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

A few reports have suggested that angiotensin-converting enzyme inhibitors (ACE-I) have a beneficial effect on mild diabetic retinopathy (DR). This pilot study was carried out to determine if a small dose of an ACE-I would retard the progression of moderate to severe DR in normotensive Type 2 diabetic patients. Normotensive patients were selected to isolate the effect on the ocular RAS independent of any lowering of blood pressure. Thirty-five normotensive Type 2 diabetic patients with <1+ dipstick proteinuria and with moderate to severe DR by modified Arlie House Classification criteria on seven field stereoscopic photographs through dilated pupils were randomized to an ACE-I (5 mg of enalapril) (n=18) or to a multivitamin (MVI) placebo (n=17). They were evaluated by an ophthalmologist every 3 months for a planned duration of 2 years. Endpoints of the study were progression to proliferative DR (PDR) or macular edema (ME) for which laser therapy was necessary or for the development of >/=1+ dipstick proteinuria times two (sustained proteinuria) for which an ACE-I was indicated. There were no differences in baseline age, gender, duration of diabetes, body mass indices, blood pressure, treatment of hyperglycemia or Hb A1C levels between the two groups. Blood pressure and Hb A1C levels did not change in either group during the study. The study was stopped prematurely after a mean duration of 7.2 months after an interim analysis revealed that it was very unlikely that a beneficial effect of ACE-I could be shown. At that time in the ACE-I group, four patients had progressed to PDR, three to ME and one had developed sustained proteinuria. In the MVI group, three patients had progressed to PDR, one to ME and one had developed sustained proteinuria. Small doses of an ACE-I did not exert a beneficial effect on the progression of moderate to severe DR over a short period of follow-up. An analysis of previously published clinical information on the effects of ACE-I, most of which evaluated patients with milder DR, supports only a limited (if any) beneficial effect of this class of drugs on the early stages of this microvascular complication.
J Diabetes Complications
PMID:Angiotensin-converting enzyme inhibition for the treatment of moderate to severe diabetic retinopathy in normotensive Type 2 diabetic patients. A pilot study. 1247 20

Hyperglycemic control in diabetes mellitus is a major key to prevent the development and progression of diabetic retinopathy. One important pathomechanism in the development of diabetic complications is the activation of protein kinase C (PKC) induced by high glucose due to an increased diacylglycerol (DAG) level. Resulting vascular dysfunctions are increased vascular permeability and contractility, increased production of extracellular matrix and cell proliferation. The PKC isoenzyme family plays a fundamental role in the cellular signal transduction via phosphorylation and modification of enzymes, receptors, transcription factors and kinases. The PKC activation influences the gene transcription and ion transport. Different PKC isoenzymes function as mediators but also as inhibitors of the insulin effects. The hyperglycemia induced DAG production seems to predominantly activate PKC-beta in retinal vascular endothelial cells. The development of selective PKC-beta inhibitors enables new pharmacological therapeutical approaches for treatment of diabetic retinopathy. Ongoing clinical studies investigate if the treatment with specific PKC-beta inhibitors can prevent the progression of diabetic retinopathy and diabetic macular edema.
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PMID:[The role of protein kinase C in the pathophysiology of diabetic retinopathy]. 1249 66

Despite the results of clinical trials showing the efficacy of panretinal and focal photocoagulation of proliferative retinopathy with high-risk characteristics for severe visual loss and for clinically significant macular edema, retinopathy remains an important cause of visual loss. Because these treatments are associated with cost, may not always prevent visual loss, and may result in complications, other nonsurgical interventions have been sought to prevent visual loss from retinopathy. Data from epidemiological studies showed an association between hyperglycemia, hypertension, and dyslipidemia and the incidence and progression of retinopathy and macular edema in people with diabetes. These findings resulted in a number of clinical trials that have shown the efficacy of intensive control of hyperglycemia and hypertension in reducing the incidence and progression of diabetic retinopathy. Despite these findings, the majority of persons with diabetes fail to achieve American Diabetes Association-targeted guidelines for glycosylated hemoglobin, blood pressure, and lipid levels. Thus, new approaches for achieving normalization of blood glucose levels are needed and new clinical trials are underway to assess these new interventions.
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PMID:Prevention of visual loss from diabetic retinopathy. 1250 26

