losartan-potassium and Macular-Edema

Diabetic retinopathy (DR) is the most common microvascular complication of diabetes mellitus (DM). DR is complex and the term encompasses several clinical subtypes of diabetic eye disease, including diabetic macular edema (DME), the most frequent cause of central vision loss in DR patients. Both genetic and environmental factors contribute to the pathophysiology of DR and its subtypes. While numerous studies have identified several susceptibility genes for DR, few have investigated the impact of genetics on DME susceptibility. This review will focus on the current literature surrounding genetic risk factors associated with DME. We will also highlight the small number of studies investigating the genetics of response to antivascular endothelial growth factor (anti-VEGF) injection, which is used to treat DME.

Topics: Aldehyde Reductase; Angiogenesis Inhibitors; Apolipoproteins E; Bevacizumab; Diabetic Retinopathy; Erythropoietin; Eye Proteins; Genetic Predisposition to Disease; Humans; Macular Edema; MicroRNAs; Nerve Growth Factors; Nitric Oxide Synthase; Ranibizumab; Receptors, Vascular Endothelial Growth Factor; Recombinant Fusion Proteins; Serpins; Superoxide Dismutase; Treatment Outcome; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factor C

Topics: Aged; Aqueous Humor; Biomarkers; Diabetic Retinopathy; Erythropoietin; Eye Proteins; Female; Humans; Laser Therapy; Macular Edema; Male; Middle Aged; Nerve Growth Factors; Serpins

The earliest and most significant change in diabetic retinopathy (DR) is blood-retinal barrier (BRB) dysfunction, followed by two main pathologies that may cause severe visual impairment: Diabetic Macular Edema (DME) and Proliferative Diabetic Retinopathy (PDR). The pathological hallmarks of BRB dysfunction include loss of tight junction integrity, VEGF- and AGE-induced damage, oxidative stress, and inflammatory changes. Recently, several BRB protective factors have been reported. Our aim is to give a review of those protective factors and discuss new potential therapeutic targets for DR.

Topics: Animals; Blood-Retinal Barrier; Diabetic Retinopathy; Erythropoietin; Fenofibrate; Humans; Insulin-Like Growth Factor Binding Protein 3; Macular Edema; Protective Factors; Pyrazines; Sitagliptin Phosphate; Triazoles; Vascular Endothelial Growth Factor A

Proliferative diabetic retinopathy (PDR), characterized by pathologic retinal angiogenesis, is a major cause of blindness in the USA and globally. Treatments targeting vascular endothelial growth factor (VEGF) have emerged as a beneficial part of the therapeutic armamentarium for this condition, highlighting the utility of identifying and targeting specific pathogenic molecules. There continues to be active research into the molecular players regulating retinal angiogenesis, including pro-angiogenic factors, anti-angiogenic factors, and integrins and matrix proteinases. New insights have been especially prominent regarding molecules which regulate specialized endothelial cells called tip cells, which play a lead role in endothelial sprouting. Together, these research efforts are uncovering new, important molecular regulators of retinal angiogenesis, which provide fertile areas for therapeutic exploration. This review discusses potential molecular targets, with an emphasis towards newer targets.

Topics: Angiogenesis Inhibitors; Blindness; Diabetic Retinopathy; Disease Progression; Erythropoietin; Female; Humans; Hyperglycemia; Macular Edema; Male; Retinal Neovascularization; Vascular Endothelial Growth Factor A

The hypothesis that soluble vasoproliferative growth factors cause new blood vessel growth (neovascularization) in proliferative diabetic retinopathy and other proliferative diseases of the retina was first proposed by Isaac Michaelson in 1948. Until recently, laser photocoagulation has been the preferred treatment for these diseases. VEGF, first identified in 1983 and associated with diabetic retinopathy in 1994, has been the focus of increasing research in this field. Several types of anti-VEGF molecules are being evaluated for efficacy; however, it is becoming evident that VEGF may not be the only, or even the major, molecule responsible for diabetic macular edema.

