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 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ocular vascular diseases such as diabetic retinopathy, retinal vein occlusion, and age-related macular degeneration, whose population increases along with aging, have become leading causes of severe visual disturbance. Macular edema and serous retinal detachment are associated with abnormal vascular leakage and tractional retinal detachment, and neovascular glaucoma is caused by retinal neovascularization. Such ocular vascular diseases are caused by vascular cell aging and vascular damage associated with lifestyle-related diseases including diabetes mellitus, hypertension, hyperlipidemia, and obesity. In the present study, we investigated molecular mechanisms in such vascular deficiencies using vascular cell biology methodology, and we propose novel strategies for the treatment of such vascular diseases. Along with aging, oxidative stress and physical stress, such as mechanical stretch, continuously and directly insult vascular cells. Such stress induces apoptosis by intracellular signaling through stress kinases in cultured retinal vascular cells. Inhibition of such stress kinases could be an effective treatment to protect the vascular cells against age-related damage. In a retinal vascular developmental model, pericyte loss causes pathology mimicking macular edema and proliferative diabetic retinopathy. Angiopoietin 1 (Ang 1) secreted by pericytes suppresses oxidative stress-induced intracellular signaling through stress kinases linked to cell apoptosis and normalizes such retinal pathology. This suggests that the paracrine action of Ang 1 in the pericytes is necessary to sustain normal retinal vasculature, and that Ang 1-triggered intracellular signaling is useful for the treatment of vascular cell pathology associated with pericyte loss. In diabetic retinopathy and retinal vein occlusion, retinal vessels regress along with retinal vascular cell apoptosis, and the retina becomes ischemic followed by pathological retinal neovascularization. VEGF has been recognized as a predominant factor to induce the ischemic retinal neovascularization. We found that retinal vascular cells have a characteristic pattern in VEGF receptor expression, which causes vascular pathology more frequently in the retina than in other organs. Neuropilin 1 (NRP 1), which enhances VEGF receptor function, is abundantly expressed in the retinal endothelial cells and is upregulated by VEGF itself and by hypoxia to regulate a positive feedback mechanism in retinal neovascularization. This receptor could be a unique target for retina-specific therapy. Lifestyle-related diseases increase along with aging and have further increased due to changes in Japanese lifestyle imitating that of Western countries. We found that the renin-angiotensin system which regulates hypertension and cardiovascular diseases, and adipocytokines which are abnormally secreted in obesity, act as proangiogenic factors. Regulation of such lifestyle-related disease factors is important for the treatment of retinal vascular diseases. Finally, we found that erythropoietin is an ischemia-induced angiogenic factor that acts independently and as potently as VEGF in proliferative diabetic retinopathy (PDR). Our study utilizing human vitreous samples demonstrates that the VEGF level is particularly high and strongly associated with angiogenic activity in PDR patients. The potential of VEGF inhibitors has recently been recognized in clinical applications. The manipulation of each angiogenic factor and adipocytokine that we report here could become potential therapy in the near future.
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PMID:[Aging and retinal vascular diseases]. 1740 63

Diabetic retinopathy continues to be the leading cause of legal blindness among working-age individuals. The earliest histological features of diabetic retinopathy include neuroretinal damage, capillary basement membrane thickening, loss of pericytes and loss of endothelial cells. At advanced stages, neovascularization, the hallmark of proliferative diabetic retinopathy (PDR) occurs, and blindness can result from relentless abnormal fibrovascular proliferation with subsequent bleeding and retinal detachment. Macular oedema is another retinal complication of diabetes that is responsible for a major part of vision loss, particularly in type 2 diabetes. The breakdown of the blood retinal barrier and the consequent vascular leakage and thickening of retina are the main events involved in its pathogenesis. Although a tight control of both blood glucose levels and hypertension are essential to prevent or arrest progression of the disease, the recommended goals are difficult to achieve in many patients. Laser photocoagulation treatment soon after the onset of PDR significantly reduces the incidence of severe vision loss. However, the optimal timing for laser treatment is frequently passed and, in addition, it is not uniformly successful in halting visual decline. For all these reasons, new pharmacological treatments based on the understanding of the pathophysiological mechanisms of diabetic retinopathy have been developed in recent years. There is mounting evidence to suggest that angiogenic factors play a crucial role in PDR development, vascular endothelial growth factor (VEGF) being the most relevant. Other growth factors or cytokines such as insulin-like growth factor I (IGF-1), hepatocyte growth factor (HGF), basic fibroblast growth factor (b-FGF), platelet derived growth factor (PDGF), pro-inflammatory cytokines and angiopoetins, are also involved in the pathogenesis of PDR. However, the intraocular synthesis of angiogenic factors is counterbalanced by the synthesis of antiangiogenic factors. Therefore, the balance between the angiogenic and antiangiogenic factors rather than angiogenic factors themselves will be crucial in determining the progression of PDR. The main antiangiogenic factor is the pigment epithelium derived factor (PEDF) but the transforming growth factor beta (TGF-beta), thrombospondin (TSP) and somatostatin are also among the intraocullary synthesized antiangiogenic factors.
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PMID:Angiogenic and antiangiogenic factors in proliferative diabetic retinopathy. 1822 Jun 19