Retinal microvascular dysfunction in diabetes is a major component of diabetic retinopathy. This review highlights recent observations regarding the cellular anatomy that contributes to the blood-retinal barrier and its breakdown, the alterations of macroglial, neuronal, and microglial cells in diabetes, and how these changes lead to loss of vision. In addition, the effects of systemic pathophysiologic influences, including metabolic control, blood pressure, and fluid volume on the formation of diabetic macular edema are discussed. Finally, an overview of inflammatory mechanisms and responses in the retina in diabetes is provided. Together, these new observations provide a broader clinical and research perspective on diabetic retinal vascular dysfunction than previously considered, and provide new avenues for improved treatments to prevent loss of vision.
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PMID:Diabetic retinopathy: more than meets the eye. 1250 27

Diabetic retinopathy is one of the most debilitating complications of diabetes mellitus. Despite major advances in understanding the pathogenesis of this disease and the efficacy of current therapies, diabetic retinopathy remains the leading cause of new-onset blindness among working-age people. The mainstay of current therapy, laser photocoagulation, is useful in preventing blindness and severe vision loss but is not often effective in restoring lost visual acuity. In addition, troublesome side effects and potentially serious complications may occur. Diabetic retinopathy is characterized by a progression of abnormalities. Nonproliferative retinopathy results from a series of biochemical and cellular changes that ultimately cause progressive retinal ischemia. The subsequent elaboration of growth factors in response to ischemia leads to the development of proliferative retinopathy, which is characterized by aberrant neovacularization of the retina-potentially leading to severe, irreversible visual loss. Increased retinal vascular leakage may also occur at any stage in this process, resulting in macular edema and possible progressive visual impairment. Although numerous biochemical factors are thought to play a role in the development of retinopathy, activation of protein kinase C (PKC), specifically the beta isoform of PKC (PKC beta), is implicated for both the early and late-stage manifestations of retinopathy. Studies suggest that orally administered LY333531, a beta-isoform specific PKC inhibitor, may be effective in ameliorating retinopathy progression, proliferation, and retinal vascular leakage. The status of ongoing clinical trials aimed at addressing the efficacy of PKC beta with regard to diabetes-induced retinal complications and perspectives on the role of PKC beta are presented.
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PMID:The potential role of PKC beta in diabetic retinopathy and macular edema. 1250 28

Trials of new compounds (e.g., protein kinase C inhibitors) for the treatment of diabetic retinopathy and diabetic macular edema historically have used tools such as seven-field stereoscopic fundus photography to grade retinopathy, and endpoints such as the need for retinal photocoagulation to evaluate efficacy. Improvements in diabetes care have led to slower spontaneous progression of retinopathy than anticipated, however. A consequence of this trend is that clinical trials for diabetic retinopathy and diabetic macular edema are expected to last for many years and require large numbers of patients before evidence-based conclusions can be made. Therefore, interest in new assessment tools is growing. This review briefly describes the basic pathophysiologic factors involved in the pathogenesis of diabetic macular edema to provide a basis for the introduction of new quantitative and objective endpoints. Special consideration is given to measuring fluorescein permeability of the blood-retinal barrier. The quantitative measurement of retinal thickness using optical coherence tomography is a promising noninvasive method. Microaneurysm counts, assessment of length and diameter of retinal vessels, and computerized quantification of all pathologic elements may also be useful as diagnostic tools and/or efficacy endpoints.
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PMID:Mechanisms for monitoring changes in retinal status following therapeutic intervention in diabetic retinopathy. 1250 29