Topics: Angiogenesis Inhibitors; Angiogenic Proteins; Animals; Anti-Inflammatory Agents; Antioxidants; Diabetic Retinopathy; Erythropoietin; Eye Proteins; Fatty Acids, Omega-6; Hormone Antagonists; Humans; Immunosuppressive Agents; Insulin-Like Growth Factor I; Macular Edema; Nerve Growth Factors; Protein Kinase C; Protein Kinase Inhibitors; Receptors, Somatotropin; Serpins; Signal Transduction; Vascular Endothelial Growth Factor A

To evaluate the effect of three intravitreal bevacizumab (IVB) injections alone or in combination with intravitreal erythropoietin (EPO) in the treatment of refractory diabetic macular edema (DME).. In a randomized double-blind clinical trial, 48 eyes of 34 diabetic patients with refractory DME were enrolled. Eyes were randomly assigned to receive either 3 monthly injections of 0.05 cc (1.25 mg) IVB plus 0.05 cc (1000 unit) EPO or 0.05 cc (1.25 mg) IVB alone. Main outcome was best-corrected visual acuity (BCVA) changes and secondary outcome was central macular thickness (CMT). The patients were followed for 6 months.. Mean BCVA changes up to 4 and 6 months were insignificant in both groups. It changed from 0.72 ± 0.56 logMAR at baseline to 0.74 ± 0.5 (P = 0.85) and 0.71 ± 0.44 (P = 0.40) in the combination group and from 0.48 ± 0.39 logMAR to 0.47 ± 0.35 (P = 0.48) and 0.52 ± 0.33 (P = 0.69) in the IVB alone group, at 4 and 6 months, respectively. The difference of mean BCVA changes between the groups was insignificant at both 4 and 6 months (P = 0.07 and P = 0.36, respectively). Within the group changes of mean CMT were significant only in the combination group at 4 and 6 months, from 518 ± 134 μ at baseline to 472 ± 151 to 475 ± 167 μ, respectively (P = 0.01 and P = 0.05). Corresponding changes were not significant in the IVB alone group. However, the difference between the groups was not significant at all visits (P = 0.51 and P = 0.71, respectively).. This clinical trial demonstrated that intravitreal erythropoietin had no additional effect to IVB in the treatment of refractory DME in the short term.. Clinical trials.gov identifier: NCT03821168.

Topics: Aged; Angiogenesis Inhibitors; Bevacizumab; Diabetic Retinopathy; Double-Blind Method; Drug Therapy, Combination; Erythropoietin; Female; Follow-Up Studies; Humans; Intravitreal Injections; Macula Lutea; Macular Edema; Male; Middle Aged; Tomography, Optical Coherence; Treatment Outcome; Vascular Endothelial Growth Factor A

Erythropoietin was administered to five anemic azotemic diabetic subjects for 1 year to assess the effect of increasing red cell mass on clinical well-being and the course of renal functional decline. None of the subjects manifested worsened hypertension or cerebrovascular or cardiovascular complications despite an increase in mean hematocrit from a baseline mean of 29.6% to a mean of 39.5%. The serum creatinine concentration after 1 year of treatment with erythropoietin was 3.7 mg/dL, which was unchanged from the baseline value of 3.5 mg/dL. Plasma viscosity remained constant as red cell mass increased. Although the viscosity of whole blood rose as the hematocrit increased, it was within the range of normal blood viscosity for an equivalent hematocrit. The favorable impact of erythropoietin treatment on three diabetic subjects who had macular edema and anemia is described. One hypothesis to explain the benefit of a raised hematocrit on both diabetic nephropathy and retinopathy is that the metabolic, hormonal, and hemodynamic components of the diabetic syndrome, in concert, produce tissue and cellular hypoxia that is ameliorated in part by the greater oxygen-transporting capacity of a raised red cell mass. The pseudohypoxia of diabetes may be implicated in the pathogenesis of diabetic neuropathy, retinopathy, muscular dysfunction, and nephropathy.

Topics: Blood Viscosity; Creatinine; Diabetic Nephropathies; Diabetic Retinopathy; Erythropoietin; Female; Hematocrit; Humans; Kidney Failure, Chronic; Macular Edema; Middle Aged; Recombinant Proteins

To investigate the intravitreal levels of potent vasoactive, angiogenic and extracellular matrix remodelling factors in the diabetic patients with simvastatin treatment.. This is an institutional, prospective, observational case-control study. Type-1 and type-2 diabetic patients on lipophilic simvastatin (N = 14) compared with patients without statin medication (N = 50). Vitreous samples were subjected to protein measurements of angiopoietin (Ang)-1 and Ang-2, erythropoietin (EPO), transforming growth factor (TGF)-β1, vascular endothelial growth factor (VEGF) by ELISA and matrix metalloproteinase (MMP)-2 and MMP-9 by gelatin zymography.. Intravitreal levels of Ang-2 (p = 0.029), VEGF (p = 0.001) and proMMP-9 (p = 0.015) were lower in simvastatin-treated than in non-statin-treated controls. In diabetics with macular oedema (DME), intravitreal Ang-2 (p = 0.006) and VEGF (p = 0.002) levels were lower in simvastatin-treated patients compared with non-statin-treated controls. In those patients with proliferative diabetic retinopathy (PDR), intravitreal Ang-2 (p = 0.002), TGF-β1 (p = 0.037), VEGF (p = 0.001) and pro- and totalMMP-9 (p = 0.004 and p = 0.007) levels were lower when receiving simvastatin medication.. In diabetic patients with DME or PDR, the intravitreal levels of permeability and proangiogenic factors Ang-2 and VEGF were lower in simvastatin-treated than in those without statin medication. Moreover, the levels of MMP-9 and TGF-β1, factors involved in the breakdown of basement membrane and fibroproliferation, were lower in patients with PDR having simvastatin medication. When acetylsalicylic acid was combined with simvastatin treatment, the intraocular levels of Ang-2 and VEGF were significantly lower than in diabetics treated with simvastatin alone. These data provide a novel insight into the potential protective mechanisms underlying simvastatin medication in patients with diabetic retinopathy complications.