Diabetic retinopathy is the one of the leading cause of visual impairment in world including Nepal. The objective of the study is to estimate the prevalence of and factors associated with Diabetic Retinopathy among diabetics in a Tertiary Eye Care Centre, Nepal. A hospital-based, cross sectional study, was conducted at Tilganga Eye Centre, Nepal. 371 consecutive subjects were recruited during a period of study. Ophthalmologist performed comprehensive eye examinations, which were reconfirmed by senior ophthalmologist. Diabetic Retinopathy was graded using the Early Treatment Diabetic Retinopathy Study. Total 371 consecutive diabetics were examined, mean of 57.4 years (SD 12.0) having the sex ratio of 0.72 male per female. The prevalence of Diabetic Retinopathy was 44.7% (166) with non-proliferative Diabetic Retinopathy presented 85.5% (142) and 14.5% (24) were proliferative Diabetic Retinopathy. Clinically significant macular edema was found in 19.2% (32). The age at onset of diabetes, duration of diabetes and hypertension were significantly associated with Diabetic Retinopathy (p = < 0.05) whereas ethnicity, sex and cataract surgery were not associated with it (p = > 0.05). The prevalence of Diabetic Retinopathy was within the range of previous studies with a high rate of proliferative diabetic retinopathy. Factors associated with diabetic retinopathy were similar to other developed countries. To prevent this condition of Diabetic Retinopathy, the coordination between physician and ophthalmologist needs to be strengthened.
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PMID:Prevalence of and factors associated with diabetic retinopathy among diabetics in Nepal: a hospital based study. 1829 9

Vascular endothelial growth factor (VEGF) plays a key role in the development of both proliferative diabetic retinopathy (PDR) and diabetic macular oedema (DMO). In recent years, anti-VEGF agents have emerged as new approaches to the treatment of these devastating diabetic complications. Although Phase III studies in the diabetic population are needed, intravitreal anti-VEGF therapy is currently being used in clinical practice. Intravitreal injection is an effective means of delivering anti-VEGF drugs to the retina. However, this is an invasive procedure associated with potentially serious complications, such as endophthalmitis or retinal detachment, which may be significant for patients requiring serial treatment over many years. In addition, although delivered within the vitreous, anti-VEGF drugs could pass into the systemic circulation, which could potentially result in hypertension, proteinuria, increased cardiovascular events and impaired wound healing. Pegaptanib, ranibizumab and bevacizumab are the currently available anti-VEGF agents. Ranibizumab and bevacizumab block all VEGF isoforms, thus impairing both physiological and pathological neovascularisation. Pegaptanib only blocks the VEGF(165) isoform, and would therefore seem the best option for avoiding systemic adverse effects in diabetic patients, although this remains to be demonstrated in clinical trials. In this regard, head-to-head studies designed to evaluate not only the efficacy, but also the systemic adverse effects of these drugs in a high-risk population such as diabetic patients are warranted.
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PMID:Intravitreous anti-VEGF for diabetic retinopathy: hopes and fears for a new therapeutic strategy. 1860 60