Impairment in the visual acuity and quality of life of diabetic patients with macular edema can undeniably be decreased with systemic and ocular therapeutic intervention, as shown by numerous controlled studies. Such interventions, with early screening and periodic examination, are even more crucial given the increasing survival of patients with diabetic retinopathy. In the 1950s, adjusted 5-year survival rates for patients with PDR were less than 30%, whereas by the end of the century age- and sex-adjusted 5-year survival rates approached 90% for patients with early-onset diabetes and 60% for patients with late-onset diabetes [83]. Furthermore, advances in our understanding of diabetic retinopathy have led to biochemical adjuncts that offer the potential for further reduction of visual loss caused by diabetic macular edema. Despite such advances, the implementation of effective treatments has been hampered by concerns over hypoglycemia after intensive insulin regimens, poor physician compliance regarding guidelines for dilated ophthalmic examinations, and economic barriers to access [84]. Therefore, it is imperative for the ophthalmologist not only to discuss the progression and treatment of diabetic macular edema and the importance of routine examination with patients but also to work with other health care professionals to ensure the evaluation and treatment of associated cardiovascular and neurologic disease. Educational programs, such as those created by the National Eye Health and Education Program [85], may also assist the ophthalmologist in providing patients with the optimal care available in the 21st century.
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PMID:Diabetic macular edema: review and update. 1251 87

Diabetic retinopathy (DR) and diabetic macular edema (DME) are leading causes of blindness in the working-age population of most developed countries. The increasing number of individuals with diabetes worldwide suggests that DR and DME will continue to be major contributors to vision loss and associated functional impairment for years to come. Early detection of retinopathy in individuals with diabetes is critical in preventing visual loss, but current methods of screening fail to identify a sizable number of high-risk patients. The control of diabetes-associated metabolic abnormalities (i.e., hyperglycemia, hyperlipidemia, and hypertension) is also important in preserving visual function because these conditions have been identified as risk factors for both the development and progression of DR/DME. The currently available interventions for DR/DME, laser photocoagulation and vitrectomy, only target advanced stages of disease. Several biochemical mechanisms, including protein kinase C-beta activation, increased vascular endothelial growth factor production, oxidative stress, and accumulation of intracellular sorbitol and advanced glycosylation end products, may contribute to the vascular disruptions that characterize DR/DME. The inhibition of these pathways holds the promise of intervention for DR at earlier non-sight-threatening stages. To implement new therapies effectively, more individuals will need to be screened for DR/DME at earlier stages-a process requiring both improved technology and interdisciplinary cooperation among physicians caring for patients with diabetes.
Diabetes Care 2003 Sep
PMID:Diabetic retinopathy and diabetic macular edema: pathophysiology, screening, and novel therapies. 1294 34

Retinal neovascularization and macular edema are central features of diabetic retinopathy, the major cause of blindness in the developed world. Current treatments are limited in their efficacy and are associated with significant adverse effects. Characterization of the molecular and cellular processes involved in vascular growth and permeability has led to the recognition that the angiogenic growth factor and vascular permeability factor vascular endothelial growth factor (VEGF) plays a pivotal role in the retinal microvascular complications of diabetes. Therefore, VEGF represents an exciting target for therapeutic intervention in diabetic retinopathy. This review highlights the current understanding of the mechanisms that regulate VEGF gene expression and mediate its biological effects and how these processes may become altered during diabetes. The cellular and molecular alterations that characterize experimental models of diabetes are considered in relation to the influence of high glucose-mediated oxidative stress on VEGF expression and on the mechanisms of VEGF's actions under hyperglycemic induction. Finally, potential therapeutic strategies for preventing VEGF overexpression or blocking its pathological effects in the diabetic retina are considered.
Diabetes Metab Res Rev
PMID:Vascular endothelial growth factor and diabetic retinopathy: pathophysiological mechanisms and treatment perspectives. 1464 3

Angiostatin is a potent angiogenic inhibitor. The present study identified a new activity of angiostatin: reducing vascular leakage, which is associated with diabetic macular edema, tumor growth and inflammation. An intravitreal injection of angiostatin significantly reduced retinal vascular permeability in rats with oxygen-induced retinopathy and in those with streptozotocin-induced diabetes, but not in normal rats. Consistent with its effect on permeability, angiostatin downregulated vascular endothelial growth factor (VEGF) expression in the retina in both the rat models but not in normal controls. These results suggest that the effect of angiostatin on vascular leakage is mediated, at least in part, through blockade of VEGF overexpression.
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PMID:The effect of angiostatin on vascular leakage and VEGF expression in rat retina. 1509 37


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