Topics: Adult; Aged; Angiopoietin-2; Biomarkers; Case-Control Studies; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Retinopathy; Enzyme-Linked Immunosorbent Assay; Erythropoietin; Female; Humans; Hypolipidemic Agents; Macular Edema; Male; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Middle Aged; Prospective Studies; Simvastatin; Transforming Growth Factor beta1; Vascular Endothelial Growth Factor A; Vitrectomy; Vitreous Body

The aim of this study was to evaluate concentrations of erythropoietin (EPO) and vascular endothelial growth factor (VEGF) in serum, aqueous and vitreous humour of diabetic patients with proliferative retinopathy (PDR) and to verify their possible modifications induced by intravitreal injection of bevacizumab (IVB).. This prospective observational study was performed on patients who underwent vitrectomy for proliferative diabetic retinopathy and macular hole or pucker. The study sample consisted of 33 patients with proliferative diabetic retinopathy and 20 non-diabetic patients with macular hole or pucker. EPO and VEGF levels in serum, aqueous and vitreous humour were measured in both groups. In diabetic patients measures were performed before and after IVB.. EPO and VEGF levels in aqueous and vitreous humour were markedly increased in diabetic patients with PDR as compared with those recorded in the control group (P<0.001); contrarily, EPO serum levels were similar in both groups (p=not significant). IVB did not affect EPO levels (aqueous 39.1 ± 29.2 vs. 38.6 ± 26.1; vitreous 179.3 ± 88.3 vs. 131.6 ± 67.8; serum 9.2 ± 5.8 vs. 6.9 ± 3.7 mUI/mL); conversely, VEGF concentration significantly decreased 15 days after IVB in serum and ocular fluids (aqueous 141.6 ± 12.3 vs. 81.4 ± 5.4; vitreous 180.4 ± 45.8 vs. 95.8 ± 23.6; serum 113.9 ± 52.8 vs. 73.2 ± 65.6 mUI/mL).. These findings demonstrate that the production of VEGF and EPO is regulated by different mechanisms. Intraocular levels of EPO in diabetic patients were significantly higher than those recorded in serum, suggesting a local production. In addition, bevacizumab does not influence intraocular levels of EPO.

Topics: Aged; Antibodies, Monoclonal, Humanized; Aqueous Humor; Bevacizumab; Body Fluid Compartments; Comorbidity; Diabetic Retinopathy; Erythropoietin; Female; Humans; Intravitreal Injections; Macular Edema; Male; Middle Aged; Prospective Studies; Retinal Perforations; Serum; Vascular Endothelial Growth Factor A; Vitrectomy; Vitreoretinopathy, Proliferative; Vitreous Body; Vitreous Hemorrhage

To evaluate the effect of intravitreal injection of erythropoietin for the treatment of non-arteritic anterior ischaemic optic neuropathy (NAION).. In this prospective interventional case series, 31 eyes of 31 patients with NAION were included. Patients received intravitreal injection of 2000 unit (0.2 cm³) of erythropoietin within 1 month of the onset of the disease. Visual acuity and visual field were recorded before injections and 1 week, 1 month, 3 months and 6 months after the injections.. The mean duration of symptoms before injections was 11.2 ± 5.5 days. Six months after injections, visual acuity improved in 27 eyes (87%), and 17 eyes (54.8%) had ≥ 3 lines of visual improvement. The mean preinjection visual acuity was 1.01 ± 0.88 logMAR and 0.58 ± 0.58 logMAR (p<0.001) at last follow-up. Visual acuity improvement occurred in 61.2% of patients within the first month. It followed a biphasic pattern in which there was continuous improvement up to 3 months and then started to deteriorate, although it remained significantly better than baseline until the last follow-up. No patient lost any lines of visual acuity compared with the baseline values. The mean of mean deviations of visual field was -19.6 ± 5.7 dB at baseline and -18.6 ± 6.3 dB (p = 0.6) at last follow-up.. Intravitreal injection of erythropoietin may be safe and effective in the treatment of NAION. The effect may last for a few months and then decline.