Ethnicity has been shown to be associated with micro- and macrovascular complications of diabetes in European and North American populations. We analyzed the contribution of ethnicity to the prevalence of micro- and macrovascular complications in Brazilian subjects with type 2 diabetes attending the national public health system. Data from 1810 subjects with type 2 diabetes (1512 whites and 298 blacks) were analyzed cross-sectionally. The rates of ischemic heart disease, peripheral vascular disease, stroke, distal sensory neuropathy, and diabetic retinopathy were assessed according to self-reported ethnicity using multiple logistic regression models. Compared to whites, black subjects [odds ratio = 1.72 (95%CI = 1.14-2.6)] were more likely to have ischemic heart disease when data were adjusted for age, sex, fasting plasma glucose, HDL cholesterol, hypertension, smoking habit, and serum creatinine. Blacks were also more likely to have end-stage renal disease [3.2 (1.7-6.0)] and proliferative diabetic retinopathy [1.9 (1.1-3.2)] compared to whites when data were adjusted for age, sex, fasting plasma glucose, HDL cholesterol, hypertension, and smoking habit. The rates of peripheral vascular disease, stroke and distal sensory neuropathy did not differ between groups. The higher rates of ischemic heart disease, end-stage renal disease and proliferative diabetic retinopathy in black rather than in white Brazilians were not explained by differences in conventional risk factors. Identifying which aspects of ethnicity confer a higher risk for these complications in black patients is crucial in order to understand why such differences exist and to develop more effective strategies to reduce the onset and progression of these complications.
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PMID:Vascular complications of black patients with type 2 diabetes mellitus in Southern Brazil. 1879 99

We present general guidelines to help us with the treatment of diabetic retinopathy (DR) at a time when numerous therapeutic alternatives have been developed although their role has not yet been adequately defined. This protocol is not directed at experienced retinologists but rather at general ophthalmologists who require a practical and up to date guide of a pathology as prevalent as RD. The different therapeutic options available, and their most accepted indications depending on the degree of diabetic retinopathy that patients have, are reviewed. We propose what to do in cases of mild, moderate and severe non-proliferative diabetic retinopathy as well as in cases of proliferative diabetic retinopathy (panphotocoagulation/antiangiogenic drugs/vitreorretinal surgery). The treatment of diabetic macular edema depending on its angiographic and topographic characteristics is also discussed. The importance of metabolic control of the patient is stressed (tight glycemic control, control of arterial hypertension and dyslipemia) in aiding the treatment of diabetic retinopathy. This therapeutic proposal has been discussed widely by retinologists from the four largest hospitals in the Canary Islands, and is therefore an agreed text based on recent scientific literature.
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PMID:[Review of the protocol for the treatment of diabetic retinopathy]. 1925 76

Diabetic retinopathy should be carefully monitored during certain risk situations. Indeed, diabetic retinopathy in pregnant type 1 diabetic patients can rapidly progress and threaten vision, as in other situations such as puberty, glycemic equilibration, or ocular surgery. During pregnancy, five major risk factors for progression have been identified: pregnancy itself, diabetic retinopathy grade at baseline, duration of diabetes, important glycated hemoglobin reduction, and high blood pressure. These factors must be taken into account when planning pregnancy in diabetic patients and during the follow-up of their diabetic retinopathy. Diabetic women should be counseled about the risks of progression of their disease before planning pregnancy. Careful eye examination before and during the first trimester should be done in these patients, in order to detect severe non-proliferative diabetic retinopathy and/or high-risk diabetic retinopathy and perform rapid laser treatment if needed. Follow-up visit frequency should be adapted to the severity of the diabetic retinopathy. Very few authors have studied diabetic macular edema during pregnancy. This complication can spontaneously regress postpartum and should not be treated too rapidly.
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PMID:[Progression of diabetic retinopathy during pregnancy]. 2045 94

