes of the retina with the multifocal electroretinogram (mfERG). This objective measure allows the simultaneous recording of responses from over 100 small retinal patches across the central 45 degrees field. We describe the sensitivity of mfERG implicit time measurement for revealing functional alterations of the retina in diabetes, the local correspondence between functional (mfERG) and structural (vascular) abnormalities in eyes with early nonproliferative retinopathy, and longitudinal studies to formulate models to predict the retinal sites of future retinopathic signs. A multivariate model including mfERG implicit time delays and 'person' risk factors achieved 86% sensitivity and 84% specificity for prediction of new retinopathy development over one year at specific locations in eyes with some retinopathy at baseline. A preliminary test of the model yielded very positive results. This model appears to be the first to predict, quantitatively, the retinal locations of new nonproliferative diabetic retinopathy development over a one-year period. In a separate study, the predictive power of a model was assessed over one- and two-year follow-ups. This permitted successful prediction of new retinopathy development in eyes with and without retinopathy at baseline. Finally, we briefly describe our current research efforts to (a) locally predict future sight-threatening diabetic macular edema, (b) investigate local retinal function change in adolescent patients with diabetes, and (c) better understand the physiological bases of the mfERG delays. The ability to predict the retinal locations of future retinopathy based on mfERG implicit time provides clinicians a powerful tool to screen, follow-up, and even consider early prophylactic treatment of the retinal tissue in diabetic patients. It also aids identification of 'at risk' populations for clinical trials of candidate therapies, which may greatly reduce their cost by decreasing the size of the needed sample and the duration of the trial.
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PMID:A multifocal electroretinogram model predicting the development of diabetic retinopathy. 1694 55

This study was designed to investigate whether V16A polymorphism of the manganese superoxide dismutase (Mn-SOD) gene is associated with the development of type 2 diabetes mellitus and with progression of diabetic retinopathy (DR) and diabetic macular edema (DME). We simultaneously analyzed insertion/deletion polymorphism of the angiotensin-converting enzyme (ACE) gene in the 16th intron to avoid its confounding effect. A total of 192 nondiabetic subjects and 304 type 2 diabetic patients were included in the study. Diabetic retinopathy was classified as nonretinopathy, nonproliferative retinopathy, and proliferative retinopathy. Diabetic macular edema was defined as thickening of the retina and/or hard exudates within a 1-disk diameter of the center of the macula. Diabetic macular edema was further classified into focal, diffuse, and ischemic types. The A allele frequency of the Mn-SOD gene was not different between nondiabetic and type 2 diabetic subjects, between the normotensive and hypertensive groups, between the DR (-) and DR (+) groups, and among the stages of DR. In the DR (+) group, the DME (+) group had a lower A allele frequency than that of the DME (-) group. In the DME (+) group, focal, diffuse, and ischemic types were found in 8, 23, and 6 patients, respectively. The A allele frequency of each type was 0.188, 0.109, and 0.0. The D allele frequency of the angiotensin-converting enzyme gene did not differ in any of the comparisons. Clinical and laboratory parameters of the A allele carriers were not different from those of the noncarriers except for the prevalence of hypertension and DME. Hypertension, diabetic duration, and insulin therapy were related to DR. The A allele, hypertension, and insulin therapy were associated with DME. In conclusion, our results suggest that V16A polymorphism of the Mn-SOD gene is not related to the development of diabetes and progression of DR, but is associated with DME in Korean type 2 diabetic patients.
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PMID:Association of manganese superoxide dismutase gene polymorphism (V16A) with diabetic macular edema in Korean type 2 diabetic patients. 1714 44

Vascular endothelial growth factor (VEGF) is a central regulator of both physiological and pathological angiogenesis. Pegaptanib, a 28-nucleotide RNA aptamer specific for the VEGF(165) isoform, binds to it in the extracellular space, leaving other isoforms unaffected, and inhibits such key VEGF actions as promotion of endothelial cell proliferation and survival, and vascular permeability. Pegaptanib already has been examined as a treatment for two diseases associated with ocular neovascularization, age-related macular degeneration (AMD) and diabetic macular edema (DME). Preclinical studies have shown that VEGF(165) alone mediates pathological ocular neovascularization and that its inactivation by pegaptanib inhibits the choroidal neovascularization observed in patients with neovascular AMD. In contrast, physiological vascularization, which is supported by the VEGF(121) isoform, is unaffected by this inactivation of VEGF(165). In addition, animal model studies have shown that intravitreous injection of pegaptanib can inhibit the breakdown of the blood-retinal barrier characteristic of diabetes and even can reverse this damage to some degree. These preclinical findings formed the basis for randomized controlled trials examining the efficacy of pegaptanib as a therapy for AMD and DME. The VEGF Inhibition Study in Ocular Neovascularization (VISION) trial comprising two replicate, pivotal phase 3 studies, demonstrated that intravitreous injection of pegaptanib resulted in significant clinical benefit, compared with sham injection, for all prespecified clinical end points, irrespective of patient demographics or angiographic subtype, and led to pegaptanib's approval as a treatment for AMD. A phase 2 trial has provided support for the efficacy of intravitreous pegaptanib in the treatment of DME.
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PMID:Anti-VEGF aptamer (pegaptanib) therapy for ocular vascular diseases. 1714 36

Laser treatment of diabetic retinopathy is still the gold standard of treatment for focal and diffuse diabetic macular edema and proliferative diabetic retinopathy. When properly treated, the 5-year risk of blindness is reduced by 90% in patients with proliferative diabetic retinopathy and the risk of visual loss from macular edema is reduced by 50%. However, only about 35-50% of patients with diabetes mellitus receive regular eye examinations, which are important for timely diagnosis and proper treatment. The necessary goals are better patient education to improve the control of diabetes and better screening programs to reduce the risk of blindness from diabetic retinopathy.
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PMID:Laser treatment of diabetic retinopathy. 1724 78


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