Topics: Cohort Studies; Erythropoietin; Female; Humans; Intravitreal Injections; Macular Edema; Male; Middle Aged; Optic Neuropathy, Ischemic; Prospective Studies; Tomography, Optical Coherence; Treatment Outcome; Visual Acuity; Visual Field Tests

To determine the aqueous humour levels of vascular endothelial growth factor (VEGF) and erythropoietin (EPO) in eyes with diabetic macular oedema before and after intravitreal EPO injection.. Prospective interventional case series.. Eleven eyes of 11 patients with diabetic macular oedema, and 10 eyes of 10 patients with cataract surgery as controls.. EPO and VEGF levels in aqueous humour before and after intravitreal EPO injection in patients and compared with controls.. Eyes with diabetic macular oedema received an intravitreal injection of EPO (1000 IU/0.05 mL), followed by various intraocular procedures at different intervals (1-54 days) after injection. An aqueous humour sample was obtained and aqueous humour levels of EPO and VEGF were measured using enzyme-linked immunosorbent assay.. The aqueous levels of EPO and VEGF were significantly elevated in diabetic macular oedema eyes compared to control eyes (P < 0.05). EPO levels in patients correlated with VEGF levels (r = 0.816, P = 0.002) and central macular thickness at baseline (r = 0.618, P = 0.043). After intravitreal EPO injection, aqueous EPO levels were significantly elevated, whereas aqueous VEGF levels were varied according to the time interval since injection. Visual acuity and central macular thickness were not different after injection, compared to before injection. Aqueous EPO levels did not correlate with serum EPO levels(r = 0.299, P = 0.371).. EPO is locally expressed and is correlated with VEGF in eyes with diabetic macular oedema. The role of EPO and the effect of intravitreal EPO in patients with diabetic macular oedema need to be further defined.

Topics: Adult; Aqueous Humor; Diabetic Retinopathy; Enzyme-Linked Immunosorbent Assay; Epoetin Alfa; Erythropoietin; Female; Fluorescein Angiography; Humans; Intravitreal Injections; Macular Edema; Male; Middle Aged; Prospective Studies; Recombinant Proteins; Tomography, Optical Coherence; Vascular Endothelial Growth Factor A; Visual Acuity

Topics: Erythropoietin; Female; Humans; Macular Edema; Male; Optic Neuropathy, Ischemic; Visual Acuity

This study compares vitreal levels of erythropoietin (EPO) in patients with retinal vein occlusion (RVO) with control subjects. In addition, it investigates different RVO disease parameters (time of vein occlusion, patient age, vitreal vascular endothelial growth factor (VEGF) levels, and extent of central macular edema) for possible correlations with vitreal EPO levels.. Serum and vitreal EPO were measured from 6 patients with branch retinal vein occlusion, 6 patients with central retinal vein occlusion, and 12 control subjects (10 macular puckers and 2 macular holes).. Serum EPO levels (9.8 ± 4.9 mU/mL) did not differ between the RVO and control groups and were significantly lower than vitreal EPO levels in all groups. Vitreal EPO was elevated both in branch RVO (91 ± 59 mU/mL) and central RVO (182 ± 70 mU/mL) compared with controls (35 ± 24 mU/mL). Increased vitreal EPO correlated with higher vitreal VEGF (r = 0.64, P = 0.0008) and more pronounced central macular edema (r = 0.66, P = 0.001).. The results from this study indicate that EPO is locally expressed in the retina and that it is upregulated together with VEGF in RVO eyes. Because of its role both in neuroprotection and angiogenesis, ocular EPO might represent an interesting target to investigate in patients with RVO, especially in light of the current anti-VEGF treatments.