The incidence of type 1 diabetes is increasing in Denmark as well as the rest of the world. Due to diabetes-related micro- and macrovascular complications, the morbidity and the mortality is higher among type 1 diabetic patients. The aim of this thesis was to examine a population-based cohort of 727 type 1 diabetic patients from Fyn County, Denmark, with an onset of diabetes before 1 July 1973 in order to: (1) Evaluate the all-cause mortality rates and the influence of sex, duration of diabetes and calendar year of diagnosis in a 33-year follow-up (Paper I). (2) Examine glycaemic regulation, lipids and renal dysfunction as risk factors for all-cause mortality, cardiovascular mortality and IHD (Paper II). (3) Estimate the prevalence of DR as well as the 25-year incidence of PDR and associated risk factors in long-time surviving patients (Paper III). (4) To compare the grading of DR between ETDRS seven standard field 30 degrees stereoscopic colour films and nine field 45 degrees monoscopic digital colour images in long-term surviving patients (Paper IV). In the years 1973-2006 an overall MR of 22.3 per 1000 person-years was found. Furthermore a relative mortality of 3.4 was found as compared to the general population in Denmark. The relative mortality was especially high for patients aged 30-39 (SMR 9.8). There was a tendency towards a better survival for patients diagnosed after 1964. This was especially seen for men. Diabetes was the most common cause of death for those who died in the group. In 1993-1996 blood samples were drawn and glycaemic regulation, lipids and renal markers were subsequently used as predictors of all-cause mortality, cardiovascular mortality and ischaemic heart disease. Glycaemic regulation, dyslipidaemia and creatinine were all significantly associated with all three endpoints. Furthermore, variations in glycaemic control were also identified as a risk factor for overall mortality. Two hundred and one patients were examined for diabetic retinopathy in 1981-1982 and 2007-2008. At follow-up, 97.0% had DR and 42.9% of all patients without PDR at baseline developed this during the follow-up period. Patients who had had a poor glycaemic regulation as well as those who had NPDR at baseline were more likely to develop PDR than the remaining patients. On the other hand, other risk factors such as high blood pressure and proteinuria did not predict PDR. In the comparative study between ETDRS seven standard field 30 degrees stereoscopic colour films and nine field 45 degrees monoscopic digital colour images, 43 eyes of 43 patients were examined in 2008. A poor correlation was found between the two methods: only 29.3% were graded alike. In the remaining, the level of DR was graded higher in the digital photos. Among these, PDR was detected in three eyes using digital photos but remained undetected on all films. This suggests that digital photos with wide fields are the best way to detect DR in long-term type 1 diabetic patients. Overall, it is concluded that mortality is still higher among type 1 diabetic patients. This depends, among other things, on glycaemic regulation, lipid status and, partly, renal dysfunction. Diabetic retinopathy is almost universal in long-term type 1 diabetic patients, and almost half of all patients will develop PDR in 25 years. Nine field digital photos provide the best grading of retinopathy in long-term type 1 diabetic patients.
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PMID:Long-term mortality and retinopathy in type 1 diabetes. 2050 Jul 31

The vascular endothelial growth factor (VEGF) plays a key role in the development of proliferative diabetic retinopathy (PDR) and diabetic macular edema (DME), resulting in a significant visual loss among patients with diabetes mellitus. Systemic VEGF-A and the interplay between membrane-bound VEGF receptors and VEGF-R1 (soluble form) are key to angiogenesis and vasculogenesis. Furthermore, patients with diabetes have a higher risk of hypertension and proteinuria, two surrogate markers of systemic VEGF inhibition. Pegaptanib, ranibizumab, bevacizumab and roboxistaurin are the currently available anti-VEGF agents. Agents with activity occurring later down the angiogenic pathway and those drugs with potential to synergize with anti-VEGF-A technologies are being developed. In recent years, inhibition of ocular VEGF has emerged as a promising treatment modality for diabetes and is currently undergoing evaluation in clinical trials. A potential role for these anti-VEGF agents in the prevention of PDR and DME are also emerging.
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PMID:Anti-angiogenesis drugs in diabetic retinopathy. 2093 97

The association between subclinical hypothyroidism (SCH) and microvascular complications of type 2 diabetes is unclear. We examined whether SCH is associated with diabetic retinopathy or nephropathy in Korean patients with type 2 diabetes. Data from 489 patients who visited the diabetes clinic at a university hospital between 2001 and 2007 were analyzed retrospectively. Participants were evaluated for glycemic control, thyroid function, and diabetic retinopathy and nephropathy. Diabetic retinopathy was classified into five grades. Diabetic nephropathy was assessed by the presence of albuminuria. Patients in the SCH group had a higher proportion of women, older age, longer duration of diabetes, higher systolic and diastolic blood pressure, and higher insulin resistance index compared with the euthyroid group. No significant difference in family history of diabetes or body mass index was found between groups. The prevalence of severe diabetic retinopathy (severe nonproliferative diabetic retinopathy or proliferative diabetic retinopathy) was significantly higher in the SCH group than the euthyroid group (32.8% vs. 19.6%, P = 0.036), whereas no between-group difference was found in the prevalence of diabetic nephropathy. After adjustment for potential confounding factors (HbA1c, BMI, duration of diabetes, diabetic nephropathy, and hypertension) by multivariate logistic regression analysis, SCH remained significantly associated with severe diabetic retinopathy (odds ratio 2.086 (95% CI, 1.010-4.307), P = 0.047). These results suggest that SCH was independently associated with severe diabetic retinopathy in patients with type 2 diabetes. Further prospective studies are required to confirm the association between SCH and diabetic retinopathy.
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PMID:Association between subclinical hypothyroidism and severe diabetic retinopathy in Korean patients with type 2 diabetes. 2205 23


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