Topics: Aged; Aged, 80 and over; Enzyme-Linked Immunosorbent Assay; Erythropoietin; Female; Humans; Luminescent Measurements; Macular Edema; Male; Middle Aged; Retinal Perforations; Retinal Vein Occlusion; Up-Regulation; Vascular Endothelial Growth Factor A; Vitreous Body

In a recent study, we found high levels of erythropoietin (EPO) in patients with diabetic macular oedema (DME), suggesting a role of EPO in the pathogenesis of this condition. To investigate a possible relationship between EPO and other diseases causing macular oedema, we determined vitreous levels of this peptide in patients with macular oedema secondary to retinal vein occlusion (RVO) and compared them with levels in patients with DME and control patients.. Vitreous and serum samples were obtained from patients with macular oedema secondary to RVO, DME, epiretinal membrane, and macular hole (controls). EPO was measured by radioimmunoassay.. No differences were found in median vitreous EPO levels between patients with RVO and controls: RVO, 76 mU/ml (30-806) vs controls, 25 mU/ml (10-75) (P=0.105). Median EPO concentration was higher in DME patients than in patients with RVO or controls: DME, 430 mU/ml (41-3000) vs RVO, 76 mU/ml (30-806) (P<0.0001) vs controls, 25 mU/ml (10-75) (P<0.0001).. EPO levels are not elevated in patients with macular oedema secondary to RVO. Patients with DME have high levels of EPO. These results suggest that EPO could be involved in the pathogenesis of diabetic retinopathy, but not in macular oedema secondary to RVO.

Topics: Aged; Biomarkers; Diabetic Retinopathy; Erythropoietin; Female; Humans; Macular Edema; Male; Middle Aged; Radioimmunoassay; Retinal Vein Occlusion; Vitreous Body

Topics: Diabetic Retinopathy; Erythropoietin; Humans; Macular Edema

Topics: Diabetic Retinopathy; Erythropoietin; Humans; Macular Edema; Somatostatin; Vitreous Body

The purpose of this study was to evaluate whether the concentration of erythropoietin as another potent ischemia-induced angiogenic factor is elevated in eyes with neovascular (age-related macular degeneration [AMD]) or oedematous (diabetic retinopathy) maculopathies. The clinical comparative study included 28 patients with diabetic macular oedema, 59 patients with exudative AMD, and 49 patients with cataract. For all patients, aqueous humour was collected during cataract surgery or during an intravitreal injection of triamcinolone acetonide. Erythropoietin levels were measured using a solid-phase chemiluminescence immunoassay. The mean concentration of erythropoietin was significantly higher in the diabetic group (60.1 +/- 46.7 mUnits/mL; P < 0.001) than in the age-related macular degeneration group (22.9 +/- 23.2 mUnits/mL) and in the control group (22.0 +/- 21.0 mUnits/mL; P < 0.001). The two latter groups did not vary significantly (P = 0.41). The results indicate that erythropoietin may be present in considerably higher concentrations in eyes with diabetic macular oedema than in eyes with exudative AMD or normal eyes.

Topics: Aged; Aqueous Humor; Cataract; Diabetic Retinopathy; Erythropoietin; Exudates and Transudates; Humans; Luminescent Measurements; Macular Degeneration; Macular Edema

Erythropoietin has been recently found to be increased in the vitreous fluid from ischemic retinal diseases such as proliferative diabetic retinopathy (PDR). The aims of the present study were 1) to measure erythropoietin levels in the vitreous fluid from patients with diabetic macular edema (DME), a condition in which the ischemia is not a predominant event, and 2) to compare erythropoietin mRNA expression between human retinas from nondiabetic and diabetic donors without retinopathy.. Vitreous samples from 12 type 2 diabetic patients with DME without significant retinal ischemia and 12 PDR patients were prospectively analyzed. Ten nondiabetic patients with macular holes served as the control group. Erythropoietin was assessed by radioimmunoassay (milliunits per milliliter). Erythropoietin mRNA expression was measured by quantitative real-time RT-PCR analysis in the retina from eight nondiabetic and eight age-matched diabetic donors without diabetic retinopathy. Intravitreal erythropoietin concentration was higher in both PDR and DME patients than in nondiabetic control subjects (PDR vs. control subjects: median 302 [range 117-1,850] vs. 30 mU/ml [10-75], P < 0.01; DME vs. control subjects: 430 [41-3,000] vs. 30 mU/ml [10-75], P < 0.01). However, no significant differences were found between DME and PDR patients. Erythropoietin mRNA expression was detected in the human retina, and it was higher in the retina from diabetic than from nondiabetic donors.. As occurs in PDR, intravitreous erythropoietin concentrations are strikingly higher in DME. Erythropoietin is expressed in the human retina, and it is upregulated in diabetic patients even without retinopathy. These findings suggest that other factors apart from ischemia are involved in the overexpression of erythropoietin in diabetic retinopathy.

Topics: Aged; Case-Control Studies; Diabetes Mellitus, Type 2; Diabetic Retinopathy; Erythropoietin; Female; Humans; Macular Edema; Male; Middle Aged; Prospective Studies; Radioimmunoassay; Retina; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger